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Indigenous chicken breeds from Fujian Province, China, exhibit unique and distinctive phenotypic characteristics, including morphology, behaviour, integumentary pigmentation, feather colouration, and production performance. However, the underlying genetic basis governing these specific traits remains unclear. This study aimed to elucidate the population structure of six Fujian local chicken breeds [Bairong chickens (BRCs), Jinhu chickens (JHCs), Minqing chickens (MQCs), Dehua chickens (DHCs), Xiangdong chickens (XDCs), and Hetian chickens (HTCs)] in terms of their genetic resources within the province. The whole-genome resequencing revealed 8 678 612 single nucleotide polymorphisms (SNPs) in a cohort of 36 chickens. The results revealed a partial mismatch between the clustering patterns and geographic distributions of the six populations, with BRC displaying a noticeable genetic divergence from other chickens. Moreover, the genetic distance between XDC and HTC in Longyan County was relatively close and converged with JHC, MQC, and DHC into a subgroup. These findings provide a comprehensive understanding of the intrinsic characteristics and utilisation prospects of chicken germplasm resources in Fujian Province.

In this paper, Fe–Cr–C–W surfacing alloys was prepared by adopting arc additive surfacing technology with optimized Cr and W contents in flux-cored wire. The microstructure, hard phase, hardness and wear resistance of surfacing alloys was investigated by optical microscopy, electron microscopy, hardness and wear testing. The results show that with the increase of Cr and W, microstructure of the surfacing alloys changes from full ferrite to martensite, ferrite, retained austenite, carbides and other multiphase such as (Cr, Fe)7C3, WC and Fe2W, etc. The damage behavior gradually changes from severe abrasive wear to abrasive wear and a small amount of adhesive wear. Cr and W can significantly improve the hardness and wear resistance of the surfacing alloys. The surfacing alloys of arc additive manufactured by D4 wire with 5.91% Cr and 0.85%W exhibits good performance with a hardness of 37.9HRC and a wear amount of 0.0011g, which meets the requirements of railway wheels.

Abstract Zinc-alpha2-glycoprotein (AZGP1) has been implicated in peripheral metabolism; however, its role in regulating energy metabolism in the brain, particularly in POMC neurons, remains unknown. Here, we show that AZGP1 in POMC neurons plays a crucial role in controlling whole-body metabolism. POMC neuron-specific overexpression of Azgp1 under high-fat diet conditions reduces energy intake, raises energy expenditure, elevates peripheral tissue leptin and insulin sensitivity, alleviates liver steatosis, and promotes adipose tissue browning. Conversely, mice with inducible deletion of Azgp1 in POMC neurons exhibit the opposite metabolic phenotypes, showing increased susceptibility to diet-induced obesity. Notably, an increase in AZGP1 signaling in the hypothalamus elevates STAT3 phosphorylation and increases POMC neuron excitability. Mechanistically, AZGP1 enhances leptin-JAK2-STAT3 signaling by interacting with acylglycerol kinase (AGK) to block its ubiquitination degradation. Collectively, these results suggest that AZGP1 plays a crucial role in regulating energy homeostasis and glucose/lipid metabolism by acting on hypothalamic POMC neurons.

Abstract Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet‐induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination‐proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.

ABSTRACT: The assessment of animal genetic structure had significant importance for the preservation and breeding of animal germplasm resources. Selection signals are genotype markers generated during the process of biological evolution, and the detection of selection signals could reveal the direction of species evolution. The aim of this study was to generate a whole-genome resequencing data from Jinding duck, Shanma duck, Youxian Partridge duck, and Taiwan Brown tsaiya duck to reveal their population structure and selection signals. The population structure analysis revealed significant genetic differences among the 4 indigenous laying ducks, indicating their independent lineage. Specifically, Shanma duck and Youxian partridge duck were closely and likely originated from a common ancestor. In addition, selection sweep analysis was performed using the population genetic differentiation coefficient (Fst) and nucleotide diversity ratio (π ratio). The top 5% was used as the threshold for the Fst and π ratio, and the 2 thresholds were combined to identify selected genomic regions. In the selected regions of the 3 comparison groups, 136, 143, and 268 candidate genes were detected. Further screening of all candidate genes revealed that 35 candidate genes appeared simultaneously in 3 comparative groups, with 16 genes annotated. The 16 genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results revealed 5 functional genes (AQP3, PIK3C3, NOL6, RPP25, and DCTN3) that may be related to important economic traits in laying ducks and involved mainly invasopressin-regulated water reabsorption, ribosome biogenesis, and the PI3K signaling pathway. The results provide insights into the protection and exploitation of genetic resources of Chinese indigenous laying ducks.

Summary: Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

Abstract Background Roux-en-Y gastric bypass (RYGB) surgery is an effective metabolic surgery against diabetes and obesity. Clinical evidence indicates that patients with severe obesity have a poor curative effect in losing weight if they suffer from leptin or its receptor deficiency, but the underlying mechanism remains elusive. Here, we investigated the effect of leptin receptor deficiency on metabolic dysfunction in db/db mice treated by RYGB surgery. Methods The db/db mice and their heterozygote control db/m mice were subjected to RYGB or sham surgery. Body weight, blood glucose, food intake and glucose tolerance were evaluated. Micro-PET/CT and histological analysis were performed to examine the glucose uptake of tissues and the fat changes in mice. The key factors in glucose and fatty acid metabolism were detected by western blot analysis. Results Compared with the sham group, the db/db mice in the RYGB group showed more significant weight regain after surgical recovery and improvement in hyperinsulinemia and glucose tolerance. However, the total body fat and multiple organ lipid deposition of RYGB-treated db/db mice was increased. The underlying mechanism studies suggested that the activation of AMPK regulated GLUT4 to increase glucose uptake, but AMPK could not promote fatty acid oxidation through the JAK2/STAT3 pathway under leptin receptor deficiency in db/db mice. Conclusion We conclude that leptin receptor deficiency impedes the AMPK activation-mediated fat catabolism but does not affect AMPK-related glucose utilization after metabolic surgery in db/db mice. This result helps select surgical indications for patients with obesity and diabetes.

In this paper, the ER5356 aluminum alloy wire was used for cold metal transfer (CMT) welding of the 5083-H111 base metal with 20 mm thickness. The effects of four shielding gases, which were 100%Ar, 75%Ar+25%He, 50%Ar+50%He and 100%He on the weld formation, microstructure and mechanical properties were investigated using optical microscope, scanning electron microscope (SEM), x-ray diffraction (XRD) and mechanical testing. The results showed that with the increase of He in the shielding gas, the weld penetration and width increased, and the porosity in the weld zone decreased significantly; the microstructure changed from coarse dendrites to fine equiaxed crystals, and the microstructure was gradually refined; the tensile strength of deposited metal increased from 220 MPa to 270 MPa, with an increase of 22.7%, the tensile fracture was quintessential ductile fracture, and the hardness increased from 64.2 HV to 68.4 HV. The addition of He in the shielding gas can effectively inhibit the generation of pores and promote the β-Al3Mg2 phase in the weld microstructure, thus improving the mechanical properties of the deposited metal.

Abstract Objectives Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn’s disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat. Methods In this study, patients with known or suspected Crohn’s disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn’s disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat–water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann–Whitney U test, Kruskal–Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups. Results A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat–water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn’s disease at the enteric phase (all p

Abstract Background This retrospective multicenter study evaluated the efficacy and safety of bariatric surgery in Chinese patients with obesity. Methods Patients with obesity who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux‐en‐Y gastric bypass and completed a 12‐month follow‐up between February 2011 and November 2019 were enrolled. Weight loss, glycemic and metabolic control, insulin resistance, cardiovascular risk, and surgery‐related complications at 12 months were analyzed. Results We enrolled 356 patients aged 34.3 ± 0.6 years with a mean body mass index of 39.4 ± 0.4 kg/m2. Successful weight loss occurred in 54.6%, 86.8%, and 92.7% of patients at 3, 6, and 12 months, respectively, with no difference in percent excess weight loss between the laparoscopic sleeve gastrectomy and laparoscopic Roux‐en‐Y gastric bypass surgery groups. The average percentage of total weight loss was 29.5% ± 0.6% at 12 months; 99.4%, 86.8%, and 43.5% of patients achieved at least 10%, 20%, and 30% weight loss, respectively, at 12 months. Significant improvements in metabolic indices, insulin resistance, and inflammation biomarkers were observed at 12 months. Conclusions Bariatric surgery resulted in successful weight loss and improved metabolic control, insulin resistance, and cardiovascular risk in Chinese patients with obesity. Both laparoscopic sleeve gastrectomy and laparoscopic Roux‐en‐Y gastric bypass are suitable approaches for such patients.

ABSTRACT: The aim of the study was to explore the regulatory mechanism of differences in embryonic gonadal development between intergeneric distance hybrid offspring Mulard ducks and parent ducks. The morphological differences gonadal tissues of Muscovy ducks, Pekin ducks and Mulard ducks at 12.5-day embryonic age were observed by sectioning and hematoxylin-eosin (HE) staining. Then followed by transcriptome sequencing to screen for gonadal development-related differentially expressed circRNAs and mRNAs to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, qRT-PCR and luciferase reporter system were used to verify the sequencing data and targeting relationship of ceRNA pairs. The results showed that the seminiferous tubule lumen of Mulard ducks was not obvious, while there were obvious seminiferous tubules and tubular structures in testis of Pekin ducks and Muscovy ducks, with number and shape indicating maturity. There were 18 upregulated circRNAs and 16 downregulated circRNAs in Mulard ducks and Pekin ducks, respectively, and 39 upregulated circRNAs and 1 downregulated circRNA in Mulard ducks and Muscovy ducks, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis found that genes involves in dorso-ventral axis formation, for example, neurogenic locus notch homolog protein 1 (NOTCH1), were significantly enriched (P < 0.05). The novel_circ_0002265-gga-miR-122-5p-PAFAH1B2 regulatory network was constructed. The qRT-PCR results showed that the sequencing results were reliable. The dual-luciferase reporter assay showed that gga-miR-122-5p exists binding site of circ_0002265 and PAFAH1B2, indicating circ_0002265-gga-miR-122-5p-PAFAH1B2 targeting relationship. In summary, the embryonic gonadal development of intergeneric hybrid Mulard ducks may be regulated by differentially expressed circRNAs and genes, such as novel_circ_0000519, novel_circ_0003537, NOTCH1, FGFR2, PAFAH1B1, and PAFAH1B2, among which circ_0002265-gga-miR-122-5p-PAFAH1B2 may participate in the targeted regulation of gonadal development in Mulard ducks. The findings of this study are helpful for analyzing the mechanism of embryonic gonadal development differences in avians.

ABSTRACT: To explore the differential regulation mechanism of heat stress on the egg production performance and egg quality of Jinding ducks, 200 Jinding ducks (360-day-old) in good health and with similar body weights and a normal appetite were selected and randomly divided into a control (normal temperature [NT]) group (20°C–25°C) and a heat stress (HS) group (32°C–36°C), with 4 replicates in each group and 25 ducks in each replicate. The pretrial period was 1 wk, and the formal trial period was 4 wk. At the end of the 4th wk, 12 duck eggs were collected from each replicate to determine egg quality. Pituitary and ovarian tissues of Jinding ducks were collected, transcriptome sequencing was performed to screen differentially expressed miRNAs and mRNAs related to high temperature and heat stress, and a competitive endogenous RNA regulatory network was constructed. The sequencing data were verified by qRT‒PCR method. The following results were obtained: (1) Compared with the NT group, the HS group had a significantly lower laying rate, total egg weight, average egg weight, total feed intake, and feed intake per duck (P < 0.01), an extremely significantly higher feed-to-egg ratio (P < 0.01), and a higher mortality rate. (2) Compared with the NT group, the HS group had an extremely significantly lower egg weight, egg yolk weight, eggshell weight, and eggshell strength (P < 0.01) and an extremely significantly lower yolk ratio and eggshell thickness (P < 0.01, P < 0.05); however, there was no significant difference in the egg shape index, Haugh unit or protein height (P > 0.05). (3) A total of 1,974 and 1,202 genes were identified in the pituitary and ovary, respectively, and there were 5 significantly differentially expressed miRNAs. The differentially expressed genes were involved in the arginine and proline metabolism pathways, ether lipid metabolism pathway, and drug metabolism–cytochrome P450 pathway, which are speculated to be related to the egg production performance of Jingding ducks under high-temperature heat stress. (4) Novel_221 may target the PRPS1 gene to participate in egg production performance; novel_168 and novel_289 may target PIGW; novel_289 may target Q3MUY2; and novel_289 and novel_208 may target PIGN or genes that may be related to high-temperature heat stress. (5) In pituitary tissue, upregulated novel_141 (center of the network) formed a regulatory network with HSPB1 and HSP30A, and downregulated novel_366 (center of the network) formed a regulatory network with the JIP1 gene. In ovarian tissue, downregulated novel_289 (center of the network) formed a regulatory network with the ZSWM7, ABI3, and K1C23 genes, novel_221 formed a regulatory network with the IGF1, BCL7B, SMC6, APOA4, and FARP2 genes, and upregulated novel_40 formed a regulatory network with the HA1FF10 gene. In summary, heat stress affects the production performance and egg quality of Jinding ducks by regulating the secretion of endocrine-related hormones and the release of neurotransmitters as well as the expression of miRNAs and mRNAs in pituitary and ovarian tissues. The miRNA‒mRNA regulatory network provides a theoretical basis for the molecular mechanism that regulates the stress response in pituitary and ovarian tissues, egg quality, and production performance under heat stress.

ABSTRACT: Liancheng white duck is a typical local duck breed in Fujian Province famous for its meat traits. To better understand how meat quality varies with breed, the chemical composition of breast meats of Liancheng white ducks (LD) and Cherry Valley ducks (CD) were examined using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS).The correlation between meat quality and the differential metabolites was further analyzed. The results showed that the effects of breed on duck breast meat were significant for pH, color, cooking loss, and shear force. Liancheng white duck breast meat exhibited a higher shear force and pH, and lower cooking loss and lightness (L*24), redness (a*24), and yellowness (b*24) than CD. Metabolomic analysis revealed significant differences between the meat extracts from the 2 duck breeds. A total of 49 and 57 significantly different metabolites were identified in positive and negative ion modes, respectively. These differentially accumulated metabolites (DAMs) could be divided into 28 classes, of which the 4 main categories were carbohydrates, amino acids, fatty acids, and eicosanoids. Liancheng white duck might have better nutritional and medicinal value considering the higher content of (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,16,19-docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), and prostaglandinF3α (PGF3α), having anti-inflammatory orantioxidant effects. Carbohydrate concentration negatively correlated with pH24. The 4 metabolites positively correlated with the shear force. These results provide an overall perspective for bridging the gap between variation of duck meat quality and metabolites with respect to breed.

Forkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3 splicing isoforms show distinct abilities in the cofactor interaction and the nuclear translocation, resulting in different effects on the differentiation, cytokine secretion, suppressive function, linage stability, and environmental adaptation of Tregs. The balance of FOXP3 splicing isoforms is related to autoimmune diseases, inflammatory diseases, and cancers. In response to environmental challenges, FOXP3 transcription and splicing can be finely regulated by T cell antigen receptor stimulation, glycolysis, fatty acid oxidation, and reactive oxygen species, with various signaling pathways involved. Strategies targeting energy metabolism and FOXP3 splicing isoforms in Tregs may provide potential new approaches for the treatment of autoimmune diseases, inflammatory diseases, and cancers. In this review, we summarize recent discoveries about the FOXP3 splicing isoforms and address the metabolic regulation and specific functions of FOXP3 splicing isoforms in Tregs.

Diet High in salt content have been associated with cardiovascular disease and chronic inflammation. We recently demonstrated that transient receptor potential canonical 3 (TRPC3) channels regulate myofibroblast transdifferentiation in hypertrophic scars. Here, we examined how high salt activation of TRPC3 participates in hypertrophic scarring during wound healing. In vitro, we confirmed that high salt increased the TRPC3 protein expression and the marker of myofibroblast alpha smooth muscle actin (α-SMA) in wild-type mice (WT) primary cultured dermal fibroblasts but not Trpc3−/− mice. Activation of TRPC3 by high salt elevated cytosolic Ca2+ influx and mitochondrial Ca2+ uptake in dermal fibroblasts in a TRPC3-dependent manner. High salt activation of TRPC3 enhanced mitochondrial respiratory dysfunction and excessive ROS production by inhibiting pyruvate dehydrogenase action, that activated ROS-triggered Ca2+ influx and the Rho kinase/MLC pathway in WT mice but not Trpc3−/− mice. In vivo, a persistent high-salt diet promoted myofibroblast transdifferentiation and collagen deposition in a TRPC3-dependent manner. Therefore, this study demonstrates that high salt enhances myofibroblast transdifferentiation and promotes hypertrophic scar formation through enhanced mitochondrial Ca2+ homeostasis, which activates the ROS-mediated pMLC/pMYPT1 pathway. TRPC3 deficiency antagonizes high salt diet-induced hypertrophic scarring. TRPC3 may be a novel target for hypertrophic scarring during wound healing.

Abstract Objective To investigate the potential of employing sublingual microcirculation as an early noninvasive screening technique for diabetic nephropathy (DN). Research design and methods We recruited 89 patients with type 2 diabetes mellitus (T2DM) and 41 healthy subjects in this cross-sectional observational study. All participants underwent fluorescein fundus angiography, vibration perception testing, 10 g (Semmes–Weinstein) monofilament examination, nerve conduction velocity, and 24-h urine microalbumin determination. HbA1c, fasting plasma glucose, blood lipid, and estimated glomerular filtration rate(eGFR) were measured. Sublingual microcirculatory images were captured using side-stream dark-field (SDF) microcirculation microscopy, and total and perfused vascular density (TVD and PVD) were calculated. Results The sublingual microcirculatory parameters denoting microvascular density and perfusion were negatively correlated with both fasting plasma glucose (TVD, r = − 0.316, P

Abstract Background Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated. Methods 33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM + PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT). Results The circulating levels of asprosin in DM + PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD. Logistic regression analysis revealed that asprosin is an independent risk factor for PAD and receiver-operator characteristic (ROC) curve determined a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD. Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in patients with PAD and activation of TGF-β signaling pathway appeared in the aortic tissue of db/db mice. Asprosin directly induces EndMT in HUVECs in a TGF-β-dependent manner as TGF-β signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT. Conclusions Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-β signaling pathway. Trial registration This trial was registered at clinicaltrials.gov as NCT05068895

AimTo identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM).MethodsT2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values.ResultsA total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p

IntroductionDigital finance is the combination of digital information technology and traditional finance. And digital financial agglomeration plays a pivotal role in the process of improving economic resilience in the new era.MethodThis paper introduces digital financial agglomeration, measures the economic resilience of each province and conducts spatial correlation tests by using 30 inter-provincial (except Hainan Province) panel data from 2011 to 2020, and constructs a Spatial Durbin Model to empirically analyze the relationship between digital financial agglomeration and economic resilience based on the theory of diffusion effect of digital financial agglomeration and research hypotheses.ResultThe results show that: (1) Digital financial agglomeration can have a positive effect on economic resilience by expanding the scale of consumption. (2) Digital financial agglomeration has a direct effect on the economic resilience of the region and an indirect spillover effect on the economic resilience of neighboring regions. (3) The effects of the main explanatory variables on economic resilience pass the robustness test: the positive effects of digital financial agglomeration, consumption scale and the interaction term of the two on economic resilience are significant.DiscussionThis paper focuses on the phenomenon of digital financial agglomeration, which is a unique perspective, and explores the influence mechanism of digital financial agglomeration on economic resilience from the perspective of spatial spillover effects of digital financial agglomeration, which is somewhat innovative.

ObjectiveThis study aims to construct and use natural language processing and other methods to analyze major depressive disorder (MDD) and radiology studies’ publications in the PubMed database to understand the historical growth, current state, and potential expansion trend.MethodsAll MDD radiology studies publications from January 2002 to January 2022 were downloaded from PubMed using R, a statistical computing language. R and the interpretive general-purpose programming language Python were used to extract publication dates, geographic information, and abstracts from each publication’s metadata for bibliometric analysis. The generative statistical algorithm “Latent Dirichlet allocation” (LDA) was applied to identify specific research focus and trends. The unsupervised Leuven algorithm was used to build a network to identify relationships between research focus.ResultsA total of 5,566 publications on MDD and radiology research were identified, and there is a rapid upward trend. The top-cited publications were 11,042, and the highly-cited publications focused on improving diagnostic performance and establishing imaging standards. Publications came from 76 countries, with the most from research institutions in the United States and China. Hospitals and radiology departments take the lead in research and have an advantage. The extensive field of study contains 12,058 Medical Subject Heading (MeSH) terms. Based on the LDA algorithm, three areas were identified that have become the focus of research in recent years, “Symptoms and treatment,” “Brain structure and imaging,” and “Comorbidities research.”ConclusionLatent Dirichlet allocation analysis methods can be well used to analyze many texts and discover recent research trends and focus. In the past 20 years, the research on MDD and radiology has focused on exploring MDD mechanisms, establishing standards, and constructing imaging methods. Recent research focuses are “Symptoms and sleep,” “Brain structure study,” and “functional connectivity.” New progress may be made in studies on MDD complications and the combination of brain structure and metabolism.

Background Salt‐sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodium‐glucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive. Methods and Results Dahl salt‐sensitive rats and salt‐insensitive controls were fed with 8% high‐salt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced high‐salt‐induced hypertension and this effect was not totally dependent on urinary sodium excretion in salt‐sensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high‐salt diet. High salt intake increased vascular expression of TRPC3 in salt‐sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt‐induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, high‐salt‐induced activation of NCX1 (sodium‐calcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high‐salt‐induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt‐sensitive hypertension.

SH2-domain-containing protein tyrosine phosphatases (PTPs), belonging to the class I PTP superfamily, are responsible for the dephosphorylation on the phosphorylated tyrosine residues in some proteins that are involved in multiple biological processes in eukaryotes. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway transduce signaling responding to interferons and initiate cellular antiviral responses. The activity of the JAK/STAT pathway is generally orchestrated by the de-/phosphorylation of the tyrosine and serine residues of JAKs and STATs, in which the dephosphorylation processes are mainly controlled by PTPs. In the present study, an SH2-domian-contianing PTP, temporally named as LvPTPN6, was identified in Litopenaeus vannamei. LvPTPN6 shares high similarity with PTPN6s from other organisms and was phylogenetically categorized into the clade of arthropods that differs from those of fishes and mammals. LvPTPN6 was constitutively expressed in all detected tissues, located mainly in the cytoplasm, and differentially induced in hemocyte and gill after the challenge of stimulants, indicating its complicated regulatory roles in shrimp immune responses. Intriguingly, the expression of LvPTPN6 was regulated by interferon regulatory factor (IRF), which could directly bind to the LvPTPN6 promoter. Surprisingly, unlike other PTPN6s, LvPTPN6 could promote the dimerization of STAT and facilitate its nuclear localization, which further elevated the expression of STAT-targeting immune effector genes and enhanced the antiviral immunity of shrimp. Therefore, this study suggests a PTPN6-mediated regulatory approach from IRF to the JAK/STAT signaling pathway in shrimp, which provides new insights into the regulatory roles of PTPs in the JAK/STAT signaling pathway and contributes to the further understanding of the mechanisms of antiviral immunity in invertebrates.

Abstract Background Primary aldosteronism (PA) is highly prevalent in hypertensive population. Adrenal vein sampling (AVS) is the only procedure to assess adrenal aldosterone hypersecretion in PA. PA patients without aldosterone-producing adenomas (APA) frequently have unilateral aldosterone hypersecretion (UAH). These patients could bear inappropriate adrenalectomy without AVS. This study aims to identify which clinical characteristics should be recommended to perform AVS in these PA patients. Methods This study was performed from January 2018 to July 2019 at a center for hypertension and metabolic diseases. Adrenal computed tomography (CT) scan, biochemical evaluation, and AVS were performed. Results Total 141 patients were included in this study. Aldosterone to renin ratio (ARR) after confirmatory test is highly associated with adrenal laterality. The specificity of ARR > 10 (ng/dL)/(mU/L) after confirmatory test is 100%. After confirmatory test, patients with ARR > 10 (ng/dL)/(mU/L) had higher plasma aldosterone concentration and incidences of ischemic heart diseases and renal damage(p 10 (ng/dL)/(mU/L) indicates adrenal laterality, with increasingly cardiorenal damage in PA patients without APA. Thus, AVS should be recommended in these patients before surgery. Trial registration NCT03398785 , Date of Registration: December 24, 2017.

Currently, the most effective strategy for dealing with Alzheimer’s disease (AD) is delaying the onset of dementia. Severe hypoglycemia is strongly associated with dementia; however, the effects of recurrent moderate hypoglycemia (RH) on the progression of cognitive deficits in patients with diabetes with genetic susceptibility to AD remain unclear. Here, we report that insulin-controlled hyperglycemia slightly aggravated AD-type pathologies and cognitive impairment; however, RH significantly increased neuronal hyperactivity and accelerated the progression of cognitive deficits in streptozotocin-induced (STZ-induced) diabetic APP/PS1 mice. Glucose transporter 3–mediated (GLUT3-mediated) neuronal glucose uptake was not significantly altered under hyperglycemia but was markedly reduced by RH, which induced excessive mitochondrial fission in the hippocampus. Overexpression of GLUT3, specifically in the dentate gyrus (DG) area of the hippocampus, enhanced mitochondrial function and improved cognitive deficits. Activation of the transient receptor potential channel 6 (TRPC6) increased GLUT3-mediated glucose uptake in the brain and alleviated RH-induced cognitive deficits, and inactivation of the Ca2+/AMPK pathway was responsible for TRPC6-induced GLUT3 inhibition. Taken together, RH impairs brain GLUT3-mediated glucose uptake and further provokes neuronal mitochondrial dysfunction by inhibiting TRPC6 expression, which then accelerates progression of cognitive deficits in diabetic APP/PS1 mice. Avoiding RH is essential for glycemic control in patients with diabetes, and TRPC6/GLUT3 represents potent targets for delaying the onset of dementia in patients with diabetes.

The aim of this study is to investigate the prevalence of metabolic disorders in patients with primary aldosteronism (PA) and target organ damage (TOD) in different subtypes of patients with PA with or without metabolic syndrome (MS). Patients with PA were screened out from those with secondary hypertension and then subtyped via adrenal venous sampling (AVS). Baseline clinical characteristics (blood pressure, blood glucose, abdominal circumference, and lipid profile) were collected for the diagnosis of MS. Organ damage was evaluated according to cardiac and carotid ultrasound and urine microalbumin measurements. In all 261 patients with PA, 113 patients had concomitant MS and experienced more severe cardiac hypertrophy and increased intima-media thickness (IMT). The incidence of MS and diabetes mellitus (DM) had no statistic difference between the two groups, moreover, the rates of TOD were not different except microalbuminuria. However, metabolic disorders caused more remarkable TOD in PA patients with unilateral hypersecretion. It showed that cardiac hypertrophy was associated with obesity while microalbuminuria was related to plasma aldosterone concentration (PAC) in PA patients. In this retrospective study, our findings suggest that the effect of metabolic disorders on organ damage is more remarkable in patients with unilateral PA.

Potato late blight, caused by Phytophthora infestans, leads to a significant reduction in the yield and value of potato. Biocontrol displays great potential in the suppression of plant diseases. Diallyl trisulfide (DATS) is a well-known natural compound for biocontrol, although there is little information about it against potato late blight. In this study, DATS was found to be able to inhibit the hyphae growth of P. infestans, reduce its pathogenicity on detached potato leaves and tubers, and induce the overall resistance of potato tubers. DATS significantly increases catalase (CAT) activity of potato tubers, and it does not affect the levels of peroxidase (POD), superoxide dismutase (SOD), and malondialdehyde (MDA). The transcriptome datasets show that totals of 607 and 60 significantly differentially expressed genes (DEGs) and miRNAs (DEMs) are detected. Twenty-one negatively regulated miRNA-mRNA interaction pairs are observed in the co-expression regulatory network, which are mainly enriched in metabolic pathways, biosynthesis of secondary metabolites, and starch and sucrose metabolism based on the KEGG pathway. Our observations provide new insight into the role of DATS in biocontrol of potato late blight.

Phytophthora infestans, the notorious pathogen of potato late blight, leads to a severe decline in potato yields and even harvest failure. We isolated 201 endophytic isolates from healthy root tissues of potatoes, among which 41 showed strong antagonistic activity against P. infestans. Further, the tolerance to stress and the potential application against potato late blight of these antagonistic isolates were tested. Most of them were extremely tolerant to stresses such as acid–alkali, temperature, UV, salt, and heavy metal stress. However, some antagonistic isolates with excellent stress tolerance might be pathogenic to potatoes. Combining the screening results, a total of 14 endophytes had excellent comprehensive performance in all the tests. In this paper, the endophyte 6-5 was selected among them for the preliminary exploration of the anti-oomycete mechanism. Analysis of the 16S rDNA sequence revealed that 6-5 had a high homology to the corresponding sequence of Bacillus velezensis (99.72%) from the NCBI database. Endophyte 6-5 significantly inhibited the mycelial growth of P. infestans, with an inhibition rate of over 90% in vitro assays, and deformed the hyphal phenotype of P. infestans. In addition, endophyte 6-5 could secrete protease and cellulase, and produce antagonistic substances with high thermal stability, which might be helpful to its antagonistic activity against P. infestans. Furthermore, it was demonstrated that 6-5 had the ability to improve the resistance of potato tubers to late blight. In short, our study described the process of isolating and screening endophytes with antagonistic activity against P. infestans from potato roots, and further explored the potential of biocontrol candidate strain 6-5 in potato late blight control.

Abstract Background Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. Methods We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. Results A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28–2.57, p

Toll-like receptors (TLRs) are canonical cell membrane receptors functioning to recognize pathogens and transduce signals to activate immune responses. It has been known that Toll3 in Pacific white shrimp Litopenaeus vannamei (LvToll3) plays a critical role in antiviral immunity by inducing the transcription of interferon regulatory factor (IRF), which mediates a signaling axis that is similar to the interferon system of vertebrates. However, the regulatory mechanism of the Toll3-IRF signaling is still unclear. In this study, a novel microRNA (miRNA) of miR-10 family, temporarily named as miR-10c, was identified from L. vannamei. miR-10c may play a nonnegligible regulatory role in shrimp immune responses since it was constitutively expressed in all detected tissues and transcriptionally induced by immune stimulation. Functional analysis validated that miR-10c could target LvToll3 to inhibit its expression, through which miR-10c blocked the nuclear translocation of IRF and facilitated white spot syndrome virus (WSSV) infection. To our knowledge, the present study revealed the first report of a Toll targeted by miRNA in crustaceans and provided a solid evidence base for supporting the role of LvToll3 in antiviral defense by activating IRF signaling in L. vannamei. Identification of the miR-10c/Toll3/IRF regulatory axis in shrimp provides new insights into the participation of miRNA in the regulation of immune responses and contributes to in-depth understanding of the mechanisms of Toll-induced immune responses in L. vannamei.

Background: Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota. Methods: 16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC–MS systems. Findings: Although DPP-4i and α-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate. Interpretation: Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis. Fund: This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518). Keywords: DPP-4i, Gut microbiota, Glucose tolerance, GF mice

Context: The interplay between taste perception and salt sensation is crucial for salt intake. Our hemodynamic neuroimaging research has shown that the administration of capsaicin (the major spicy component of chili peppers) enhances the metabolic activity of the insula and orbitofrontal cortex (OFC) in response to high salt intake. Aims: The aim is to study how the brain processes underlying salty taste and spicy perception within the first second after stimulation. Settings and Design: This electrophysiological study included 25 participants (10 males) who were recruited by advertisement flyers in Chongqing. Subjects and Methods: The present study investigated the responses of the OFC and insular to the interaction of spicy flavor and salty taste by recording the event-related potentials (ERPs). Two concentrations of sodium chloride solution (150 and 200 mmol/L) with or without 0.5 μM capsaicin were applied to the tongue of the study's participants. Statistical Analysis Used: One-way ANOVA with Games-Howell's multiple comparison post-hoc tests and linear regression analysis. Results: N1 amplitudes were positively correlated with participants' levels of salt intake and their salty preference scores. Source analysis performed on the ERP N1 wave in the 120–180 ms time window showed that the sources were located approximately in the insula and OFC. The amplitudes of the N1 and P2 components in the 200 mmol/L NaCl group were higher than those in 150 mmol/L NaCl group, but not significantly different than the group administered 150 mmol/L of NaCl and 0.5 μmol/L of capsaicin. Conclusions: The present study provides novel insights into the use of flavor or saltiness enhancers for salt reduction in humans through cortical responses to the spicy-salty interaction.

Abstract Background Ghrelin modulates many physiological processes. However, the effects of intestinal ghrelin on hepatic glucose production (HGP) are still unclear. The current study was to explore the roles of intestinal ghrelin on glucose homeostasis and insulin signaling in the liver. Methods The system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-3H] glucose as a tracer were used to analyze the effect of intestinal ghrelin. Intraduodenal co-infusion of ghrelin, tetracaine and Activated Protein Kinase (AMPK) activator (AICAR), or pharmacologic and molecular inhibitor of N-methyl-D-aspartate receptors within the dorsal vagal complex, or hepatic vagotomy in rats were used to explore the possible mechanism of the effect of intestinal ghrelin on HGP. Results Our results demonstrated that gut infusion of ghrelin inhibited duodenal AMP-dependent protein kinase (AMPK) signal pathways, increased HGP and expression of gluconeogenic enzymes, and decreased insulin signaling in the liver of the rat. Intraduodenal co-infusion of ghrelin receptor antagonist [D-Lys3]-GHRP-6 and AMPK agonist with ghrelin diminished gut ghrelin-induced increase in HGP and decrease in glucose infusion rate (GIR) and hepatic insulin signaling. The effects of gut ghrelin were also negated by co-infusion with tetracaine, or MK801, an N-methyl-D-aspartate (NMDA) receptor inhibitor, and adenovirus expressing the shRNA of NR1 subunit of NMDA receptors (Ad-shNR1) within the dorsal vagal complex, and hepatic vagotomy in rats. When ghrelin and lipids were co-infused into the duodenum, the roles of gut lipids in increasing the rate of glucose infusion (GIR) and lowering HGP were reversed. Conclusions The current study provided evidence that intestinal ghrelin has an effect on HGP and identified a neural glucoregulatory function of gut ghrelin signaling.

Background/Aims: Alarin has been reported to be related with increased food intake and body weight. The relationship of circulating Alarin with insulin resistance or metabolic syndrome (MetS), however, is unknown. This study aimed to investigate the physiological role of Alarin and its association with MetS in humans. Methods: Newly diagnosed MetS patients (n=237) and age-matched healthy subjects (n=192) were recruited for this study. Oral glucose tolerance test, treadmill exercise, lipid infusions and euglycemic-hyperinsulinemic clamp (EHCs) were performed. Circulating Alarin and TNFα levels were measured by ELISA. Results: Circulating Alarin levels were significantly higher in MetS patients compared with healthy subjects (0.46 ± 0.22 vs. 0.41 ± 0.14 µg/L, P < 0.01). In all studied subjects, circulating Alarin levels were positively correlated with WC, blood pressure, FBG, triglyceride, HbA1c, HOMA-IR, AUCglucose, and TNFα (P < 0.05 or P < 0.01). Multivariate logistic regression analyses revealed that circulating Alarin levels were correlated with MetS and insulin resistance. There was no significant change of circulating Alarin levels in the subjects with treadmill exercise for 45 min. In healthy individuals, however, glucose challenge, acute hyperglycemia and lipid infusions resulted in increased circulating Alarin levels, while acute hyperinsulinaemia transiently decreased circulating Alarin levels. Conclusion: The present study provides the evidence that circulating Alarin levels are associated with MetS and insulin resistance.

Metabolic surgery (MS) is one of the most effective therapies for treating obesity. Due to the lack of multicenter cohort research on nutritional evaluations after surgery in Chinese patients, we explored the changes in nutritional status following MS in Chinese patients. This was a retrospective study of patients (n = 903) who underwent sleeve gastrectomy (SG) (n = 640) or Roux-en-Y gastric bypass (RYGB) (n = 263) for obesity at five different hospitals in China between 17 February 2011, and 20 December 2019. Major nutrients were evaluated at baseline and 1, 3, 6, and 12 months postoperatively. Hb levels decreased, and anemia prevalence increased at 12 months after MS in the premenopausal female group. Moreover, patients with preoperative anemia had an increased risk of postoperative anemia. The ferritin levels (p < 0.001) decreased and iron deficiency increased (p < 0.001) at 12 months after MS among premenopausal females. No significant changes in folate deficiency and vitamin B12 deficiency were found throughout the study. The bone mineral density (BMD) of the femoral neck, lumbar spine, and total hip significantly decreased from baseline to 12 months after MS; however, no new patients developed osteopenia or osteoporosis after MS. Based on 12 months of follow-up, premenopausal females presented a high incidence of anemia after MS. Although we found no differences in osteopenia and osteoporosis prevalence after MS, the BMD did decrease significantly, which suggests that nutrient supplements and long-term follow-up are especially necessary postoperation.

In the present paper, the continuous-drive friction welding (CDFW) technology has been successfully applied to join the U75V rail steel. The base metal (BM) of U75V rail steel is lamellar pearlite, and the weld zone could be clearly divided into three subzones (i.e., heat affected zone, thermo-mechanical affected zone (TMAZ), and central weld zone (CWZ)). Electron back-scattered diffraction examinations revealed the martensitic evolution in TMAZ and CWZ, suggesting that the experienced high temperature, severe plastic deformation, and fast cooling rate induce the microstructure transition during the CDFW process. The hard and brittle martensite structure explains the raised microhardness profiles and the reduced impact absorption energy of the as-welded joints. The CDFW process parameters govern the joint properties via influencing the welding heat input and plastic deformation by spindle speed and friction pressure at the friction stage, and the plastic deformation layer (flash) extrusion by upsetting pressure at the upsetting stage. More favorable results could be obtained at small set values of spindle speed (1800 rpm) and friction pressure (75 MPa) with less heat input and plastic deformation, and a large set value of upsetting pressure (175 MPa) with more flash extrusion, whose tensile strength reached 94.3% of that of the BM.

Vision sensing is a key technology to realize on-line detection of welding groove sizes and welding torch relative position and posture parameters during the arc welding process of intelligent production. For the specially designed vision sensor based on combined laser structured lights, an integrated calibration method for its internal parameters is proposed firstly, which improves the efficiency, accuracy and comprehensiveness of internal parameter calibration for a line structured light vision sensor and provides a good foundation for industrial application of the vision sensor. Then, the high precision integrated detection algorithms are derived for the V-groove size parameters and the spatial position and posture (SPP) parameters of the welding torch relative to the welding groove based on a single modulated laser lines image. The algorithms make full use of the data in a single modulated laser lines image, adopting data segmentation and plane fitting to realize the 3D reconstruction of V-groove surfaces and its adjacent workpiece surfaces of planar workpiece, so solving the parameters with high precision. In the verification tests, the relative detection error of V-groove size parameters of planar workpiece is less than 1%, and the relative detection error of SPP parameters of welding torch relative to the welding groove is less than 5%, which separately shows the effectiveness and accuracy of the calibration method and the detection algorithms. This research work provides a good technical support for the practical application of the specially designed vision sensor in the intelligent welding production.

The endoplasmic reticulum (ER) and mitochondria are physically connected to form dedicated structural domains known as mitochondria-associated ER membranes (MAMs), which participate in fundamental biological processes, including lipid and calcium (Ca2+) homeostasis, mitochondrial dynamics and other related cellular behaviors such as autophagy, ER stress, inflammation and apoptosis. Many studies have proved the importance of MAMs in maintaining the normal function of both organelles, and the abnormal amount, structure or function of MAMs is related to the occurrence of cardiovascular diseases. Here, we review the knowledge regarding the components of MAMs according to their different functions and the specific roles of MAMs in cardiovascular physiology and pathophysiology, focusing on some highly prevalent cardiovascular diseases, including ischemia-reperfusion, diabetic cardiomyopathy, heart failure, pulmonary arterial hypertension and systemic vascular diseases. Finally, we summarize the possible mechanisms of MAM in cardiovascular diseases and put forward some obstacles in the understanding of MAM function we may encounter.

Abstract Background Recurrent moderate hypoglycemia (RH), a major adverse effect of hypoglycemic therapy in diabetic patients, is one of the main risk factors for cognitive impairment and dementia. Transient receptor potential canonical channel 6 (TRPC6) is a potential therapeutic target for Alzheimer's disease (AD) and its expression is highly regulated by glucose concentration. Objective To investigate whether RH regulates the expression of TRPC6 in brain and whether TRPC6 dysfunction can drive hypoglycemia‐associated cognitive impairment in diabetes, and reveal the underlying mechanism. Methods Histological staining, in vivo two‐photon Ca2+ imaging, and behavioral tests were used to measure neuronal death, brain network activity, and cognitive function in mice, respectively. High‐resolution respirometry and transmission electron microscope were used to assess mitochondrial structure and function. Intracellular calcium measurement and molecular biology techniques were conducted to uncover the underlying mechanism. Results Here, we report that the expression of TRPC6 in hippocampus was specifically repressed by RH in streptozocin‐induced type 1 diabetic mice, but not in nondiabetic mice. TRPC6 knockout directly leads to neuron loss, neuronal activity, and cognitive function impairment under diabetic condition, the degree of which is similar to that of RH. Activation of TRPC6 with hyperforin substantially improved RH‐induced cognitive impairment. Mechanistically, TRPC6 inhibited mitochondrial fission in the hippocampus of diabetic mice undergoing RH episodes by activating adenosine 5‘‐monophosphate‐activated protein kinase, and TRPC6‐mediated cytosolic calcium influx was required for this process. Clinically, dysfunction of TRPC6 was closely associated with cognitive impairment in type 2 diabetic patients with RH. Conclusions Our results indicate that TRPC6 is a critical sensitive cation channel to hypoglycemia and is a promising target to prevent RH‐induced cognitive impairment by properly orchestrating the mitochondrial dynamics in diabetic patients.

Oxidative stress and inflammation are two important pathological mechanisms in diabetic nephropathy (DN). Aucubin (AU), a natural iridoid glucoside, possessing remarkable anti-inflammatory and anti-oxidation activity, has been used to treat diabetic complications. However, underlying mechanism of protective action in DN remains unclear. In the present study, AU significantly alleviated albuminuria, glomerular extracellular matrix expansion, renal fibrosis, and inflammation caused by diabetes after ten weeks of treatment. Moreover, AU significantly inhibited oxidative stress markers in kidney tissue. In addition, we demonstrated that AU promoted endogenous antioxidant defenses by triggering Nrf2 and FOXO3a nuclear translocation, respectively, and up-regulation of antioxidant genes, including NQO1, HO-1, Mn-SOD, and CAT. These effects may be, in part, mediated by inducing SIRT1 and SIRT3 activities. Furthermore, AU also attenuated pro-inflammatory cytokines in renal tissue by inhibiting the NF-κB signaling pathway. Taken together, our results suggested that AU is a potential natural agent for the prevention of diabetes-induced DN.

Background. Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods. The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results. Serum Fetuin-B and TNF-α levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-α, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion. Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.

Abstract While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH−/− attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes.

Abstract Background The development of potent non-toxic chemotherapeutic drugs against castration resistant prostate cancer (CRPC) remains a major challenge. Corosolic acid (CA), a natural triterpenoid, has anti-cancer activity with limited side effects. However, CA anti-prostate cancer activities and mechanisms, particularly in CRPC, are not clearly understood. In this study, we investigated CA anti-tumor ability against human CRPC and its mechanism of action. Methods The cell apoptosis and proliferation effects were evaluated via MTT detection, colony formation assay and flow cytometry. Western blot, gene transfection and immunofluorescence assay were applied to investigate related protein expression of Endoplasmic reticulum stress. A xenograft tumor model was established to investigate the inhibitory effect of CA on castration resistant prostate cancer in vivo. Results The results showed that CA inhibited cell growth and induced apoptosis in human prostate cancer cell (PCa) line PC-3 and DU145, as well as retarded tumor growth in a xenograft model, exerting a limited toxicity to normal cells and tissues. Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. IRE-1, PERK or CHOP knockdown partially attenuated CA cytotoxicity against PCa cells. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. CHOP silencing resulted in PCa cells sensitive to CA-induced apoptosis. Conclusion Our data demonstrated, for the first time, that CA might represent a novel drug candidate for the development of an anti-CRPC therapy.

Summary: High salt intake is one independent risk factor for cardiac hypertrophy. Polycystic kidney disease 2-like 1 (PKD2L1, also called TRPP3) acts as a sour sensor in taste cells, and its possible role in the cardiovascular system is unknown. Here, we report that knockout of PKD2L1 exacerbated high-salt diet (HSD)-induced cardiac hypertrophy and fibrosis, accompanied by cardiac dysfunction and reduced cardiac mitochondrial oxidative phosphorylation and enzyme activity. Furthermore, knockdown of PKD2L1 led to more serious mitochondrial Ca2+ overload and reduced Ca2+ uptake in cardiomyocytes on high salt loading. Mechanistically, PKD2L1 deficiency increased p300-mediated acetylation of histone 3 lysine 27 on the promoter of sodium/calcium exchange 1 (NCX1) by repressing AMP-activated protein kinase (AMPK) activity, resulting in NCX1 overexpression and mitochondrial Ca2+ overload. These results reveal an inhibitory effect of PKD2L1 on cardiac hypertrophy and provide a mechanistic insight into the link between mitochondrial Ca2+ homeostasis and cardiac hypertrophy. : Lu et al. reveal a role of a mitochondria-localized TRPP member, PKD2L1, in high salt-induced cardiac hypertrophy. PKD2L1 knockout leads to overexpression of NCX1 through increasing the acetylation level of histone 3 lysine 27 on NCX1 promoter and thus exacerbates mitochondrial calcium overload by activating the reverse mode of NCX1 in cardiomyocytes. Keywords: high-salt diet, cardiac hypertrophy, PKD2L1, mitochondria, NCX1