ILT4 reprograms glucose metabolism to promote tumor progression in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive and poorly treated subtype of breast cancer. Identifying novel drivers and mechanisms for tumor progression is essential for precise targeted therapy of TNBC. Immunoglobulin-like transcript 4 (ILT4; also known as LILRB2) is a classic myeloid suppressor for their activation and immune response. Our recent results found that ILT4 is also highly expressed in lung cancer cells, where it has a role in promoting immune evasion and thus tumor formation. However, the expression and function of ILT4 in breast cancer remains elusive. Here, using our patient cohort and public database analysis, we found that TNBC displayed the most abundant ILT4 expression among all breast cancer subtypes. Functionally, enriched ILT4 promoted TNBC cell proliferation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Our study identified a novel driver for TNBC progression and proposed a promising strategy to combat TNBC by targeting ILT4.

Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex Into Microglial Exosomes.

Microglia modulate pro-inflammatory and neurotoxic activities. Edible plant-derived factors improve brain function. Current knowledge of the molecular interactions between edible plant-derived factors and the microglial cell is limited. Here an alcohol-induced chronic brain inflammation model is used to identify that the microglial cell is the novel target of oat nanoparticles (oatN). Oral administration of oatN inhibits brain inflammation and improves brain memory function of mice that are fed alcohol. Mechanistically, ethanol activates dectin-1 mediated inflammatory pathway. OatN is taken up by microglial cells via ß-glucan mediated binding to microglial hippocalcin (HPCA) whereas oatN digalactosyldiacylglycerol (DGDG) prevents assess of oatN ß-glucan to dectin-1. Subsequently endocytosed ß-glucan/HPCA is recruited in an endosomal recycling compartment (ERC) via interaction with Rab11a. This complex then sequesters the dectin-1 in the ERC in an oatN ß-glucan dependent manner and alters the location of dectin-1 from Golgi to early endosomes and lysosomes and increases exportation of dectin-1 into exosomes in an Rab11a dependent manner. Collectively, these cascading actions lead to preventing the activation of the alcoholic induced brain inflammation signing pathway(s). This coordinated assembling of the HPCA/Rab11a/dectin-1 complex by oral administration of oatN may contribute to the prevention of brain inflammation.

Balancing selection maintains ancient polymorphisms at conserved enhancers for the olfactory receptor genes of a Chinese marine fish.

The study of balancing selection, as a selective force maintaining adaptive genetic variation in gene pools longer than expected by drift, is currently experiencing renewed interest due to the increased availability of new data, methods of analysis, and case studies. In this investigation, evidence of balancing selection operating on conserved enhancers of the olfactory receptor (OR) genes is presented for the Chinese sleeper (Bostrychus sinensis), a coastal marine fish that is emerging as a model species for evolutionary studies in the Northwest Pacific marginal seas. Coupled with tests for Gene Ontology enrichment and transcription factor binding, population genomic data allow for the identification of an OR cluster in the sleeper with a downstream flanking region containing three enhancers that are conserved with human and other fish species. Phylogenetic and population genetic analyses indicate that the enhancers are under balancing selection as evidenced by their translineage polymorphisms, excess common alleles, and increased within-group diversities. Age comparisons between the translineage polymorphisms and most recent common ancestors of neutral genealogies substantiate that the former are old, and thus, due to ancient balancing selection. The survival and reproduction of vertebrates depend on their sense of smell, and thereby, on their ORs. In addition to locus duplication and allelic variation of structural genes, this study highlights a third mechanism by which receptor diversity can be achieved for detecting and responding to the huge variety of environmental odorants (i.e., by balancing selection acting on OR gene expression through their enhancer variability).

[Design of functional array electrode stimulation system with surface electromyography feedback].

In order to solve the problems of insufficient stimulation channels and lack of stimulation effect feedback in the current electrical stimulation system, a functional array electrode electrical stimulation system with surface electromyography (sEMG) feedback was designed in this paper. Firstly, the effectiveness of the system was verified through in vitro and human experiments. Then it was confirmed that there were differences in the number of amperage needed to achieve the same stimulation stage among individuals, and the number of amperage required by men was generally less than that of women. Finally, it was verified that the current required for square wave stimulation was smaller than that for differential wave stimulation if the same stimulation stage was reached. This system combined the array electrode and sEMG feedback to improve the accuracy of electrical stimulation and performed the whole process recording of feedback sEMG signal in the process of electrical stimulation, and the electrical stimulation parameters could change with the change of the sEMG signal. The electrical stimulation system and sEMG feedback worked together to form a closed-loop electrical stimulation working system, so as to improve the efficiency of electrical stimulation rehabilitation treatment. In conclusion, the functional array electrode electrical stimulation system with sEMG feedback developed in this paper has the advantages of simple operation, small size and low power consumption, which lays a foundation for the introduction of electrical stimulation rehabilitation treatment equipment into the family, and also provides certain reference for the development of similar products in the future.

Genetic diversity within grouper species and a method for interspecific hybrid identification using DNA barcoding and RYR3 marker.

Groupers (family Epinephelidae) are an assemblage of coral reef fishes comprising more than 160 species in 16 genera, many of which are both environmentally and economically valuable. Because of their similar morphology, variable color patterns, and tendency for interspecies hybridization, morphological identification of groupers usually leads to taxonomic confusion. To find an effective method for identifying different grouper species and hybrids, evaluate genetic diversity and uncover any synonymous or cryptic species, we sampled a total of 221 specimens representing 57 species in 9 genera in the China Seas. Both mitochondrial (mt) cytochrome oxidase subunit I (COI) and NADH dehydrogenase subunit 2 (ND2) were found to be effective barcoding genes. We also developed an efficient protocol for identifying hybrid groupers using mt markers and the nuclear RYR3 gene and found the first record of wide interspecies hybridization in genus Epinephelus. This barcoding study revealed high genetic divergence in many widespread species and possible synonyms. In addition to providing a molecular method for identifying grouper species, this study offers important resources for the further study of grouper conservation genetics, speciation, hybridization and other evolutionary traits.

Novel 8-hydroxyquinoline derivatives targeting ß-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease.

A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced Aß1-42 aggregation and potential antioxidant properties especially compound 5b (IC50 = 5.64 µM for self-induced Aß aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu2+/Zn2+-induced Aß1-42 aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H2O2 and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood-brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo. Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy.

Covalent Grafting of Antifouling Phosphorylcholine-Based Copolymers with Antimicrobial Nitric Oxide Releasing Polymers to Enhance Infection-Resistant Properties of Medical Device Coatings.

Medical device coatings that resist protein adhesion and bacterial contamination are highly desirable in the healthcare industry. In this work, an antifouling zwitterionic terpolymer, 2-methacryloyloxyethyl phosphorylcholine-co-butyl methacrylate-co-benzophenone (BPMPC), is covalently grafted to a nitric oxide (NO) releasing antimicrobial biomedical grade copolymer of silicone-polycarbonate-urethane, CarboSil, to significantly enhance the biocompatibility, nonspecific protein repulsion and infection-resistant properties. The NO donor embedded into CarboSil is S-nitroso-N-acetylpenicillamine (SNAP) and covalent grafting of the BPMPC is achieved through rapid UV-cross-linking, providing a stable, hydrophilic coating that has excellent durability over a period of several weeks under physiological conditions. The protein adsorption test results indicate a significant reduction (∼84-93%) of protein adhesion on the test samples compared to the control samples. Bacteria tests were also performed using the common nosocomial pathogen, Staphylococcus aureus. Test samples containing both NO donor and BPMPC show a 99.91 ± 0.06% reduction of viable bacteria when compared to control samples. This work demonstrates a synergistic combination of both antimicrobial and antifouling properties in medical devices using NO donors and zwitterionic copolymers that can be covalently grafted to any polymer surface.

Thymosin ß4 is involved in the antimicrobial immune response of Golden pompano, Trachinotus ovatus.

Thymosin beta belongs to the thymosin family, which consists of a series of highly conserved peptides involved in various biological processes. In teleosts, understanding of the immunological functions of thymosin beta is limited, particularly in vivo, which is essentially unknown. In the current study, we cloned and identified thymosin beta 4 from the teleost fish Golden pompano (Trachinotus ovatus), which we have named TroTß4. We investigated the expression patterns and functions of TroTß4 in both in vivo and in vitro assays. TroTß4 is composed of 44 amino acids and shares high sequence identities with known thymosin ß4 species in other teleosts, which contains a highly conserved actin-binding motif (LKKTET). The expression of TroTß4 was most abundant in immune organs, and was significantly up-regulated in response to infection bacterial with one of a number of bacteria (including Edwardsiella tarda, Vibrio harveyi, and Streptococcus agalactiae). Purified recombinant TroTß4 (rTroTß4) inhibited the growth of bacteria, as measured using an automatic growth curve analyzer, indicating that TroTß4 has antimicrobial functions. When administered in vivo, overexpression of TroTß4 in T. ovatus, bacterial colonization of tissues was significantly reduced. In contrast, when a DNA vector-based siRNA technology was used to knock down TroTß4 expression, bacterial dissemination and colonization of tissues increased significantly. Taken together, these results provide the first in vivo evidence to indicate that teleost thymosin beta 4 plays a significant role in innate antibacterial immune responses in addition to in vitro bacteriostatic activity. This provides valuable information regarding the biological functions of teleost thymosin beta.

Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease.

A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-ß (Aß) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aß1-42 aggregation (91.3±2.1%, 25µM), inhibition of hMAO-B (IC50, 1.73±0.39µM), antioxidant effects (43.4±2.6µM of IC50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H2O2-induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs.

Synthesis and pharmacological evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease.

In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC50 value of 5.12µM for hMAO-A and 0.816µM for hMAO-B), moderate inhibition of Aß aggregation (75.1% at 20µM), metal chelation, control of ROS generation and antioxidant activity (ORAC=3.62). In addition, s19 could reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results suggested that s19 might be a promising multitargeted compound for AD treatment.

Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease.

The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.

Arabidopsis C3HC4-RING finger E3 ubiquitin ligase AtAIRP4 positively regulates stress-responsive abscisic acid signaling.

Degradation of proteins via the ubiquitin system is an important step in many stress signaling pathways in plants. E3 ligases recognize ligand proteins and dictate the high specificity of protein degradation, and thus, play a pivotal role in ubiquitination. Here, we identified a gene, named Arabidopsis thaliana abscisic acid (ABA)-insensitive RING protein 4 (AtAIRP4), which is induced by ABA and other stress treatments. AtAIRP4 encodes a cellular protein with a C3HC4-RING finger domain in its C-terminal side, which has in vitro E3 ligase activity. Loss of AtAIRP4 leads to a decrease in sensitivity of root elongation and stomatal closure to ABA, whereas overexpression of this gene in the T-DNA insertion mutant atairp4 effectively recovered the ABA-associated phenotypes. AtAIRP4 overexpression plants were hypersensitive to salt and osmotic stresses during seed germination, and showed drought avoidance compared with the wild-type and atairp4 mutant plants. In addition, the expression levels of ABA- and drought-induced marker genes in AtAIRP4 overexpression plants were markedly higher than those in the wild-type and atairp4 mutant plants. Hence, these results indicate that AtAIRP4 may act as a positive regulator of ABA-mediated drought avoidance and a negative regulator of salt tolerance in Arabidopsis.

A Novel Score Based on Controlled Attenuation Parameter Accurately Predicts Hepatic Steatosis in Individuals With Metabolic Dysfunction Associated Steatotic Liver Disease: A Derivation and Independent Validation Study.

INTRODUCTION: In metabolic dysfunction-associated steatotic liver disease, the diagnostic efficacy of controlled attenuation parameter (CAP) was not very accurate in evaluating liver fat content. The aim of this study was to develop a score, based on CAP and conventional clinical parameters, to improve the diagnostic performance of CAP regarding liver fat content. METHODS: A total of 373 participants from 2 independent Chinese cohorts were included and divided into derivation (n = 191), internal validation (n = 75), and external validation (n = 107) cohorts. Based on the significant difference index between the 2 groups defined by the magnetic resonance imaging-proton density fat fraction (MRI-PDFF) in derivation cohort, the optimal model (CAP-BMI-AST score [CBST]) was screened by the number of parameters and the area under the receiver operating characteristic curve (AUROC). In the internal and external validation cohorts, the AUROC and corresponding 95% confidence intervals (CIs) were used to compare the diagnostic performance of CBST with that of CAP. RESULTS: We constructed the CBST = -14.27962 + 0.05431 × CAP - 0.14266 × body mass index + 0.01715 × aspartate aminotransferase. When MRI-PDFF was ≥20%, ≥10%, and ≥5%, the AUROC for CBST was 0.77 (95% CI 0.70-0.83), 0.89 (95% CI 0.83-0.94), and 0.93 (95% CI 0.88-0.98), which was higher than that for CAP respectively. In the internal validation cohort, the AUROC for CBST was 0.80 (95% CI 0.70-0.90), 0.95 (95% CI 0.91-1.00), and 0.98 (95% CI 0.94-1.00). The optimal thresholds of CBST were -0.5345, -1.7404, and -1.9959 for detecting MRI-PDFF ≥20%, ≥10%, and ≥5%, respectively. DISCUSSION: The CBST score can accurately evaluate liver steatosis and is superior to the CAP.

Efficacy and safety of Qushi Huayu, a traditional Chinese medicine, in patients with nonalcoholic fatty liver disease in a randomized controlled trial.

BACKGROUND: The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation. HYPOTHESIS/PURPOSE: This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial. STUDY DESIGN: A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24. RESULTS: Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p < 0.05). Compared to DFLG, QSHY treatment improved ALT (ß, -0.128 [95 % CI, -0.25, -0.005], p = 0.041), aspartate transaminase (ß, -0.134 [95 % CI, -0.256 to -0.012], p = 0.032), and fibrosis-4 score (ß, -0.129 [95 % CI, -0.254 to -0.003], p = 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid. CONCLUSION: Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.

Rice protein exerts a hypocholesterolemic effect through regulating cholesterol metabolism-related gene expression and enzyme activity in adult rats fed a cholesterol-enriched diet.

The major aim of this study is to elucidate the hypocholesterolemic mechanism exerted by rice protein (RP) in adult rats under cholesterol-enriched dietary condition. Compared with casein, the cholesterol levels in plasma and the liver were significantly reduced by RP, accompanying significant inhibition of cholesterol absorption. RP increased the activity and mRNA level of cholesterol 7α-hydroxylase, whereas acyl-CoA:cholesterol acyltransferase activity and gene expression were significantly depressed with consumption of RP. Neither the activity nor gene expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase of RP differed from that of casein. The gene expression of the peroxisome proliferator-activated receptor α and liver X receptor α were significantly activated by consumption of RP. RP did not modify the mRNA level of sterol regulatory element-binding protein-2 with respect to casein. These results suggest RP can induce a cholesterol-lowering effect through modifying cholesterol metabolism-related gene expression and enzyme activity in adult rats.

HMA-Net: A deep U-shaped network combined with HarDNet and multi-attention mechanism for medical image segmentation.

BACKGROUND: Automatic segmentation of lesion, organ, and tissue from the medical image is an important part of medical image analysis, which are useful for improving the accuracy of disease diagnosis and clinical analysis. For skin melanomas lesions, the contrast ratio between lesions and surrounding skin is low and there are many irregular shapes, uneven distribution, and local and boundary features. Moreover, some hair covering the lesions destroys the local context. Polyp characteristics such as shape, size, and appearance vary at different development stages. Early polyps with small sizes have no distinctive features and could be easily mistaken for other intestinal structures, such as wrinkles and folds. Imaging positions and illumination conditions would alter polyps' appearance and lead to no visible transitions between polyps and surrounding tissue. It remains a challenging task to accurately segment the skin lesions and polyps due to the high variability in the location, shape, size, color, and texture of the target object. Developing a robust and accurate segmentation method for medical images is necessary. PURPOSE: To achieve better segmentation performance while dealing with the difficulties above, a U-shape network based on the encoder and decoder structure is proposed to enhance the segmentation performance in target regions. METHODS: In this paper, a novel deep network of the encoder-decoder model that combines HarDNet, dual attention (DA), and reverse attention (RA) is proposed. First, HarDNet68 is employed to extract the backbone features while improving the inference speed and computational efficiency. Second, the DA block is adopted to capture the global feature dependency in spatial and channel dimensions, and enrich the contextual information on local features. At last, three RA blocks are exploited to fuse and refine the boundary features to obtain the final segmentation results. RESULTS: Extensive experiments are conducted on a skin lesion dataset which consists of ISIC2016, ISIC2017, and ISIC 2018, and a polyp dataset which consists of several public datasets, that is, Kvasir, CVC-ClinicDB, CVC-ColonDB, ETIS, Endosece. The proposed method outperforms some state-of-art segmentation models on the ISIC2018, ISIC2017, and ISIC2016 datasets, with Jaccard's indexes of 0.846, 0.881, and 0.894, mean Dice coefficients of 0.907, 0.929, and 03939, precisions of 0.908, 0.977, and 0.968, and accuracies of 0.953, 0.975, and 0.972. Additionally, the proposed method also performs better than some state-of-art segmentation models on the Kvasir, CVC-ClinicDB, CVC-ColonDB, ETIS, and Endosece datasets, with mean Dice coefficients of 0.907, 0.935, 0.716, 0.667, and 0.887, mean intersection over union coefficients of 0.850, 0.885, 0.644, 0.595, and 0.821, structural similarity measures of 0.918, 0.953, 0.823, 0.807, and 0.933, enhanced alignment measures of 0.952, 0.983, 0.850, 0.817, and 0.957, mean absolute errors of 0.026, 0.007, 0.037, 0.030, and 0.009. CONCLUSIONS: The proposed deep network could improve lesion segmentation performance in polyp and skin lesion images. The quantitative and qualitative results show that the proposed method can effectively handle the challenging task of segmentation while revealing the great potential for clinical application.

New insights into the role of dietary triglyceride absorption in obesity and metabolic diseases.

The incidence of obesity and associated metabolic diseases is increasing globally, adversely affecting human health. Dietary fats, especially triglycerides, are an important source of energy for the body, and the intestine absorbs lipids through a series of orderly and complex steps. A long-term high-fat diet leads to intestinal dysfunction, inducing obesity and metabolic disorders. Therefore, regulating dietary triglycerides absorption is a promising therapeutic strategy. In this review, we will discuss diverse aspects of the dietary triglycerides hydrolysis, fatty acid uptake, triglycerides resynthesis, chylomicron assembly, trafficking, and secretion processes in intestinal epithelial cells, as well as potential targets in this process that may influence dietary fat-induced obesity and metabolic diseases. We also mention the possible shortcomings and deficiencies in modulating dietary lipid absorption targets to provide a better understanding of their administrability as drugs in obesity and related metabolic disorders.

LOANet: a lightweight network using object attention for extracting buildings and roads from UAV aerial remote sensing images.

Semantic segmentation for extracting buildings and roads from uncrewed aerial vehicle (UAV) remote sensing images by deep learning becomes a more efficient and convenient method than traditional manual segmentation in surveying and mapping fields. In order to make the model lightweight and improve the model accuracy, a lightweight network using object attention (LOANet) for buildings and roads from UAV aerial remote sensing images is proposed. The proposed network adopts an encoder-decoder architecture in which a lightweight densely connected network (LDCNet) is developed as the encoder. In the decoder part, the dual multi-scale context modules which consist of the atrous spatial pyramid pooling module (ASPP) and the object attention module (OAM) are designed to capture more context information from feature maps of UAV remote sensing images. Between ASPP and OAM, a feature pyramid network (FPN) module is used to fuse multi-scale features extracted from ASPP. A private dataset of remote sensing images taken by UAV which contains 2431 training sets, 945 validation sets, and 475 test sets is constructed. The proposed basic model performs well on this dataset, with only 1.4M parameters and 5.48G floating point operations (FLOPs), achieving excellent mean Intersection-over-Union (mIoU). Further experiments on the publicly available LoveDA and CITY-OSM datasets have been conducted to further validate the effectiveness of the proposed basic and large model, and outstanding mIoU results have been achieved. All codes are available on https://github.com/GtLinyer/LOANet.

Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling.

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.

Rice protein improves adiposity, body weight and reduces lipids level in rats through modification of triglyceride metabolism.

BACKGROUND: To elucidate whether rice protein can possess a vital function in improving lipids level and adiposity, the effects of rice proteins extracted by alkaline (RP-A) and α-amylase (RP-E) on triglyceride metabolism were investigated in 7-week-old male Wistar rats fed cholesterol-enriched diets for 2 weeks, as compared with casein (CAS). RESULTS: Compared with CAS, plasma concentrations of glucose and lipids were significantly reduced by RP-feeding (P < 0.05), as well as hepatic accumulation of lipids (P < 0.05). RP-A and RP-E significantly depressed the hepatic activities of fatty acid synthase (FAS), glucose 6-phosphate dehydrogenase (G6PD) and malate dehydrogenase (MDH) (P < 0.05), whereas the activities of lipoprotein lipase (PL) and hepatic lipase (HL) were significantly stimulated (P < 0.05), as compared to CAS. Neither lipids level nor activities of enzymes were different between RP-A and RP-E (P > 0.05). There was a significant positive correlation between protein digestibility and deposit fat (r = 0.8567, P < 0.05), as well as the plasma TG concentration (r = 0.8627, P < 0.05). CONCLUSIONS: The present study demonstrates that rice protein can modify triglyceride metabolism, leading to an improvement of body weight and adiposity. Results suggest that the triglyceride-lowering action as well as the potential of anti-adiposity induced by rice protein is attributed to upregulation of lipolysis and downregulation of lipogenesis, and the lower digestibility of rice protein may be the main modulator responsible for the lipid-lowering action.