Clinical characteristics and prognosis of pancreatitis associated with immune checkpoint inhibitors.

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown remarkable efficacy against various cancers in clinical practice. However, ICIs can cause immune checkpoint inhibitor-associated pancreatic injury, often leading to drug withdrawal, and then patients must go to specialized treatment. The patients, their primary tumors are sensitive to ICIs therapy, may experience treatment delays due to such adverse reactions. Therefore, there is a need for systematic clinical researches on immune-related pancreatic toxicity to provide a clinical basis for its prevention and treatment. METHODS: This study involved the collection of data from patients treated with ICIs and addressed pancreatic injury with preemptive treatment before continuing ICIs therapy. Then, we also statistically analyzed the incidence of pancreatic injury in patients with different courses and combined treatment, and the success rate of rechallenge treatment. RESULTS: The study included 62 patients, with 33.9% (21/62) experiencing varying degrees of pancreatic injury. Patients with pancreatic injury, 10 cases evolved into pancreatitis, representing 47.6% (10/21) in the pancreatic injury subgroup and 16.1% (10/62) of the total patient cohort. Preemptive treatment was administered to 47.6% (10/21) of patients with pancreatitis, the effective rate was 100%. Among these patients, 70% (7/10) underwent successful rechallenge with ICIs. The occurrence of pancreatic injury was positively correlated with the treatment duration (P < 0.05) but showed no significant correlation with combination therapies (P > 0.05). CONCLUSION: The likelihood of pancreatic injury increased with longer treatment durations with ICIs; no significant association was found between the incidence of ICIs-related pancreatic damage and combination therapies. Preemptive treatment for immune-related pancreatitis is feasible, allowing some patients to successfully undergo rechallenge with ICIs therapy.

Mulberry Leaf Dietary Supplementation Can Improve the Lipo-Nutritional Quality of Pork and Regulate Gut Microbiota in Pigs: A Comprehensive Multi-Omics Analysis.

Mulberry leaves, a common traditional Chinese medicine, represent a potential nutritional strategy to improve the fat profile, also known as the lipo-nutrition, of pork. However, the effects of mulberry leaves on pork lipo-nutrition and the microorganisms and metabolites in the porcine gut remain unclear. In this study, multi-omics analysis was employed in a Yuxi black pig animal model to explore the possible regulatory mechanism of mulberry leaves on pork quality. Sixty Yuxi black pigs were divided into two groups: the control group (n = 15) was fed a standard diet, and the experimental group (n = 45) was fed a diet supplemented with 8% mulberry leaves. Experiments were performed in three replicates (n = 15 per replicate); the two diets were ensured to be nutritionally balanced, and the feeding period was 120 days. The results showed that pigs receiving the diet supplemented with mulberry leaves had significantly reduced backfat thickness (p < 0.05) and increased intramuscular fat (IMF) content (p < 0.05) compared with pigs receiving the standard diet. Lipidomics analysis showed that mulberry leaves improved the lipid profile composition and increased the proportion of triglycerides (TGs). Interestingly, the IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, the cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG-005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, and Limosilactobacillus. Simultaneously, the relative levels of L-tyrosine-ethyl ester, oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, and mulberrin were increased. Furthermore, we found that mulberry leaf supplementation significantly increased the mRNA expression of lipoprotein lipase, fatty acid-binding protein 4, and peroxisome proliferators-activated receptor γ in muscle (p < 0.01). Mulberry leaf supplementation significantly increased the mRNA expression of diacylglycerol acyltransferase 1 (p < 0.05) while significantly decreasing the expression of acetyl CoA carboxylase in backfat (p < 0.05). Furthermore, mulberry leaf supplementation significantly upregulated the mRNA expression of hormone-sensitive triglyceride lipase and peroxisome proliferator-activated receptor α (p < 0.05) in backfat. In addition, mulberry leaf supplementation led to increased serum leptin and adiponectin (p < 0.01). Collectively, this omic profile is consistent with an increased ratio of IMF to backfat in the pig model.

Unveiling new horizons in heart research: the promise of multi-chamber cardiac organoids.

Human cardiac and other organoids have recently emerged as a groundbreaking tool for advancing our understanding the developmental biology of human organs. A recent paper from Sasha Mendjan's laboratory published in the journal Cell on December 7, 2023, reported the generation of multi-chamber cardioids from human pluripotent stem cells, a transformative technology in the field of cardiology. In this short highlight paper, we summarize their findings. Their cardioids remarkably recapitulate the complexity of the human embryonic heart, including tissue architecture, cellular diversity, and functionality providing an excellent in vitro model for investigation of human heart development, disease modeling, precision medicine, and regenerative medicine. Thus, generating cardioids is an important step forward for understanding human heart development and developing potential therapies for heart diseases.

The large-scale group consensus multi-attribute decision-making method based on probabilistic dual hesitant fuzzy sets.

We proposed a novel decision-making method, the large-scale group consensus multi-attribute decision-making method based on probabilistic dual hesitant fuzzy sets, to address the challenge of large-scale group multi-attribute decision-making in fuzzy environments. This method concurrently accounted for the membership and non-membership degrees of decision-making experts in fuzzy environments and the corresponding probabilistic value to quantify expert decision information. Furthermore, it applied to complex scenarios involving groups of 20 or more decision-making experts. We delineated five major steps of the method, elaborating on the specific models and algorithms used in each phase. We began by constructing a probabilistic dual hesitant fuzzy information evaluation matrix and determining attribute weights. The following steps involved classifying large-scale decision-making expert groups and selecting the optimal classification scheme based on effectiveness assessment criteria. A global consensus degree threshold was established, followed by implementing a consensus-reaching model to synchronize opinions within the same class of expert groups. Decision information was integrated within and between classes using an information integration model, leading to a comprehensive decision matrix. Decision outcomes for the objects were then determined through a ranking method. The method's effectiveness and superiority were validated through a case study on urban emergency capability assessment, and its advantages were further emphasized in comparative analyses with other methods.

Elucidating the role of TWIST1 in ulcerative colitis: a comprehensive bioinformatics and machine learning approach.

Background: Ulcerative colitis (UC) is a common and progressive inflammatory bowel disease primarily affecting the colon and rectum. Prolonged inflammation can lead to colitis-associated colorectal cancer (CAC). While the exact cause of UC remains unknown, this study aims to investigate the role of the TWIST1 gene in UC. Methods: Second-generation sequencing data from adult UC patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and characteristic genes were selected using machine learning and Lasso regression. The Receiver Operating Characteristic (ROC) curve assessed TWIST1's potential as a diagnostic factor (AUC score). Enriched pathways were analyzed, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA). Functional mechanisms of marker genes were predicted, considering immune cell infiltration and the competing endogenous RNA (ceRNA) network. Results: We found 530 DEGs, with 341 upregulated and 189 downregulated genes. TWIST1 emerged as one of four potential UC biomarkers via machine learning. TWIST1 expression significantly differed in two datasets, GSE193677 and GSE83687, suggesting its diagnostic potential (AUC = 0.717 in GSE193677, AUC = 0.897 in GSE83687). Enrichment analysis indicated DEGs associated with TWIST1 were involved in processes like leukocyte migration, humoral immune response, and cell chemotaxis. Immune cell infiltration analysis revealed higher rates of M0 macrophages and resting NK cells in the high TWIST1 expression group, while TWIST1 expression correlated positively with M2 macrophages and resting NK cell infiltration. We constructed a ceRNA regulatory network involving 1 mRNA, 7 miRNAs, and 32 long non-coding RNAs (lncRNAs) to explore TWIST1's regulatory mechanism. Conclusion: TWIST1 plays a significant role in UC and has potential as a diagnostic marker. This study sheds light on UC's molecular mechanisms and underscores TWIST1's importance in its progression. Further research is needed to validate these findings in diverse populations and investigate TWIST1 as a therapeutic target in UC.

Genome-Based Identification and Characterization of Bacteriocins Selectively Inhibiting Staphylococcus aureus in Fermented Sausages.

The bacteriocin-producing Lactiplantibacillus plantarum SL47 was isolated from conventional fermented sausages, and the bacteriocin SL47 was purified using ethyl acetate, Sephadex G-25 gel chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC). Bacteriocin SL47 was identified by HPLC-MS/MS combined with whole-genome sequencing, and the results showed it consisted of plantaricin A, J, K, and N. Further characterization analysis showed that the bacteriocin SL47 was highly thermostable (30 min, 121 °C), pH stable (2-10), sensitive to protease and exhibited broad-spectrum antibacterial ability against Gram-positive and Gram-negative bacteria. The mechanism of action showed that the bacteriocin SL47 increased cell membrane permeability, and 2 × minimum inhibitory concentration (MIC) treatment for 40 min caused apoptosis of Staphylococcus aureus F2. The count of S. aureus in the sausage that was inoculated with L. plantarum SL47 and bacteriocin SL47 decreased by about 64% and 53% of that in the initial stage, respectively. These results indicated the potential of L. plantarum SL47 and bacteriocin SL47 as a bio-preservative in meat products.

Diversity of astroviruses in wild animals in Yunnan province, China.

BACKGROUND: Astroviruses (AstVs) are single-stranded RNA viruses that have been detected in a wide range of mammals and birds. They are associated with numerous interspecies transmissions and viral recombination events, posing a threat to human and animal health. METHODS: We collected 1,333 samples from wild animals, including bats, rodents, wild boars, and birds, from various states and cities in the Yunnan Province, China, between 2020 and 2023 to investigate the presence of AstVs. AstVs were detected using a polymerase chain reaction targeting the RdRp gene. Finally, the Molecular Evolutionary Genetics Analysis software was used to construct the phylogenetic tree. RESULTS: The overall positivity rate for AstVs was 7.12% in four species, indicating their widespread occurrence in the region. High genetic diversity among AstVs was observed in different animal species, suggesting the potential for interspecies transmission, particularly among rodents and birds. Additionally, we identified a novel AstV strain and, for the first time, provided information on the presence of bastroviruses in Yunnan, China. CONCLUSIONS: The widespread distribution and high genetic diversity of AstVs, along with the observed potential for interspecies transmission, highlight the importance of further investigation and surveillance in the region. The findings emphasize the need for increased attention to AstVs and their potential impact on human and animal health in Yunnan and other regions.

Comprehensive lipidomic analysis revealed the effects of fermented Morus alba L. intake on lipid profile in backfat and muscle tissue of Yuxi black pigs.

Mulberry leaf is a widely used protein feed and is often used as a strategy to reduce feed costs and improve meat quality in the livestock industry. However, to date, there is a lack of research on the improvement of meat quality using mulberry leaves, and the exact mechanisms are not yet known. The results showed that fermented mulberry leaves significantly reduced backfat content but had no significant effect on intramuscular fat (IMF). Lipidomic analysis showed that 98 and 303 differential lipid molecules (p < 0.05) were identified in adipose and muscle tissues, respectively, including triglycerides (TG), phosphatidylcholine, phosphatidylethanolamine, sphingolipids, and especially TG; therefore, we analysed the acyl carbon atom number of TG. The statistical results of acyl with different carbon atom numbers of TG in adipose tissue showed that the acyl group containing 13 carbon atoms (C13) in TG was significantly upregulated, whereas C15, C16, C17, and C23 were significantly downregulated, whereas in muscle tissue, the C12, C19, C23, C25, and C26 in TG were significantly downregulated. Acyl changes in TG were different for different numbers of carbon atoms in different tissues. We found that the correlations of C (14-18) in adipose tissue were higher, but in muscle tissue, the correlations of C (18-26) were higher. Through pathway enrichment analysis, we identified six and four metabolic pathways with the highest contributions of differential lipid metabolites in adipose and muscle tissues respectively. These findings suggest that fermented mulberry leaves improve meat quality mainly by inhibiting TG deposition by downregulating medium- and short-chain fatty acids in backfat tissue and long-chain fatty acids in muscle tissue.

The proteolytic activity in inflammatory bowel disease: insight from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease caused by the destruction of the intestinal mucosal epithelium that affects a growing number of people worldwide. Although the etiology of IBD is complex and still elucidated, the role of dysbiosis and dysregulated proteolysis is well recognized. Various studies observed altered composition and diversity of gut microbiota, as well as increased proteolytic activity (PA) in serum, plasma, colonic mucosa, and fecal supernatant of IBD compared to healthy individuals. The imbalance of intestinal microecology and intestinal protein hydrolysis were gradually considered to be closely related to IBD. Notably, the pivotal role of intestinal microbiota in maintaining proteolytic balance received increasing attention. In summary, we have speculated a mesmerizing story, regarding the hidden role of PA and microbiota-derived PA hidden in IBD. Most importantly, we provided the diagnosis and therapeutic targets for IBD as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes.

Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

Advances in the treatment of malignant ascites in China.

PURPOSE: Malignant ascites (MA) often occurs in recurrent abdominal malignant tumors, and the large amount of ascites associated with cancerous peritonitis not only leads to severe abdominal distension and breathing difficulties, but also reduces the patient's quality of life and ability to resist diseases, which usually makes it difficult to carry out anti-cancer treatment. The exploration of MA treatment methods is also a key link in MA treatment. This article is going to review the treatment of MA, to provide details for further research on the treatment of MA, and to provide some guidance for the clinical treatment of MA. METHOD: This review analyzes various expert papers and summarizes them to obtain the paper. RESULT: There are various treatment methods for MA, including systemic therapy and local therapy. Among them, systemic therapy includes diuretic therapy, chemotherapy, immunotherapy, targeted therapy, anti angiogenic therapy, CAR-T, and vaccine. Local therapy includes puncture surgery, peritoneal vein shunt surgery, acellular ascites infusion therapy, radioactive nuclide intraperitoneal injection therapy, tunnel catheter, and intraperitoneal hyperthermia chemotherapy. And traditional Chinese medicine treatment has also played a role in enhancing efficacy and reducing toxicity to a certain extent. CONCLUSION: Although there has been significant progress in the treatment of MA, it is still one of the clinical difficulties. Exploring the combination or method of drugs with the best therapeutic effect and the least adverse reactions to control MA is still an urgent problem to be solved.

Efficacy of extracellular vesicles as a cell-free therapy in colitis: a systematic review and meta-analysis of animal studies.

Background: Extracellular vesicles (EVs) mediate inflammation, immune responses, gut barrier integrity, and intestinal homeostasis. Recently, the application of EVs in the treatment of inflammatory bowel disease (IBD) has been under intensive focus. Some studies have been conducted in animal models of colitis, while systematic reviews and meta-analyses are lacking. The current study aimed to conduct a systematic review and meta-analysis of studies investigating the efficacy of EVs on IBD. Methods: A systematic retrieval of all studies in PubMed, EMBASE, MEDLINE, Web of Science, and Cochrane Library reported the effects of EVs in the colitis model up to 22 June 2023. The methodological quality was assessed based on SYRCLE's risk of bias (RoB) tool. Disease activity index (DAI), myeloperoxidase activity (MPO), histopathological score (HS), and inflammatory cytokines (TNF-α, NF-κB, IL-1ß, IL-6, and IL-10) were extracted as analysis indicators by Web Plot Digitizer 4.5. A meta-analysis was performed to calculate the standardized mean difference and 95% confidence interval using random-effect models by Review Manager 5.3 and STATA 14.0 software. Results: A total of 21 studies were included in this meta-analysis. Although the heterogeneity between studies and the potential publication bias limits confidence in the extent of the benefit, EV treatment was superior to the control in the colitis evaluation with reduced DAI, HS, MPO activity, and pro-inflammatory cytokines, including TNF-α, NF-κB, IL-1ß, and IL-6, while increasing the content of anti-inflammatory cytokine IL-10 (all p < 0.05). Conclusion: Our meta-analysis results supported the protective effect of EVs on colitis rodent models based on their potential role in IBD therapy and propelling the field toward clinical studies.

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects more than 3.5 million people, with rising prevalence. It deeply affects patients' daily life, increasing the burden on patients, families, and society. Presently, the etiology of IBD remains incompletely clarified, while emerging evidence has demonstrated that altered gut microbiota and decreased aryl hydrocarbon receptor (AHR) activity are closely associated with IBD. Furthermore, microbial metabolites are capable of AHR activation as AHR ligands, while the AHR, in turn, affects the microbiota through various pathways. In light of the complex connection among gut microbiota, the AHR, and IBD, it is urgent to review the latest research progress in this field. In this review, we describe the role of gut microbiota and AHR activation in IBD and discussed the crosstalk between gut microbiota and the AHR in the context of IBD. Taken as a whole, we propose new therapeutic strategies targeting the AHR-microbiota axis for IBD, even for other related diseases caused by AHR-microbiota dysbiosis.

A proximity labeling strategy enables proteomic analysis of inter-organelle membrane contacts.

Inter-organelle membrane contacts are highly dynamic and act as central hubs for many biological processes, but the protein compositions remain largely unknown due to the lack of efficient tools. Here, we developed BiFCPL to analyze the contact proteome in living cells by a bimolecular fluorescence complementation (BiFC)-based proximity labeling (PL) strategy. BiFCPL was applied to study mitochondria-endoplasmic reticulum contacts (MERCs) and mitochondria-lipid droplet (LD) contacts. We identified 403 highly confident MERC proteins, including many transiently resident proteins and potential tethers. Moreover, we demonstrated that mitochondria-LD contacts are sensitive to nutrient status. A comparative proteomic analysis revealed that 60 proteins are up- or downregulated at contact sites under metabolic challenge. We verified that SQLE, an enzyme for cholesterol synthesis, accumulates at mitochondria-LD contact sites probably to utilize local ATP for cholesterol synthesis. This work provides an efficient method to identify key proteins at inter-organelle membrane contacts in living cells.

Strain-induced giant enhancement of anisotropic dielectric constant in layered nitrides SrHfN2 and SrZrN2.

The development of information technology puts forward huge demand for electronic materials with high dielectric constants; first-principles calculations and simulations have been demonstrated as an efficient technique for screening and exploring novel dielectric materials. In the present study, first-principles calculations combined with density functional perturbation theory are employed to study the dielectric properties of two newly discovered layered nitrides SrHfN2 and SrZrN2 under strain. By analyzing the evolution of lattice distortion, dielectric constant, Born effective charge, and phonon modes along with the applied strain, we find that the biaxial strain and isotropic strain can effectively modulate the dielectric constant. The two nitrides SrHfN2 and SrZrN2 are dynamically stable up to biaxial tensile strains of 2.1% and 1.8%, and the dielectric constants have been enlarged to about 500 and 2000. Furthermore, the dielectric constant is dramatically enhanced by 15 (9) times to a maximum value of ∼2600 (2700) under an isotropic tensile strain of 1.2% (0.7%) for SrHfN2 (SrZrN2), which is mainly due to the softening of the lowest-frequency infrared-active phonon mode and the increasing octahedral distortion degree. Particularly, the ionic contribution of the dielectric constant shows very remarkable anisotropy and plays a dominant role in the change of the dielectric constant, whose in-plane components exhibit giant enhancement by 18 (10) times for SrHfN2 (SrZrN2). This work not only sheds light on the experimentally observed high dielectric constants of SrHfN2 and SrZrN2, but also provides an effective route to regulate the anisotropic dielectric constants by applied strain, which indicates promising applications in optical and electronic devices.

Exploration of surgical approach to reconstruct smile-like lip shape in East-Asian women.

BACKGROUND: To investigate the clinical effects of surgical treatment to improve the lip morphology for a smile-like appearance (joy and happiness) in East-Asian women. METHODS: From October 2016 to April 2020, 63 patients who had received surgery to lift the commissure of the mouth and adjust the shape of the upper red lip to form a smile-like shape were analyzed and evaluated. RESULTS: The lip shape of enrolled patients was improved to a certain extent after surgery without any obvious scar hyperplasia, and the satisfaction rate of people after the surgery was 85.71%. CONCLUSION: For East-Asian women with thin and flat lips, surgical approach can be used to improve the shape of lip, such that the appearance of the lip is in a smile-like shape, which can enhance affinity and also exhibit the aesthetic characteristics of East-Asian women. This treatment can be used for clinical reference. LEVEL OF EVIDENCE: Level IV.

CSAST: Content self-supervised and style contrastive learning for arbitrary style transfer.

Arbitrary artistic style transfer has achieved great success with deep neural networks, but it is still difficult for existing methods to tackle the dilemma of content preservation and style translation due to the inherent content-and-style conflict. In this paper, we introduce content self-supervised learning and style contrastive learning to arbitrary style transfer for improved content preservation and style translation, respectively. The former one is based on the assumption that stylization of a geometrically transformed image is perceptually similar to applying the same transformation to the stylized result of the original image. This content self-supervised constraint noticeably improves content consistency before and after style translation, and contributes to reducing noises and artifacts as well. Furthermore, it is especially suitable to video style transfer, due to its ability to promote inter-frame continuity, which is of crucial importance to visual stability of video sequences. For the latter one, we construct a contrastive learning that pull close style representations (Gram matrices) of the same style and push away that of different styles. This brings more accurate style translation and more appealing visual effect. A large number of qualitative and quantitative experiments demonstrate superiority of our method in improving arbitrary style transfer quality, both for images and videos.

Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration.

Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.

The Mef2c/AdipoR1 axis is responsible for myogenic differentiation and is regulated by resistin in skeletal muscles.

Previous studies have shown that accumulated lipid and insulin resistance emerges in skeletal muscle after the onset of obesity and diabetes. We have previously shown that resistin significantly increases lipid contents in C2C12 cells. However, studies evaluating the effects of resistin on skeletal muscle cells and tissues are limited; despite that, an understanding of resistin action and function on lipid alteration in skeletal muscle tissues is critical for understanding obesity-related diseases. In this study, we document that resistin increases lipid deposition both in vitro and in vivo. Further, resistin promotes fiber type transformation, decreases enzyme activities, inhibits myogenic differentiation, and decreases muscle grip and excise endurance. In addition, adiponectin signaling is activated during myocyte differentiation, but it is inhibited at elevated resistin concentrations. Mechanistic investigation revealed that mef2c is responsible for adiponectin signaling pathway inhibition by inhibiting adipoR1 expression at the transcriptional level. In conclusion, this is the first study to document that resistin increases ectopic lipid deposition in skeletal muscles via a mef2c-adipoR1 signaling pathway, which reveals for the first time the presence of crosstalk between resistin and adiponectin in skeletal muscles.

A Deep Neural Network-Based Model for Quantitative Evaluation of the Effects of Swimming Training.

This paper analyzes the quantitative assessment model of the swimming training effect based on the deep neural network by constructing a deep neural network model and designing a quantitative assessment model of the swimming training effect. This paper addresses the problem of not considering the influence of the uncertainties existing in the virtual environment when evaluating swimming training and adds the power of the delays in the actual training operation environment, which is used to improve the objectivity and usability of swimming training evaluation results. To better measure the degree of influence of uncertainties, a training evaluation software module is developed to validate the usability of the simulated training evaluation method using simulated case data and compare it with the data after training evaluation using the unimproved evaluation method to verify the correctness and objectivity of the evaluation method in this paper. In the experiments, the feature extractor is a deep neural network, and the classifier is a gradient-boosting decision tree with integrated learning advantages. In the experimental comparison, we can achieve more than 60% accuracy and no more than a 1.00% decrease in recognition rate on DBPNN + GBDT, 78.5% parameter reduction, and 54.5% floating-point reduction on DPBNN. We can effectively reduce 32.1% of video memory occupation. It can be concluded from the experiments that deep neural network models are more effective and easier to obtain relatively accurate experimental results than shallow learning when facing high-dimensional sparse features. At the same time, deep neural networks can also improve the prediction results of external learning models. Therefore, the experimental results of this model are most intuitively accurate when combining deep neural networks with gradient boosting decision trees.