The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

OBJECTIVE To establish a comprehensive platform for regional pharmaceutical care among Jiangxi provincial pediatric alliance to realize the management of pediatric hierarchical diagnosis and treatment, and improve the quality of pharmaceutical care. METHODS A unified diagnosis and treatment information standard and a knowledge base of children's rational drug use rules were established among the medical institutions of Jiangxi provincial pediatric alliance. On this basis, the medical records and drug use information of patients in various medical institutions in the region were uploaded to the chain in a structured manner in real time, and a comprehensive platform for regional pharmaceutical care was built. RESULTS The comprehensive platform for regional pharmaceutical care built based on blockchain technology could share medical resources and information among medical institutions, realize rational drug use management, remote prescription review, individualized drug use guidance, popular science education, government supervision, etc., and improve the quality of pharmaceutical care. CONCLUSION The comprehensive platform for regional pharmaceutical care among Jiangxi provincial pediatric alliance can help allocate high-quality medical resources (drug safety knowledge base and pediatric pharmacists) for primary medical institutions. Further more, it lays the foundation for government supervision at the same time ensuring children’s medication safety, which has great practical significance.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Objective This study used resting-state functional magnetic resonance imaging(rs-fMRI)to investigate the changes of local brain regional homogeneity in patients with depression and childhood maltreatment,and we calculated the relationship between altered ReHo values and the severity of childhood maltreatment.Methods 25 patients with depression and childhood maltreatment,25 patients with depression without childhood maltreatment,and 25 age,gender,and education-matched healthy controls were prospectively enrolled.All subjects underwent resting-state functional magnetic resonance imaging and ReHo analysis.One-way analysis of variance was used to compare the group differences,along with multiple comparison correction.Pearson correlation analysis was used to explore the relationship between region ReHo values with clinical scales.Results Compared with the group of depression without childhood maltreatment,the abnormal brain regions of depression with childhood maltreatment are mainly located in the dorsolateral prefrontal cortex,cerebellum,parietal gyrus,and precentral gyrus.The ReHo values of depression with childhood maltreatment in the left cerebellum and the left dorsolateral prefrontal cortex are correlated with the severity of childhood maltreatment.Conclusions Depression with childhood mal-treatment is associated with changes in local spontaneous brain activity,which are correlated with the severity of childhood maltreatment.The brain changes in the dorsolateral prefrontal cortex and cerebellum may explain the neurobiological mechanisms of depression with childhood maltreatment.

Objective To explore the influencing factors of pancreatitis after duodenoscopic common bile duct stone removal surgery(DCBDSR).Methods A total of 387 patients with DCBDSR were included in this study.Patients were divided into the pancreatitis group(36 cases)and the non-pancreatitis group(351 cases).General data and laboratory indexes were compared between the two groups.The influencing factors of postoperative pancreatitis after DCBDSR were analyzed by regression analysis.Results Compared with the non-pancreatitis group,the pancreatitis group had a younger age,a higher proportion of hypertension,hyperlipidemia and pancreatic history,and a higher average number of intubations(P＜0.05).There were no significant differences in gender,body mass index,drinking history,smoking history,diabetes,gallbladder size,number of stones,stone diameter,operation time,number of angiography,aspartate aminotransferase(AST),glutamyl transpeptidase(GTP),alanine aminotransferase(ALT),direct bilirubin(DBIL)and total bilirubin(TBIL)levels between the two groups(P＞0.05).Young age,combined hypertension,concomitant hyperlipidemia,history of pancreatic disease and frequent intubation were independent risk factors for postoperative pancreatitis after DCBDSR.Conclusion Young age,concomitant hypertension,concomitant hyperlipidemia,history of pancreatic disease and frequent intubation are risk factors for developing pancreatitis after DCBDSR.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.

Ulcerative colitis is a common disease of the digestive system in China,which seriously affects the quality of life of patients due to its disease characteristics,such as easy recurrence,repeated course of disease and carcinogenic tendency.Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are considered as new inflammatory biomarkers,which have been found to be related with ulcerative colitis.This article reviewed the clinical value of NLR and PLR in ulcerative colitis.