The food security risks in the Yangtze River Delta of China associated with water scarcity, grain production, and grain trade.

Grain production consumes a large amount of water and is affected by the degree of water scarcity and participation in the grain trade in various regions. The grain trade has changed the food security risks in regions where grain exports and imports. Therefore, it is crucial to consider regional water scarcity to understand food security risks from the grain trade network. Here, we construct a new framework for measuring regional food security risks associated with water scarcity, grain production, and grain trade based on a cross-city grain trade network combined with virtual water flows to evaluate the regional food security risks in the Yangtze River Delta region (YRD) of China in 2017. The results show that under the current domestic grain trade pattern in China, the YRD and its four provincial-level administrative regions are in a net grain import state. The grain trade within the YRD is concentrated in exports from the two major grain-producing areas of Anhui and Jiangsu to Zhejiang and Shanghai, especially from northern Jiangsu to southeastern Zhejiang. The net import results of virtual blue water in most cities indicate that the YRD has shifted its water resource pressure to other grain exporting regions in China, with Shanghai and Zhejiang being the greatest beneficiaries. Extreme risk only exists in Shanghai, and severe and moderate risks are concentrated in Jiangsu. The current grain trade has reduced the overall food security risk in the YRD by 1.3 % but increased the risks in Shanghai and Zhejiang by 2.1 % and 0.8 % respectively. This study highlights the potential risks that excessive production of food in water-scarce areas in the grain trade system may bring to a stable food supply, providing useful information for a comprehensive understanding of the food and water security situation and for future trade-offs.

Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor).

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease (NAFLD), coupled with hepatitis and insulin resistance. Yet the details of the underlying mechanisms are not fully understood. Here, we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD. Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation (FAO), and induced insulin resistance. Conversely, hepatic Zbtb18 overexpression alleviated hepato-steatosis, insulin resistance, and hyperglycemia in mice fed on a high-fat diet (HFD) or in diabetic mice. Notably, in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor (FXR) mediated FAO and Clathrin Heavy Chain (CLTC) protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte's Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR's deletion and forced expression in mice and cultured mouse primary hepatocytes (MPHs). Moreover, CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages. Altogether, Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression, which inhibits NLRP3 inflammasome's activity alleviating inflammatory stress and insulin resistance, representing an attractive remedy for hepatic steatosis and fibrosis.

Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis.

BACKGROUND: The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to the prevention of this disease. AIM: To explore the possible mechanism of glycyrrhizic acid (GA) and its therapeutic effect on HAEC. METHODS: We developed a model of enteritis induced by trinitrobenzenesulfonic acid (TNBS) in zebrafish, and treated it with different concentrations of GA. We analyzed the effect of GA on the phenotype and inflammation of zebrafish. RESULTS: After treatment with TNBS, the area of the intestinal lumen in zebrafish was significantly increased, but the number of goblet cells in the intestinal lumen was significantly reduced, but these did not increase the mortality of zebrafish, indicating that the zebrafish enteritis model was successfully developed. Different concentrations of GA protected zebrafish with enteritis. In particular, high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area, increased the number of goblet cells in the intestinal lumen, and reduced the levels of interleukin (IL)-1ß and IL-8. CONCLUSION: GA significantly reduced the intestinal luminal area, increased the number of intestinal goblet cells, and decreased IL-1ß and IL-8 in zebrafish, and is important for prevention and control of HAEC.

Microglia Sirt6 modulates the transcriptional activity of NRF2 to ameliorate high-fat diet-induced obesity.

BACKGROUND: Microglia play a pivotal role in neuroinflammation, while obesity triggers hypothalamic microglia activation and inflammation. Sirt6 is an important regulator of energy metabolism in many peripheral tissues and hypothalamic anorexic neurons. However, the exact mechanism for microglia Sirt6 in controlling high-fat diet-induced obesity remain unknown. METHODS: Microglia Sirt6 expression levels under various nutritional conditions were measured in the hypothalamus of mice. Also, microglia Sirt6-deficient mice were provided various diets to monitor metabolic changes and hypothalamic inflammatory response. Besides, RNA-seq and Co-IP of microglia with Sirt6 alterations were conducted to further investigate the detailed mechanism by which Sirt6 modulated microglia activity. RESULTS: We found that Sirt6 was downregulated in hypothalamic microglia in mice given a high-fat diet (HFD). Additionally, knockout of microglia Sirt6 exacerbated high-fat diet-induced hypothalamic microglial activation and inflammation. As a result, mice were more prone to obesity, exhibiting a decrease in energy expenditure, impaired glucose tolerance, insulin and leptin resistance, and increased food intake. In vitro, Sirt6 overexpression in BV2 cells displayed protective effects against oleic acid and palmitic acid treatment-derived inflammatory response. Mechanically, Sirt6 deacetylated and stabilised NRF2 to increase the expression of anti-oxidative genes and defend against reactive oxygen species overload. Pharmacological inhibition of NRF2 eliminated the beneficial modulating effects of Sirt6 on microglial activity. CONCLUSION: Collectively, our results revealed that microglial Sirt6 was a primary contributor of microglial activation in the central regulation of obesity. Thus, microglial Sirt6 may be an important therapeutic target for obesity.

Harnessing the Therapeutic Potential of Ginsenoside Rd for Activating SIRT6 in Treating a Mouse Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global condition and a common precursor to liver cancer, yet there is currently no specific medication available for its treatment. Ginseng, renowned for its medicinal and dietary properties, has been utilized in NAFLD management, although the precise underlying mechanism remains elusive. To investigate the effectiveness of ginsenoside Rd, we employed mouse and cell models to induce NAFLD using high-fat diets, oleic acid, and palmitic acid. We explored and confirmed the specific mechanism of ginsenoside Rd-induced hepatic steatosis through experiments involving mice with a liver-specific knockout of SIRT6, a crucial protein involved in metabolic regulation. Our findings revealed that administration of ginsenoside Rd significantly reduced the inflammatory response, reactive oxygen species (ROS) levels, lipid peroxide levels, and mitochondrial stress induced by oleic acid and palmitic acid in primary hepatocytes, thereby mitigating excessive lipid accumulation. Moreover, ginsenoside Rd administration effectively enhanced the mRNA content of key proteins involved in fatty acid oxidation, with a particular emphasis on SIRT6 and its target proteins. We further validated that ginsenoside Rd directly binds to SIRT6, augmenting its deacetylase activity. Notably, we made a significant observation that the protective effect of ginsenoside Rd against hepatic disorders induced by a fatty diet was almost entirely reversed in mice with a liver-specific SIRT6 knockout. Our findings highlight the potential therapeutic impact of Ginsenoside Rd in NAFLD treatment by activating SIRT6. These results warrant further investigation into the development of Ginsenoside Rd as a promising agent for managing this prevalent liver disease.

Hepatic ZBTB22 promotes hyperglycemia and insulin resistance via PEPCK1-driven gluconeogenesis.

Excessive gluconeogenesis can lead to hyperglycemia and diabetes through as yet incompletely understood mechanisms. Herein, we show that hepatic ZBTB22 expression is increased in both diabetic clinical samples and mice, being affected by nutritional status and hormones. Hepatic ZBTB22 overexpression increases the expression of gluconeogenic and lipogenic genes, heightening glucose output and lipids accumulation in mouse primary hepatocytes (MPHs), while ZBTB22 knockdown elicits opposite effects. Hepatic ZBTB22 overexpression induces glucose intolerance and insulin resistance, accompanied by moderate hepatosteatosis, while ZBTB22-deficient mice display improved energy expenditure, glucose tolerance, and insulin sensitivity, and reduced hepatic steatosis. Moreover, hepatic ZBTB22 knockout beneficially regulates gluconeogenic and lipogenic genes, thereby alleviating glucose intolerance, insulin resistance, and liver steatosis in db/db mice. ZBTB22 directly binds to the promoter region of PCK1 to enhance its expression and increase gluconeogenesis. PCK1 silencing markedly abolishes the effects of ZBTB22 overexpression on glucose and lipid metabolism in both MPHs and mice, along with the corresponding changes in gene expression. In conclusion, targeting hepatic ZBTB22/PEPCK1 provides a potential therapeutic approach for diabetes.

Minimizing the makespan and carbon emissions in the green flexible job shop scheduling problem with learning effects.

One of the most difficult challenges for modern manufacturing is reducing carbon emissions. This paper focuses on the green scheduling problem in a flexible job shop system, taking into account energy consumption and worker learning effects. With the objective of simultaneously minimizing the makespan and total carbon emissions, the green flexible job shop scheduling problem (GFJSP) is formulated as a mixed integer linear multiobjective optimization model. Then, the improved multiobjective sparrow search algorithm (IMOSSA) is developed to find the optimal solution. Finally, we conduct computational experiments, including a comparison between IMOSSA and the nondominated sorting genetic algorithm II (NSGA-II), Jaya and the mixed integer linear programming (MILP) solver of CPLEX. The results demonstrate that IMOSSA has high precision, good convergence and excellent performance in solving the GFJSP in low-carbon manufacturing systems.

Hepatic ZBTB22-mediated detoxification ameliorates acetaminophen-induced liver injury by inhibiting pregnane X receptor signaling.

Overdose acetaminophen (APAP) can cause acute liver injury (ALI), but the underlying mechanism remains undetermined. This study explored the role of hepatic Zinc Finger And BTB Domain Containing 22 (ZBTB22) in defense against APAP-mediated hepatotoxicity. The results showed that hepatic ZBTB22 expression was significantly reduced in patients with ALI and mice. In mouse primary hepatocytes (MPHs), ZBTB22 deletion aggravated APAP overdose-induced ALI, whereas ZBTB22 overexpression attenuated that pathological progression. The results were further verified in ZBTB22 over-express or knockout mice models. In parallel, hepatocyte-specific ZBTB22 knockout also enhanced ALI. Furthermore, ZBTB22 decreased pregnane X receptor (PXR) expression, and the PXR activator pregnane-16α-carbonitrile suppressed the protective effect of ZBTB22 in APAP-induced ZBTB22-overexpressing mice. Collectively, our findings highlight the protective effect of ZBTB22 against APAP-induced ALI and unravel PXR signaling as the potential mechanism. Strategies to increase hepatic ZBTB22 expression represent a promising therapeutic approach for APAP overdose-induced ALI.

Effect of modified transanal Soave assisted by laparoscopy in the treatment of Hirschsprung's disease in children and its influencing factors.

OBJECTIVE: To investigate the effect of modified transanal Soave assisted by laparoscopy in children with Hirschsprung's disease (HD). METHODS: The clinical data of 120 children with Hirschsprung's disease admitted to Fujian Children's Hospital from January 2018 to November 2021 were retrospectively analyzed. Based on the surgical methods, 58 children treated with modified transanal Soave were regarded as the modified group and 62 children treated with modified transanal Soave assisted by laparoscopy were divided into the laparoscopic group. The operative indexes, anal function, quality of life and perianal pressure 6 months after surgery, complications within 1 month after surgery, and recovery within 6 months after surgery of the two groups were compared. The risk factors influencing the postoperative recovery of hirschsprung's disease in children were analyzed by univariate and logistic regression analysis. RESULTS: The operation time, intraoperative blood loss, length of hospital stay and gastrointestinal recovery time in the laparoscopic group were lower than those in modified group (P < 0.05). The excellent and good rate of postoperative anal function in laparoscopic group was 87.10%, which was higher than that in modified group (68.97%) (P < 0.05). The proportion of patients with good quality of life in laparoscopic group (90.32%) was higher than that in modified group (74.14%) (P < 0.05). The anal resting pressure and systolic pressure in laparoscopic group were lower than those in modified group (all P < 0.05). The total complication rate of laparoscopic group (6.45%) was lower than that of modified group (22.41%) (P < 0.05). After 6 months, 64 cases (53.33%) were cured and 56 cases (46.67%) were not. After univariate analysis, there were statistically significant differences in enteritis, abdominal distension, and anastomotic stenosis between cured children and uncured children (all P < 0.05). There was no significant difference in other factors (P > 0.05). Logistic regression analysis showed that enteritis, abdominal distension and anastomotic stenosis were the risk factors affecting the recovery of hirschsprung's disease in children (all P < 0.05). CONCLUSIONS: Modified transanal Soave assisted by laparoscopy can improve anal function and quality of life, relieve anal pressure, and have a low complication rate. Enteritis, abdominal distension, and anastomotic stenosis are the factors affecting the recovery of Hirschsprung's disease in children.

Ginsenoside Rc attenuates DSS-induced ulcerative colitis, intestinal inflammatory, and barrier function by activating the farnesoid X receptor.

Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling. Materials and Methods: In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR-/-) mice were used for further validation. Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1ß, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1ß, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR-/- mice. Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.

Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress.

Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes. Additionally, Ginsenoside Rc effectively alleviates APAP-induced cellular apoptosis and NAPQI accumulation in MPHs. In vivo, Ginsenoside Rc administration remarkably attenuates APAP-induced hepatotoxicity, repairing liver damage and improving survival. Moreover, Ginsenoside Rc treatment modulates genes involved in APAP metabolism, leading to a decrease in NAPQI and resulting in the alleviation of fatal oxidative stress and inflammatory response after APAP exposure, along with the expression of their related indicators. Furthermore, our RNA-seq and molecular docking analysis implies that FXR expression and FXR transcriptional activity are stimulated by Ginsenoside Rc treatment. Notably, due to the lack of FXR in mice and MPHs, ginsenoside Rc can no longer play its original protective role against hepatotoxicity and cell damage caused by APAP, and it is difficult to improve the corresponding survival rate and prevent hepatic apoptosis, NAPQI generation, fatal oxidative stress, and the inflammatory response induced by APAP and the expression of related genes. In summary, our results indicate that Ginsenoside Rc could act as an effective FXR activator and effectively regulate FXR-induced antioxidant stress and eliminate inflammation while also having an anti-apoptotic function.

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from Panax ginseng, whose pharmacological effects counteract oxidative stress, inflammation, and lipid accumulation. However, it is still unclear whether ginsenoside Rc might exert beneficial effects on alcohol-induced liver injury. To this aim, mice primary hepatocytes (MPHs) were challenged with alcohol to test ginsenoside Rc's effects on their intracellular alcohol metabolism. C57BL/6J mice or SIRT6alb-/- mice were chronically fed a diet with added alcohol or given a single gavage of alcohol with or without ginsenoside Rc. Analyses of alcohol metabolism, oxidative stress, inflammation, lipid metabolism, and RNaseq expression were conducted to explore potential targets exploited by ginsenoside Rc to protect against ALD. Our results showed that ginsenoside Rc attenuated alcohol-induced liver injury by regulating oxidative stress, inflammation, and lipid accumulation both in vivo and in vitro. Ginsenoside Rc did increase the deacetylase activity of SIRT6, thereby lowering acetylated NRF2 levels, which elevated NRF2's stability, and subsequently exerting an antioxidant effect. In keeping with this, the hepatic knockout of SIRT6 almost abolished the hepatoprotective effects of ginsenoside Rc against ALD. Therefore, our results suggest that ginsenoside Rc attenuated hepatocytes' damage and oxidative stress in ALD by up-regulating the SIRT6/NRF2 pathway. Hence, ginsenoside Rc may be a promising drug to treat or relieve ALD.

Down-Regulation of Double C2 Domain Alpha Promotes the Formation of Hyperplastic Nerve Fibers in Aganglionic Segments of Hirschsprung's Disease.

Hirschsprung's disease (HSCR) is a common developmental anomaly of the gastrointestinal tract in children. The most significant characteristics of aganglionic segments in HSCR are hyperplastic extrinsic nerve fibers and the absence of endogenous ganglion plexus. Double C2 domain alpha (DOC2A) is mainly located in the nucleus and is involved in Ca2+-dependent neurotransmitter release. The loss function of DOC2A influences postsynaptic protein synthesis, dendrite morphology, postsynaptic receptor density and synaptic plasticity. It is still unknown why hyperplastic extrinsic nerve fibers grow into aganglionic segments in HSCR. We detected the expression of DOC2A in HSCR aganglionic segment colons and established three DOC2A-knockdown models in the Neuro-2a cell line, neural spheres and zebrafish separately. First, we detected the protein and mRNA expression of DOC2A and found that DOC2A was negatively correlated with AChE+ grades. Second, in the Neuro-2a cell lines, we found that the amount of neurite outgrowth and mean area per cell were significantly increased, which suggested that the inhibition of DOC2A promotes nerve fiber formation and the neuron's polarity. In the neural spheres, we found that the DOC2A knockdown was manifested by a more obvious connection of nerve fibers in neural spheres. Then, we knocked down Doc2a in zebrafish and found that the down-regulation of Doc2a accelerates the formation of hyperplastic nerve fibers in aganglionic segments in zebrafish. Finally, we detected the expression of MUNC13-2 (UNC13B), which was obviously up-regulated in Grade3/4 (lower DOC2A expression) compared with Grade1/2 (higher DOC2A expression) in the circular muscle layer and longitudinal muscle layer. The expression of UNC13B was up-regulated with the knocking down of DOC2A, and there were protein interactions between DOC2A and UNC13B. The down-regulation of DOC2A may be an important factor leading to hyperplastic nerve fibers in aganglionic segments of HSCR. UNC13B seems to be a downstream molecule to DOC2A, which may participate in the spasm of aganglionic segments of HSCR patient colons.

Siloxane-modified MnOx catalyst for oxidation of coal-related o-xylene in presence of water vapor.

In coal-combustion energy production, presence of water vapor in flue gas causes catalyst deactivation and leads to the release of large quantities of volatile organic compounds (VOCs). In this study, design of a low-temperature, hydrophobic catalyst for flue gas purification was achieved by modifying support material with inorganic siloxane. Introduction of 5% water vapor into simulated flue gas at 300 °C reduced oxidation efficiency for o-xylene removal by 26% with unmodified MnOx/γ-Al2O3 catalyst, whereas with modified catalyst MnOx-Si0.9/γ-Al2O3 oxidation efficiency was reduced by only 5%. MnOx-Si0.9/γ-Al2O3 exhibited stable catalytic efficiency for o-xylene gas oxidation containing water vapor for over 200 min. Water-resistance of the catalyst was effective for removal of multi-coal combustion pollutants (Hg0 and NO) and moreover, hydrophobicity of the catalyst led to a reduction in surface sulfate deposition, thereby lowering toxicity of SO2 from simulated flue gas. DRIFTS analysis showed that the hydrophobic catalyst surface not only reduces water adsorption, but also promotes water volatilization. Based on molecular adsorption energies, catalyst support modification with siloxane inhibits water adsorption and promotes organic adsorption and thus provides a new strategy for preparing water-resistant catalysts for flue gas purification.

Hepatic SIRT6 Modulates Transcriptional Activities of FXR to Alleviate Acetaminophen-induced Hepatotoxicity.

BACKGROUND & AIMS: Excessive acetaminophen (APAP) intake causes oxidative stress and inflammation, leading to fatal hepatotoxicity; however, the mechanism remains unclear. This study aims to explore the protective effects and detailed mechanisms of sirtuin 6 (SIRT6) in the defense against APAP-induced hepatotoxicity. METHODS: Hepatocyte-specific SIRT6 knockout mice, farnesoid X receptor (FXR) knockout mice, and mice with genetic or pharmacological activation of SIRT6 were subjected to APAP to evaluate the critical role of SIRT6 in the pathogenesis of acute liver injury. RNA sequences were used to investigate molecular mechanisms underlying this process. RESULTS: Hepatic SIRT6 expression was substantially reduced in the patients and mice with acute liver injury. The deletion of SIRT6 in mice and mice primary hepatocytes led to high N-acetyl-p-benzo-quinoneimine and low glutathione levels in the liver, thereby enhancing APAP overdose-induced liver injury, manifested as increased hepatic centrilobular necrosis, oxidative stress, and inflammation. Conversely, overexpression or pharmacological activation of SIRT6 enhanced glutathione and decreased N-acetyl-p-benzo-quinoneimine, thus alleviating APAP-induced hepatotoxicity via normalization of liver damage, inflammatory infiltration, and oxidative stress. Our molecular analysis revealed that FXR is regulated by SIRT6, which is associated with the pathological progression of ALI. Mechanistically, SIRT6 deacetylates FXR and elevates FXR transcriptional activity. FXR ablation in mice and mice primary hepatocytes prominently blunted SIRT6 overexpression and activation-mediated ameliorative effects. Conversely, pharmacological activation of FXR mitigated APAP-induced hepatotoxicity in SIRT6 knockout mice. CONCLUSIONS: Our current study suggests that SIRT6 plays a crucial role in APAP-induced hepatotoxicity, and pharmacological activation of SIRT6 may represent a novel therapeutic strategy for APAP overdose-induced liver injury.

Free Triiodothyronine Is Independently Associated with Nonalcoholic Fatty Liver Disease in Hospitalized Type 2 Diabetes Mellitus Patients.

OBJECTIVE: Free triiodothyronine (FT3) is an independent risk factor for nonalcoholic fatty liver disease (NAFLD) in patients with euthyroid. However, whether FT3 has an independent effect on NAFLD in a population of type 2 diabetes remains unknown. The purpose of this study was to identify the potential role of FT3 in NAFLD with T2DM. DESIGN: A cross-sectional study. Patient. A total of 859 T2DM patients who met the inclusion criteria were included. There were 506 T2DM patients without NAFLD and 353 T2DM patients with NAFLD. METHODS: The independent samples t-test or Wilcoxon rank sum test were used for continuous variables of different distribution types, while the chi-square test was used for categorical variables. Pearson correlation analysis and linear regression were used to analyze the correlation between FT3 and clinical measurements and biochemical indicators. Multivariate logistic regression analysis was used to determine independent predictors. RESULTS: Patients with NAFLD had higher BMI, SBP, and DBP, longer duration of T2DM, and higher islet function index, blood glucose index, liver function index, renal function index, blood lipid index, and FT3. We also found that FT3 was affected by other five indicators, including ALT, CR, GGT, TC, and LDL-C only in the NAFLD group but not in the non-NAFLD group. FT3 was significantly associated with NAFLD in T2DM patients, and the prevalence of NAFLD increased gradually from the lowest FT3 tertile to the highest FT3 tertile (P for trend < 0.001). CONCLUSION: FT3 is independently associated with NAFLD in hospitalized T2DM patients after rigorous adjustment for various metabolic parameters.

Research Status of Differentially Expressed Noncoding RNAs in Type 2 Diabetes Patients.

AIMS: Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. METHODS: The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA-miRNA and circRNA-miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE-RAGE signaling pathways of diabetic complications. RESULTS: A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE-RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE-RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. CONCLUSION: Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.

Stratified meta-analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was associated with coronary artery disease in Asians, but not in Caucasians.

BACKGROUND: Previous studies demonstrated that ADRB3, beta-3 adrenergic receptor, participated in lipolysis and thermogenesis in adipose tissue. Consequently, this gene has attracted an increasing number of genetic studies examining its association with coronary artery disease (CAD) in different ethnicities in recent years, but no conclusion has been reached so far. The aim of this study was to explore whether the well-studied locus ADRB3 Trp64Arg in this gene confers a race-specific effect to CAD by conducting a stratified meta-analysis involving 15 independent studies and 11,802 subjects. METHODS: Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. Publication bias was quantified and examined with Begg's funnel plot test and Egger's linear regression method. The overall meta-analysis or stratified meta-analysis by ethnicity was performed by using STATA 12.0 software. RESULTS: A total of 15 eligible studies involving 5779 CAD cases and 6023 health controls were included in this meta-analysis. The pooled results indicated that ADRB3 Trp64Arg polymorphism was significantly associated with an increased risk of CAD. Further stratified analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was significantly associated with CAD in Asians (allelic: OR = 1.48, 95%CI 1.13-1.94, P = .005; homozygous: OR = 2.66, 95%CI 1.87-3.77, P < .001; recessive: OR = 2.46, 95%CI 1.74-3.47, P < .001), but not in Caucasians (allelic: OR = 1.09, 95%CI 0.93-1.27, P = .290; homozygous: OR = 1.31, 95%CI 0.61-2.86, P = .490; recessive: OR = 1.31, 95%CI 0.60-2.84, P = 2.494). CONCLUSIONS: This meta-analysis suggests that ADRB3 Trp64Arg polymorphism confers a race-specific effect to CAD.