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ECH was observed to inhibit [Ca2+]cyt increase in NE-induced PASMCs in a concentration-dependent manner, effectively reducing abnormal cell proliferation. It also reduced the expression of Transient receptor potential channel (TRPC) 1 (TRPC1), TRPC4, TRPC6, and calmodulin in PASMCs. In vivo studies demonstrated that ECH lowered the expression of these proteins in lung tissues of HPH rats, significantly decreased mean pulmonary artery pressure, and mitigated PVR.

ObjectiveTo develop a rapid and quantitative method for the detection of enrofloxacin in chicken and pork using magnetic solid phase extraction （MSPE） combined with surface enhanced Raman spectroscopy （SERS）.MethodsMagnetic Fe3O4@ covalent organic framework （COF） nanocomposites were synthesized and applied as absorbent to separate and enrich enrofloxacin. The SERS spectra of enrofloxacin were collected by a portable Raman spectrometer with Ag nanoparticles as enhancing substrate. The characteristic SERS signals of enrofloxacin were used to realize its quantification.ResultsIntensities of SERS signals at 745.77 cm-1 and the logarithmic values of the concentrations of enrofloxacin in the range of 5.0×10-7 to 1.0×10-5 mol/L displayed a good linear relationship with a coefficient of determination of 0.962. The limit of detection and limit of quantitation were 0.07 and 0.23 µg/g respectively. The recoveries of enrofloxacin in chicken and pork were 80.97%~100.98% with relative standard deviations of 1.6%~4.6%.ConclusionThe developed method has the advantages of simple in operate， short in time， high in sensitivity and stability， which provides a new method for the rapid detection and on-site detection of enrofloxacin.

Background & Aims: Acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury worldwide. Uric acid (UA) is involved in sterile inflammation in many organs, but its role in APAP-induced liver injury remains elusive. Methods: We quantified the concentration of UA in the serum and liver tissues of APAP-overdosed mice and explored the changes in proteins involved in UA synthesis, absorption, and degeneration on APAP stimulation. We also examined the effects of inhibiting hepatocyte UA synthesis or reabsorption on APAP-induced liver injury in mice. Furthermore, we explored the process of UA clearance by peripheral macrophages. Results: APAP overdose significantly increased intrahepatic UA contents, which occurred earlier than apparent hepatocyte injury in APAP-overdosed mice. APAP overdose induced significant DNA leakage and may thereby increase the substrate of UA synthesis. APAP overdose also significantly increased the enzymatic activity of xanthine oxidase and urate oxidase and decreased the expression of the UA reabsorption transporter GLUT9 in hepatocytes. Inhibiting hepatocyte UA synthesis by febuxostat or reabsorption by hepatic-specific knockout of GLUT9 alleviated APAP-induced liver injury. Further experiments showed that monosodium urate but not soluble UA may be a major form of UA mediating hepatocyte injury. Additionally, monosodium urate further recruited circulating macrophages into the liver and then aggravated inflammation by increasing the levels of inflammatory factors and reactive oxygen species. Deletion of macrophages significantly ameliorated APAP-induced liver injury in mice. Conclusions: APAP overdose induces excessive UA production and leads to local high concentrations in the liver, which further injures cells and induces liver inflammation. Inhibiting the production of UA may be a potential therapeutic option for treating APAP-induced liver injury.

Abstract There are significant risks of adverse events following oesophageal endoscopic submucosal dissection (ESD), such as stricture, delayed bleeding and perforation. Therefore, it is necessary to protect artificial ulcers and promote the healing process. The current study was performed to investigate the protective role of a novel gel against oesophageal ESD-associated wounds. This was a multicentre, randomized, single-blind, controlled trial that recruited participants who underwent oesophageal ESD in four hospitals in China. Participants were randomly assigned to the control or experimental group in a 1:1 ratio and the gel was used after ESD in the latter. Masking of the study group allocations was only attempted for participants. The participants were instructed to report any adverse events on post-ESD days 1, 14, and 30. Moreover, repeat endoscopy was performed at the 2-week follow-up to confirm wound healing. Among the 92 recruited patients, 81 completed the study. In the experimental group, the healing rates were significantly higher than those in the control group (83.89 ± 9.51% vs. 73.28 ± 17.81%, P = 0.0013). Participants reported no severe adverse events during the follow-up period. In conclusion, this novel gel could safely, effectively, and conveniently accelerate wound healing following oesophageal ESD. Therefore, we recommend applying this gel in daily clinical practice.

Background & aims: Excessive inflammatory responses and oxidative stress are considered the main characteristics of inflammatory bowel disease (IBD). Endogenous hydrogen sulfide (H2S) has been reported to show anti-inflammatory activity in IBD. The main aim of this study was to explore the role of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous H2S biosynthesis, in IBD. Methods: Colonic MPST expression was evaluated in mice and patients with IBD. Various approaches were used to explore the concrete mechanism underlying MPST regulation of the progression of colitis through in vivo and in vitro models. Results: MPST expression was markedly decreased in colonic samples from patients with ulcerative colitis (UC) or Crohn's disease (CD) and from mice treated with DSS. MPST deficiency significantly aggravated the symptoms of murine colitis, exacerbated inflammatory responses and apoptosis, and inhibited epithelium stem cell-derived organoid formation in an H2S-independent manner. Consistently, when HT29 cells were treated with TNF-α, inhibition of MPST significantly increased the expression of proinflammatory cytokines, the amount of ROS and the prevalence of apoptosis, whereas overexpression of MPST markedly improved these effects. RNA-seq analysis showed that MPST might play a role in regulating apoptosis through AKT signaling. Mechanistically, MPST directly interacted with AKT and reduced the phosphorylation of AKT. Additionally, MPST expression was positively correlated with AKT expression in human IBD samples. In addition, overexpression of AKT rescued IEC apoptosis caused by MPST deficiency, while inhibition of AKT significantly aggravated it. Conclusions: MPST protects the intestines from inflammation most likely by regulating the AKT/apoptosis axis in IECs. Our results may provide a novel therapeutic strategy for the treatment of colitis.

Abstract Background Newer epidemiological studies suggest that the incidence of ulcerative colitis might be increasing rapidly. Furthermore, osteoporosis in ulcerative colitis patients has gained great attention, but the epidemiologic evidence remains controversial. Therefore, a meta‐analysis was performed to explore the association between bone density and ulcerative colitis. Methods Two investigators used PubMed, EMBASE and the Cochrane Library databases to identify all studies published before August 2019. Depending on the outcomes, investigators divided these studies into four groups (OR, SMD [BMD], SMD [z-score] and SMD [t-score]). To address the use of steroids, which is a major confounding factor in this analysis, another subgroup analysis of studies of steroid-free patients was conducted. Additionally, heterogeneity, sensitivity and stratified analyses were also performed. Results A total of 13 cross-sectional studies that involved 1154 participants were included in the present meta-analysis, and three of them were included in the steroid-free subgroup analysis. The pooled OR was 6.41 (95% CI 2.59–15.87) and the pooled SMD (BMD), SMD (t-score) and SMD (z-score) were − 0.24 (95% CI − 0.44 to − 0.04), − 0.55 (95% CI − 0.72 to − 0.37), and − 0.38 (95% CI − 0.56 and − 0.19), respectively. Since steroids are a significant confounder, the pooled SMD of the steroid-free subgroup was − 0.55 (− 0.85 to − 0.25), which revealed a strong negative relationship between bone density and ulcerative colitis in steroid-free patients. Additionally, other subgroup analyses also revealed a strong relationship. Conclusions This meta-analysis provides evidence for the potential association between ulcerative colitis and decreased bone density. It is essential for clinicians to consider bone mineral density in ulcerative colitis patients regardless of steroid-therapy.

Afamin is a member of the hepatokine that are strongly associated with various metabolic diseases. The relationship between afamin and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aimed to explore the correlation between serum afamin levels and NAFLD. We analyzed 88 NAFLD patients and 88 age- and sex-matched healthy controls who took their health examinations at the First Affiliated Hospital, Zhejiang University School of Medicine. The association was further confirmed in 22 biopsy-confirmed NAFLD patients and 36 healthy controls. Serum afamin levels were evaluated using an enzyme-linked immunosorbent assay (ELISA). NAFLD patients had significantly higher serum afamin levels than the healthy controls (14.79 ± 5.04 mg/L versus 10.83 ± 3.24 mg/L; P

Helicobacter pylori (H. pylori) is proved to be the main pathogenic agent of various diseases, including chronic gastritis, gastric ulcer, duodenal ulcer, and gastric cancer. In addition, chronic cholecystitis and cholelithiasis are common worldwide, which are supposed to increase the total mortality of patients. Epidemiologic evidence on the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis still remains unclear. We conducted a systematic review and meta-analysis of overall studies to investigate the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis. Two researchers searched PubMed, Embase, and Cochrane Library databases to obtain all related and eligible studies published before July 2020. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by the random-effects model. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also conducted. Twenty studies were included in the meta-analysis, involving 1735 participants and 1197 patients with chronic cholecystitis/cholelithiasis. Helicobacter species infection of the gallbladder was positively correlated with increased risk of chronic cholecystitis and cholelithiasis, especially H. pylori (OR = 3.05; 95% CI, 1.81–5.14; I2 = 23.5%). Besides, country-based subgroup analysis also showed a positive correlation between the gallbladder H. pylori positivity and chronic cholecystitis/cholelithiasis risk. For Asian and non-Asian country studies, the ORs were 4.30 (95% CI, 1.76–10.50; I2 = 37.4%) and 2.13 (95% CI, 1.23–3.70; I2 = 0.0%), respectively. The association was more obvious using the bile sample and urease gene primer. In conclusion, this meta-analysis provided evidence that there is a positive correlation between H. pylori infection in the gallbladder and increased risk of chronic cholecystitis and cholelithiasis.

To investigate the relationship between the solidification cooling rate and the size fluctuation of different V-containing phases, Al-4 wt. % V master alloys with various V-containing constituents were prepared at different cooling rates carried out by a wedge-shaped water-cooled copper mold, a graphite mold and a refractory mold at 1050°C, respectively. The variance of lognormal density function was used to characterize the size fluctuation of V-containing phases quantitatively. The results show that the largest size difference of both Al10V phases and Al3V phases is simultaneously present in the ingot prepared by the average solidification cooling rate of 2°C·s-1, while the smallest difference of Al10V phases in size is present in the ingot prepared by the average solidification cooling rate of 271°C·s-1. The size fluctuation of the Al3V phases first increases slightly and then decreases with increasing average solidification cooling rate in the range of 30~195°C·s-1.

Fermented soybeans are popular among many for their rich soy sauce-like aroma. However, the precise composition of this aroma remains elusive, with key aroma compounds unidentified. In this study, we screened the candidate genes ilvA and serA in BJ3-2 based on previous multi-omics data, and we constructed three mutant strains, BJ3-2-ΔserA, BJ3-2-ΔilvA, and BJ3-2-ΔserAΔilvA, using homologous recombination to fermented soybeans with varying intensities of soy sauce-like aroma. Our objective was to analyze samples that exhibited different aroma intensities resulting from the fermented soybeans of BJ3-2 and its mutant strains, thereby exploring the key flavor compounds influencing soy sauce-like aroma as well analyzing the effects of ilvA and serA on soy sauce-like aroma. We employed quantitative descriptive sensory analysis (QDA), gas chromatography–olfactometry–mass spectrometry (GC-O-MS), relative odor activity value analysis (rOAV), principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and partial least squares regression analysis (PLSR). QDA revealed the predominant soy sauce-like aroma profile of roasted and smoky aromas. GC-MS detected 99 volatile components, predominantly pyrazines and ketones, across the four samples, each showing varying concentrations. Based on rOAV (>1) and GC-O, 12 compounds emerged as primary contributors to soy sauce-like aroma. PCA and OPLS-DA were instrumental in discerning aroma differences among the samples, identifying five compounds with VIP > 1 as key marker compounds influencing soy sauce-like aroma intensity levels. Differential analyses of key aroma compounds indicated that the mutant strains of ilvA and serA affected soy sauce-like aroma mainly by affecting pyrazines. PLSR analysis indicated that roasted and smoky aromas were the two most important sensory attributes of soy sauce-like aroma, with pyrazines associated with roasted aroma and guaiacol associated with smoky aroma. In addition, substances positively correlated with the intensity of soy sauce-like aroma were verified by additional experiments. This study enhances our understanding of the characteristic flavor compounds in soy sauce-like aroma ferments, provides new perspectives for analyzing the molecular mechanisms of soy sauce-like aroma formation, and provides a theoretical framework for the targeted enhancement of soy sauce-like aroma in various foods. [ABSTRACT FROM AUTHOR]