BACKGROUND: Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure.
METHODS: This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification.
RESULTS: A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients.
CONCLUSIONS: Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

Clostridium perfringens is one of the critical causative agents causing diarrhea in piglets, with significant economic losses to the pig industry. Under normal gut microbiota homeostasis and well-managed barns, diarrhea caused by C. perfringens could be controlled. Some reports show that probiotics, such as Bacillus subtilis, are beneficial in preventing necrotic enteritis (NE) in chickens, but few reports on piglets. Clostridium perfringens was found in the piglets\' diarrhea with intestinal microbiota dysbiosis in our survey. Bacillus subtilis G2B9-Q, which was isolated from the feces of healthy pigs, was found to have anti-Clostridium activity after screening. Clostridium perfringens was used to challenge mice by intraperitoneal injection for modeling to evaluate the anti-infective activity of cell-free supernatant (CFS) of B. subtilis G2B9-Q and different concentrations of B. subtilis G2B9-Q by oral administration. The results showed that G2B9-Q can mitigate intestinal lesions caused by C. perfringens infection, reduce inflammatory reactions, and modulate intestinal microbiota. The CFS of G2B9-Q can alleviate the pathological damage of intestinal tissues caused by C. perfringens infection, reduce the concentration of TNF-α and IL-10 in the sera of mice, as well as the relative expression levels of alpha toxin (CPA), perfringolysin O (PFO) toxin, IL-10, IL-22, and TNF-α in the jejunum and colon tissues, and alleviate the changes in gut microbiota structure caused by C. perfringens infection, which showed better therapeutic effects and indicated that the metabolites of G2B9-Q are essential mediators for their beneficial effects. Therefore, the CFS of G2B9-Q could potentially replace antibiotics in treating C. perfringens infection.

BACKGROUND: MASH is a common clinical disease that can lead to advanced liver conditions, but no approved pharmacotherapies are available due to an incomplete understanding of its pathogenesis. Damaged DNA binding protein 1 (DDB1) participates in lipid metabolism. Nevertheless, the function of DDB1 in MASH is unclear.
METHODS: Clinical liver samples were obtained from patients with MASH and control individuals by liver biopsy. Hepatocyte-specific Ddb1-knockout mice and liver Hmgb1 knockdown mice were fed with a methionine-and choline-deficient diet to induce MASH.
RESULTS: We found that the expression of DDB1 in the liver was significantly decreased in MASH models. Hepatocyte-specific ablation of DDB1 markedly alleviated methionine-and choline-deficient diet-induced liver steatosis but unexpectedly exacerbated inflammation and fibrosis. Mechanistically, DDB1 deficiency attenuated hepatic steatosis by downregulating the expression of lipid synthesis and uptake genes. We identified high-mobility group box 1 as a key candidate target for DDB1-mediated liver injury. DDB1 deficiency upregulated the expression and extracellular release of high-mobility group box 1, which further increased macrophage infiltration and activated HSCs, ultimately leading to the exacerbation of liver inflammation and fibrosis.
CONCLUSIONS: These data demonstrate the independent regulation of hepatic steatosis and injury in MASH. These findings have considerable clinical implications for the development of therapeutic strategies for MASH.

BACKGROUND: The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
METHODS: Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).
RESULTS: Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.
CONCLUSIONS: We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.

Corynebacterium pseudotuberculosis (C. p), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of C. p infection is still unclear. In this study, we established a C. p infection model in C57BL/6 mice and examined the impact of preemptive oral administration Lactobacillus acidophilus (L. acidophilus) on infection. Our findings revealed that C. p infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of L. acidophilus before infection with C. p. Additionally, we further found that during C. p infection, peritoneal macrophages (PMs) of mice orally administered with L. acidophilus accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral L. acidophilus administration showed a stronger C. p clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of L. acidophilus protected the gut microbiota disorder in C57BL/6 mice caused by C. p infection. In summary, our study demonstrates that oral administration of L. acidophilus confers effective protection against C. p infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position L. acidophilus as a viable probiotic candidate for the clinical prevention of C. p infection.
OBJECTIVE: Corynebacterium pseudotuberculosis (C. p) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C. p infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body\'s immune system and maintaining health. In this study, we established a C. p infection model in C57BL/6 mice to explore the impact of Lactobacillus acidophilus during C. p infection. Our results showed that L. acidophilus effectively protected against C. p infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C. p infection.

Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia.
OBJECTIVE: As a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

Gut microbiota of the bumblebee is critical as it modulates the health and fitness of the host. However, the mechanisms underlying the formation and maintenance of the diversity of bumblebee gut bacteria over a long period of evolution have yet to be elucidated. In particular, the gut bacterial diversity and community assembly processes of Bombus pyrosoma across the Chinese border remain unclear. In this study, we systematically carried out unprecedented sampling of 513 workers of the species Bombus pyrosoma across the Chinese landscape and used full-length 16S rRNA gene sequencing to examine their gut microbiota diversity and biogeography. The gut microbiota composition and community structure of Bombus pyrosoma from different geographical locations were diverse. On the whole, the gut bacteria Gilliamella and Snodgrassella are dominant in bumblebees, but opportunistic pathogens Serratia and Pseudomonas are dominant in some sampling sites such as Hb15, Gs1, Gs45, Qhs15, and Ssx35. All or part of environmental factors such as latitude, annual mean temperature, elevation, human footprint, population density, and annual precipitation can affect the alpha diversity and community structure of gut bacteria. Further analysis showed that the assembly and shift of bumblebee gut bacterial communities under geographical variation were mainly driven by the stochastic drift of the neutral process rather than by variable selection of niche differentiation. In conclusion, our unprecedented sampling uncovers bumblebee gut microbiome diversity and shifts over evolutionary time.
OBJECTIVE: The microbiotas associated with organisms facilitates host health and fitness, and the homeostasis status of gut microbiota also reflects the habitat security faced by the host. In addition, managing gut microbiota is important to improve bumblebee health by understanding the ecological process of the gut microbiome. Thus, we first carried out an runprecedented sampling of 513 workers of the species Bombus pyrosoma across the Chinese landscape and used full-length 16S rRNA gene sequencing to uncover their gut microbiota diversity and biogeography. Our study provides new insights into the understanding of gut microbiome diversity and shifts for Chinese Bumblebee over evolutionary time.

OBJECTIVE: This study aims to investigate the effects and mechanism of Morinda Officinalis How (MOH), a lianoid shrub with potential therapeutic properties, on Metabolism- Associated Fatty Liver Disease (MAFLD). bjective: The objective of this study was to construct a MOH-MAFLD network prediction model and explore the effect of MOH on MAFLD and its underlying mechanism in vivo.
METHODS: Screening of MAFLD targets was performed using the DisGeNET database. Venny database was used to establish the MOH-MAFLD interaction network map, while the STRING database was applied to assess the Protein-Protein Interaction (PPI) network. The central target gene was screened using Gene Ontology (GO) function analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.
RESULTS: GO function enrichment analysis revealed that MOH affected MAFLD through apoptosis and estrogen-related pathways. KEGG pathway enrichment and PPI network analysis indicated that MOH might mitigate MAFLD by reducing apoptosis and improving lipid metabolism. Additionally, 6 weeks of MOH treatment in rats decreased caspase-3 levels and increased Bcl-2, Estrogen receptor α(Esr1), and JUN proteins, thus ameliorating MAFLD progression.
CONCLUSIONS: MOH could delay the progression of MAFLD by affecting estrogen-related pathways, reducing cell stress, and inhibiting apoptosis.

UNASSIGNED: Foodborne diseases present a significant public health concern, particularly in China, where they represent a significant food safety challenge. Currently, there is a need for a thorough and systematic analysis of the extended epidemiological patterns of foodborne diseases in Beijing Municipality.
UNASSIGNED: Monitoring results show that Norovirus and diarrheagenic Escherichia coli (DEC) are the most commonly identified foodborne diarrheal pathogens. Individuals aged 19-30 are at a higher risk of foodborne diarrhea in Beijing, with Salmonella infection being associated with fever symptoms.
UNASSIGNED: This study analyzes 11 years of consecutive monitoring data to enhance understanding of the epidemiological and clinical features of foodborne diarrhea in Beijing. It aims to identify high-risk populations, assist in clinical pathogen identification and treatment, and support the development of tailored preventive strategies.