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Abstract African swine fever virus (ASFV) is the causal agent of African swine fever (ASF), which is contagious and highly lethal to domestic pigs and wild boars. The genome of ASFV encodes many proteins important for ASFV life cycle. The functional importance of topoisomerase AsfvTopII has been confirmed by in vivo and in vitro assays, but the structure of AsfvTopII is poorly studied. Here, we report four AsfvTopII complex structures. The ATPase domain structures reveal the detailed basis for ATP binding and hydrolysis, which is shared by AsfvTopII and eukaryotic TopIIs. The DNA-bound structures show that AsfvTopII follows conserved mechanism in G-DNA binding and cleavage. Besides G-DNA, a T-DNA fragment is also captured in one AsfvTopII structure. Mutagenesis and in vitro assays confirm that Pro852 and the T-DNA-binding residue Tyr744 are important for the function of AsfvTopII. Our study not only advances the understanding on the biological function of AsfvTopII, but also provides a solid basis for the development of AsfvTopII-specific inhibitors.

Abstract Mpox virus (MPXV) can cause mpox in humans. Due to its quick and wide spread in the past two years, mpox has turned into a significant public health concern. Helicase E5 is a multi-domain protein; its primer synthesis and DNA unwinding activity are required for genome uncoating and DNA replication of MPXV. However, the in vitro DNA unwinding activity has never been demonstrated. Here, we report the structural and biochemical studies of MPXV E5, showing that the full-length protein adopts an auto-inhibited conformation. Truncation of the N-terminus can recover the in vitro unwinding activity of E5 towards the forked DNA. Further structural analysis reveals that MPXV E5 shares a conserved mechanism in DNA unwinding and primer synthesis with the homologous proteins. These findings not only advance our understanding on the function of MPXV E5, but also provide a solid basis for the development of anti-poxvirus drugs.

Microbial functional composition is important for biogeochemical cycles, and is usually constrained by taxonomic species pool and natural environmental gradients. However, the distribution of functional genes in deep lakes and the driving factors remains elusive. Here, we quantified the abundance of 71 functional genes relevant to carbon degradation, carbon fixation, methane metabolism, nitrogen cycling, phosphorus cycling, and sulfur cycling in 38 sediments along the water depth ranging from 0 to 90 m in Lugu Lake, China, using Quantitative Microbial Ecology Chip (QMEC) and then explored their water-depth diversity pattern and abiotic and biotic drivers. Functional gene diversity showed a hump-shaped pattern along the depth and peaked at around 50 m which is the low boundary of thermocline layer. There were specific environmental preferences among functional gene subgroups such as nitrogen and sulfur cycling genes preferring to deeper and shallow waters, respectively. The dissimilarity of total functional genes increased with water depth distance indicating a distance-decay relationship. There was a congruence between functional and taxonomic composition by showing the positive correlations between the compositions of functional genes and bacteria or archaea. This phenomenon is consistently observed for the six functional gene subgroups, and the congruence strength was highest for nitrogen cycling while lowest for sulfur cycling. Compared to abiotic factors, biotic factors were more relevant to the functional gene diversity and composition. Biotic factors explained 28.5 % of the variance of functional gene diversity, while water depth and other environmental factors such as water total phosphorus and sediment carbon explained 4.2 % and 3.8 %, respectively. For functional gene composition, biotic factors accounted for 25.2 % of the variance, whereas water depth and other environmental factors contributed to 0.7 % and 4.4 %, respectively. Among all explanatory variables for function genes, bacterial composition had the highest contribution, which was further supported by showing its direct effects of 1.45 and 0.86 on functional diversity and composition, respectively. This study for the first time quantified the microbial functional genes along water depth in deep lakes and provided a more comprehensive understanding of the functional dynamics in microbial communities within aquatic ecosystems.

Abstract Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4 iKO ) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4 iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4 iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.

ABSTRACTBackground Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis.Method C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics.Result In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice.Conclusion Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.

Mechanism underlying the metabolic benefit of intermittent fasting remains largely unknown. Here, we reported that intermittent fasting promoted interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s) and subsequent beigeing of subcutaneous white adipose tissue. Adoptive transfer of intestinal ILC3s increased beigeing of white adipose tissue in diet-induced-obese mice. Exogenous IL-22 significantly increased the beigeing of subcutaneous white adipose tissue. Deficiency of IL-22 receptor (IL-22R) attenuated the beigeing induced by intermittent fasting. Single-cell sequencing of sorted intestinal immune cells revealed that intermittent fasting increased aryl hydrocarbon receptor signaling in ILC3s. Analysis of cell-cell ligand receptor interactions indicated that intermittent fasting may stimulate the interaction of ILC3s with dendritic cells and macrophages. These results establish the role of intestinal ILC3s in beigeing of white adipose tissue, suggesting that ILC3/IL-22/IL-22R axis contributes to the metabolic benefit of intermittent fasting.

The poor tear resistance of silicone rubber dramatically limits its application range. In this study, a topological entanglement structure of molecular chains was constructed at the interface between the matrix and silica by introducing epoxidized silicone rubber into silicone rubber/silica composites. We found that this topologically entangled structure could improve the crack propagation resistance of the composites by inducing the orientation of molecular chains. The results showed that adding 5 phr of 15% epoxy silicone rubber raised the silicone rubber composite’s tear strength and elongation at break, they increased by 330% and 140, respectively. This work provides a new idea for preparing silicone rubber composites with high tear resistance to better expand the application field of silicone rubber.

The hydrochemical characteristics were analyzed by mathematical statistics, the hydrochemical types were analyzed by Piper three line diagram, and the sources and influencing factors of main ions in surface water were discussed by Gibbs diagram and ion correlation analysis. The results show that the TDS of surface water in the study area is 109–559 mg·L−1, and the average value is 318.67 mg·L−1; The pH value is 6.81–8.62, and the average value is 7.85. Most of them belong to weakly alkaline water. The surface water cation is mainly Ca2+ and Mg2+, the anion is mainly HCO3- and the hydrochemical type is HCO3–Ca. Through the correlation analysis of the main ions, it can be seen that TDS has a significant positive correlation with Na+, K+, Mg2+, Ca2+ and HCO3−, and these ions contribute to TDS. HCO3− has a significant correlation with Na+, K+ and Mg2+ and comes from carbonate rocks. According to the analysis of water–rock model, the hydrochemical genesis of surface water in the study area is mainly controlled by rock weathering, most ions are weathered and dissolved by carbonate rock and evaporated salt rock and a few cations are affected by water ion exchange. HIGHLIGHTS Our article is about hydrochemical characteristics and factors of travertine deposition in Huanglong, a world Natural Heritage site. China.; This is a first for the industry.; It has original and innovative meaning.;

Long-term intermediate fasting before pregnancy in mice disrupts intestinal homeostasis of offspring with subsequent glucose and lipid metabolism disorder, mediated by a reduction in beneficial microbiota such as Lactobacillus intestinalis.

Abstract Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease, and there is no proven drug treatment for this condition. In this study, by using the Connectivity Map (CMap) approach, we explored naringenin, a naturally occurring citrus flavonoid, as a putative agent for inhibiting AAA. We then validated the prediction with two independent mouse models of AAA, calcium phosphate (CaPO4)-induced C57BL/6J mice and angiotensin II-infused ApoE−/− mice. Naringenin effectively blocked the formation of AAAs and the progression of established AAAs. Transcription factor EB (TFEB) is the master regulator of lysosome biogenesis. Intriguingly, the protective role of naringenin on AAA was abolished by macrophage-specific TFEB depletion in mice. Unbiased interactomics, combined with isothermal titration calorimetry (ITC) and cellular thermal shift assays (CETSAs), further revealed that naringenin is directly bound to 14-3-3 epsilon blocked the TFEB-14-3-3 epsilon interaction, and therefore promoted TFEB nuclear translocation and activation. On one hand, naringenin activated lysosome-dependent inhibition of the NLRP3 inflammasome and repressed aneurysmal inflammation. On the other hand, naringenin induced TFEB-dependent transcriptional activation of GATA3, IRF4, and STAT6 and therefore promoted reparative M2 macrophage polarization. In summary, naturally derived naringenin or macrophage TFEB activation shows promising efficacy for the treatment of AAA.

Infection of human parvovirus B19 (B19V) can cause a variety of diseases, such as hydrops fetalis, erythema infectiosum in children and acute arthropathy in women. Although B19V infection mainly occurs during childhood, about 50 % of adults are still susceptible to B19V infection. As the major replication protein of B19V, deletion of NS1 completely abolishes the infectivity of the virus. The nuclease domain of NS1 (NS1_Nuc) is responsible for DNA Ori binding and nicking that is critical for B19V viral DNA replication. NS1 has various variants, the structure and function for the majority of the variants are poorly studied. Here, we report two high-resolution crystal structures of NS1_Nuc, revealed the detailed conformations of many key residues. Structural comparison indicates that these residues are important for ssDNA or dsDNA binding by NS1. NS1 belongs to the HUH-endonuclease superfamily and it shares conserved ssDNA cleavage mechanism with other HUH-endonuclease members. However, our structural analyses, mutagenesis and in vitro assay results all suggested that NS1_Nuc utilizes one unique model in ssDNA binding.

To investigate the effects of stirrup ratio and connection type of stirrups on axial compression performance of stirrup-confined concrete-filled steel tubular (CFST) stub column, experiments were conducted on 16 CFST stub columns. The axial compressive bearing capacity and ductility of square and circular CFST stub columns with welded and non-welded stirrups were studied. Besides, numerical models of the stirrup-confined CFST stub columns were established to validate whether the numerical modeling method for welded stirrup-confined CFST column is suitable for the non-welded counterparts. Then, the applicability of the formulas for the axial compressive bearing capacity of the large stirrup ratio CFST stub column was investigated. The results indicated that the stirrups have a significant constraint effect on the steel tube and improve the axial compressive bearing capacity and ductility of the CFST stub column obviously. The effects of the stirrups on the square composite column are more significant than the circular composite column. The welded stirrups are more effective on the bearing capacity and ductility. The numerical modeling method and formulas are suitable for the non-welded stirrup-confined and large stirrup ratio CFST stub columns.

Microbial beta diversity has been recently studied along the water depth in aquatic ecosystems, however its turnover and nestedness components remain elusive especially for multiple taxonomic groups. Based on the beta diversity partitioning developed by Baselga and Local Contributions to Beta Diversity (LCBD) partitioning by Legendre, we examined the water-depth variations in beta diversity components of bacteria, archaea and fungi in surface sediments of Hulun Lake, a semi-arid lake in northern China, and further explored the relative importance of environmental drivers underlying their patterns. We found that the relative abundances of Proteobacteria, Chloroflexi, Euryarchaeota, and Rozellomycota increased toward deep water, while Acidobacteria, Parvarchaeota, and Chytridiomycota decreased. For bacteria and archaea, there were significant (p

Saline lakes possess substantial carbon storage and play essential roles in global carbon cycling. Benthic microorganisms mine and decompose sediment organic matter via extracellular enzymes to acquire limiting nutrients and thus meet their element budgets, which ultimately causes variations in sediment carbon storage. However, current knowledge about microbial nutrient limitation and the associated organic carbon changes especially in saline lake remains elusive. Therefore, we took Qinghai Lake, the largest saline lake of China, as an example to identify the patterns and drivers of microbial metabolic limitations quantified by the vector analyses of extracellular enzyme stoichiometry. Benthic microorganisms were dominantly colimited by carbon (C) and nitrogen (N). Such microbial C limitation was aggravated upon the increases in water salinity and sediment total phosphorus, which suggests that sediment C loss would be elevated when the lake water is concentrated (increasing salinity) and phosphorus becomes enriched under climate change and nutrient pollution, respectively. Microbial N limitation was predominantly intensified by water total nitrogen and inhibited by C limitation. Among the microbial drivers of extracellular enzyme investments, bacterial community structure consistently exerted significant effects on the C, N, and P cycles and microbial C and N limitations, while fungi only altered the P cycle through species richness. These findings advance our knowledge of microbial metabolic limitation in saline lakes, which will provide insights towards a better understanding of global sediment C storage dynamics under climate warming and intensified human activity.

ObjectiveRoux-en-Y gastric bypass is an effective intervention for metabolic disorder. We aim to elucidate whether ghrelin contributes to weight reduction, and glycemic and lipid control after Roux-en-Y gastric bypass (RYGB).DesignFour-week-old WT and Ghrl-TSC1-/- mice were fed high fat diet for 12 weeks before surgery, and continued to be on the same diet for 3 weeks after surgery. Body weight, food intake, glycemic and lipid metabolism were analyzed before and after surgery.ResultsGastric and circulating ghrelin was significantly increased in mice with RYGB surgery. Hypoghrelinemia elicited by deletion of TSC1 to activate mTOR signaling in gastric X/A like cells demonstrated no effect on weight reduction, glycemic and lipid control induced by Roux-en-Y gastric bypass surgery.ConclusionLower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.

Cyanobacteria bloom is a global aquatic ecological problem that seriously threatens human health and social development. The outbreak of cyanobacteria bloom is affected by various environmental factors, among which light dose is an essential factor. In this study, the growth changes of cyanobacteria under different amounts of natural light were studied by simulating different depths of Taihu Lake, and we used 16S rRNA and non-targeted metabolomics for sequencing to reveal the effects of light on the diversity of cyanobacteria and coexisting microorganisms, and to analyze the changes of related genes, functional structures and internal metabolism involved in nitrogen cycling. The result shows that excessive and insufficient light could limit the growth, photosynthesis, and EPS secretion of cyanobacteria, resulting in an antioxidant stress response. At the same time, the amount of natural light affects the vertical distribution of cyanobacteria, and under the condition of 1/3 natural light, cyanobacteria first appeared to float. In addition, the amount of natural light affects the diversity, abundance, and metabolites of cyanobacteria and coexisting microorganisms, and the expression of nifH, nirK, and nirS, three nitrogen-fixing genes, is significantly different in different genera. This study provides valuable information on the molecular mechanism of the effects of the amount of natural light on cyanobacteria bloom.

Microorganisms can both indicate the water quality characteristics and the health of the aquatic environment, which have an important influence on the cycling of organic carbon, nitrogen (N), and phosphorus (P) in nature. In this study, we took Taihu Lake, a typical eutrophic lake in China, as the research object, and monitored the northern (Changzhou City) and southern (Changxing County) regions of Taihu Lake for three consecutive years (2019–2021), respectively. We also analyzed the microbial diversity in sediments, and then summarized the effects of different nutrient environments on microorganisms in the aquatic environment. The results showed that the pollution level in the northern part of Taihu Lake was higher than that in the southern region of Taihu Lake, where the pollution was mainly in summer (June–July). The pollution in the southern region of Taihu Lake is relatively stable between 2019 and 2021; the changes in the northern part of Taihu Lake are relatively significant. Microbial diversity in the study area was negatively correlated with the degree of eutrophication of water bodies; microbial abundance was positively correlated with nutrient levels. The functional difference analysis indicated that the microorganisms in the sediments of Taihu Lake in the study area were involved in the nutrient transport and transformation, and played an important role in the purification of the lake water body. This study reveals the relationship between water eutrophication and microbial diversity, and then provides a theoretical basis for the management of eutrophic lakes.

“Whale Fall” is a collective term for the whale carcass, the process of dead whale fall, and the formed deep-sea ecosystem. The whale fall process produces a lot of unstable organic matter that has a significant impact on deep-sea ecosystems. Scientists speculate that organic matter input is the source of energy and material for organisms in deep-sea ecosystems. In the seafloor of the North Pacific, whale fall supports the survival of at least 12,490 organisms of 43 species, contributing to the prosperity of deep-sea life. Due to the specificity of the time and space of the formation of whale fall, there are few studies on whale fall and its impact on the deep-sea ecosystem. This article summarizes and analyses the current research status on the distribution of whale fall and its impact on the deep-sea ecosystem at home and abroad. The results show that the current distribution of whale fall is mainly concentrated in the Pacific and Atlantic regions, and the research on the impact of whale fall on deep-sea ecosystems focuses on the formation process, degradation rate and impact on deep-sea biological systems. This article has some significance to the understanding of biodiversity and ecosystem succession in the deep-sea “desert area.”

Obesity, a growing chronic metabolic disease, greatly increases the risk of metabolic syndrome which includes type 2 diabetes, fatty liver and cardiovascular diseases. Obesity-associated metabolic diseases significantly contribute to mortality and reduce life expectancy. Recently, innate lymphoid cells (ILCs) have emerged as crucial regulators of metabolic homeostasis and tissue inflammation. This review focuses on the roles of ILCs in different metabolic tissues, including adipose tissue, liver, pancreas, and intestine. We briefly outline the relationship between obesity, inflammation, and insulin resistance. We then discuss how ILCs in distinct metabolic organs may function to maintain metabolic homeostasis and contribute to obesity and its associated metabolic diseases. The potential of ILCs as the therapeutic target for obesity and insulin resistance is also addressed.

Lake level or water depth are key physical variables known to respond dramatically to climate change, especially in arid regions, and their fluctuations exert substantial influences on lake biodiversity and ecosystem functioning. However, it is unclear how multiple ecosystem functions (i.e., ecosystem multifunctionality, EMF) respond to changes in water depth and how aquatic community attributes, such as species richness, evenness and community compositions, are linked to EMF along water depth gradients. Lake Hulun, a representative of semiarid-region lake in China, has experienced serious lake area shrinkage over the past 20 years. Here, we explored the water-depth patterns of three microbial taxonomic groups of bacteria, archaea and fungi and nine ecosystem functions related to nutrient cycling in Lake Hulun. We further examined the relative importance of different community attributes on EMF variations. We found that the community compositions of bacteria, archaea and fungi showed consistent water-depth decay patterns, and EMF and most individual ecosystem functions involved in C, N, P and S cycling increased with water depth. Further, EMF was predominantly mediated by microbial evenness and community composition, but not species richness, as predicted by the traditional theory of biodiversity-ecosystem functioning relationships. In addition, water depth indirectly affected the relationships between the microbial community and EMF via sediment nutrient contents. These findings indicate that the water depth changes under climate change could substantially alter ecosystem structure and functioning in arid regions. We further emphasize the necessity of including multiple community attributes in biodiversity-EMF relationship research to clarify the biotic and abiotic forces underlying EMF variations.

Asthma is a complex chronic airway inflammatory disease that seriously impacts patients’ quality of life. As a novel approach to exploring the pathogenesis of diseases, metabolomics provides the potential to identify biomarkers of asthma host susceptibility and elucidate biological pathways. The aim of this study was to screen potential biomarkers and biological pathways so as to provide possible pharmacological therapeutic targets for asthma. In the present study, we merged the differentially expressed genes (DEGs) of asthma in the GEO database with the metabolic genes obtained by Genecard for bioinformatics analysis and successfully screened out the metabolism-related hub genes (HIF1A, OCRL, NNMT, and PER1). Then, untargeted metabolic techniques were utilized to reveal HDM-induced metabolite alterations in 16HBE cells. A total of 45 significant differential metabolites and 5 differential metabolic pathways between the control group and HDM group were identified based on the OPLS-DA model. Finally, three key metabolic pathways, including glycerophospholipid metabolism, galactose metabolism, and alanine, aspartate, and glutamate metabolism, were screened through the integrated analysis of bioinformatics data and untargeted metabolomics data. Taken together, these findings provide valuable insights into the pathophysiology and targeted therapy of asthma and lay a foundation for further research.

Cyanobacteria blooms are a global aquatic environment problem. In recent years, due to global warming and water eutrophication, the surface cyanobacteria accumulate in a certain area to form cyanobacteria blooms driven by wind. Cyanobacteria blooms change the physical and chemical properties of water and cause pollution. Moreover, cyanobacteria release organic matter, N (nitrogen) and P (phosphorus) into the water during their apoptosis, accelerating the eutrophication of the water, threatening aquatic flora and fauna, and affecting the community structure and abundance of microorganisms in the water. Simultaneously, toxins and carcinogens released from cyanobacteria can be enriched through the food chain/web, endangering human health. This study summarized and analyzed the research of the influence of cyanobacteria blooms on the aquatic environment and human health, which is helpful to understand further the harm of cyanobacteria blooms and provide some reference for a related research of cyanobacteria blooms.

The mammalian target of rapamycin (mTOR) is an important protein kinase that senses changes in extracellular and intracellular energy levels and plays a key role in regulating energy metabolism. Brown adipose tissue, which can be converted to white adipose tissue, contains a large number of mitochondria and regulates energy expenditure through thermogenesis. Because obesity is a process of fat accumulation due to chronic excessive energy intake, we attempted to determine whether the mTOR signaling pathway can affect the mitochondrial quality control of brown adipocytes through sensing energy status, thereby regulating brown/white adipocyte transformation. In the present study, through activation or inhibition of mTOR signaling, we detected mitochondrial biogenesis, dynamics, and autophagy-related markers in brown adipocytes. We found that activation of mTOR signaling downregulated the expression of mitochondrial biogenesis, dynamics, and autophagy-relevant markers and inhibited the mitochondrial quality control of brown adipocytes, indicating a phenotypic transformation of brown to white adipocytes. In contrast, inhibition of mTOR signaling upregulated the expression of mitochondrial biogenesis, dynamics, and mitophagy-relevant markers and strengthened mitochondrial quality control, suggesting an inhibition of the phenotypic transformation of brown to white adipocytes. In conclusion, the mTOR signaling pathway plays an important role in modulating the transformation of adipocytes by regulating mitochondrial quality control.

A patient’s response to immune checkpoint inhibitors (ICIs) is a complex quantitative trait, and determined by multiple intrinsic and extrinsic factors. Three currently FDA-approved predictive biomarkers (progra1mmed cell death ligand-1 (PD-L1); microsatellite instability (MSI); tumor mutational burden (TMB)) are routinely used for patient selection for ICI response in clinical practice. Although clinical utility of these biomarkers has been demonstrated in ample clinical trials, many variables involved in using these biomarkers have poised serious challenges in daily practice. Furthermore, the predicted responders by these three biomarkers only have a small percentage of overlap, suggesting that each biomarker captures different contributing factors to ICI response. Optimized use of currently FDA-approved biomarkers and development of a new generation of predictive biomarkers are urgently needed. In this review, we will first discuss three widely used FDA-approved predictive biomarkers and their optimal use. Secondly, we will review four novel gene signature biomarkers: T-cell inflamed gene expression profile (GEP), T-cell dysfunction and exclusion gene signature (TIDE), melanocytic plasticity signature (MPS) and B-cell focused gene signature. The GEP and TIDE have shown better predictive performance than PD-L1, and PD-L1 or TMB, respectively. The MPS is superior to PD-L1, TMB, and TIDE. The B-cell focused gene signature represents a previously unexplored predictive biomarker to ICI response. Thirdly, we will highlight two combined predictive biomarkers: TMB+GEP and MPS+TIDE. These integrated biomarkers showed improved predictive outcomes compared to a single predictor. Finally, we will present a potential nucleic acid biomarker signature, allowing DNA and RNA biomarkers to be analyzed in one assay. This comprehensive signature could represent a future direction of developing robust predictive biomarkers, particularly for the cold tumors, for ICI response.

Background: R-spondins (Rspo) and leucine-rich repeat-containing G-protein-coupled receptors (LGR) play important roles in development, stem cells survival, and tumorigenicity by activating Wnt signaling pathway. Whether R-spondins-LGR signaling affects the progression of squamous cell carcinoma (SCC) remain unknown. This study aims to uncover the role of R-spodin2/LGR4 in tongue SCC (TSCC). Methods: The expression of Rspo2 in TSCC specimens and its correlation with TSCC clinical outcome were evaluated. Levels of Rspo2 or LGR4 were altered by pharmacological and genetic approaches, and the effects on TSCC progression were assessed. Findings: Aberrantly high levels of Rspo2 were detected in TSCC specimens. Its levels were closely related with lymph node metastasis, clinical stage and survival rate in patients with tongue SCC. Exogenous Rspo2 or overexpression of Rspo2 promoted growth, migration and invasion, epithelial-mesenchymal transition (EMT) and stem-like properties in SCC both in vivo and in vitro. Silence of Rspo2 abolished these phenotypes. LGR4 was functionally upregulated by Rspo2 in TSCC. Overexpression of Rspo2 increased, whereas Rspo2 silencing decreased the expression of LGR4, leading to subsequent phosphorylation of LRP6 and nuclear translocation of β-catenin in TSCC cell lines. This nuclear translocation of β-catenin was associated with a significant alteration in TCF-1, a downstream nuclear transcription factor of β-catenin, as well as its target genes: CD44, CyclinD1 and c-Myc. Interpretation: Rspo2-LGR4 system regulates growth, migration and invasion, EMT and stem-like properties of TSCC via Wnt/β-catenin signaling pathway. Keywords: R-spodin2-LGR4, Tongue squamous cell carcinoma, Proliferation, Epithelial-Mesenchymal transition, Stem-like properties, Wnt/β-catenin signaling

This study was conducted to evaluate the changes in microbial communities and metabolites during the Chinese traditional sourdough fermentation. A gradual decrease in pH values was observed throughout the fermentation process. A considerable increase in LAB and yeasts counts was noticed during the primary stage of fermentation with the corresponding increase in amino acids, glucose, lactic acid and acetic acid. During the secondary fermentation stage, LAB count started decreasing slowly, while yeast count still increased, and reached to the maximum value. However, glucose, amino acid, lactic acid and acetic acid contents decreased slightly. PCR-DGGE results identified nine bacteria, six yeasts and one mold species during the whole fermentation process. Saccharomyces cerevisiae and Lactobacillus sanfranciscensis were the predominant species. These results would help to understand the LAB and yeasts influence on the metabolic process during the fermentation of steamed bread by Chinese traditional sourdoughs.

The hot-dry environment in high geothermal tunnels negatively affects the development of properties of cementitious materials. In order to improve the mechanical properties of cementitious materials in such environments, a proper curing system was developed, the material compositions were taken into account, and the related mechanism was analyzed by microscopic tests. The results showed that the mechanical properties and microstructure of cementitious materials can be improved effectively by adopting film curing and an adequate dosage of fly ash in a hot-dry environment. Compared with standard curing, a hot-dry environment accelerates the evaporation of water in fresh cementitious materials and the early hydration rate of cementitious materials, resulting in lots of unhydrated cement particles and an uneven distribution of hydration products, seriously decreasing the properties of the cementitious materials. Film curing keeps the water from evaporating and ensures enough water is available for hydration at an early age. The addition of FA reduces the amount of cement clinker and decreases hydration reaction rate in high temperature environments at an early stage, avoiding the unevenness of hydration products. High temperatures stimulate the pozzolanic activity of fly ash and promote the degree of secondary hydration reaction, producing more hydration products, as well as contributing to the improvement of the mechanical properties and microstructure of cementitious materials. In this study, in a hot-dry environment, the mechanical properties of mortar with 25% fly ash and 2–3 d film curing are better than those of other experimental groups, including those of standard curing.

Microplastics (MPs) have aroused widespread concern due to their extensive distribution in aquatic environments and adverse effects on aquatic organisms. However, the underlying toxicity of different kinds of MPs on freshwater microalgae has not been examined in detail. In this study, we investigated the effects of polyvinyl chloride (PVC), polystyrene (PS) and polyethylene (PE) MPs on the growth of Microcystis aeruginosa, as well as on its toxin production and oxidative stress. We found that all three kinds of MPs had an obvious inhibition effect on the growth of M. aeruginosa. Considering the results of antioxidant-related indicators, the activity of superoxide dismutase (SOD) and catalase (CAT), and cell membrane integrity were greatly affected with exposure to PVC, PS and PE MPs. Moreover, the content of intracellular (intra-) and extracellular (extra-) microcystins (MCs) had a noticeable increase due to the presence of PVC, PS, and PE MPs. Finally, according to the comprehensive stress resistance indicators, the resistance of M. aeruginosa to three MPs followed the order: PE (3.701)> PS (3.607)> PVC (2.901). Our results provide insights into the effects of different kinds of MPs on freshwater algae and provide valuable data for risk assessment of different types of MPs.

Health-related quality of life (HRQoL) is an important aspect in the management of patients with hepatitis B (HB), which remains a serious health problem in China. There have been relatively few HRQoL studies involving Chinese patients with HB. The aim of this study was to analyze HRQoL in patients diagnosed with HB living in Zhejiang Province, China. A cross-sectional sample of 98 patients with chronic HB (CHB), 56 patients with advanced HB that have developed cirrhosis, and 48 healthy controls (HCs), all from Zhejiang Province, was used in this study. HRQoL was assessed using Short-Form 36 (SF-36) version 2, European quality of life questionnaire-5 dimensions (EQ-5D), and chronic liver disease questionnaire (CLDQ). Intergroup score differences were detected with U tests. Factors with a significant effect on HRQoL were identified with Spearman correlational analyses. Patients with HB (both groups) had lower SF-36 scores than HCs (p

Colletotrichum lentis Damm causes anthracnose in Vicia sativa L, otherwise known as common vetch. It was first reported in China in 2019. This study evaluates the effects of the arbuscular mycorrhizal (AM) fungus Sieverdingia tortuosa (N.C. Schenck & G.S. Sm.) Błaszk., Niezgoda, & B.T. Goto on growth and disease severity in common vetch. Our main finding is that the AM fungus increased root biomass and reduced anthracnose severity of common vetch. Responses correlated with defense, such as chitinase activity, polyphenol oxidase (PPO) activity, the concentrations of jasmonic acid and proline, and the expression of resistance-related genes (e.g., upregulated “signal transduction,” “MAPK signaling pathway,” “chitinase activity,” “response to stress,” and the KEGG pathways “phenylpropanoid biosynthesis,” “MAPK signaling pathways,” and “plant-pathogen interactions”), were also affected These findings provide insight into the mechanism by which this AM fungus regulates the defense response of common vetch to C. lentis.

Information on temporal dynamics of phytoplankton communities and their responses to environmental factors can provide insights into mechanisms driving succession of phytoplankton communities that is useful in programs to manage and or remediate undesirable assemblages. Populations of phytoplankton can be controlled by bottom-up factors such as nutrients and temperature or top-down such as predation by zooplankton. Traditionally, taxonomic diversity based on morphologies has been the measure used for analysis of responses to environmental factors. Recently, according to functional groupings, including functional groups (FG), morpho-FG (MFG), and morphology-based FG (MBFG), functional diversity has been used to represent functional aspects of phytoplankton communities. However, to what extent these taxonomic and functional groupings are congruent at seasonal time-scales and the main environmental factors, which drive succession, have remained less studied. Here, we analyzed absolute and relative proportions of a phytoplankton community during a 3-year period in Lake Erhai, a eutrophic highland lake in China. Alpha diversity and beta diversity, as measured by Shannon-Wiener and Bray-Curtis indices of taxonomic grouping and three functional groupings (FG, MFG, and MBFG) were applied to investigate environmental factors determining diversity. Significant, positive relationships were observed between taxonomic diversity and functional diversity that were strongly linked through seasons. In order to exclude the influence of dominant species' tolerance to extreme environments, the dominant species were excluded one by one, and the results showed that residual communities still exhibited similar patterns of succession. This synchronous temporal pattern was not principally driven by the dominant genera (Microcystis, Psephonema, and Mougeotia). Instead, the entire phytoplankton community assemblages were important in the pattern. Most diversity indices of taxonomic and functional groupings were significantly correlated with solar irradiance, but not nutrient concentrations. Because the lake is eutrophic and there were already sufficient nutrients available, additional nutrients had little effect on seasonal taxonomic and functional diversity of phytoplankton in Lake Erhai.

Chronic infection with hepatitis B virus (HBV) has long been recognized as a dominant hazard factor for hepatocellular carcinoma (HCC) and accounts for at least half of HCC instances globally. However, the underlying molecular mechanism of HBV-linked HCC has not been completely elucidated. Here, three microarray datasets, totally containing 170 tumoral samples and 181 adjacent normal tissues from the liver of patients suffering from HBV-related HCC assembled from the Gene Expression Omnibus (GEO) database, were subjected to integrated analysis of differentially expressed genes (DEGs). Subsequently, the analysis of function and pathway enrichment as well as the protein-protein interaction network (PPI) was performed. The ten hub genes screened out from the PPI network were further subjected to expression profile and survival analysis. Overall, 329 DEGs (67 upregulated and 262 downregulated) were identified. Ten DEGs with the highest degree of connectivity included cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), PDZ-binding kinase (PBK), abnormal spindle microtubule assembly (ASPM), nuclear division cycle 80 (NDC80), aurora kinase A (AURKA), targeting protein for xenopus kinesin-like protein 2 (TPX2), kinesin family member 2C (KIF2C), and centromere protein F (CENPF). Kaplan-Meier analysis unveiled that overexpression levels of KIF2C and TPX2 were relevant to both the poor overall survival and relapse-free survival. In summary, the hub genes validated in the present study may provide promising targets for the diagnosis, prognosis, and therapy of HBV-associated HCC. Additionally, our work uncovers various crucial biological components (e.g., extracellular exosome) and signaling pathways that participate in the progression of HCC induced by HBV, serving comprehensive knowledge of the mechanisms regarding HBV-related HCC.

Background/Aims: Obesity is associated with a reduction in ghrelin, a 28 aa gastric hormone. Whether reduced ghrelin contributes to the impaired proliferation of hepatocytes associated with obesity-related steatosis remains largely unknown. Here we examined the effects of ghrelin on the proliferation of hepatocytes derived from lean and obese mice. Methods: AML 12 cells or hepatocytes isolated from mice fed normal chow diet (NCD) or high fat diet (HFD) were used. Effects of ghrelin on hepatocyte proliferation were detected with CCK8 assay and EdU staining. Cell cycle was analyzed by flow cytometry. Levels of proliferation markers was examined by Western blot. Results: Growth hormone secretagogue receptor 1a (GHS-R1a) mRNA and protein were present in hepatocytes. Levels of GHS-R1a were increased upon ghrelin treatment. Ghrelin significantly increased hepatocyte proliferation measured by Cell Counting Kit-8(CCK8) assay and EdU staining in a dose- and time-dependent manner. Proportion of cells in S phase was markedly increased upon treatment with ghrelin. Ghrelin significantly increased levels of proliferating cell nuclear antigen (PCNA) and cyclin D1, while reducing p27 in hepatocytes from mice fed NCD or HFD. Deletion of GHS-R1a completely abolished the effects of ghrelin in cultured hepatocytes. Ghrelin stimulated the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), leading to subsequent increase of nuclear β-catenin in hepatocytes derived from lean and obese mice. This effect was dependent on the GHS-R1a. Conclusion: Ghrelin activates GHS-R1a to stimulate hepatocyte proliferation via GSK3/β-catenin signaling pathway.

Abstract Background Although diabetic retinopathy (DR) has long been considered as a microvascular disorder, mounting evidence suggests that diabetic retinal neurodegeneration, in particular synaptic loss and dysfunction of retinal ganglion cells (RGCs) may precede retinal microvascular changes. Key molecules involved in this process remain poorly defined. The microtubule-associated protein tau is a critical mediator of neurotoxicity in Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the effect of tau, if any, in the context of diabetes-induced retinal neurodegeneration has yet to be ascertained. Here, we investigate the changes and putative roles of endogeneous tau in diabetic retinal neurodegeneration. Methods To this aim, we combine clinically used electrophysiological techniques, i.e. pattern electroretinogram and visual evoked potential, and molecular analyses in a well characterized high-fat diet (HFD)-induced mouse diabetes model in vivo and primary retinal ganglion cells (RGCs) in vitro. Results We demonstrate for the first time that tau hyperphosphorylation via GSK3β activation causes vision deficits and synapse loss of RGCs in HFD-induced DR, which precedes retinal microvasculopathy and RGCs apoptosis. Moreover, intravitreal administration of an siRNA targeting to tau or a specific inhibitor of GSK3β reverses synapse loss and restores visual function of RGCs by attenuating tau hyperphosphorylation within a certain time frame of DR. The cellular mechanisms by which hyperphosphorylated tau induces synapse loss of RGCs upon glucolipotoxicity include i) destabilizing microtubule tracks and impairing microtubule-dependent synaptic targeting of cargoes such as mRNA and mitochondria; ii) disrupting synaptic energy production through mitochondria in a GSK3β-dependent manner. Conclusions Our study proposes mild retinal tauopathy as a new pathophysiological model for DR and tau as a novel therapeutic target to counter diabetic RGCs neurodegeneration occurring before retinal vasculature abnormalities.

Pancreatic cancer risk increases in obese and diabetic people. In this manuscript, the authors show that Roux-en-Y gastric bypass surgery (RYGB) decreases the impact of pancreatic cancer in a mouse model; this effect seems independent of weight loss or decreased hyperglycemia pointing to an involvement of mTOR pathway.

Background: Pancreatic fibrosis is a pathophysiological process associated with excessive deposition of extracellular matrix in pancreas, leading to reduced insulin secretion and derangement of glucose metabolism. X/A-like cells, a group of unique endocrine cells in gastric oxyntic mucosa, produce and secret ghrelin to influence energy balance. Whether gastric X/A-like cells affect pancreatic fibrosis and subsequent glucose homeostasis remains unclear. Methods: We established a Ghrl-cre transgene in which the cre enzyme is expressed in X/A-like cells under the control of ghrelin-promoter. TSC1flox/flox mice were bred with Ghrl-cre mice to generate Ghrl-TSC1−/− (TG) mice, within which mTORC1 signaling was activated in X/A-like cells. Pancreatic fibrosis and insulin secretion were analyzed in the TG mice. Findings: Activation of mTORC1 signaling by deletion of TSC1 gene in gastric X/A-like cells induced spontaneous pancreatic fibrosis. This alteration was associated with reduced insulin expression and secretion, as well as impaired glucose metabolism. Activation of mTORC1 signaling in gastric X/A-like cells reduced gastric and circulating ghrelin levels. Exogenous ghrelin reversed pancreatic fibrosis and glucose intolerance induced by activation of mTORC1 signaling in these cells. Rapamycin, an inhibitor of mTOR, reversed the decrease of ghrelin levels and pancreatic fibrosis. Interpretation: Activation of mTORC1 signaling in gastric X/A-like cells induces spontaneous pancreatic fibrosis and subsequently impairs glucose homeostasis via suppression of ghrelin. Keywords: Ghrelin, Fibrosis, Matrix metalloproteinases, Glucose metabolism, Pancreatic islets

Background: The mechanism by which Roux-en-Y Gastric Bypass (RYGB) increases the secretion of glucagon-like peptide-1 (GLP-1) remains incompletely defined. Here we investigated whether TGR5-mTORC1 signaling mediates the RYGB-induced alteration in GLP-1 production in mice and human beings. Methods: Circulating bile acids, TGR5-mTORC1 signaling, GLP-1 synthesis and secretion were determined in lean or obese male C57BL/6 mice with or without RYGB operation, as well as in normal glycemic subjects, obese patients with type 2 diabetes before and after RYGB. Results: Positive relationships were observed among circulating bile acids, ileal mechanistic target of rapamycin complex 1 (mTORC1) signaling and GLP-1 during changes in energy status in the present study. RYGB increased circulating bile acids, ileal Takeda G protein-coupled receptor 5 (TGR5) and mTORC1 signaling activity, as well as GLP-1 production in both mice and human subjects. Inhibition of ileal mTORC1 signaling by rapamycin significantly attenuated the stimulation of bile acid secretion, TGR5 expression and GLP-1 synthesis induced by RYGB in lean and diet-induced obese mice. GLP-1 production and ileal TGR5-mTORC1 signaling were positively correlated with plasma deoxycholic acid (DCA) in mice. Treatment of STC-1 cells with DCA stimulated the production of GLP-1. This effect was associated with a significant enhancement of TGR5-mTORC1 signaling. siRNA knockdown of mTORC1 or TGR5 abolished the enhancement of GLP-1 synthesis induced by DCA. DCA increased interaction between mTOR-regulatory-associated protein of mechanistic target of rapamycin (Raptor) and TGR5 in STC-1 cells. Interpretation: Deoxycholic acid-TGR5-mTORC1 signaling contributes to the up-regulation of GLP-1 production after RYGB. Keywords: Deoxycholic acid, GLP-1, mTORC1, RYGB, TGR5

Background: Despite of its significant therapeutic effects on obesity and metabolic diseases, Roux-en-Y gastric bypass (RYGB) has limited clinical application because of considerable impacts on the gastrointestinal structure and postoperative complications. This study aims to develop a simplified surgical approach with less damage and complication but efficient metabolic benefit. Methods: The effects of Esophagus-Duodenum gastric bypass (EDGB) on body weight, food intake, glucose and lipid metabolism were compared to RYGB in mice. Findings: EDGB is simple, has higher survival rate and less complication. Relative to RYGB, EDGB demonstrated modest body weight control, identical improvement of glucose and lipid metabolism in obese mice. Blood glucose increased significantly 15 and 30 min after oral glucose administration, then markedly decreased in both EDGB and RYGB groups relative to the sham surgery, indicating a quicker absorption of oral glucose and improvement in glucose uptake by insulin targeted tissues. Insulin sensitivity was identically improved. EDGB significantly decreased plasma and hepatic triglyceride levels, while increased browning in visceral and subcutaneous white adipose tissue to the extent identical to RYGB. Levels of ghrelin and nesfatin-1 increased significantly after EDGB and RYGB. Interpretation: EDGB is a valuable model to study the metabolic benefit of bariatric surgery in mice.

Lipoteichoic acid (LTA) induces neuroinflammatory molecules, contributing to the pathogenesis of neurodegenerative diseases. Therefore, suppression of neuroinflammatory molecules could be developed as a therapeutic method. Although previous data supports an immune-modulating effect of curcumin, the underlying signaling pathways are largely unidentified. Here, we investigated curcumin’s anti-neuroinflammatory properties in LTA-stimulated BV-2 microglial cells. Inflammatory cytokine tumor necrosis factor-α [TNF-α, prostaglandin E2 (PGE2), and Nitric Oxide (NO] secretion in LTA-induced microglial cells were inhibited by curcumin. Curcumin also inhibited LTA-induced inducible NO synthases (iNOS) and cyclooxygenase-2 (COX-2) expression. Subsequently, our mechanistic studies revealed that curcumin inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including ERK, p38, Akt and translocation of NF-κB. Furthermore, curcumin induced hemeoxygenase (HO)-1HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf-2) expression in microglial cells. Inhibition of HO-1 reversed the inhibition effect of HO-1 on inflammatory mediators release in LTA-stimulated microglial cells. Taken together, our results suggest that curcumin could be a potential therapeutic agent for the treatment of neurodegenerative disorders via suppressing neuroinflammatory responses.

Enhanced activity of interleukin 17 (IL-17) producing T helper 17 (Th17) cells plays an important role in autoimmune and inflammatory diseases. Significant loss of body weight and appetite is associated with chronic inflammation and immune activation, suggesting the cross talk between immune and neuroendocrine systems. Ghrelin has been shown to regulate the organism immune function. However, the effects of ghrelin on the differentiation of Th17 cells remain elusive. In the present study, we observed the enhanced differentiation of Th17 cells in spleens of growth hormone secretagogue receptor 1a (GHSR1a)-/- mice. Treatment of ghrelin repressed Th17 cell differentiation in a time- and concentration-dependent manner. Phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) was increased in the spleens of GHSR1a-/- mice. Activation of mTOR signaling by injection of Cre-expressiong adenovirus into tuberous sclerosis complex 1 (TSC1) loxp/loxp mice increased the differentiation of Th17 cells in spleen, which was associated with an increment in the phosphorylation of STAT3. Activation of mTOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1 (S6K1) activated mTOR signaling in isolated T cells, while reversed the ghrelin-induced inhibition of iTh17 cell differentiation. In conclusion, mTOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.

AIMS/HYPOTHESIS:The actions of peripherally administered nesfatin-1 on glucose homeostasis remain controversial. The aim of this study was to characterize the mechanisms by which peripheral nesfatin-1 regulates glucose metabolism. METHODS:The effects of nesfatin-1 on glucose metabolism were examined in mice by continuous infusion of the peptide via osmotic pumps. Changes in AKT phosphorylation and Glut4 were investigated by Western blotting and immnuofluorescent staining. Primary myocytes, adipocytes and hepatocytes were isolated from male mice. RESULTS:Continuous peripheral infusion of nesfatin-1 altered glucose tolerance and insulin sensitivity in mice fed either normal or high fat diet, while central administration of nesfatin-1 demonstrated no effect. Nesfatin-1 increases insulin secretion in vivo, and in vitro in cultured min6 cells. In addition, nesfatin-1 up-regulates the phosphorylation of AKT in pancreas and min6 islet cells. In mice fed normal diet, peripheral nesfatin-1 significantly increased insulin-stimulated phosphorylation of AKT in skeletal muscle, adipose tissue and liver; similar effects were observed in skeletal muscle and adipose tissue in mice fed high fat diet. At basal conditions and after insulin stimulation, peripheral nesfatin-1 markedly increased GLUT4 membrane translocation in skeletal muscle and adipose tissue in mice fed either diet. In vitro studies showed that nesfatin-1 increased both basal and insulin-stimulated levels of AKT phosphorylation in cells derived from skeletal muscle, adipose tissue and liver. CONCLUSIONS:Our studies demonstrate that nesfatin-1 alters glucose metabolism by mechanisms which increase insulin secretion and insulin sensitivity via altering AKT phosphorylation and GLUT 4 membrane translocation in the skeletal muscle, adipose tissue and liver.

Ghrelin is a 28-amino acid orexigenic peptide synthesized mainly in the stomach. Acute administration of ghrelin has been found to decrease insulin secretion. However, little data is available regarding whether ghrelin contributes to the long-term regulation of insulin resistance at the population level. The aim of this study is to investigate the association between circulating ghrelin and insulin resistance in a large population based study.A total of 2082 CODING study (Complex Diseases in the Newfoundland population: Environment and Genetics) subjects were assessed. Subjects were of at least third generation Newfoundland descent, between the ages of 20 and 79 years, and had no serious metabolic, cardiovascular, or endocrine diseases. Ghrelin was measured with an Enzyme Immunoassay method. Insulin and fasting glucose were measured by Immulite 2500 autoanalyzer and Lx20 clinical chemistry analyzer, respectively. Homeostatic Model Assessment of β cell function (HOMA-β) and Insulin Resistance (HOMA-IR) and Quantitative Insulin-sensitivity Check Index (QUICKI) were used for measurement of insulin resistance.Partial correlation analyses showed a significant negative correlation between circulating ghrelin and insulin level and insulin resistance in the entire cohort and also in men and women separately. The aforementioned correlation was independent of age, percentage of trunk fat and HDL-cholesterol. According to menopausal status, only pre-menopausal women revealed negative correlations.Our results suggest that except for postmenopausal women, high circulating ghrelin level is associated with lower insulin resistance in the general population.

Ghrelin, an orexigenic gut hormone secreted primarily from the stomach, is involved in energy homeostasis. However, little data is available regarding its response to energy surplus and the development of human obesity.The present study investigated the response of circulating acylated ghrelin to a 7-day positive energy challenge.A total of 68 healthy young men were overfed 70% more calories than required, for 1-week. Subjects were classified based on percent body fat (measured by dual-energy X-ray absorptiometry) as normal weight, overweight, and obese. Serum acylated ghrelin concentration was measured before and after the positive energy challenge. Additionally, the relationship between acylated ghrelin and obesity-related phenotypes including weight, body mass index, percent body fat, cholesterol, HDL-c, LDL-c, glucose, insulin and homeostasis model assessment of insulin resistance and β-cell function at baseline and change due to overfeeding, were assessed.Contrary to our expectations, serum acylated ghrelin was significantly increased in response to overfeeding and the increase was independent of obesity status. There was no significant difference in fasting acylated ghrelin between normal weight, overweight, and obese men at baseline. Acylated ghrelin was negatively correlated with weight and BMI for normal weight and with BMI in overweight men. Also ghrelin was correlated with change in weight and BMI in overweight (negative relationship) and obese (positive relationship) groups.Our results showed that circulating acylated ghrelin was increased after a 7-day positive energy challenge regardless of adiposity status. However, acylated ghrelin was correlated with change in weight and BMI in opposing directions, in overweight and obese subjects respectively, thus dependent on obesity status.

Sporobolus alterniflorus (S. alterniflorus) is a widespread invasive plant that poses significant threats to coastal wetland ecosystems and local economies worldwide. However, most existing management methods for S. alterniflorus are costly and provide only temporary relief due to reoccurrences and reinvasion. Additionally, limited attention has been paid to examining the application of invasion mechanisms in the design of management measures, hindering the development of effective strategies. In this paper, we reviewed the literature on the mechanisms and management of S. alterniflorus invasion. We identified the key factors enabling invasion mechanisms, analyzed how they are targeted in current control methods, and pointed out their implications for future research. We recommend that the invasion mechanisms of S. alterniflorus should be comprehensively considered during the design of management measures. Furthermore, future research on invasion mechanisms could focus on the joint effects and the relative roles of individual factors in successful invasion, the impact of S. alterniflorus invasion on the coupled human and natural systems, and the systematic review of studies at different scales. [ABSTRACT FROM AUTHOR]