Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
This review develops a region-specific Multi-Criteria Decision Analysis (MCDA)-based screening framework for evaluating food-processing residues for biochar applications, offering a transparent and replicable decision-support tool for policymakers and bioeconomy stakeholders in Turkey and beyond. Using Turkey as a region-specific case context, ten underutilized residues—boza fermentation residue, tarhana fines, rosehip seed cake, mulberry syrup press-cake, carob syrup pulp residue, pumpkin seed oil cake, saffron floral by-products, fig-jam seed fraction, lupin brining sediment, and date syrup filter cake—were compiled from the literature and characterized in terms of moisture, ash, organic fractions, higher heating value, and macro-mineral composition. Drawing on thermochemical fundamentals, the review synthesizes how these traits influence biochar properties relevant to fuel use, soil amendment, pollutant adsorption, anaerobic digestion (AD) enhancement, and composite materials, and qualitatively links residue groups to suitable conversion windows such as hydrothermal carbonization and low- or high-severity slow pyrolysis. To convert this information into a transparent screening tool, all indicators were normalized via min–max transformation and aggregated into four mechanistic proxies capturing fuel quality, nutrient release, an adsorption-oriented screening proxy, and AD compatibility. A Simple Additive Weighting (SAW) method was then used to calculate 0–1 suitability scores and 0–100 indices for five application domains: fuel, soil amendment, adsorption/remediation, AD enhancement, and composite/material use. Under the selected criteria and weighting assumptions, rosehip seed cake, pumpkin seed oil cake, carob syrup pulp residue, and fig-jam seed fraction emerged as comparatively high-priority feedstocks, whereas saffron floral by-products and lupin brining sediment showed consistently low relative suitability. By linking feedstock chemistry to application-oriented screening scores, the framework supports rapid comparison of residue-to-application pathways while acknowledging that rankings may evolve as additional performance data, logistical constraints, or alternative weighting scenarios are incorporated. The online version contains supplementary material available at 10.1186/s40643-026-01067-8. Keywords: Biochar, Pyrolysis, Food-processing residues, Multi-criteria decision analysis (MCDA), Circular bioeconomy

Candidates:
A. To convert this information into a transparent screening tool, all indicators were not normalized via min–max transformation and aggregated into four mechanistic proxies capturing fuel quality, nutrient release, an adsorption-oriented screening proxy, and AD compatibility.
B. This review develops a region-specific Multi-Criteria Decision Analysis (MCDA)-based screening framework for evaluating food-processing residues for biochar applications, offering a transparent and replicable decision-support tool for policymakers and bioeconomy stakeholders in Turkey and beyond.
C. To convert this information into a transparent screening tool, all indicators were normalized via min–max transformation and aggregated into four mechanistic proxies capturing fuel quality, nutrient release, an adsorption-oriented screening proxy, and AD compatibility.
D. The evidence does not state that using Turkey as a region-specific case context, ten underutilized residues—boza fermentation residue, tarhana fines, rosehip seed cake, mulberry syrup press-cake, carob syrup pulp residue, pumpkin seed oil cake, saffron floral by-products, fig-jam seed fraction, lupin brining sediment, and date syrup filter cake—were compiled from the literature and characterized in terms of moisture, ash, organic fractions, higher heating value, and macro-mineral composition.
E. The evidence does not state that this review develops a region-specific Multi-Criteria Decision Analysis (MCDA)-based screening framework for evaluating food-processing residues for biochar applications, offering a transparent and replicable decision-support tool for policymakers and bioeconomy stakeholders in Turkey and beyond.
F. The evidence does not state that drawing on thermochemical fundamentals, the review synthesizes how these traits influence biochar properties relevant to fuel use, soil amendment, pollutant adsorption, anaerobic digestion (AD) enhancement, and composite materials, and qualitatively links residue groups to suitable conversion windows such as hydrothermal carbonization and low- or high-severity slow pyrolysis.
G. Using Turkey as a region-specific case context, ten underutilized residues—boza fermentation residue, tarhana fines, rosehip seed cake, mulberry syrup press-cake, carob syrup pulp residue, pumpkin seed oil cake, saffron floral by-products, fig-jam seed fraction, lupin brining sediment, and date syrup filter cake—were compiled from the literature and characterized in terms of moisture, ash, organic fractions, higher heating value, and macro-mineral composition.
H. Drawing on thermochemical fundamentals, the review synthesizes how these traits influence biochar properties relevant to fuel use, soil amendment, pollutant adsorption, anaerobic digestion (AD) enhancement, and composite materials, and qualitatively links residue groups to suitable conversion windows such as hydrothermal carbonization and low- or high-severity slow pyrolysis.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Fungal solid-state fermentation can improve the nutritional quality of plant-based foods, yet most processes rely on substrates whose properties are inherited from raw materials rather than intentionally designed. This perspective addresses this limitation by reframing the substrate as an active process component. Integrating biochemical, mechanical, and architectural principles into substrate design enables the development of engineered substrates that promote volumetric and spatially uniform bioconversion during solid-state fermentation of food materials.

Candidates:
A. The evidence does not state that integrating biochemical, mechanical, and architectural principles into substrate design enables the development of engineered substrates that promote volumetric and spatially uniform bioconversion during solid-state fermentation of food materials.
B. Fungal solid-state fermentation can improve the nutritional quality of plant-based foods, yet most processes rely on substrates whose properties are inherited from raw materials rather than intentionally designed.
C. Fungal solid-state fermentation can improve the nutritional quality of plant-based foods, yet most processes rely on substrates whose properties are not inherited from raw materials rather than intentionally designed.
D. This perspective addresses this limitation by reframing the substrate as an active process component.
E. The evidence does not state that this perspective addresses this limitation by reframing the substrate as an active process component.
F. Integrating biochemical, mechanical, and architectural principles into substrate design enables the development of engineered substrates that promote volumetric and spatially uniform bioconversion during solid-state fermentation of food materials.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
The ubiquitin-like domain 2 (Ubl2) of the SARS-CoV-2 virus is necessary for the stability and catalytic efficiency of its papain-like protease (PLpro). Our crystallographic study reveals that the Ubl2 domain exhibits notable flexibility and can adopt a conformation that places itself away from the PLpro catalytic domain, representing a new conformation from those reported so far for SARS-CoV-1 or SARS-CoV-2. The structural flexibility of Ubl2 could be allosterically related to the stability of the zinc-finger domain.

Candidates:
A. Our crystallographic study reveals that the Ubl3 domain exhibits notable flexibility and can adopt a conformation that places itself away from the PLpro catalytic domain, representing a new conformation from those reported so far for SARS-CoV-1 or SARS-CoV-2.
B. The ubiquitin-like domain 2 (Ubl2) of the SARS-CoV-2 virus is necessary for the stability and catalytic efficiency of its papain-like protease (PLpro).
C. The structural flexibility of Ubl3 could be allosterically related to the stability of the zinc-finger domain.
D. The structural flexibility of Ubl2 could be allosterically related to the stability of the zinc-finger domain.
E. Our crystallographic study reveals that the Ubl2 domain exhibits notable flexibility and can adopt a conformation that places itself away from the PLpro catalytic domain, representing a new conformation from those reported so far for SARS-CoV-1 or SARS-CoV-2.
F. The ubiquitin-like domain 3 (Ubl2) of the SARS-CoV-2 virus is necessary for the stability and catalytic efficiency of its papain-like protease (PLpro).


Prompt:
Some candidate values differ from the evidence by only one number. Select only the strings that appear verbatim, preserving candidate order. Return JSON using exactly this schema: {"reported_values":["candidate string"]}. Candidates: ["6.49 g/L", "5.46 g/L", "4.46 g/L", "4.82 g/L", "49.8 g/L", "5.82 g/L", "50.8 g/L", "5.49 g/L"]

Evidence:
l -Histidine is an essential amino acid with important applications in pharmaceuticals and nutrition, highlighting the demand for efficient microbial production platforms. This study developed a high-performance Escherichia coli cell factory through systematic metabolic engineering. First, we mined a feedback-resistant hisG∗ smar and the entire mutant his operon from a previously obtained high l -histidine-producing mutant of Serratia marcescens , offering novel enzymatic parts beyond conventional sources. Combined with precursor supply enhancement and redox balancing, the engineered strain yielded 4.46 g/L l -histidine. Second, a machine learning-based platform (TransDW) was utilized to predict and validate a novel efflux transporter, Cgl1374, increasing titer to 4.82 g/L. Third, we implemented a growth phase-dependent system to dynamically regulate pgi expression, redirecting carbon flux and achieving 5.49 g/L in shake flasks. Finally, applying a novel carbon evolution rate (CER)-based control strategy in fed-batch fermentation, the optimized strain achieved 49.8 g/L of l -histidine in a 5-L bioreactor, with a yield of 0.265 g/g glucose, which is the highest yield reported for engineered E. coli . This work establishes a synergistic framework combining non-model gene discovery, computational transport engineering, and real-time physiological feedback control, providing a versatile blueprint for next-generation microbial cell factories.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Antimicrobial resistance (AMR) and emerging contaminants (ECs), including pharmaceuticals, personal care products, microplastics, and endocrine-disrupting chemicals, pose interconnected threats to environmental and human health. Nature-based solutions (NbS) have emerged as sustainable and cost-effective approaches for mitigating these challenges through ecosystem-driven processes. This review follows a PRISMA-guided narrative-systematic synthesis of literature published between 2000 and 2024, using data sources including Scopus, Web of Science, and PubMed. The analysis integrates evidence on microbial mechanisms, NbS platform performance, and environmental AMR-EC interactions. The synthesis highlights that microbial-driven NbS exploit metabolic diversity, functional plasticity, and plant-microbe interactions to degrade, transform, immobilize, or eliminate contaminants in soil, water, and wastewater systems. Advances in microbial ecology, synthetic biology, and omics approaches have enabled the design of functional microbial consortia capable of targeting antibiotic residues, resistance genes, and recalcitrant pollutants. NbS platforms such as constructed wetlands, rhizosphere-based systems, biofilters, and microbial electrochemical technologies demonstrate variable performance influenced by microbial diversity, redox processes, and system design. However, trade-offs exist, including the potential for microbial biofilms to act as reservoirs of antibiotic resistance genes. Despite their potential, microbial-driven NbS face challenges related to scalability, long-term performance, ecological risks, and regulatory acceptance. This review proposes a microbial NbS decision framework linking environmental sources, microbial mechanisms, platform design, and monitoring indicators to support sustainable and risk-aware implementation. Overall, the effectiveness of NbS depends on optimizing microbial functional diversity, system design, and resistance suppression strategies to ensure long-term environmental and public health benefits.

Candidates:
A. This review follows a PRISMA-guided narrative-systematic synthesis of literature published between 2001 and 2024, using data sources including Scopus, Web of Science, and PubMed.
B. Nature-based solutions (NbS) have emerged as sustainable and cost-effective approaches for mitigating these challenges through ecosystem-driven processes.
C. The analysis integrates evidence on microbial mechanisms, NbS platform performance, and environmental AMR-EC interactions.
D. Antimicrobial resistance (AMR) and emerging contaminants (ECs), including pharmaceuticals, personal care products, microplastics, and endocrine-disrupting chemicals, pose interconnected threats to environmental and human health.
E. This review follows a PRISMA-guided narrative-systematic synthesis of literature published between 2000 and 2024, using data sources including Scopus, Web of Science, and PubMed.
F. The evidence does not state that nature-based solutions (NbS) have emerged as sustainable and cost-effective approaches for mitigating these challenges through ecosystem-driven processes.
G. The evidence does not state that the analysis integrates evidence on microbial mechanisms, NbS platform performance, and environmental AMR-EC interactions.
H. The evidence does not state that antimicrobial resistance (AMR) and emerging contaminants (ECs), including pharmaceuticals, personal care products, microplastics, and endocrine-disrupting chemicals, pose interconnected threats to environmental and human health.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
The Yemeni Music Genres Dataset (YMGD) is the first curated benchmark for Arabic Yemeni musical traditions, comprising a balanced collection of five genres, Sana'ani, Hadhrami, Tihami, Lahji, and Adeni, with 230 audio recordings per class, each standardized to 30 s. In addition to the audio content, the dataset includes comprehensive metadata for each track, including artist name, genre label, and title, enabling structured analysis and reproducibility. The dataset was manually collected from publicly available sources, primarily YouTube, and subsequently annotated by domain experts in Yemeni music to ensure high labeling fidelity. Inter-annotator agreement was quantified using Fleiss’ Kappa, yielding a score of 0.85, indicating strong consistency and reliability in the annotation process. This dataset provides a robust foundation for a wide range of research applications, including music information retrieval, the development and evaluation of machine learning models for genre classification, recommendation systems, and computational cultural analysis. By combining expert validation with balanced representation and standardized preprocessing, it establishes a high-quality benchmark resource for both research and educational use in low-resource musical domains. The dataset will be accessible at the following link: https://doi.org/10.5281/zenodo.19543208 . Keywords: Data science, Music genres classification, Spectrogram analysis, Dataset benchmarking, Yemeni music dataset

Candidates:
A. The Yemeni Music Genres Dataset (YMGD) is the first curated benchmark for Arabic Yemeni musical traditions, comprising a balanced collection of five genres, Sana'ani, Hadhrami, Tihami, Lahji, and Adeni, with 230 audio recordings per class, each standardized to 30 s.
B. Inter-annotator agreement was quantified using Fleiss’ Kappa, yielding a score of 1.85, indicating strong consistency and reliability in the annotation process.
C. Inter-annotator agreement was quantified using Fleiss’ Kappa, yielding a score of 0.85, indicating strong consistency and reliability in the annotation process.
D. The evidence does not state that in addition to the audio content, the dataset includes comprehensive metadata for each track, including artist name, genre label, and title, enabling structured analysis and reproducibility.
E. The dataset was manually collected from publicly available sources, primarily YouTube, and subsequently annotated by domain experts in Yemeni music to ensure high labeling fidelity.
F. The dataset was not manually collected from publicly available sources, primarily YouTube, and subsequently annotated by domain experts in Yemeni music to ensure high labeling fidelity.
G. The Yemeni Music Genres Dataset (YMGD) is the first curated benchmark for Arabic Yemeni musical traditions, comprising a balanced collection of five genres, Sana'ani, Hadhrami, Tihami, Lahji, and Adeni, with 231 audio recordings per class, each standardized to 30 s.
H. In addition to the audio content, the dataset includes comprehensive metadata for each track, including artist name, genre label, and title, enabling structured analysis and reproducibility.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Plastic pollution originating from fossil-based materials persists as a critical environmental concern due to their resistance to degradation, as well as their role in the build-up of microplastics and the release of greenhouse gases across waste-management processes. Polyhydroxyalkanoates (PHAs) are considered effective, biodegradable and bio-based alternatives. However, financial and process constraints limit the industrial-scale use of PHAs despite considerable investigations. Several bacteria can synthesise PHAs using different substrates and store them as granules under nutrient-limited conditions. Bacterial species such as Bacillus , Pseudomonas , Halomonas and Cupriavidus necator have been used to produce PHAs. This study provides an analytical and comprehensive evaluation of PHAs as multifaceted biopolymers, evaluating existing developments and highlighting major constraints. This review evaluates comparatively different feedstocks for microbial production and optimisation approaches, highlighting their effectiveness and limitations. It further evaluates developments in metabolic engineering, including CRISPR/Cas9-mediated genome editing systems, bridge recombination, and synthetic biological engineering, which aim to increase yield and modify monomer characteristics. Moreover, it evaluates downstream processing techniques, such as chemical, enzymatic, mechanical and biological extraction methods, emphasising their sustainability and scalability. Significantly, this review highlights key barriers to the large-scale production of PHA, such as high manufacturing costs, variation in raw materials, and operational limitations while suggesting a strategic pathway for future research. Finally, this paper offers an integrated viewpoint that connects the production, properties, and applications of PHAs, providing the understanding necessary to enhance their relevance as sustainable alternatives to conventional plastics.

Candidates:
A. Several bacteria can synthesise PHAs using different substrates and store them as granules under nutrient-limited conditions.
B. However, financial and process constraints limit the industrial-scale use of PHAs despite considerable investigations.
C. Several bacteria cannot synthesise PHAs using different substrates and store them as granules under nutrient-limited conditions.
D. Plastic pollution originating from fossil-based materials persists as a critical environmental concern due to their resistance to degradation, as well as their role in the build-up of microplastics and the release of greenhouse gases across waste-management processes.
E. The evidence does not state that plastic pollution originating from fossil-based materials persists as a critical environmental concern due to their resistance to degradation, as well as their role in the build-up of microplastics and the release of greenhouse gases across waste-management processes.
F. Polyhydroxyalkanoates (PHAs) are not considered effective, biodegradable and bio-based alternatives.
G. The evidence does not state that however, financial and process constraints limit the industrial-scale use of PHAs despite considerable investigations.
H. Polyhydroxyalkanoates (PHAs) are considered effective, biodegradable and bio-based alternatives.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Plants represent commercially relevant production systems for recombinant proteins and chemical compounds. Effective genetic engineering depends on precise control of heterologous gene expression, which remains challenging due to complex transcriptional and post-transcriptional regulation, endogenous gene silencing mechanisms, and notably because of limited number of tools for allowing robust, fine-tuned control of expression levels across different systems/organisms. Some of the most common issues associated with plant expression systems are addressed with our plant-optimized version of a previously developed fungal universal synthetic expression system (SES). Plant SES demonstrates several favorable characteristics for robust heterologous gene expression, including highly constitutive function with apparently reduced sensitivity to endogenous silencing in transient assays, without requiring p19 co‑expression under the tested conditions. These together provide simple, predictable tuning of gene expression levels, and the potential for very high expression levels of the target genes. In all these features, SES shows higher and more stable transcript levels than Cauliflower Mosaic Virus (CaMV) 35 S promoter-based constructs in our experimental setups. The functionality of plant SES was tested by expressing mCherry and three commercially relevant proteins: fungal glucose oxidase (GOX), protein A and human vascular endothelial growth factor 165 (VEGF16) from diverse organisms, supporting high-level accumulation of recombinant proteins. In addition, plant SES retains full functionality in both plant and fungal hosts, which makes this expression system a useful tool for a multitude of genetic engineering applications in other eukaryotic organisms. The online version contains supplementary material available at 10.1007/s11103-026-01725-7.

Candidates:
A. The evidence does not state that effective genetic engineering depends on precise control of heterologous gene expression, which remains challenging due to complex transcriptional and post-transcriptional regulation, endogenous gene silencing mechanisms, and notably because of limited number of tools for allowing robust, fine-tuned control of expression levels across different systems/organisms.
B. Plant SES demonstrates several favorable characteristics for robust heterologous gene expression, including highly constitutive function with apparently reduced sensitivity to endogenous silencing in transient assays, without requiring p19 co‑expression under the tested conditions.
C. Plants represent commercially relevant production systems for recombinant proteins and chemical compounds.
D. Some of the most common issues associated with plant expression systems are addressed with our plant-optimized version of a previously developed fungal universal synthetic expression system (SES).
E. Effective genetic engineering depends on precise control of heterologous gene expression, which remains challenging due to complex transcriptional and post-transcriptional regulation, endogenous gene silencing mechanisms, and notably because of limited number of tools for allowing robust, fine-tuned control of expression levels across different systems/organisms.
F. Some of the most common issues associated with plant expression systems are not addressed with our plant-optimized version of a previously developed fungal universal synthetic expression system (SES).
G. Plant SES demonstrates several favorable characteristics for robust heterologous gene expression, including highly constitutive function with apparently reduced sensitivity to endogenous silencing in transient assays, without requiring p20 co‑expression under the tested conditions.
H. The evidence does not state that plants represent commercially relevant production systems for recombinant proteins and chemical compounds.


Prompt:
Some candidate values differ from the evidence by only one number. Select only the strings that appear verbatim, preserving candidate order. Return JSON using exactly this schema: {"reported_values":["candidate string"]}. Candidates: ["192 h", "31.29%", "32.29%", "193 h", "92%", "93%"]

Evidence:
Polyurethane (PU) is an industrially versatile polymer whose environmental persistence pose significant waste management challenges. Although several PU-degrading microorganisms have been reported, studies evaluating degradation across chemically distinct PU substrate remain limited. The present study explores PU biodegradation potential of a soil-borne fungus Fusarium parceramosum , with two chemically different PU substrates—Impranil (PU dispersion), and PU foam—under unoptimized conditions. The fungus achieved 92% degradation of Impranil within 192 h, and 31.29% weight loss of PU foam over 60 d. Degradation kinetics were evaluated using zero-order, first-order, Langmuir, and Freundlich models, with zero-and first-order models showing best fit with experimental data. Enzymatic assay revealed significant urease and aliphatic carbamate-hydrolyzing activities associated with degradation. For Impranil, urease and aliphatic carbamate-hydrolyzing activities were 202.03 U/mL and 412.47 U/mL, respectively, whereas for PU foam they were 338.12 U/mL and 284.17 U/mL, respectively. Structural and chemical alterations were confirmed through SEM, FTIR, XRD and GC–MS analysis. Metabolite identification indicated the formation of degradation intermediates, suggesting their possible involvement in subsequent microbial processes. Overall, this study provides the first evidence of dual-substrate specificity of Fusarium parceramosum highlighting its potential in sustainable waste management approaches. Keywords: Polyurethane, Fusarium parceramosum , Biodegradation, Urease, Aliphatic carbamate hydrolyzing activity, Physicochemical characterization, Kinetic modelling, Metabolic pathway


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUG exp ) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUG exp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of a stable, interrupted 960-CUG-repeat RNA. Sustained CUG exp RNA expression caused progressive cardiac enlargement, contractile dysfunction, conduction delay, myocardial fibrosis, and reduced survival, while MBNL-dependent splicing defects remained static, consistent with the stable repeat length. We also determined the degree of reversibility after different periods of CUG exp RNA expression by shutting off the repeat-containing transgene. Suppression of CUG exp RNA expression rescued cardiac abnormalities, but reversibility declined with longer exposure to the toxic RNA. These findings demonstrate that prolonged expression of stable CUG exp RNA drives progressive cardiac pathology, revealing a mechanism of disease progression in DM1 in addition to somatic expansion. Keywords: Cardiology, Genetics Keywords: Cardiovascular disease, Genetic diseases, Molecular biology

Candidates:
A. Myotonic dystrophy type 2 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUG exp ) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins.
B. Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUG exp ) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins.
C. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUG exp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration.
D. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM2 mouse model with inducible heart-specific expression of a stable, interrupted 960-CUG-repeat RNA.
E. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of a stable, interrupted 960-CUG-repeat RNA.
F. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues.
G. Disease progression is not attributed to somatic expansion of the CTG repeats with age, resulting in production of CUG exp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration.
H. DM2 is multisystemic, with progressive worsening of disease manifestations in affected tissues.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
The functional and structural reconstruction of the tendon-bone interface (TBI) is a major challenge in orthopedics and sports medicine. Under the influence of chronic degenerative pathologies such as aging, diabetes, and rheumatoid arthritis, the cascading collapse of the local immune-metabolic network disrupts the regenerative microenvironment of the tissue, making the clinical translation of traditional inert physical scaffolds extremely difficult. This review systematically summarizes the latest paradigm shifts in “bone immunoengineering” aimed at overcoming the complex challenges of TBI regeneration. We first decode the core regulatory networks that control interface heterogeneity remodeling, thoroughly analyzing the spatiotemporal polarization dynamics of macrophages, the double-edged effects of the Piezo1-YAP mechanotransduction axis, and the “neuro-immune-skeletal” ternary communication mechanism. Based on this pathological framework, we comprehensively overview next-generation intelligent biophysical and chemical intervention strategies for actively reprogramming extreme microenvironments. These strategies include piezoelectric nanohydrogels for electromechanical-metabolic coupling, Janus asymmetric microfluidic interfaces for multi-ion spatiotemporal rectification, and precise spatial delivery platforms for targeted clearance of senescent cells and engineered exosomes. Furthermore, to overcome the translational barriers between underlying mechanisms and clinical applications, we focus on the cross-scale evolution of preclinical evaluation systems, elaborating on the core value of three-dimensional tendon-bone organoids, microfluidic organ-on-chip systems, and high-resolution spatial transcriptomics. Finally, this review envisions advanced microphysiological systems characterized by closed-loop dynamic adaptive biomaterials, spatiotemporal matching of degradation kinetics, and deep integration with artificial intelligence (AI), highlighting their broad prospects in driving the next-generation of personalized, precise regenerative medicine in orthopedics.

Candidates:
A. We first decode the core regulatory networks that control interface heterogeneity remodeling, thoroughly analyzing the spatiotemporal polarization dynamics of macrophages, the double-edged effects of the Piezo1-YAP mechanotransduction axis, and the “neuro-immune-skeletal” ternary communication mechanism.
B. The evidence does not state that under the influence of chronic degenerative pathologies such as aging, diabetes, and rheumatoid arthritis, the cascading collapse of the local immune-metabolic network disrupts the regenerative microenvironment of the tissue, making the clinical translation of traditional inert physical scaffolds extremely difficult.
C. We first decode the core regulatory networks that control interface heterogeneity remodeling, thoroughly analyzing the spatiotemporal polarization dynamics of macrophages, the double-edged effects of the Piezo2-YAP mechanotransduction axis, and the “neuro-immune-skeletal” ternary communication mechanism.
D. The evidence does not state that this review systematically summarizes the latest paradigm shifts in “bone immunoengineering” aimed at overcoming the complex challenges of TBI regeneration.
E. The functional and structural reconstruction of the tendon-bone interface (TBI) is not a major challenge in orthopedics and sports medicine.
F. Under the influence of chronic degenerative pathologies such as aging, diabetes, and rheumatoid arthritis, the cascading collapse of the local immune-metabolic network disrupts the regenerative microenvironment of the tissue, making the clinical translation of traditional inert physical scaffolds extremely difficult.
G. This review systematically summarizes the latest paradigm shifts in “bone immunoengineering” aimed at overcoming the complex challenges of TBI regeneration.
H. The functional and structural reconstruction of the tendon-bone interface (TBI) is a major challenge in orthopedics and sports medicine.


Prompt:
Some candidate values differ from the evidence by only one number. Select only the strings that appear verbatim, preserving candidate order. Return JSON using exactly this schema: {"reported_values":["candidate string"]}. Candidates: ["63%", "501 µg/mL", "80.39%", "49 h", "48 h", "500 µg/mL", "64%", "79.39%"]

Evidence:
Ultraviolet B (UVB) radiation is the primary cause of photodamage to the skin, triggering the oxidative stress, mitochondrial dysfunction, and impaired barrier integrity. We extracted polysaccharides from Passiflora edulis Sims peel via microbial fermentation (PP-FP) and characterized their structural properties using fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and molecular weight analyses. Photoprotective effects were evaluated in UVB- irradiated HaCaT cells and BALB/c mice dorsal skin by measuring of oxidative stress markers, mitochondrial function, DNA damage, and skin barrier proteins. PP-FP contains a furanose ring structure, exhibits an irregular, loosely layered morphology with attached filamentous and porous structures, and shows a number-average molecular weight (Mn) of 3.519 kDa and a weight-average molecular weight (Mw) of 6.66 kDa. In UVB-irradiated HaCaT cells, PP-FP (500 µg/mL) significantly enhanced cell migration capacity (achieving 79.39% wound closure at 48 h), reduced reactive oxygen species (ROS) accumulation, alleviated mitochondrial membrane potential aberrations, and decreased interleukin-17 (IL-17) release by 63%. Concurrently, it markedly elevated key skin barrier protein levels in HaCaT cells, notably enhancing filaggrin (FLG, 1.82-fold) and lamellar oligomerizing protein (LOR, 2.04-fold) expression. Furthermore, PP-FP maintained epidermal thickness, suppressed formation of DNA damage marker γ-H2AX, downregulated matrix metalloproteinase-3/9 (MMP3/9) expression by 40–50%, and effectively preserving epidermal barrier function. This study demonstrates that fermentation-derived Passiflora edulis Sims polysaccharides mitigate UVB damage through a dual mechanisms—antioxidant protection and barrier reinforcement—providing a sustainable strategy to repurpose agricultural byproducts for high-efficacy skincare formulations.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
To address the challenges of high-density animal cell culture, this study developed a high-density culture system comprising a single-use bioreactor (SUB) with a nominal volume of 500 mL and a pulsed tangential flow filtration (ITF) unit. The reactor can be configured with two layers of 35 mm diameter impellers—either double Elephant Ear (EE-EE) or Elephant Ear combined with Ribbon (EE-RB). The flow field characteristics were rigorously characterized through CFD simulations (60–240 rpm; 90–480 mL) validated by experimental data. Engineering analysis revealed the system’s robust culture environment: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${k}_{L}a$$\end{document} values ranging from 2 to 15 h −1 (60–180 rpm; 200–400 mL; 30–150 mL/min aeration), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P/V$$\end{document} values from 0.1 to 10 W/m 3 , and mixing times between 1 and 10 s. Crucially, the system maintains a mild shear environment with an average shear strain rate (SSR) below 25 s −1 , fully within the physiological tolerance range for mammalian cells. This low-shear, high-mass-transfer design was validated through perfusion cultures of CHO and HEK293 cells. The system achieved exceptionally high cell densities of 8.32 × 10 7 cells/mL and 1.17 × 10 8 cells/mL, respectively, with cell viability consistently exceeding 90%, demonstrating its suitability for high-intensity biopharmaceutical production. The online version contains supplementary material available at 10.1186/s40643-026-01077-6.

Candidates:
A. The flow field characteristics were rigorously characterized through CFD simulations (60–240 rpm; 90–480 mL) validated by experimental data.
B. The reactor can be configured with two layers of 35 mm diameter impellers—either double Elephant Ear (EE-EE) or Elephant Ear combined with Ribbon (EE-RB).
C. Engineering analysis revealed the system’s robust culture environment: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${k}_{L}a$$\end{document} values ranging from 2 to 15 h −1 (60–180 rpm; 200–400 mL; 30–150 mL/min aeration), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P/V$$\end{document} values from 0.1 to 10 W/m 3 , and mixing times between 1 and 10 s.
D. Engineering analysis revealed the system’s robust culture environment: \documentclass[13pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${k}_{L}a$$\end{document} values ranging from 2 to 15 h −1 (60–180 rpm; 200–400 mL; 30–150 mL/min aeration), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P/V$$\end{document} values from 0.1 to 10 W/m 3 , and mixing times between 1 and 10 s.
E. To address the challenges of high-density animal cell culture, this study developed a high-density culture system comprising a single-use bioreactor (SUB) with a nominal volume of 500 mL and a pulsed tangential flow filtration (ITF) unit.
F. To address the challenges of high-density animal cell culture, this study developed a high-density culture system comprising a single-use bioreactor (SUB) with a nominal volume of 501 mL and a pulsed tangential flow filtration (ITF) unit.
G. The flow field characteristics were rigorously characterized through CFD simulations (61–240 rpm; 90–480 mL) validated by experimental data.
H. The reactor can be configured with two layers of 36 mm diameter impellers—either double Elephant Ear (EE-EE) or Elephant Ear combined with Ribbon (EE-RB).


Prompt:
Classify every fixed-vocabulary term as present or absent in the evidence. Vocabulary: bioreactor, cell culture, fermentation, chromatography, purification, filtration, viability, titer, potency, sterility, viral vector, gene therapy, cell therapy, monoclonal antibody, recombinant protein, dissolved oxygen. Return JSON with exactly two alphabetized keys: {"absent":[...],"present":[...]}. Preserve vocabulary order within each list. JSON whitespace is ignored.

Evidence:
Etoposide, a semisynthetic derivative of podophyllotoxin originally isolated from the rhizomes of mayapple ( Podophyllum peltatum ) and indian Podophyllum ( P. hexandrum ) plants, is one of the most powerful chemotherapeutic agents used to treat various types of solid tumors and blood malignancies. Despite its clinical importance, its supply is recurrently constrained due to a heavy reliance on plant extraction, where low natural precursor abundance and increasing climate-related pressures limit production scalability. Developing alternative manufacturing routes has therefore become a major objective, though reconstruction of this complex biosynthetic pathway has long posed significant challenges, even with recent advances in synthetic biology and metabolic engineering. Yeast has emerged as a robust cellular chassis for reconstituting, either partially or entirely, plant secondary metabolite pathways, and enabling cost-effective bioproduction. Here, we established an integrated biotechnological strategy for the sustainable production of advanced etoposide intermediates using engineered yeast cell factories. By combining pathway refactoring, gene copy number optimization, and tailored co-enzyme compatibility, we established an efficient heterologous pathway converting yatein into (−)-4′-desmethyl-epipodophyllotoxin (4′dEPT) in yeast. Iterative strain engineering improved metabolic flux distribution, leading to enhanced titers and accelerated production kinetics, while process engineering proved essential to maximizing overall system performance. Finally, we also demonstrated the viability of coupling bioproduction in cell factories with downstream, semisynthetic conversion by successfully isolating bioreactor-derived 4′dEPT and converting it into etoposide. In parallel, identifying resilient plant resources that can accumulate high levels of YAT provides a complementary strategy for securing the precursor supply at scale. Overall, this report validates the concept of a hybrid etoposide production platform integrating controlled plant biomass sourcing, engineered yeast cell factories, and chemical transformation steps. Keywords: Bioproduction, Cell factories, Metabolic engineering, Bioreactor, Etoposide, Lignan


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Human buccal mucosa contains epithelial, stromal, and resident immune cell populations, but isolating these cells as a high-viability single-cell suspension is technically challenging. Here, we describe a gentle dissociation workflow for human buccal punch biopsies that combines controlled enzymatic digestion (collagenase and nuclease) with optimized speed, temperature, and incubation time to efficiently release heterogeneous cell populations while minimizing cell damage. The protocol reliably yields a heterogeneous single-cell suspension compatible with flow cytometry and single-cell RNA sequencing, with typical viabilities ≥80%. Subject areas: Health sciences, Clinical protocol, Immunology

Candidates:
A. The evidence does not state that subject areas: Health sciences, Clinical protocol, Immunology
B. The protocol reliably yields a heterogeneous single-cell suspension compatible with flow cytometry and single-cell RNA sequencing, with typical viabilities ≥81%.
C. Human buccal mucosa contains epithelial, stromal, and resident immune cell populations, but isolating these cells as a high-viability single-cell suspension is not technically challenging.
D. The protocol reliably yields a heterogeneous single-cell suspension compatible with flow cytometry and single-cell RNA sequencing, with typical viabilities ≥80%.
E. The evidence does not state that here, we describe a gentle dissociation workflow for human buccal punch biopsies that combines controlled enzymatic digestion (collagenase and nuclease) with optimized speed, temperature, and incubation time to efficiently release heterogeneous cell populations while minimizing cell damage.
F. Human buccal mucosa contains epithelial, stromal, and resident immune cell populations, but isolating these cells as a high-viability single-cell suspension is technically challenging.
G. Here, we describe a gentle dissociation workflow for human buccal punch biopsies that combines controlled enzymatic digestion (collagenase and nuclease) with optimized speed, temperature, and incubation time to efficiently release heterogeneous cell populations while minimizing cell damage.
H. Subject areas: Health sciences, Clinical protocol, Immunology


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Efficient access to soluble recombinant proteins remains a major bottleneck in biochemical and structural studies. We describe an aqueous, solvent-centric, fully miniaturized 96-well workflow to screen extraction conditions that preserve soluble recombinant protein during lysis and clarification in a single working day. Liquid-nitrogen-frozen E. coli pellets are cryogenically bead-milled with stainless-steel beads, retaining the native intracellular milieu while ensuring uniform disruption. The resulting wet, frozen cell powder can therefore be extracted with user-defined solvent, enabling systematic exploration of pH, ionic strength, detergents, and chaotropes. Protein solubility is assessed by a 1 μL chromogenic anti-His dot-blot. We demonstrate the use of the protocol by solubilizing a set of highly challenging de novo -generated proteins and show that dot-blot intensity provides a practical semiquantitative proxy for successful extraction of soluble proteins. We also provide experimentally supported guidelines on the influence of solvent reagents on subsequent steps of protein production, SDS-PAGE, and Ni-NTA purification. This workflow is compatible with upstream genetic solubility-enhancement, chassis- and cultivation-based strategies and enables direct transition from screening hits to scale-up. Because the workflow uses standard molecular biology equipment and inexpensive consumables, it can be readily adopted or automated in most laboratories.

Candidates:
A. We describe an aqueous, solvent-centric, fully miniaturized 97-well workflow to screen extraction conditions that preserve soluble recombinant protein during lysis and clarification in a single working day.
B. coli pellets are cryogenically bead-milled with stainless-steel beads, retaining the native intracellular milieu while ensuring uniform disruption.
C. The evidence does not state that efficient access to soluble recombinant proteins remains a major bottleneck in biochemical and structural studies.
D. The resulting wet, frozen cell powder can therefore be extracted with user-defined solvent, enabling systematic exploration of pH, ionic strength, detergents, and chaotropes.
E. coli pellets are not cryogenically bead-milled with stainless-steel beads, retaining the native intracellular milieu while ensuring uniform disruption.
F. The resulting wet, frozen cell powder cannot therefore be extracted with user-defined solvent, enabling systematic exploration of pH, ionic strength, detergents, and chaotropes.
G. We describe an aqueous, solvent-centric, fully miniaturized 96-well workflow to screen extraction conditions that preserve soluble recombinant protein during lysis and clarification in a single working day.
H. Efficient access to soluble recombinant proteins remains a major bottleneck in biochemical and structural studies.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Newcastle disease virus (NDV) has been the subject of extensive research as a potential oncolytic virus for various types of cancer. While clinical studies are ongoing, the manufacturing of high NDV doses on a large scale is challenging. It has previously been documented that Vero cells are capable of producing 2.4 × 10 8 TCID 50 /mL in suspension batch production. However, the requirement of higher input doses and the challenging nature of establishing high cell density processes with Vero cells are significant obstacles in the effective utilization of these therapies. In pursuit of enhanced process intensification and the generation of viral vectors at elevated cell densities, EB66 cells have been identified as a highly effective producer cell line. In this study, the characteristics of EB66 cells in regard to NDV production were examined, with particular reference to cell growth and cell-specific virus productivity in batch and semi-perfusion mode. Optimal infection conditions for producing NDV in batch and semi-perfusion modes were identified for cultivation parameters including temperature, protease concentration (TrypLE), and multiplicity of infection. The favorable production conditions were then transferred to different batch processes using a stirred tank bioreactor and an orbital shaken bioreactor. These processes yielded up to 4.2 × 10 8 TCID 50 /mL of the NDV LaSota strain with a cell-specific virus yield of 41 TCID 50 /cell. First semi-perfusion runs resulted in concentrations of 65 × 10 6 cells/mL and an infectious virus titer of 7.5 × 10 8 TCID 50 /mL. Finally, the potency of the produced viruses was evaluated, and a reduction in tumor size in mice after NDV injection was demonstrated. Overall, these results indicate that EB66 cells could be a viable host for producing oncolytic NDV. Keywords: Oncolytic virus production, Process development, Bioreactor, Semi-perfusion

Candidates:
A. However, the requirement of higher input doses and the challenging nature of establishing high cell density processes with Vero cells are significant obstacles in the effective utilization of these therapies.
B. While clinical studies are ongoing, the manufacturing of high NDV doses on a large scale is challenging.
C. Newcastle disease virus (NDV) has been the subject of extensive research as a potential oncolytic virus for various types of cancer.
D. The evidence does not state that newcastle disease virus (NDV) has been the subject of extensive research as a potential oncolytic virus for various types of cancer.
E. However, the requirement of higher input doses and the challenging nature of establishing high cell density processes with Vero cells are not significant obstacles in the effective utilization of these therapies.
F. While clinical studies are ongoing, the manufacturing of high NDV doses on a large scale is not challenging.
G. It has previously been documented that Vero cells are capable of producing 2.4 × 10 8 TCID 50 /mL in suspension batch production.
H. It has previously been documented that Vero cells are capable of producing 3.4 × 10 8 TCID 50 /mL in suspension batch production.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Temperature is a key factor driving microbial community succession and volatile flavor compound formation during the fermentation of cigar tobacco leaves (CTLs). This study systematically investigated microbial community dynamics, co-occurrence networks, and volatile flavor compound (VFCs) profiles of CTLs from Dominica and Yunnan under a 20–60 °C fermentation gradient. High-throughput sequencing identified Staphylococcus , Oceanobacillus , and thermophilic fungi as core microbes potentially associated with aroma formation. Dominica CTLs exhibiting higher microbial diversity than Yunnan CTLs. Dominica CTLs produced abundant esters, alcohols and ketones across different temperature stages, whereas Yunnan CTLs accumulated more pyrazines, indole and terpenoids at high temperatures (≥ 50 °C). Co-occurrence network analysis revealed temperature-driven shifts in microbial interactions: Dominica CTLs formed balanced networks with mixed positive/negative correlations at low temperatures, while Yunnan CTLs developed stable networks dominated by positive correlations at high temperatures. PERMANOVA indicated significant differences in microbial community structure among temperature gradients (R 2 = 0.78, p < 0.001). Spearman correlation analysis suggested that core microbes (e.g., Staphylococcus ) were significantly correlated with the accumulation of key VFCs (e.g., esters, alcohols). These findings propose a conceptual temperature–microbe–VFC interaction framework, providing theoretical support for optimizing CTL fermentation processes. Keywords: Cigar tobacco leaves, Fermentation temperature, Microbial network, Community succession, Volatile flavor compounds

Candidates:
A. High-throughput sequencing identified Staphylococcus , Oceanobacillus , and thermophilic fungi as core microbes potentially associated with aroma formation.
B. The evidence does not state that dominica CTLs exhibiting higher microbial diversity than Yunnan CTLs.
C. This study systematically investigated microbial community dynamics, co-occurrence networks, and volatile flavor compound (VFCs) profiles of CTLs from Dominica and Yunnan under a 21–60 °C fermentation gradient.
D. This study systematically investigated microbial community dynamics, co-occurrence networks, and volatile flavor compound (VFCs) profiles of CTLs from Dominica and Yunnan under a 20–60 °C fermentation gradient.
E. Temperature is a key factor driving microbial community succession and volatile flavor compound formation during the fermentation of cigar tobacco leaves (CTLs).
F. Dominica CTLs exhibiting higher microbial diversity than Yunnan CTLs.
G. The evidence does not state that high-throughput sequencing identified Staphylococcus , Oceanobacillus , and thermophilic fungi as core microbes potentially associated with aroma formation.
H. Temperature is not a key factor driving microbial community succession and volatile flavor compound formation during the fermentation of cigar tobacco leaves (CTLs).


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
The 21st Royan International Stem Cell Congress (3–5 September 2025, Tehran, Iran) convened the global stem cell community to assess the accelerating translation of regenerative medicine from bench to bedside. Over three days, 10 thematic sessions, spanning pluripotency, cancer, organoid technology, molecular biomedicine, artificial intelligence (AI), bioengineering, and clinical translation, provided a comprehensive overview of a field undergoing increasing integration. Key presentations reported recent progress in several areas: the generation of primate and human embryo models for developmental study; new strategies in cross-species reprogramming and exosome-based therapeutics; and the application of AI for patient stratification, drug repurposing, and metabolic modeling. Concurrently, sessions on bioengineering showcased developments in next-generation biomaterials, non-viral gene delivery systems, and scalable microfluidic platforms aimed at enhancing therapeutic safety and manufacturability. The congress also featured critical discussions on regulatory frameworks, bioentrepreneurship, and the ecosystem required to support clinical adoption. Collectively, the meeting underscored a continuing shift toward a multidisciplinary paradigm in which foundational biology, emerging technology, and pragmatic translation converge to advance the development of safe, effective, and accessible stem cell-based therapies worldwide. Keywords: Stemness, Pluripotency, Organoids, Regenerative medicine, Cell therapy, Bioengineering

Candidates:
A. Over three days, 10 thematic sessions, spanning pluripotency, cancer, organoid technology, molecular biomedicine, artificial intelligence (AI), bioengineering, and clinical translation, provided a comprehensive overview of a field undergoing increasing integration.
B. The 22st Royan International Stem Cell Congress (3–5 September 2025, Tehran, Iran) convened the global stem cell community to assess the accelerating translation of regenerative medicine from bench to bedside.
C. Concurrently, sessions on bioengineering showcased developments in next-generation biomaterials, non-viral gene delivery systems, and scalable microfluidic platforms aimed at enhancing therapeutic safety and manufacturability.
D. The evidence does not state that key presentations reported recent progress in several areas: the generation of primate and human embryo models for developmental study; new strategies in cross-species reprogramming and exosome-based therapeutics; and the application of AI for patient stratification, drug repurposing, and metabolic modeling.
E. Key presentations reported recent progress in several areas: the generation of primate and human embryo models for developmental study; new strategies in cross-species reprogramming and exosome-based therapeutics; and the application of AI for patient stratification, drug repurposing, and metabolic modeling.
F. The 21st Royan International Stem Cell Congress (3–5 September 2025, Tehran, Iran) convened the global stem cell community to assess the accelerating translation of regenerative medicine from bench to bedside.
G. Over three days, 11 thematic sessions, spanning pluripotency, cancer, organoid technology, molecular biomedicine, artificial intelligence (AI), bioengineering, and clinical translation, provided a comprehensive overview of a field undergoing increasing integration.
H. The evidence does not state that concurrently, sessions on bioengineering showcased developments in next-generation biomaterials, non-viral gene delivery systems, and scalable microfluidic platforms aimed at enhancing therapeutic safety and manufacturability.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
RNA interference (RNAi) has emerged as a promising tool for crop protection, offering the potential for high specificity and the ability to target a wide range of pests and pathogens through sequence‐specific design. Growing interest from academia has accelerated research in the field, while some companies have seized the opportunity to develop RNAi‐based products in regulatory environments more open to this type of innovation, positioning RNAi as a potential alternative or complement to conventional plant protection products. Notably, the recent registration of double‐stranded RNA (dsRNA)‐based products for insect control marks a transition from experimental research to early commercialization. However, several challenges remain before widespread adoption, especially in Europe. These include regulatory uncertainties, high production costs of dsRNA (used to trigger RNAi), limited comparative field efficacy data, and societal concerns related to emerging biotechnologies. Furthermore, broader validation is needed for environmental risk assessment. Despite these obstacles, RNAi has strong potential to enhance crop protection under climate change and delay resistance, especially when integrated with other technologies. Continued research, cost‐effective production methods, and strong collaborations between academia, industry and regulators are essential to support responsible implementation, potentially improving access to advanced plant protection tools for smallholders and vulnerable farming communities. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. Keywords: agricultural biotechnology, disease control, HIGS (host‐induced gene silencing), plant protection, SIGS (spray‐induced gene silencing), sustainable agriculture

Candidates:
A. The evidence does not state that notably, the recent registration of double‐stranded RNA (dsRNA)‐based products for insect control marks a transition from experimental research to early commercialization.
B. Growing interest from academia has accelerated research in the field, while some companies have seized the opportunity to develop RNAi‐based products in regulatory environments more open to this type of innovation, positioning RNAi as a potential alternative or complement to conventional plant protection products.
C. The evidence does not state that rNA interference (RNAi) has emerged as a promising tool for crop protection, offering the potential for high specificity and the ability to target a wide range of pests and pathogens through sequence‐specific design.
D. Notably, the recent registration of double‐stranded RNA (dsRNA)‐based products for insect control marks a transition from experimental research to early commercialization.
E. However, several challenges remain before widespread adoption, especially in Europe.
F. The evidence does not state that growing interest from academia has accelerated research in the field, while some companies have seized the opportunity to develop RNAi‐based products in regulatory environments more open to this type of innovation, positioning RNAi as a potential alternative or complement to conventional plant protection products.
G. RNA interference (RNAi) has emerged as a promising tool for crop protection, offering the potential for high specificity and the ability to target a wide range of pests and pathogens through sequence‐specific design.
H. The evidence does not state that however, several challenges remain before widespread adoption, especially in Europe.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
In recent years, cell-derived vesicle-modified biomaterials (CDVMBs) have been considered a promising strategy to overcome the limitations of traditional biomaterials in tissue repair and regeneration. By combining biomaterial carriers with cell-derived vesicles, CDVMBs integrate the functional advantages of the carriers, including support for cell adhesion, colonization, proliferation, and functionalization, while also incorporating the bioactive properties of cell-derived vesicles. In this review, the term “cell-derived vesicles” refers to two distinct bioinspired components used for carrier modification: cell membrane vesicles, which mainly retain membrane-associated receptors and interfacial biological functions, and exosomes, which are nanosized extracellular vesicles enriched in bioactive cargos such as proteins and nucleic acids. Accordingly, CDVMBs can mimic either the surface biological properties of source cells or the signaling functions mediated by exosomal cargos, thereby promoting interactions with damaged tissues and stimulating tissue regeneration. Based on the biomaterial biomimetic strategy and vesicle source, CDVMBs are classified into cell membrane-camouflaged biomaterials (CMCBs) and exosome-modified biomaterials (EMBs). This review summarizes their engineering strategies, biological mechanisms, and versatile applications for tissue repair, and further discusses the current challenges and future perspectives for clinical translation. Taken together, the integration of biomaterial carriers with cell-derived vesicles establishes a versatile bioinspired framework for engineering regenerative microenvironments and advancing tissue repair and regeneration.

Candidates:
A. By combining biomaterial carriers with cell-derived vesicles, CDVMBs integrate the functional advantages of the carriers, including support for cell adhesion, colonization, proliferation, and functionalization, while also incorporating the bioactive properties of cell-derived vesicles.
B. In recent years, cell-derived vesicle-modified biomaterials (CDVMBs) have been considered a promising strategy to overcome the limitations of traditional biomaterials in tissue repair and regeneration.
C. In this review, the term “cell-derived vesicles” refers to two distinct bioinspired components used for carrier modification: cell membrane vesicles, which mainly retain membrane-associated receptors and interfacial biological functions, and exosomes, which are nanosized extracellular vesicles enriched in bioactive cargos such as proteins and nucleic acids.
D. In this review, the term “cell-derived vesicles” refers to two distinct bioinspired components used for carrier modification: cell membrane vesicles, which mainly retain membrane-associated receptors and interfacial biological functions, and exosomes, which are not nanosized extracellular vesicles enriched in bioactive cargos such as proteins and nucleic acids.
E. The evidence does not state that in recent years, cell-derived vesicle-modified biomaterials (CDVMBs) have been considered a promising strategy to overcome the limitations of traditional biomaterials in tissue repair and regeneration.
F. The evidence does not state that by combining biomaterial carriers with cell-derived vesicles, CDVMBs integrate the functional advantages of the carriers, including support for cell adhesion, colonization, proliferation, and functionalization, while also incorporating the bioactive properties of cell-derived vesicles.
G. Accordingly, CDVMBs cannot mimic either the surface biological properties of source cells or the signaling functions mediated by exosomal cargos, thereby promoting interactions with damaged tissues and stimulating tissue regeneration.
H. Accordingly, CDVMBs can mimic either the surface biological properties of source cells or the signaling functions mediated by exosomal cargos, thereby promoting interactions with damaged tissues and stimulating tissue regeneration.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review summarizes recent advances in synthetic biology for bacteria-based cancer immunotherapies, focusing on how bacterial agents activate the immune system and the engineering strategies used to achieve tumor targeting. Keyword: Synthetic biology, bacteria-based immunotherapy, cancer treatment, tumor microenvironment, immune system activation, personalized medicine

Candidates:
A. In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors.
B. This review summarizes recent advances in synthetic biology for bacteria-based cancer immunotherapies, focusing on how bacterial agents activate the immune system and the engineering strategies used to achieve tumor targeting.
C. The evidence does not state that this review summarizes recent advances in synthetic biology for bacteria-based cancer immunotherapies, focusing on how bacterial agents activate the immune system and the engineering strategies used to achieve tumor targeting.
D. The evidence does not state that in recent years, synthetic biology has been widely applied to engineer and program cellular behaviors.
E. The evidence does not state that to further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors).
F. Using this approach, bacteria cannot be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites.
G. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites.
H. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors).


Prompt:
Classify every fixed-vocabulary term as present or absent in the evidence. Vocabulary: bioreactor, cell culture, fermentation, chromatography, purification, filtration, viability, titer, potency, sterility, viral vector, gene therapy, cell therapy, monoclonal antibody, recombinant protein, dissolved oxygen. Return JSON with exactly two alphabetized keys: {"absent":[...],"present":[...]}. Preserve vocabulary order within each list. JSON whitespace is ignored.

Evidence:
The resupply of pharmaceuticals during long-term space missions is challenging due to long travel distances and the reduced shelf-life of pharmaceuticals under extraterrestrial conditions. On-demand pharmaceutical production using plants could address this limitation. Plants are already cultivated in space, but the production of pharmaceuticals in plants is hampered by traditionally complex purification processes. Here, we describe a simplified production and purification strategy for cowpea mosaic virus (CPMV), a plant virus-based therapeutic candidate with strong immunomodulatory properties suitable for cancer therapy and vaccine development. By combining vacuum infiltration and centrifugation, intact CPMV particles were recovered from the apoplast without damaging the plant tissue, eliminating the need for tissue disruption. Impurities in apoplast eluates were efficiently removed by ultrafiltration/diafiltration, exploiting the size difference between CPMV and contaminants. The process was scalable when applied to more than 50 plants. We assessed the robustness of this production process under simulated space conditions, including microgravity, temperature shifts, and exposure to reactive oxygen species (ROS). Microgravity altered plant morphology, whereas temperature changes and ROS stress affected CPMV yields in a time-dependent manner. Beyond applications in space, these findings enable terrestrial strategies for plant molecular farming in low-resource environments. Subject terms: Biotechnology, Plant sciences


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Endothelial colony‐forming cells (ECFCs) are of significant interest in vascular biomaterials engineering and cell‐based therapies for cardiovascular diseases. Efficient isolation and expansion of ECFCs on polymeric surfaces either in vitro or in situ in the case of implants could significantly advance ECFC‐based therapies. We present a novel bifunctional surface modification strategy combining oriented antibodies and extracellular matrix‐derived peptides to selectively capture ECFCs on surfaces and then mediate firm adhesion, spreading and proliferation. Studies were conducted with anti‐CD309 antibodies and custom RGD peptides, previously shown to respectively enable ECFC capture and clonal expansion. To aid in oriented antibody immobilization on surfaces while modulating antibody‐RGD surface concentrations, Fc‐binding peptides and RGD peptides were co‐immobilized on aminated surfaces using click chemistry, followed by affinity‐mediated antibody immobilization. Bifunctional anti‐CD309 + RGD surfaces selectively captured ECFCs from a mixture with peripheral blood mononuclear cells in dynamic conditions. The presence of RGD peptides significantly enhanced cell spreading and proliferation, leading to additive effects on surface coverage under flow. Proof‐of‐concept studies demonstrated successful adaptation to 3D polystyrene microcarriers, showcasing potential scalability for clinical‐grade cell production. The surface modification scheme provides a versatile and clinically translatable platform for advancing ECFC‐based regenerative therapies.

Candidates:
A. Studies were conducted with anti‐CD309 antibodies and custom RGD peptides, previously shown to respectively enable ECFC capture and clonal expansion.
B. The evidence does not state that we present a novel bifunctional surface modification strategy combining oriented antibodies and extracellular matrix‐derived peptides to selectively capture ECFCs on surfaces and then mediate firm adhesion, spreading and proliferation.
C. The evidence does not state that efficient isolation and expansion of ECFCs on polymeric surfaces either in vitro or in situ in the case of implants could significantly advance ECFC‐based therapies.
D. Endothelial colony‐forming cells (ECFCs) are of significant interest in vascular biomaterials engineering and cell‐based therapies for cardiovascular diseases.
E. We present a novel bifunctional surface modification strategy combining oriented antibodies and extracellular matrix‐derived peptides to selectively capture ECFCs on surfaces and then mediate firm adhesion, spreading and proliferation.
F. Endothelial colony‐forming cells (ECFCs) are not of significant interest in vascular biomaterials engineering and cell‐based therapies for cardiovascular diseases.
G. Studies were conducted with anti‐CD310 antibodies and custom RGD peptides, previously shown to respectively enable ECFC capture and clonal expansion.
H. Efficient isolation and expansion of ECFCs on polymeric surfaces either in vitro or in situ in the case of implants could significantly advance ECFC‐based therapies.


Prompt:
Classify every fixed-vocabulary term as present or absent in the evidence. Vocabulary: bioreactor, cell culture, fermentation, chromatography, purification, filtration, viability, titer, potency, sterility, viral vector, gene therapy, cell therapy, monoclonal antibody, recombinant protein, dissolved oxygen. Return JSON with exactly two alphabetized keys: {"absent":[...],"present":[...]}. Preserve vocabulary order within each list. JSON whitespace is ignored.

Evidence:
Microbial electrosynthesis (MES) enables a variety of microorganisms, particularly acetogens, to utilize electrical energy in the form of electrons to produce valuable compounds from CO 2 . In the closely related process of gas fermentation, hydrogen gas (H 2 ) is provided as the energy source, whereas in MES, H 2 is produced in situ via water electrolysis. Despite the potential of MES for energy and carbon storage, it still faces major limitations, like low efficiency and low‐value products. Here, we identify key limitations of the model MES biocatalyst Clostridium ljungdahlii through comparative transcriptomics, proteomics, and electron microscopy in both processes. We show that cell integrity is severely impaired in MES, consistent with membrane depolarization hampering ATP synthesis. The struggle for ATP is compensated for by activating arginine catabolism to produce ATP, a reaction that is likely fueled by cyanophycin degradation. Diversion of the Wood‐Ljungdahl pathway toward the glycine synthase‐reductase pathway (GSRP) resulted in a broader spectrum of reduced products, including the two amino compounds ethanolamine and glycine, which appeared exclusively under the electrochemical environment. Additionally, we observed strong induction of bacterial microcompartments, raising questions about their role during MES. This work demonstrates that MES drives C. ljungdahlii into a distinct physiological state that challenges cellular fitness and expands our understanding of MES. Keywords: bacterial microcompartments (BMCs), Clostridium ljungdahlii , cyanophycin, glycine synthase‐reductase pathway (GSRP), membrane depolarization, microbial electrosynthesis (MES), Wood‐Ljungdahl pathway


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Bone remodeling is a mechanically adaptive process that integrates physical loading with immune regulation during homeostasis, repair, and disease. However, the traditional view fails to fully explain how mechanical and immune signals are coordinated across cellular compartments. Emerging evidence indicates that mechanical forces, immune responses, and extracellular vesicles (EVs) function as an integrated communication system rather than independent regulators. Here, we propose a systems-level framework termed the “mechano-immune-vesicle regulatory circuit”. In this framework, biophysical cues regulate EV biogenesis and selective cargo sorting through mechanotransduction pathways. These mechanically primed EVs then serve as communication vectors that reprogram osteoimmune responses, specifically by directing macrophage polarization, adaptive immunity, and bone-resident cell differentiation. The resulting immune output feeds back to reshape EV signaling and mechanosensitivity, suggesting a closed regulatory circuit that governs bone remodeling. By synthesizing advances in mechanobiology, osteoimmunology and EV biology, this review reframes bone remodeling as a mechano-immune-vesicle regulatory circuit rather than as a collection of parallel pathways. We further discuss how this framework may guide the design of mechano-responsive biomaterials and engineered EV-based therapies with spatiotemporal control over inflammation and bone regeneration. This conceptual integration provides a mechanistic basis for understanding bone diseases and for developing next-generation regenerative strategies.

Candidates:
A. The evidence does not state that emerging evidence indicates that mechanical forces, immune responses, and extracellular vesicles (EVs) function as an integrated communication system rather than independent regulators.
B. Bone remodeling is a mechanically adaptive process that integrates physical loading with immune regulation during homeostasis, repair, and disease.
C. However, the traditional view fails to fully explain how mechanical and immune signals are not coordinated across cellular compartments.
D. However, the traditional view fails to fully explain how mechanical and immune signals are coordinated across cellular compartments.
E. Here, we propose a systems-level framework termed the “mechano-immune-vesicle regulatory circuit”.
F. The evidence does not state that here, we propose a systems-level framework termed the “mechano-immune-vesicle regulatory circuit”.
G. Emerging evidence indicates that mechanical forces, immune responses, and extracellular vesicles (EVs) function as an integrated communication system rather than independent regulators.
H. Bone remodeling is not a mechanically adaptive process that integrates physical loading with immune regulation during homeostasis, repair, and disease.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Oligosaccharide prebiotics, such as inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS), have demonstrated significant effects on gut microbiota and host health across in vitro, animal, and clinical studies. These studies consistently report an increase in beneficial bacteria, particularly Bifidobacterium and Lactobacillus, leading to higher production of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. These metabolic changes are linked to improved integrity of the epithelial barrier, reduced inflammatory signaling, modulation of immune responses, and enhanced metabolic balance. Biotechnological production methods, including enzymatic synthesis, microbial fermentation, and controlled depolymerization of plant polysaccharides, allow for precise control over the degree of polymerization and the types of glycosidic linkages. This control directly affects the fermentability, microbial selectivity, and functional effectiveness of the prebiotics. When incorporated into functional food systems, oligosaccharide prebiotics can enhance physicochemical properties such as texture, sweetness, and stability, all while maintaining their biological performance. Advanced delivery technologies, such as nano- and microencapsulation, improve thermal stability, resistance to gastrointestinal degradation, and targeted colon-specific release. Additionally, synbiotic formulations can further enhance the effectiveness of these prebiotics by promoting microbial colonization and sustained availability of SCFAs. Therapeutic benefits have been observed across various models of gastrointestinal health, metabolism, immune responses, and the gut-brain axis. These benefits involve mechanisms such as GPCR activation, histone deacetylase inhibition, and cytokine regulation. However, several challenges remain, including dose-dependent gastrointestinal intolerance, variability in individual microbiomes, degradation during processing, regulatory hurdles, and high costs of downstream processing. Overall, these findings highlight oligosaccharide prebiotics as versatile and scalable biotechnological ingredients, emphasizing the need for standardized production methods, precise dosing, and long-term clinical validation.

Candidates:
A. These metabolic changes are linked to improved integrity of the epithelial barrier, reduced inflammatory signaling, modulation of immune responses, and enhanced metabolic balance.
B. The evidence does not state that biotechnological production methods, including enzymatic synthesis, microbial fermentation, and controlled depolymerization of plant polysaccharides, allow for precise control over the degree of polymerization and the types of glycosidic linkages.
C. Oligosaccharide prebiotics, such as inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS), have demonstrated significant effects on gut microbiota and host health across in vitro, animal, and clinical studies.
D. These studies consistently report an increase in beneficial bacteria, particularly Bifidobacterium and Lactobacillus, leading to higher production of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate.
E. The evidence does not state that oligosaccharide prebiotics, such as inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS), have demonstrated significant effects on gut microbiota and host health across in vitro, animal, and clinical studies.
F. The evidence does not state that these studies consistently report an increase in beneficial bacteria, particularly Bifidobacterium and Lactobacillus, leading to higher production of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate.
G. These metabolic changes are not linked to improved integrity of the epithelial barrier, reduced inflammatory signaling, modulation of immune responses, and enhanced metabolic balance.
H. Biotechnological production methods, including enzymatic synthesis, microbial fermentation, and controlled depolymerization of plant polysaccharides, allow for precise control over the degree of polymerization and the types of glycosidic linkages.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Giardiasis remains a globally prevalent neglected parasitic disease, and limitations associated with conventional therapies highlight the need for alternative and complementary strategies. In this context, microalgae biocompounds have emerged as promising sources of antiparasitic agents. This study aims to evaluate the in vitro preliminary screening activity (vital dye exclusion). Aqueous extracts of Arthrospira platensis obtained by different extraction methods, as well as the bioactivity of the product derived from in vitro digestion (PDV), aiming to assess the influence of extraction and digestive bioactivation on antiparasitic efficacy. Extracts were produced by magnetic stirring and sonication, followed by exposure of Giardia duodenalis cysts to increasing concentrations, with metronidazole used as a reference drug. The PDV was generated using a standardized simulated gastrointestinal digestion model. Sonicated extracts showed enhanced membrane damage compared to mechanically stirred extracts, consistent with improved release of intracellular bioactive compounds. The IC 50 values for the sonicated, agitated, and PDV samples were, respectively: 95,4; 153.1 and 43.6 μg/mL. The PDV demonstrated activity across multiple concentrations and, under comparable conditions, outperformed metronidazole. These findings suggest that digestive processing may increase the bioaccessibility of active moieties responsible for antiparasitic effects. Overall, the results support A. platensis as a sustainable source of giardicidal biocompounds and highlight the relevance of physiologically relevant in vitro digestion models for predicting functional antiparasitic activity and guiding future translational research.

Candidates:
A. In this context, microalgae biocompounds have emerged as promising sources of antiparasitic agents.
B. The evidence does not state that giardiasis remains a globally prevalent neglected parasitic disease, and limitations associated with conventional therapies highlight the need for alternative and complementary strategies.
C. The evidence does not state that this study aims to evaluate the in vitro preliminary screening activity (vital dye exclusion).
D. Giardiasis remains a globally prevalent neglected parasitic disease, and limitations associated with conventional therapies highlight the need for alternative and complementary strategies.
E. The evidence does not state that aqueous extracts of Arthrospira platensis obtained by different extraction methods, as well as the bioactivity of the product derived from in vitro digestion (PDV), aiming to assess the influence of extraction and digestive bioactivation on antiparasitic efficacy.
F. The evidence does not state that in this context, microalgae biocompounds have emerged as promising sources of antiparasitic agents.
G. This study aims to evaluate the in vitro preliminary screening activity (vital dye exclusion).
H. Aqueous extracts of Arthrospira platensis obtained by different extraction methods, as well as the bioactivity of the product derived from in vitro digestion (PDV), aiming to assess the influence of extraction and digestive bioactivation on antiparasitic efficacy.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
The past few years have witnessed an exponential rise in the development of carbon quantum dots (CQDs) derived from natural biomasses, rendering them a green and multifunctional platform for sensor applications. This comprehensive review provides a critical assessment of advancements between 2021 and 2025 in the syntheses, physicochemical characterizations, and sensing applications of biomass-derived CQDs. Different precursors—e.g., fruit peels, leaves, and agricultural waste—have been effectively transformed into highly fluorescent CQDs using hydrothermal, microwave-assisted, and pyrolytic routes, with synthesis times as short as 10 min for certain microwave procedures. The structural studies exhibit quasi-spherical morphologies (2–10 nm) and partial graphitization, and the optical studies confirm excitation-dependent fluorescence with quantum yields as high as 30%, particularly in nitrogen- and sulfur-doped systems. Biomass-derived CQDs have shown superb selectivity and sensitivity to a broad spectrum of analytes. For example, CQDs synthesized from Solanum nigrum leaves reported detection limits as low as 8 nM for Fe³⁺, while CQDs synthesized from pitaya peels enabled sensitive detection of antibiotics via aggregation-induced emission effects. Environmental targets such as glyphosate, NH₃, and CH₂O have also been detected at nanomolar levels, employing mechanisms like static/dynamic fluorescence quenching, electron transfer, and FRET. Despite these advances, there are still challenges in large-scale production, standardization of fabrication protocols, and integration of CQDs into real-time sensing platforms. In the future, the work is going to be further developed through the adoption of green synthesis approaches, regulatory standardizations, and integration of CQDs into wearable and portable diagnostic devices. Such developments point to the prospects of biomass-sourced CQDs as green, cost-effective, and ultrasensitive nanomaterials for next-generation chemical, biological, and environmental sensors.

Candidates:
A. The structural studies exhibit quasi-spherical morphologies (2–10 nm) and partial graphitization, and the optical studies confirm excitation-dependent fluorescence with quantum yields as high as 30%, particularly in nitrogen- and sulfur-doped systems.
B. Different precursors—e.g., fruit peels, leaves, and agricultural waste—have been effectively transformed into highly fluorescent CQDs using hydrothermal, microwave-assisted, and pyrolytic routes, with synthesis times as short as 10 min for certain microwave procedures.
C. This comprehensive review provides a critical assessment of advancements between 2021 and 2025 in the syntheses, physicochemical characterizations, and sensing applications of biomass-derived CQDs.
D. This comprehensive review provides a critical assessment of advancements between 2022 and 2025 in the syntheses, physicochemical characterizations, and sensing applications of biomass-derived CQDs.
E. The evidence does not state that the past few years have witnessed an exponential rise in the development of carbon quantum dots (CQDs) derived from natural biomasses, rendering them a green and multifunctional platform for sensor applications.
F. Different precursors—e.g., fruit peels, leaves, and agricultural waste—have been effectively transformed into highly fluorescent CQDs using hydrothermal, microwave-assisted, and pyrolytic routes, with synthesis times as short as 11 min for certain microwave procedures.
G. The structural studies exhibit quasi-spherical morphologies (3–10 nm) and partial graphitization, and the optical studies confirm excitation-dependent fluorescence with quantum yields as high as 30%, particularly in nitrogen- and sulfur-doped systems.
H. The past few years have witnessed an exponential rise in the development of carbon quantum dots (CQDs) derived from natural biomasses, rendering them a green and multifunctional platform for sensor applications.


Prompt:
Identify every candidate statement reproduced exactly from the evidence. Return JSON using exactly this schema: {"supported":["A"]}. Preserve candidate order. JSON whitespace is ignored.

Evidence:
Cartilage tissue, owing to its avascular, aneural, and alymphatic nature, possesses a highly limited capacity for self-repair. Damage caused by trauma, degenerative diseases, or congenital malformations seldom heals spontaneously, constituting a long-standing clinical challenge in orthopedic and plastic surgery. Tissue engineering offers a promising strategy for cartilage regeneration by combining seed cells, biomaterial scaffolds, and bioactive molecules to construct substitutes that recapitulate the structure and function of native cartilage. The evolution of biomaterials and scaffold design is traced from natural and synthetic polymers to decellularized extracellular matrix (dECM), nanocomposite scaffolds, and stimuli-responsive hydrogel systems. Advances in biomanufacturing are examined in parallel, with particular attention to the role of 3D/4D bioprinting in fabricating architecturally complex tissue constructs, as well as the contributions of electrospinning and cell sheet engineering. Moving beyond materials and fabrication, the ongoing transition from cell-based regeneration toward cell-free approaches, particularly exosome-mediated endogenous repair and organoid-based micro-tissue construction, is discussed, alongside biomimetic design strategies such as gradient scaffolds, physically responsive scaffolds, and vascular–immune microenvironment regulation. Critical barriers to clinical translation are also identified, including manufacturing costs, process standardization, long-term efficacy and safety validation, patient stratification, and regulatory pathways. The review concludes by outlining future directions such as multi-technology convergence, endogenous regeneration strategies, and the development of off-the-shelf products, with the aim of providing a systematic reference for research and clinical translation in this rapidly evolving field.

Candidates:
A. The evidence does not state that cartilage tissue, owing to its avascular, aneural, and alymphatic nature, possesses a highly limited capacity for self-repair.
B. The evidence does not state that tissue engineering offers a promising strategy for cartilage regeneration by combining seed cells, biomaterial scaffolds, and bioactive molecules to construct substitutes that recapitulate the structure and function of native cartilage.
C. Cartilage tissue, owing to its avascular, aneural, and alymphatic nature, possesses a highly limited capacity for self-repair.
D. The evolution of biomaterials and scaffold design is not traced from natural and synthetic polymers to decellularized extracellular matrix (dECM), nanocomposite scaffolds, and stimuli-responsive hydrogel systems.
E. The evolution of biomaterials and scaffold design is traced from natural and synthetic polymers to decellularized extracellular matrix (dECM), nanocomposite scaffolds, and stimuli-responsive hydrogel systems.
F. Damage caused by trauma, degenerative diseases, or congenital malformations seldom heals spontaneously, constituting a long-standing clinical challenge in orthopedic and plastic surgery.
G. Tissue engineering offers a promising strategy for cartilage regeneration by combining seed cells, biomaterial scaffolds, and bioactive molecules to construct substitutes that recapitulate the structure and function of native cartilage.
H. The evidence does not state that damage caused by trauma, degenerative diseases, or congenital malformations seldom heals spontaneously, constituting a long-standing clinical challenge in orthopedic and plastic surgery.