AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

Objective To investigate the effect of ATP synthase inhibitory factor 1 (ATPIF1) on the antitumor activity of chimeric antigen receptor (CAR)-NK92 cells. Methods HER2-targeted CAR-NK92 cells with ATPIF1 overexpression or knockdown were constructed. CAR-positive expression rate was detected by flow cytometry. Cell proliferation capacity was measured using CCK-8 assay. Glycolytic capacity was analyzed by Seahorse metabolic analyzer. Mitochondrial membrane potential levels were detected using JC-1 probe. Target cell lysis rate was evaluated by firefly luciferase reporter assay. Expression levels of CD107a, natural-killer group 2 member D (NKG2D), granzyme B (GzmB), perforin, and interleukin 2 (IL-2) were detected via flow cytometry. Quantitative real-time PCR was used to measure the expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), tumor necrosis factor α (TNF-α), ATPIF1, and hexokinase 1 (HK1). The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined. Results Successfully generated HER2-targeting control CAR-NK92 cells, as well as ATPIF1-overexpressing and ATPIF1 knockdown CAR-NK92 cells. The ATPIF1-overexpressing CAR-NK92 cells showed significantly enhanced target cell lysis rate, elevated expression levels of NKG2D and CD107a, increased secretion capacities of Granzyme B (GzmB) and IL-2, and upregulated mRNA expression levels of IFIT1 and TNF-α, while ATPIF1-knockdown cells exhibited opposite effects. ATPIF1 overexpression induced metabolic reprogramming in CAR-NK92 cells, manifested by significantly decreased mitochondrial membrane potential (δpsim), markedly upregulated HK1 mRNA expression, and enhanced basal glycolysis and glycolytic capacity. After glycolysis inhibition with 2-DG (5 μmol/L), both ATPIF1-overexpressing and knockdown CAR-NK92 cells showed no significant differences in NKG2D and CD107a expression levels compared to control cells. Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.
Humans ; Glycolysis ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Granzymes/genetics* ; Hexokinase/metabolism* ; Cell Line, Tumor ; Interleukin-2/genetics* ; Cell Proliferation ; NK Cell Lectin-Like Receptor Subfamily K/genetics* ; Membrane Potential, Mitochondrial

AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

The human oral microbiome harbors one of the most diverse microbial communities in the human body,playing critical roles in oral and systemic health.Recent technological innovations are propelling the characterization and manipulation of oral microbiota.High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes.New long-read platforms improve genome assembly from complex samples.Single-cell genomics provides insights into uncultured taxa.Advanced imaging modalities including fluorescence,mass spectrometry,and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution.Fluorescence techniques link phylogenetic identity with localization.Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification.Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches.Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly,gene expression,metabolites,microenvironments,virulence mechanisms,and microbe-host interfaces in the context of health and disease.However,significant knowledge gaps persist regarding community origins,developmental trajectories,homeostasis versus dysbiosis triggers,functional biomarkers,and strategies to deliberately reshape the oral microbiome for therapeutic benefit.The convergence of sequencing,imaging,cultureomics,synthetic systems,and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict,prevent,diagnose,and treat associated oral diseases.

Objective To understand current epidemic trend of coronavirus disease-2019(COVID-19)in Anhui province in the optimization policy stage,and to analyze the pathogenic characteristics of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in different population.Methods Using a cross-sectional survey design,from December 19 to 20,2022,an online questionnaire survey was conducted among residents of Anhui province through the official Wechat public accounts of provincial and municipal institutions with high traffic,to collect infor-mation on the incidence and clinic situation of COVID-19.The chi-square test was used to compare the proportion of COVID-19 suspected symptoms in different regions,ages and occupations.Results A total of 69 014 question-naires were distributed and 68 232 valid questionnaires were recovered with an effective rate of 98.97％.The pro-portion of the participants with COVID-19 suspected symptoms in the past 2 weeks was 51.37％,of which 77.88％self-medicated at home.The top three cities were Bozhou,Fuyang and Bengbu.The age group of 15-59 had the highest proportion of COVID-19 suspected symptoms(51.96％).Among various occupations,service providers had the highest proportion of COVID-19 suspected symptoms(61.07％).70.20％of the respondents felt anxious about the infection of SARS-CoV-2 and thought it was more serious than the flu.Conclusion The relatively high number of the infected cases and the anxiety of the people are all challenges faced by Anhui province in the stage of optimizing policies.Under the new situation of the epidemic,it is necessary to continuously monitor the local preva-lent strains and strengthen the monitoring of clinical symptoms of the infected cases,and effectively control the speed of the virus spread through public health policies and various economic and publicity measures,so as not to cause a run on medical resources and excessive excess deaths.