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in 6 months. As of September 2016, no obvious progress was observed. Discussion Collagenomas belong to connective tissue nevi (hamartomas), and are composed predominantly of collagen. They are divided into inherited and acquired. Inherited collagenomas are autosomal dominantly inherited, including familial cutaneous co...	800	9111869	16
were reclassified into three groups: normal collagen group; fine, dense collagen group; and thick, dense collagen group [19]. This study indicated that different kinds of collagen could be observed in collagenomas probably in accordance with different stages of the tumor. Clinically, all previous cases of eruptive coll...	801	9111869	16
Fibromas (fibrous histiocytomas) are ill-defined, characterized by a variable number of spindle and/or rounded cells. A variable admixture of inflammatory cells, coarse collagen bundles in haphazard array are present. Plexiform fibromyxoma (plexiform angiomyxoid myofibroblastic tumor) is a rare benign mesenchymal tumor...	802	9111869	16
Hysteresis and metastability of Bose-Einstein condensed clouds of atoms confined in ring potentials We consider a Bose-Einstein condensed cloud of atoms which rotate in a toroidal/annular potential. Assuming one-dimensional motion, we evaluate the critical frequencies associated with the effect of hysteresis and the cr...	803	118447200	16
stability of the persistent currents. To attack this problem we use the method of diagonalization of the many-body Hamiltonian. Contrary to the mean-field approximation -which makes the implicit assumption of a large particle number -the diagonalization approach includes corrections due to a finite number of atoms. In ...	804	118447200	16
the mean-field approximation to consider corrections of order 1/N (and lower) due to the finiteness of the atom number N . In Sec. V we investigate the same question regarding the critical coupling for metastability and the matrix element for the decay rate of persistent currents in a small system. In Sec. VI we make c...	805	118447200	16
per atom and Lh is the total angular momentum. According to Bloch's theorem [10] E(ℓ) consists of a periodic part plus a quadratic part which comes from the motion of the center of mass. Thus, one needs consider only 0 ≤ L ≤ N (0 ≤ ℓ ≤ 1); the remainder of the spectrum follows trivially as a consequence of Bloch's theo...	806	118447200	16
problem. On the other hand, for an effective attraction between the atoms, hysteresis is absent, since the curvature of E(ℓ) is positive, and thus there are no discontinuous transitions as the rotational frequency of the trap is varied. It is convenient to write (in the interval 0 ≤ ℓ ≤ 1) the total energy per particle...	807	118447200	16
begin with the mean-field approximation and consider the limit ℓ → 1 − . One can construct a Taylor-series expansion of the energy as a function of the small parameter 1 − ℓ. Since we are interested in the slope of the dispersion relation, we only need the linear term in the expansion for the energy. To get that, it su...	808	118447200	16
κ = 1. The coefficients appearing in Eq. (3) must satisfy the normalization condition, c 2 0 + c 2 1 + c 2 2 = 1, and the constraint of fixed angular momentum, c 2 1 + 2c 2 2 = ℓ or The expectation value of the energy per particle in the above state is where c 0 and c 2 have been assumed to have opposite signs in order...	809	118447200	16
MEAN-FIELD APPROXIMATION We now examine the same problem beyond the meanfield approximation. To do this, we use the method of diagonalization of the many-body Hamiltonian. To get some insight, we start with the truncated space containing the single-particle states φ 0 , φ 1 , and φ 2 [i.e., the states used in Eq. (3)]....	810	118447200	16
2 p−1 with N atoms and L = N − 2 units of angular momentum, one can follow the same procedure as before to find that From the lowest eigenvalues of each of the last two equations it follows that Ω 2 /ω = 2 − √ 2γ + 1, in agreement with the result of the mean-field approximation, Eq. (8). The approach considered above h...	811	118447200	16
Having diagonalized the Hamiltonian, we extract the slope of the dispersion relation from the difference E 0 (L = 1) − E 0 (L = 0) to determine Ω 1 . Finally, by varying the atom number, 2 ≤ N ≤ 5 we find that Ω 1 can be approximated as for γ = 0.1. A subtle point in this calculation is the fact that the interactions s...	812	118447200	16
and of the correlations, captured by the method of diagonalization, is to decrease the value of Ω 1 from its asymptotic value (and thus to increase the value of Ω 2 ). We comment on this observation in the following section. Last but not least, we mention that the value of the angular momentum for which the winding num...	813	118447200	16
this tiny change can be described perturbatively and, although there is a violent rearrangement of the phase of the order parameter, this rearrangement can in no way prevent hysteresis. V. METASTABILITY OF PERSISTENT CURRENTS IN A SMALL SYSTEM The dispersion relation can develop an energy barrier for sufficiently stron...	814	118447200	16
value of γ for the existence of a local minimum for ℓ → 1 − is γ cr = 3/2. This is an asymptotic result, which does not include finite-N corrections. To find these corrections, we choose a fixed value of the atom number N and identify the critical value of U , U cr , which gives a zero slope in the dispersion relation ...	815	118447200	16
absent within the mean-field approximation) lower the energy of the state with L = N − 1 more than that of the state with L = N . Thus, a higher value of γ is necessary to stabilize the currents in the state with L = N . The same mechanism which increases γ cr is also responsible for the decrease (increase) of Ω 1 (Ω 2...	816	118447200	16
give a nonzero contribution to this matrix element are those that raise the angular momentum by L = N units when acting on \|L = 0 , In the absence of interactions, when all the atoms are in the single-particle state φ 1 and φ 0 , respectively, this matrix element vanishes for all N > 1. This is also the case in the mea...	817	118447200	16
rapidly as one moves away from \|0 N and \|1 N along with the nature of ∆V , which induces singleparticle excitations by N units of angular momentum, combine to make this decay matrix element extremely sensitive to N . Thus, the main result of this section is, quite generally, that a combination of sufficiently strong in...	818	118447200	16
the present theory and the experiment of Ref. [9]. An investigation of this problem using a more realistic model is underway and will be described in a future publication. If one wants nonetheless to get an estimate for the critical frequencies of hysteresis for the parameters of Ref. [9] using the present theory, it f...	819	118447200	16
value N = 10. This would reduce the interaction energy to the extent that the conditions for one-dimensional motion would be fulfilled. This reduction in N would also reduce the value of γ to ≈ 0.04. The corresponding critical frequencies would become Ω 1 ≈ 3.7 Hz and Ω 2 ≈ 3.5 Hz. While the difference between Ω 1 and ...	820	118447200	16
have evaluated those both within the meanfield approximation and beyond mean field (i.e., by numerical diagonalization of the many-body Hamiltonian) in order to determine finite-N corrections. We have also performed calculations of the critical coupling for the metastabiliity of superflow and of the matrix element asso...	821	118447200	16
Flavor Oscillations in Field Theory Neutrino flavor oscillations are discussed in terms of two coupled Dirac fields. The interacting Lagrangian is diagonalized to obtain the exact eigenvalues and eigenfunctions. Flavor wave functions are then derived directly from the quantized neutrino fields. Probability density obta...	822	14225282	16
Dirac neutrino fields ψ e , ψ µ with masses m e and m µ . The interaction is provided through a lepton number violating term with a coupling constant δ. The model allows for exact diagonalization. Neutrino and anti-neutrino flavor wave functions can be directly obtained as matrix elements of the quantized neutrino fiel...	823	14225282	16
are solved. The electron and muon neutrino fields are then quantized in terms of the two free uncoupled fields, which diagonalize Eq. (1.1), as described in Sec. 4. The total conserved charge is the sum of the electron and muon flavor charges, which are not conserved separately. The last section closes with some conclu...	824	14225282	16
given by In Eq. (2.6), the boundary condition that at production we have only a given flavor must be imposed. Suppose for example that at t = 0 a muon neutrino is produced, i.e. ¿From Eq. (2.5) at t = 0 we obtain The time evolution of the flavor amplitudes is obtained by substituting Eq. (2.8) in Eq. (2.9b) Space and t...	825	14225282	16
neutrino travels over a macroscopic distance. Hence, if a muon neutrino is produced at the space-time (x ≃ ct = 0), the probability of observing an electron neutrino is maximum for those space-time points x ≃ ct at which \|C e \| 2 = 1. If some matter is present at these points, processes such as ν e + n → p + e − , will...	826	14225282	16
of equations (3.2) and (3.3) we consider the ansatz where P is the four-momentum P = (E, p), which is unknown and is to be determined so that the system of differential equations (3.5) and (3.6) is satisfied. The coefficients a and b are Dirac spinors, which can be written as where χ 1,2 and ϕ 1,2 are two component vec...	827	14225282	16
energies −E 1,2 we have the following eigenfunctions: with φ 3 (s, p) given by and to make the transformation on the field which uncouples the interacting Lagrangian given by Eq. (3.1) Following relations are useful to see that U uncouples Eq. (3.1) Therefore the fields φ 1 and φ 2 describe the "normal modes". To quant...	828	14225282	16
t) with the electron flavor. In the same way, the matrix element is the probability amplitude for the muon flavor. To take into account the fact that neutrinos (anti-neutrinos) are created with negative (positive) chiralities, we define the "observable wave functions" as where ψ e (x, t) and ψ µ (x, t) are given by Eqs...	829	14225282	16
two uncoupled free fields φ 1 and φ 2 of mass m 1 and m 2 respectively. We notice here that because we can directly diagonalize the Lagrangian we do not need to write the interacting fields in terms of the free asymptotic fields ψ 0e , ψ 0µ of mass m e and m µ respectively. We have also derived neutrino flavor wave fun...	830	14225282	16
MICAL1 facilitates breast cancer cell proliferation via ROS‐sensitive ERK/cyclin D pathway Abstract Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono‐oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown ...	831	3789521	16
and MICAL-L2, the other members of MICAL family, has been confirmed to be related to multiple invasive phenotype of cancer cells such as increased motility, proliferation, as well as inducing epithelial-tomesenchymal transition (EMT). 10,11 Domain architecture of MICAL1 is closely related to Drosophila MICAL 4 ; howeve...	832	3789521	16
invasion. 17 In the current study, our results suggest that MICAL1 exhibits its positively regulatory function on breast cancer cell proliferation via maintaining cyclin D expression through ROS-sensitive PI3K/Akt/ERK signalling, which implicates an essential role for MICAL1 in breast cancer pathogenesis. \| Cell and pl...	833	3789521	16
cytometry analysis Cell cycle analysis was performed by flow cytometry. Briefly, cells were harvested and fixed in 80% ice-cold ethanol overnight. Then the cells were incubated with RNase A and propidium iodide staining solution at 37°C for 30 minutes in darkness. Subsequently, the stained cells were analysed using flo...	834	3789521	16
primary antibody overnight at 4°C followed by incubation with rhodamine-conjugated secondary antibody (Life Technologies) for 1 hour at room temperature within a moist chamber. After washing with PBS, the samples were mounted with DAPI Fluoromount G (Southern Biotech). Images were acquired using an Olympus BX51 microsc...	835	3789521	16
performed by a fluorescence microscope. Images were collected using a fluorescence microscope. \| Statistical analysis Statistical analysis was performed using the SPSS. Error bars represent the standard error of mean SEM, and the significance of difference between the two groups was analysed by Student's t test. P < .0...	836	3789521	16
cycle. We noticed that, among these molecules, the levels of cyclin D and CDK4 were markedly blocked after silencing MICAL1. Consistently, cyclin D and CDK4 were higher when MICAL1 overexpressed in T47D cells ( Figure 2E,F) and MCF-7 cells (Figure 2G,H). These results indicate that cyclin D and CDK4 play key roles in M...	837	3789521	16
cancer cells. \| ROS mediates ERK/cyclin D signals via phosphorylated Akt MICAL1 is well characterized in ROS generation, which has been associated with cancer cell invasion. 17 We transfected MCF-7 and T47D cells with siMICAL1 and then examined its effects on ROS production. As shown in Figure 5A, ROS level in those ce...	838	3789521	16
control actin cytoskeleton rearrangement. 21 The notion that cell cytoskeleton rearrangement contributes to cell proliferation has been confirmed by many research groups 15 ; however, up to now, no study yet addressed the function of MICAL1 in the human cancer cell proliferation process. In contrast to previous finding...	839	3789521	16
[22][23][24][25][26] MICAL1 has an important role in triggering Akt phosphorylation, which is a key signal that can endow breast cancer cells with an invasive phenotype. 17 We have noticed that MICAL1 selectively activates PI3K/Akt signalling pathway. To our surprise, p-S6K protein level, the main downstream effector o...	840	3789521	16
assembly can also be altered indirectly by the ROS produced by MICAL. 29 Oxidative stress originates from an imbalance between the generation and scavenging of ROS, activates aberrant signalling cascades and leads to tumorigenesis. A recent study reported that increased ROS production was triggered by overexpression of...	841	3789521	16
AEWAE: An Efﬁcient Ensemble Framework for Concept Drift Adaptation in IoT Data Stream —With the evolution of the ﬁfth-generation (5G) wireless network, smart technology based on the Internet of Things (IoT) has become increasingly popular. As a crucial component of smart technology, IoT systems for service delivery oft...	842	258615490	16
significant insights, which can be applied to a wide array of IoT applications, such as identifying anomalies [4]. The general structure of IoT data analytics can be visualized in Figure 1. Currently, IoT data analytics faces two main challenges. Firstly, IoT systems are vulnerable to most existing cyberthreats since I...	843	258615490	16
streams transmitted from IoT end devices using wireless communication strategies, as illustrated in Fig. 1. The effectiveness and efficiency of the proposed adaptive framework are evaluated using two public IoT cybersecurity datasets: IoTID20 [8] and CICIDS2017 [9], to evaluate the proposed framework in intrusion detec...	844	258615490	16
drift [6] [7]. The presence of concept drift may undermine the decisionmaking capabilities of IoT data analytics models, leading to significant repercussions in IoT systems. To tackle concept drift, it is essential to employ effective methods that can detect such drifts and adapt to the changes accordingly. This sectio...	845	258615490	16
concept drifts. B. Concept Drift Adaptation Upon detecting a concept drift, learning models need to adapt to new concepts and improve their performance. Current drift-adaptive learning techniques can be broadly classified into three main categories: adaptive algorithms, incremental learning, and ensemble learning metho...	846	258615490	16
Hoeffding trees. This approach makes HATT more efficient and precise in adapting to concept drift. Ensemble learning is a learning approach that combines the output of multiple base learners to create an ensemble model, which boasts improved generalization ability and performance in adapting to concept drift. Adaptive ...	847	258615490	16
data analytics framework that incorporates dynamic adjustments of ensemble methods to address different scenarios. III. PROPOSED FRAMEWORK A. System Overview The overview of the proposed framework for detecting anomalies in IoT systems by leveraging data stream analytics is shown in Fig. 2. It consists of three main ph...	848	258615490	16
infeasible and unnecessary to utilize all data samples for model development. Consequently, effective data sampling and normalization methods, such as K-means clustering and Z-score normalization, should be employed to select highly representative data samples. 1) Data Sampling: In the context of IoT data streams, Kmea...	849	258615490	16
handle outliers of IoT data streams [17]. The Z-score normalization method scales the feature value of each data sample x to a normalized value z as [18] where z represents the Z-score, x is the original data point, µ is the mean of the dataset, and σ is the standard deviation of the dataset. C. Drift Adaptation Base L...	850	258615490	16
[14] is chosen as an advanced ensemble model, which uses local subspace randomization to build HTs for drift adaptation, and incorporates a drift detector for identifying concept drift. As ARF demonstrates efficiency and effectiveness across various data stream analytics problems, two ARF models with different drift de...	851	258615490	16
the system. 3) One of the key advantages of the selected models, ARF-ADWIN, ARF-EDDM, OPA and KNN-ADWIN, is their ability to deliver strong performance while maintaining shorter execution times [16]. This balance between efficiency and effectiveness makes them well-suited for real-time IoT data stream analysis and hand...	852	258615490	16
4; w j indicates the weight of the j th base model; p j (y j = i\|L j , x) is the prediction probability of class i for the data sample x using the j th base model L j ; Finally, L j represents the j th base model. The weight w j for each base model L j is calculated using the inverse of the model's real-time error rate...	853	258615490	16
j ; // Compute cumulative error 12: ewa error rate j ← cumulative errorj 1−α (i+1) ; // Compute exponentially weighted average error rate 13: end for 14: ea ← 4 k=1 1 ewa error rate k + ; // Compute ensemble accuracy 15: for j = 1 to 4 do y pred ← I(y prob0 < y prob1 ); // Make final prediction based on the probability...	854	258615490	16
variables. The study began to consider real-time dynamic control of processes using discrete data [20]. By employing this method to calculate the weight, it can further enhance our adaptability to dynamic IoT data streams. The error rate associated with each base model L j , can be expressed as follows: where y pred j ...	855	258615490	16
base learners. The time complexity of the AEWAE algorithm itself is limited to O(nck), where n represents the number of samples, c is the number of class values in the target variable, and k indicates the number of base learners. Since both c and k are typically small values, the algorithm's overall time complexity rem...	856	258615490	16
Python 3.9 on the Google Colaboratory platform by extending the River [22] library. The system was run on a computer equipped with an Intel(R) Xeon(R) CPU @ 2.20GHz and 12.7 GB of memory, representing an IoT central server machine for big data analytics purposes. We assessed the proposed approach using two public IoT s...	857	258615490	16
from the online test set to first evaluate the learning model, followed by its integration into model training or updating. This process ensures that the model is continuously refined and updated as new data is introduced. The experimental results of the proposed framework are thoroughly analyzed from various angles to...	858	258615490	16
in Section II-B, including ARF-ADWIN [14], ARF-EDDM [14], OPA [12], SRP [15], KNN-ADWIN [11], HT [7], HATT [13], PWPAE [4], and MSANA [16]. As illustrated in Figures 3 and 4, as well as Table I, the four base models, ARF-ADWIN, ARF-EDDM, KNN-ADWIN, and OPA, achieve high accuracy while maintaining quite low latency on t...	859	258615490	16
The throughput of the proposed AEWAE model is also remarkably high, reaching 347.33 samples per second. Furthermore, to assess the efficiency and feasibility of the proposed framework, the probability density functions (PDFs) of the inference time/latency for the CICIDS2017 and IoTID20 datasets are presented in Figures...	860	258615490	16
According to performance evaluations conducted on two benchmark IoT streaming datasets, IoTID20 and CICIDS2017, our proposed framework has demonstrated its effectiveness in processing dynamic IoT streams, achieving higher accuracy rates of 99.72% and 99.69%, respectively, compared to other state-ofthe-art methods. In t...	861	258615490	16
PHYTOREMEDIATION OF SOILS CONTAMINATED WITH USED LUBRICATING OILS USING SUNFLOWER Lubricating oil is one of the most important derivatives from petrol industry, However its life cycle finished with the generation of the used oil, ham,ful to the environment and must be suitable disposed, A Brazilian law authorized the u...	862	221701809	16
metals and degraded organic and inorganic compounds in its composition, Data from the distributors companies of these products indicated that lubricating oil market is greater than one million of cubic meters per year in BraziLlt is estimated that 50% of the used lubricating oils can be collected to be reprocessed, onc...	863	221701809	16
responsibilities of the manufacturers, importers, resellers, and consumers of these products. It is unquestionable that used lubrication oils, when unsuitable discharged may lead to harmful consequences to the environment. Despite this Brazilian law is considered actual and more restrictive than similar of developed co...	864	221701809	16
24 experiments, as follow: Experiment I, 2, and 3: only soil. Experiment 4, 5, and 6: soil with sunflower. Experiment 7,8,and 9: soil with 2% of used lubricating oil. Experiment 10, I 1, and I 2: soil with 4% of used lubricating oil, Experiment I 3,I 4,and 15: soil with 6% of used lubricating oil, Experiment 16, 17, an...	865	221701809	16
to separate the species and 1 Helium was used as carrier gas at a flow rate of 1.5 ml min-, The injection temperature was 300 ° C in splitless condition with 1.0 µl of injection volume. The oven temperature starts at 60 ° C and programmed to 320 ° C at I 0 ° C min-1 , and the FID was set to 340 ° C The soil samples wer...	866	221701809	16
of oil after 90 days, and in a minor extent the 4 %, were affected by these oil contents, and some damages were observed in the leafs_ A secondary result obtained by this work indicated that the remediation process is more intense on the heavier compounds, by the observation of a more intense reduction of the chromatog...	867	221701809	16
Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. However, whether or not OP-B has any potenti...	868	1144379	16
natural and acquired resistance. Autophagy is known as a type II programmed cell death. It has been found that cell death can occur concomitantly with features of autophagy, and excessive stimulation of autophagy through over-expression of beclin1 suppresses tumorigenesis (1,2). Autophagy is a multi-step process consis...	869	1144379	16
and H460 cells showed that OP-B primarily induces autophagy but not apoptosis. Examination of the PI3K/Akt/ mTOR signaling pathway showed that OP-B selectively inhibits phosphorylation of Akt both at Ser473 and Thr308 in both of the two cell lines, suggesting that OP-B may be a potential inhibitor of the PI3K/Akt pathw...	870	1144379	16
assay. Plates were returned to the incubator and the fluorescence was read at 4 h. Data were calculated as the percentage of cell viability by the following formula: the percentage of cell viability = (At/As) x100%. At and As indicated the absorbance of the test substances and solvent control, respectively. The mean va...	871	1144379	16
fluorescence microscope (Olympus, Japan). Apoptosis and dead cells induced by OP-B were assayed using the high content screening (HCS) Kinetic Scan Reader (ThermoFisher Scientific, USA). The principle of the assay is that cells are labeled with a cocktail of fluorescent dyes (including Hoechst 33258 and Alexa Fluor 488...	872	1144379	16
and mounted on copper grids. The samples were stained with 2% aqueous uranyl acetate and lead citrate and observed in a transmission electron microscope (Jeol, Japan). Statistical analysis. Unless otherwise stated, data were expressed as the mean ± SD, and analyzed by Student's t test. P-value <0.05 was considered stat...	873	1144379	16
larger and occupied almost all of the space outside the nucleus in NCI-H157 cells. Flow cytometric analysis of cells stained with propidium iodide showed a mild increase in the cell population in G0-G1 phase after the cells were treated with different concentrations of OP-B for 24 h in medium containing 10% FBS (Fig. 2...	874	1144379	16
Detection of LC3 by immunoblotting showed that OP-B treatment increased the conversion of LC3-I to LC3-II in a dose-and time-dependent manner (Fig. 3B-E). Thus, we speculated that treatment with OP-B induced autophagy of NCI-H157 and H460 cells. Effects of OP-B on PI3K/Akt/mTOR/p70S6K signaling pathway and induction of...	875	1144379	16
p70S6K (Thr389) was inhibited by treatment with OP-B, LY294002, or rapamycin. Conversion of LC3 І to LC3-II was induced by OP-B, inhibited by LY294002, and enhanced by co-treatment with OP-B and LY294002. In fact, co-treatment with OP-B and rapamycin had an even more significant effect than single treatment with OP-B o...	876	1144379	16
on NSCLC, we chose NCI-H157 and NCI-H460 cells as our cell line models since they represent the most commonly used NSCLC cells and because they were all sensitive to OP-B in our preliminary studies. Of note, we found that after 24 h of treatment with at least 10 µmol/l OP-B in medium containing 10% FBS, a large number ...	877	1144379	16
in both cell lines, the OP-B increased the conversion of LC3 I to II in a dose-and time-dependent manner ( Fig. 3B and D). Unexpectedly, the conversion rate of LC3 I to II was more significant in NCI-H460 than in H157 (Fig. 3C and E). To further investigate the reason behind this, we assessed the PI3K/Akt/mTOR signalin...	878	1144379	16
to actin in H460 cells was performed using three independent experiments. Error bars, SD; p<0.01; * p<0.001. and rapamycin are inhibitors of PI3K and mTORC1, respectively. However, these compounds have some drawbacks. For example, LY294002 does not distinguish between class I and class III PI3K, and its inhibition...	879	1144379	16
Phenylmethimazole abrogates diet-induced inflammation, glucose intolerance and NAFLD Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease worldwide. High-fat (HF) diets promote an increased uptake and storage o...	880	4954767	16
from complications of cirrhosis and hepatocellular cancer. Thus, targeting hepatocellular inflammation is expected to significantly prevent the progression of the disease and reduce mortality in patients with NAFLD (Younossi et al. 2011). Activation of TLR4-mediated inflammation also exacerbates hepatic lipid accumulat...	881	4954767	16
& Harrison 2016, Schwenger et al. 2018) but can have significant associated complications (Chang et al. 2017). In light of this and studies suggesting a direct involvement of TLR4-mediated inflammation in the development of HF diet-induced hepatic steatosis and insulin resistance, there is a concerted effort directed a...	882	4954767	16
treatments. Reversal study Prior to the start of the experiment, mice were randomly assigned to a diet group: LF diet group or HF diet group. After 16 weeks on their respective diet, an IPGTT was performed to evaluate glucose tolerance in each mouse. Any mouse in the LF diet group that was glucose intolerant and any mo...	883	4954767	16
20/30, 60, 90, 120 and 180 min post IP injection of the glucose bolus. Histological analysis For microscopic examination of liver morphology and steatosis, liver tissue was fixed in 10% buffered formalin for 12-24 h. Formalin-fixed tissues were dehydrated in ethanol and embedded in paraffin for hematoxylin and eosin st...	884	4954767	16
was performed using GraphPad Prism 7 for Mac. Statistical differences were determined using a one-way or two-way ANOVA followed by a Tukey-Kramer or Bonferroni test for post hoc comparison. Figure 1 C10 inhibits hepatic inflammation in addition to triglyceride accumulation in cell culture. AML-12 and HepG2 cells were t...	885	4954767	16
IRF3 (McCall et al. 2010). In HFD-induced NAFLD, TLR4 expressed in hepatocytes is activated by both FFAs and LPS (Matsumura et al. 2000, Reyna et al. 2008. Stimulation of the MyD88-dependent pathway leads to pro-inflammatory cytokine expression, specifically Tnfa and Il6, while activation of the MyD88-independent TLR4 ...	886	4954767	16
tissue weights after 18 weeks on HF diet when compared to LF-fed mice. Data points on line graphs (A and B) indicate mean and error bars indicate +/− s.e.m. and bars on bar graphs (C) indicate mean + s.e.m. Significance was determined using ANOVA followed by Tukey's post hoc analysis for multiple comparison; *Different...	887	4954767	16
were interested in the effect of C10 treatment on weight and body composition in a HF diet-induced model of obesity (DIO model). Seven-week-old C57BL6/J male mice were fed either a LF diet (10% fat) or HF diet (60% fat). Mice were dosed once daily with intraperitoneal (IP) sham injections, IP injections of DMSO (vehicl...	888	4954767	16
(A) Histological examination revealed that C10 prevents hepatic lipid accumulation. All images in (A) were taken at 400× magnification. Scale bar, 40 µm. (B) Treatment with C10 decreased hepatic triglyceride content when compared to HF-fed sham and DMSO groups but had no effect on serum triglyceride levels. Dotted line...	889	4954767	16
4A) while total serum cholesterol was elevated in HF diet-fed mice when compared to LF sham controls; C10 did not affect serum cholesterol levels in HF-fed mice (Fig. 4B). C10 protects C57BL/6J male mice from HF diet-induced glucose intolerance Ectopic fat deposition in insulin target tissues impairs the function of in...	890	4954767	16
proinflammatory cytokines, in particular, Tnfa and type 1 interferons (Ifnb1). Our model of HF diet feeding promotes an increase in circulating FFAs, gut-derived LPS, as well as an increase in fat deposition and accumulation in adipose tissue and the liver (Fraulob et al. 2010). Pathologic exposure of adipose and liver...	891	4954767	16
diet-induced inflammation, adipose and liver tissue were collected from the mice in this study for analysis of pro-inflammatory gene expression. In both adipose and liver tissue, there was a significant increase in Tnfa and Ifnb1 expression in our HF sham and HF DMSO groups (Fig. 6). However, as in our in vitro studies...	892	4954767	16
mean + s.e.m. Significance was determined using ANOVA followed by Tukey's post hoc analysis for multiple comparison; *Different from HF sham and HF DMSO groups; P < 0.05, n = 8. Figure 6 C10 prevents HF diet-induced inflammation in vivo. Inflammatory gene expression was measured in liver and mesenteric adipose tissue a...	893	4954767	16
were randomly divided into HF sham, HF DMSO and HF C10 (1 mg/kg) treatment groups as described earlier for the 'prevention study' and were treated as indicated for 14 weeks. There was no difference in weights between the HF-fed treatment groups (Fig. 7A), although all HF-fed groups continued to gain weight and become m...	894	4954767	16
in this disease that is responsible for its progression (Wild et al. 2004, Dabelea et al. 2014, Imes & Burke 2014. The major inflammatory signaling pathway in chronic inflammation in a state of obesity is TLR4 (Davis et al. 2008, Pierre et al. 2013, Jia et al. 2014, Sawada et al. 2014. TLR4 is abundantly expressed in i...	895	4954767	16
exhibited potent anti-inflammatory properties by preventing FFA-and LPS-induced pro-inflammatory cytokine expression measured by a reduction in Tnfa and Ifnb1 mRNA levels in hepatocytes in culture. Similar findings were observed in vivo as pro-inflammatory cytokine expression was also significantly reduced by C10 in li...	896	4954767	16
LF-fed mice. (B) Following treatment, blood glucose levels remained elevated in the HF sham and HF DMSO groups when compared to the LF sham and HF C10-treated mice. Area under the curve was significantly lower in the C10-treated group when compared to the HF sham and DMSO groups and was nearly indistinguishable from th...	897	4954767	16
pioglitazone (Ratziu et al. 2008), acarbose (Chiasson et al. 2002), metformin (Haukeland et al. 2009) and possibly statins (Eslami et al. 2013) exhibit anti-inflammatory properties and are effective at treating NAFLD. However, there is a real need for novel, new classes of anti-inflammatory drugs for the prevention and...	898	4954767	16
of Endocrinology NAFLD (steatosis) is considered benign; however, it is now believed to be an active state of inflammation and metabolic dysfunction (Tilg & Moschen 2010, Buzzetti et al. 2016. Moreover, we now know that inflammation occurs in hepatic steatosis and thus it can be targeted by pharmacological agents befor...	899	4954767	16

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