Synthesis and Biological Activities of Scleropentaside D.

We report the first total synthesis of scleropentaside D, a unique C-glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of C-acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.

Toxicity assessment of organophosphate flame retardant triphenyl phosphate (TPHP) on intestines in mice.

Triphenyl phosphate (TPHP), one widely used organophosphate flame retardant, has attracted accumulating attention due to its high detection rate in human biological samples. Up to date, the effects of TPHP exposure on intestinal health remain unexplored. In this study, BALB/c mice were used as a model and exposed to TPHP at dose of 2, 10, or 50 mg/kg body weight for 28 days. We observed Crohn's disease-like features in ileum and ulcerative colitis disease-like features in colon, such as shorter colon length, ileum/colon structure impairment, intestinal epithelial cell apoptosis, enrichment of proinflammatory cytokines and immune cells, and disruption of tight junction. Furthermore, we found that TPHP induced production of reactive oxygen species and apoptosis in intestinal epithelial Caco-2 cells, accompanied by disruption of tight junction between cells. To understand the molecular mechanism underlying TPHP-induced changes in intestines, we build the adverse outcome pathway (AOP) framework based on Comparative Toxicogenomics and GeneCards database. The AOP framework revealed that PI3K/AKT and FoxO signaling pathway might be associated with cellular apoptosis, an increase in ROS production, and increased inflammation response in mouse ileum and colon tissues challenged with TPHP. These results identified that TPHP induced IBD-like features and provided new perspectives for toxicity evaluation of TPHP.

Diagnostic value of endoscopic ultrasound-guided fine needle aspiration with rapid on-site evaluation performed by endoscopists in solid pancreatic lesions: A prospective, randomized controlled trial.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most established diagnostic method for pancreatic tissue. Rapid on-site evaluation by a trained endoscopist (self-ROSE) can improve the diagnostic accuracy. This research is aimed to analyze the application value of self-ROSE for EUS-FNA in solid pancreatic lesions. METHODS: A total of 194 consecutive patients with solid pancreatic lesions in Nanjing Drum Tower Hospital were randomized in a 1:1 ratio to EUS-FNA with or without self-ROSE in this single-center randomized controlled trial. Before initiating self-ROSE, the endoscopist underwent training for pancreatic cytologic sample adequacy assessment and cytopathological diagnosis of EUS-FNA in pathology department for 1 month. Some parts of the slides of EUS-FNA were air dried, stained on-site with BASO Liu's reagent, and on-site evaluated in self-ROSE group. Between the two groups, the diagnostic performance of EUS-FNA was analyzed, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, with a comparison of the number of needle passes and the complication rates. RESULTS: The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 94.8%, 94.4%, 100%, 100%, and 58.3% in the self-ROSE group, respectively, and 70.1%, 65.1%, 100%, 100%, and 32.6% in the non-self-ROSE group. The diagnostic accuracy (P < 0.001) and sensitivity (P < 0.001) were both significantly increased during EUS-FNA in the self-ROSE group compared to the non-self-ROSE group. The rate of cytologic sample adequacy was 100% in self-ROSE group and 80.4% in non-self-ROSE group. The number of passes were 3.38 ± 1.00 in self-ROSE group and 3.22 ± 0.89 in non-self-ROSE group (P = 0.228). No complications were found in both. There was acceptable consistency between endoscopist and pathologist in the cytopathological diagnosis (kappa = 0.666, P < 0.05) and in the sample adequacy rate (kappa = 1.000, P < 0.001). CONCLUSION: Our results demonstrated that self-ROSE is valuable for EUS-FNA in the diagnosis of solid pancreatic lesions and is an important choice to routinely increase the accuracy of EUS-FNA in centers without ROSE assessment.

EUS-guided portal pressure gradient measurement in patients with acute or subacute portal hypertension.

BACKGROUND AND AIMS: EUS-guided portal pressure gradient (EUS-PPG) measurement is a novel method to evaluate portal hypertension severity. In this study, we determined the consistency between EUS-PPG and hepatic venous pressure gradient (HVPG) measurements in patients with acute or subacute portal hypertension. METHODS: Twelve patients were prospectively enrolled. EUS-PPG measurements were performed using a 22-gauge FNA needle and a central venous pressure measurement monitor. The HVPG measurements were performed using the transjugular approach. If an HVPG measurement was not attainable and the patient underwent transjugular intrahepatic portosystemic shunt (TIPS) treatment, a PPG was recorded as a reference standard during the procedure. We assessed the feasibility and safety of EUS-PPG and calculated the correlation between the 2 measurements. RESULTS: EUS-PPG measurements were successful in 11 patients (91.7%). Subsequent HVPG measurements failed in 2 patients with Budd-Chiari syndrome (hepatic vein occlusion subtype), 1 of whom underwent TIPS treatment to obtain transjugular PPG data. A small shunt was found during 1 HVPG measurement that introduced inaccuracy. Nine patients were included in the statistical analysis. Mean EUS-PPG and HVPG/PPG (transjugular) were 18.07 ± 4.32 mm Hg and 18.82 ± 3.43 mm Hg, respectively. Pearson's correlation coefficient between the 2 methods was .923 (P < .001). CONCLUSIONS: EUS-PPG measurement using a 22-gauge FNA needle was a safe and accurate method to evaluate portal hypertension and has the potential to supplement the measurement of HVPG in liver diseases. (Clinical trial registration number: ChiCTR1800017317.).

Effects of small nucleolar RNA SNORD44 on the proliferation, apoptosis and invasion of glioma cells.

To master the effect of small nucleolar RNA, SNORD44, on the proliferation, apoptosis and invasion of glioma cells and its relevant mechanism. SNORD44 and GAS5 expression in glioma tissues and cells was detected through qRT-PCR. Then, the glioma cell lines (U87 and U251) were divided into different groups with different treatments. Cell proliferation was determined by MTT assay, while the abilities of the cell migration and invasion were measured by wound-healing test and Transwell assay, respectively. Cell apoptosis were detected by flow cytometry and TUNEL assay. The expression of apoptosis proteins was quantified through Western blotting. Finally, the xenograft models were established on nude mice to investigate the effects of SNORD44 on the growth of glioma and the expressions of Ki67, MMP2 and MMP9 in vivo. SNORD44 and GAS5 were down-regulated in glioma tissues and cells in a positive correlation. Either SNORD44 or GAS5 overexpression decreased the proliferation, invasion and migration of U87 and U251 cells with the up-regulation of apoptosis rates, as well as the expressions of cleaved PARP, caspase 3, caspase 8 and caspase 9. Moreover, the in vivo experiment showed that overexpression of SNORD44 blocked the growth of glioma xenograft in nude mice accompanying with the inhibition of Ki67, MMP2 and MMP9 expressions. The combination overexpression of SNORD44 and GAS5 gained better inhibitory effects on glioma cells. Overexpression of SNORD44 and GAS5 activate the caspase-dependent apoptosis pathway to facilitate the apoptosis with the inhibited proliferation, invasion and migration of glioma cells.

Classification of the cystic duct patterns and endoscopic transpapillary cannulation of the gallbladder to prevent post-ERCP cholecystitis.

BACKGROUND: Endoscopic transpapillary cannulation of the gallbladder is useful but challenging. This study aimed to investigate cystic duct anatomy patterns, which may guide cystic duct cannulation. METHODS: A total of 226 patients who underwent endoscopic transpapillary cannulation of the gallbladder were analyzed retrospectively. RESULTS: According to the cystic duct take-off, 226 cystic duct patterns were divided into 3 patterns: Type I (193, 85.4%), located on the right and angled up; Type II (7, 3.1%), located on the right and angled down; and Type III (26, 11.5%), located on the left and angled up. Type I was further divided into three subtypes: Line type, S type (S1, not surrounding the common bile duct; S2, surrounding the common bile duct), and α type (α1, forward α; α2, reverse α). Types I and III cystic ducts were easier to be cannulated with a higher success rate (85.1 and 86.4%, respectively) compared with Type II cystic duct (75%) despite no statistically significant difference. The reasons for the failure of gallbladder cannulation included invisible cyst duct take-off, severe cyst duct stenosis, impacted stones in cyst duct or neck of the gallbladder, sharply angled cyst duct, and markedly dilated cyst duct with the tortuous valves of Heister. CONCLUSION: Classification of cystic duct patterns was helpful in guiding endoscopic transpapillary gallbladder cannulation.

Down-regulated of SREBP-1 in circulating leukocyte is a risk factor for atherosclerosis: a case control study.

BACKGROUND: Sterol regulatory-element binding proteins (SREBPs) and mir-33 (miR-33a, miR-33b), which are encoded by the introns of SREBPs, are key factors in the lipid metabolism pathway. SREBPs mRNA in circulating leucocyte and carotid plaques, along with various risk factors that associated with Coronary Atherosclerotic Disease (CAD) were investigated in a central Chinese cohort. METHODS: A total of 218 coronary atherosclerotic disease (CAD) patients, and 178 non-CAD controls, were recruited to collect leukocytes. Carotid plaques and peripheral blood were obtained from CAD patients undergoing carotid endarterectomy (CEA) (n = 12) while THP-1 and peripheral blood mononuclear cells (PBMCs) were stimulated with Oxidized low-density lipoprotein (ox-LDL) to establish an in vitro foam cell formation model. SREBPs and miR-33 levels were quantified by qPCR. Routine biochemical markers were measured using standard procedures. RESULTS: SREBP-1 mRNA level of circulating leucocytes in CAD patients were significantly lower than in non-CAD controls (p = 0.005). After stratification coronary artery atherosclerotic complexity, we detected a significant reduction of SREBP-1 in high-risk complexity CAD patients (SYNTAX score > 23) (p = 0.001). Logistic regression analysis indicated that decreased expression of SREBP-1 was a risk factor of CAD (odds ratio (OR) =0.48, 95% confidence interval (CI) = 0.30~0.76, p = 0.002) after adjusting clinical confounders; the mRNA levels of SREBPs in carotid plaques correlated with the corresponding value in circulating leukocytes (SREBP-1 r = 0.717, p = 0.010; SREBP-2 r = 0.612, p = 0.034). Finally, there was no significant difference in serum miR-33 levels between CAD patients and controls. CONCLUSIONS: Our finding suggesting a potential role in the adjustment of established CAD risk. The future clarification of how SREBP-1 influence the pathogenesis of CAD might pave the way for the development of novel therapeutic methods.

Risk factors for post-ERCP cholecystitis: a single-center retrospective study.

BACKGROUND: The risk factors for post-ERCP cholecystitis (PEC) have not been characterized. Hence, this study aimed to identify the potential risk factors for PEC. METHODS: The medical records of 4238 patients undergoing the first ERCP in a single center from January 2012 to December 2016 were analyzed in this study. A multivariate analysis was used to identify the risk factors. RESULTS: This study included 2672 patients who met the enrollment criteria. Of these, 36 patients (incidence rate of 1.35%) developed PEC within 2 weeks of the procedure. Univariate and multivariate analyses identified the following factors associated with PEC: history of acute pancreatitis [odds ratio (OR) = 2.60; 95% confidence interval (CI): 1.29-5.23], history of chronic cholecystitis (OR = 8.47; 95% CI: 2.54-28.24), gallbladder opacification (OR = 2.79; 95% CI: 1.37-5.70), biliary duct metallic stent placement (OR = 3.66; 95% CI: 1.78-7.54), and high leukocyte count before ERCP (OR = 1.10; 95% CI: 1.04-1.17). The prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.80-0.91). A prognostic nomogram was developed using the aforementioned variables to estimate the probability of PEC. CONCLUSIONS: The risk factors, including the history of acute pancreatitis, history of chronic cholecystitis, gallbladder opacification, biliary duct metallic stent placement, and high leucocyte counts before ERCP, increased the occurrence of PEC and were positive predictors for PEC. The constructed nomogram was used to estimate the risk of PEC, guiding the implementation of prophylactic measures to prevent PEC in clinical practice.

[Analysis of NF1 gene mutations among eleven sporadic patients with neurofibromatosis type 1].

OBJECTIVE: To explore the genetic etiology for 11 sporadic patients with neurofibromatosis type 1. METHODS: Chip targeting capture and high-throughput sequencing were employed to detect potential mutations of NF1 and NF2 genes among the 11 patients. The data was filtered through multiple mutational databases and in-house whole exome sequence database. Sanger sequencing was used for analysis of family members of the patients. RESULTS: Eleven pathogenic variants were found among the 11 patients, which included two splicing mutations, one missense mutation, two nonsense mutations, and six frame-shifting mutations. None of the mutations was recorded by the public database or the in-house database generated from 1775 samples through whole exome sequencing. None of the unaffected parents carried the same mutation. Seven mutations were associated with neurofibromatosis type 1 previously, while the remaining four were discovered for the first time. Prenatal diagnosis of two high-risk pregnancies suggested that neither fetus has inherited the NF1 mutation from their affected parents. CONCLUSION: Identification of causative mutations in patients with sporadic-type neurofibromatosis type 1 has provided a basis for genetic counseling. The four novel mutations have enriched the spectrum of NF1 gene mutations.

A novel truncation mutation in CRYBB1 associated with autosomal dominant congenital cataract with nystagmus.

PURPOSE: To identify the potential candidate genes for a large Chinese family with autosomal dominant congenital cataract (ADCC) and nystagmus, and investigate the possible molecular mechanism underlying the role of the candidate genes in cataractogenesis. METHODS: We combined the linkage analysis and direct sequencing for the candidate genes in the linkage regions to identify the causative mutation. The molecular and bio-functional properties of the proteins encoded by the candidate genes was further explored with biophysical and biochemical studies of the recombinant wild-type and mutant proteins. RESULTS: We identified a c. C749T (p.Q227X) transversion in exon 6 of CRYBB1, a cataract-causative gene. This nonsense mutation changes a phylogenetically conserved glutamine to a stop codon and is predicted to truncate the C-terminus of the wild-type protein by 26 amino acids. Comparison of the biophysical and biochemical properties of the recombinant full-length and truncated ßB1-crystallins revealed that the mutation led to the insolubility and the phase separation phenomenon of the truncated protein with a changed conformation. Meanwhile, the thermal stability of the truncated ßB1-crystallin was significantly decreased, and the mutation diminished the chaperoning ability of αA-crystallin with the mutant under heating stress. CONCLUSIONS: Our findings highlight the importance of the C-terminus in ßB1-crystallin in maintaining the crystalline function and stability, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human autosomal dominant congenital cataract.

[Study on differences of Ainsliaea fragrans from different sources based on UFLC-Q-TOF-MS/MS and PCA analysis].

A rapid and accurate method of UFLC-Q-TOF-MS/MS combined with multivariate statistical analysis was established for the identification of Ainsliaea fragrans from different origins in this study. The A. fragrans from different producing areas of Jiangxi, Yunnan, Henan and Jiangsu were determined by UFLC-Q-TOF-MS/MS in the negative ion mode. And the data of the study were analyzed by the Markerview and other software for the PCA and OPLS-DA cluster analysis as well as t test. The results of the principal component analysis(PCA)showed that the main components from different origins were well distinguished. And the results of multivariate statistical showed the differences and similarities between different producing areas. Besides, 40 different compounds were identified in the negative ion mode. This method for identifying A. fragrans from different producing areas has the advantages of rapid accuracy and simplicity, which laid the foundation for the evaluation of the quality of the A. fragrans.

Downregulation of FOXP3 inhibits invasion and immune escape in cholangiocarcinoma.

FOXP3 is known as a master control of regulatory T cells with recently studies indicating its expression in several tumor cells. In order to study the precise role of FOXP3 in cholangiocarcinoma, FOXP3 was knocked down in cholangiocarcinoma cell lines. Down regulation of FOXP3 inhibits tumor cell invasion by reducing the quantity of MMP-9 and MMP-2. With FOXP3 knocking down, IL-10 and TGF-ß1 secreted by cancer cells diminishes and the cell survival of T cells is significant up-regulation. These results suggest that FOXP3 plays an important role in tumor malignant phenotype, especially the invasion and immune escape.

[Safety and clinical efficacy of TIPS with various stents for treatment of cirrhosis with esophageal gastric varices bleeding].

OBJECTIVE: To assess the safety and clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with various stents for treating patients with cirrhosis and esophageal gastric varices bleeding. METHODS: One hundred and five patients were stratified according to stent type: bare stent group, covered stent-grafts group, combined stents group. Rates of success, shunt insufficiency, rebleeding, patient survival, and major complications were observed. The shunt insufficiency rate, rebleeding rate, and survival rate were calculated by the life tables method, the Kaplan-Meier analytical curve, and the log-rank test; a p-value less than 0.05 was considered statistically significant. RESULTS: The overall success rate of all TIPS for treating the esophageal gastric varices bleeding was 100%. The overall shunt insufficiency rates at 6-, 12-and 24-months post-TIPS were 8%, 9% and 16%, rebleeding rates were 2%, 6% and 17%, and survival rates were 100%, 97% and 94%. The shunt insufficiency rate was 26% in the bare stent group, 14% in the covered stent-grafis group, and 5% in the combined stents group (x2=1.00, P=0.61). The rebleeding rate was 33% in the bare stent group, 7% in the covered stent-grafts group, and 3%in the combined stents group (x2=1.69, P=0.43). The survival rate was 92% in the bare stent group, 93% in the covered stent-grafts group, and 100% in the combined stents group (x2=1.91, P=0.39). The shunt insufficiency rates were higher in patients with splenectomy than in those without splenectomy (30% vs.14%; x2=4.15, P=0.04). The intraperitoneal hemorrhage rates in the covered stent-grafis group and the combined stents group were significantly lower than that in the bare stent group (0% vs 0% vs 13%; x2=8.88, P=0.01). CONCLUSIONS: TIPS with an 8 mm stent effectively treated and prevented esophageal gastric varices bleeding in patients with cirrhosis. Intraperitoneal hemorrhaging caused by TIPS was significantly decreased in the covered stent-grafts group and combined stents group,which represented an improvement in safety of this treatment. However, the influence of covered stent-grafis and combined stents towards the clinical efficacy of TIPS needs further study.

Facile one-pot synthesis of a aptamer-based organic-silica hybrid monolithic capillary column by "thiol-ene" click chemistry for detection of enantiomers of chemotherapeutic anthracyclines.

In the current study, we developed a facile strategy for the one-pot synthesis of an aptamer-based organic-silica hybrid monolithic capillary column. A 5'-SH-modified aptamer, specifically targeting doxorubicin, was covalently modified in the hybrid silica monolithic column by a sol-gel method combined with "thiol-ene" click reaction. The prepared monolithic column had good stability and permeability, large specific surface, and showed excellent selectivity towards chemotherapeutic anthracyclines of doxorubicin and epirubicin. In addition, the enantiomers of doxorubicin and epirubicin can be easily separated by aptamer-based affinity monolithic capillary liquid chromatography. Furthermore, doxorubicin and epirubicin spiked in serum and urine were also successfully determined, which suggested that the complex biological matrix had a negligible effect on the detection of doxorubicin and epirubicin. Finally, we quantified the concentration of epirubicin in the serum of breast cancer patients treated with epirubicin by intravenous injection. The developed analytical method is cost-effective and rapid, and biological samples can be directly analyzed without any tedious sample pretreatment, which is extremely useful for monitoring medicines in serum and urine for pharmacokinetic studies.

Risk-Association of DNMT1 Gene Polymorphisms with Coronary Artery Disease in Chinese Han Population.

Recently, a significant epigenetic component in the pathogenesis of Coronary Artery Disease (CAD) has been realized. Here, we evaluated the possible association of candidate Single Nucleotide Polymorphisms (SNPs) in the epigenetic-regulatory gene, DNA methyltransferase 1 (DNMT1), with CAD in Chinese Han population. Five tag SNPs (rs16999593, rs2336691, rs2228611, rs4804494, rs7253062) were analyzed by High Resolution Melt (HRM) method in 476 CAD patients and 478 controls. Overall, there were significant differences in the genotype and allele distributions of rs2228611 and rs2336691, between patients and controls. The minor A allele of rs2228611 was associated with a lower risk of CAD (p = 0.034); modest effect in the additive analysis but also marginal significance was found in the recessive model [ORadditive = 0.404 (0.184, 0.884), p = 0.023 and ORrecessive = 0.452 (0.213, 0.963), p = 0.040] after adjusting for confounders. While the rs2336691 A allele were associated with a higher risk of developing CAD (p = 0.037); borderline significant association in both additive and dominant models [ORadditive = 1.632 (1.030, 2.583), p = 0.037 and ORdominant = 1.599 (1.020, 2.507), p = 0.040]. In conclusion, these data provide the first evidence that occurrence of CAD may be moderated by genetic variation in the gene involved in the epigenetic machinery.

Genome editing toward biofortified soybean with minimal trade-off between low phytic acid and yield.

Phytic acid (PA) in grain seeds reduces the bioavailability of nutrient elements in monogastric animals, and an important objective for crop seed biofortification is to decrease the seed PA content. Here, we employed CRISPR/Cas9 to generate a PA mutant population targeting PA biosynthesis and transport genes, including two multi-drug-resistant protein 5 (MRP5) and three inositol pentose-phosphate kinases (IPK1). We characterized a variety of lines containing mutations on multiple IPK and MRP5 genes. The seed PA was more significantly decreased in higher-order mutant lines with multiplex mutations. However, such mutants also exhibited poor agronomic performance. In the population, we identified  two lines carrying single mutations in ipk1b and ipk1c, respectively. These mutants exhibited moderately reduced PA content, and regular agronomic performance compared to the wild type. Our study indicates that moderately decreasing PA by targeting single GmIPK1 genes, rather than multiplex mutagenesis toward ultra-low PA, is an optimal strategy for low-PA soybean with a minimal trade-off in yield performance. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00158-4.

Predicting native papilla biliary cannulation success using a multinational Endoscopic Retrograde Cholangiopancreatography (ERCP) Quality Network.

BACKGROUND: Success in deep biliary cannulation via native ampullae of Vater is an accepted measure of competence in ERCP training and practice, yet prior studies focused on predicting adverse events alone, rather than success. Our aim is to determine factors associated with deep biliary cannulation success, with/ without precut sphincterotomy. METHODS: The ERCP Quality Network is a unique prospective database of over 10,000 procedures by over 80 endoscopists over several countries. After data cleaning, and eliminating previously stented or cut papillae, two multilevel fixed effect multivariate models were used to control for clustering within physicians, to predict biliary cannulation success, with and without allowing "precut" to assist an initially failed cannulation. RESULTS: 13018 ERCPs were performed by 85 endoscopists (March 2007 - May 2011). Conventional (without precut) and overall cannulation rates were 89.8% and 95.6%, respectively. Precut was performed in 876 (6.7%). Conventional success was more likely in outpatients (OR 1.21), but less likely in complex contexts (OR 0.59), sicker patients (ASA grade (II, III/V: OR 0.81, 0.77)), teaching cases (OR 0.53), and certain indications (strictures, active pancreatitis). Overall cannulation success (some precut-assisted) was more likely with higher volume endoscopists (> 239/year: OR 2.79), more efficient fluoroscopy practices (OR 1.72), and lower with moderate (versus deeper) sedation (OR 0.67). CONCLUSION: Biliary cannulation success appears influenced by both patient and practitioner factors. Patient- and case-specific factors have greater impact on conventional (precut-free) cannulation success, but volume influences ultimate success; both may be used to select appropriate cases and can help guide credentialing policies.

Targeting HDAC11 activity by FT895 restricts EV71 replication.

Enterovirus 71 (EV71) infection mainly causes hand, foot, and mouth disease (HFMD) and remains a serious public health problem to the children under the age of 5. Until now, there is no specific drug to treat HFMD in clinical and there is an urgent to explore the new target and the new drug to address clinical challenges. At present, we found histone deacetylase 11 (HDAC11) involves in supporting EV71 replication. We also used HDAC11 siRNA and an HDAC11 inhibitor FT895 to downregulate HDAC11 expression and found that targeting HDAC11 could significantly restrict EV71 replication in vitro and in vivo. Our results revealed the new role of HDAC11 participating in EV71 replication and broadened our knowledge regarding the functions of HDAC11 and the roles of HDACs in the epigenetic regulation of viral infectious diseases. Our results for the first time identified FT895 as an effective inhibitor of EV71 in vitro and in vivo, which may contribute to be a potential drug to treat HFMD.

Willingness to accept metaverse safety training for construction workers based on extended UTAUT.

Safety training (ST) is essential in avoiding unsafe behavior of construction workers. With the rise of metaverse technology, metaverse safety training (MST) has gradually become a new model to guide construction workers in safety production. An in-depth study of construction workers' willingness to accept the metaverse safety training (WAMST) helps improve its effectiveness, but studies need to pay more attention to it. This study constructs a conceptual model of WAMST for construction workers, and the influencing factors of WAMST are explained based on the extended Unified Theory of Acceptance and Use of Technology (UTAUT). It established a Structural equation modeling to verify the relationship between influencing factors. An example verifies the feasibility of the model. The results show that the framework significantly contributes to the willingness of construction workers to participate and improves safety awareness. Specifically, performance expectancy, effort expectancy, social influence, and convenient conditions significantly affect the construction workers' willingness to accept. Convenient conditions have a direct effect on actual behavior. Willingness to accept plays a mediating role between performance expectancy and actual behavior. Perceived trust moderates the effect between willingness to accept and actual behavior, and the force of positive interpretation increases proportionally. It confirms how to improve the safety capacity of construction workers and provides references for governments, enterprises, and projects to formulate ST strategies.