The roles of Bacteroides species in alleviating inflammation and intestinal injury has been widely demonstrated, but few studies have focused on the roles of Bacteroides vulgatus.

The occurrence of non-alcoholic fatty liver disease (NAFLD) is closely related to intestinal microbiota disturbance, and probiotics has become a new strategy to assist in alleviating NAFLD. In order to investigate the effect of Bifidobacterium on NAFLD and the possible pathway, a NAFLD model was established by using a high-fat diet (HFD) for 18 weeks. Fourteen strains of Bifidobacterium were selected (seven Bifidobacterium adolescentis and seven Bifidobacterium bifidum) for intervention. The effects of different bifidobacteria on NAFLD were evaluated from liver cell injury, liver fat deposition, liver inflammatory state and liver histopathology, and were taken as entry points to explore the mitigation approaches of bifidobacteria through energy intake, lipid metabolism, glucose metabolism and intestinal permeability. The results showed that Bifidobacterium exerts species-specific effects on NAFLD. B. bifidum exerted these effects mainly through regulating the intestinal microbiota, increasing the relative abundance of Faecalibaculum and Lactobacillus, decreasing the relative abundance of Tyzzerella, Escherichia-Shigella, Intestinimonas, Osillibacter and Ruminiclostridium, and further increasing the contents of propionic acid and butyric acid, regulating lipid metabolism and intestinal permeability, and ultimately inhibiting liver inflammation and fat accumulation to alleviate NAFLD. B. adolescentis exerted its effects mainly through changing the intestinal microbiota, increasing the content of propionic acid, regulating lipid metabolism and ultimately inhibiting liver inflammation to alleviate NAFLD.

During pregnancy and lactation, considerable factors that affect the maternal microbiome are associated with the advancement of numerous diseases, which can potentially affect offspring health. Probiotics have shown potential for the maintenance of microbiota homeostasis of mothers in this period. The specific objective of this study was to investigate whether the application of Akkermansia muciniphila (A. muciniphila) during pregnancy and lactation impacts maternal and offspring health. Here we show that dams fed with A. muciniphila is safe, enhances the intestinal barrier and alters gut microbiota composition and diversity at the end of lactation, including the significant enrichment of A. muciniphila and Ruminococcus_1 in offspring from probiotic-fed dams. However, compared with the control group, the fecal metabolites of the A. muciniphila group only changed slightly. Additionally, A. muciniphila supplementation did not significantly increase the abundance of A. muciniphila in the fecal microbiota of offspring mice. Compared with the control group, the fecal metabolic profile of three-week-old offspring of mice fed with A. muciniphila were significantly changed, containing the D-glutamine and D-glutamate metabolism pathways. These results provided evidence that A. muciniphila supplementation in mice during pregnancy and lactation is safe and seemed to have a more beneficial effect on dams. In the future, using probiotics to regulate maternal microbiomes during pregnancy and lactation could be shown to have a more lasting and beneficial effect.

Mortierella alpina has a strong capacity for lipid accumulation. Isocitrate dehydrogenase (IDH) plays an important role in affecting the flow of intracellular carbon sources and reducing power NADPH for lipid biosynthesis. In this study, the effect of various IDHs (NAD+- and NADP+-specific) in M. alpina on the lipid accumulation was investigated through homologous overexpression. The results showed that the transcription level and enzyme activity of the IDHs from M. alpina (MaIDHs) in homologous overexpressing strains were higher than those of the control strain, but that their biomass was not significantly different. Among the various NAD+-specific MaIDH1/2/3 overexpression, NAD+-MaIDH3 reduced total lipid content by 12.5%, whereas overexpression NAD+-MaIDH1 and NAD+-MaIDH2 had no effect on fatty acid content. Intracellular metabolites analysis indicated that the overexpression NAD+-MaIDH3 strain had reduced the fatty acid accumulation, due to its greater carbon flux with the tricarboxylic acid cycle and less carbon flux with fatty acid biosynthesis. For the NADP+-MaIDH4/5/6 recombinant strains overexpressing only NADP+-MaIDH4 enhanced the total fatty acid content by 8.2%. NADPH analysis suggested that this increase in lipid accumulation may have been due to the great reducing power NADPH is produced in this recombinant strain. This study provides theoretical basis and guidance for the analysis of the mechanism of IDH function and the potential to improve lipid production in M. alpina.

Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo. The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.

The continuous rise in opioid overdoses in the United States is predominantly driven by very potent synthetic opioids, mostly fentanyl and its derivatives (fentanyls). Although naloxone (NLX) has been shown to effectively reverse overdoses by conventional opioids, there may be a need for higher or repeated doses of NLX to revert overdoses from highly potent fentanyls. Here, we used positron emission tomography (PET) to assess NLX's dose-dependence on both its rate of displacement of [11C]carfentanil ([11C]CFN) binding and its duration of mu opioid receptor (MOR) occupancy in the male rat brain. We showed that clinically relevant doses of intravenously (IV) administered NLX (0.035 mg/kg, Human Equivalent Dose (HED) 0.4 mg; 0.17 mg/kg, HED 2 mg) rapidly displaced the specific binding of [11C]CFN in the thalamus in a dose-dependent manner. Brain MOR occupancy by IV NLX was greater than 90% at 5 min after NLX administration for both doses, but at 27.3 min after 0.035 mg/kg dose and at 85 min after 0.17 mg/kg NLX, only 50% occupancy remained. This indicates that the duration of NLX occupancy at MORs is short-lived. Overall, these results show that clinically relevant doses of IV NLX can promptly displace fentanyls at brain MORs, but repeated or higher NLX doses may be required to prevent re-narcotization following overdoses with long-acting fentanyls.

Fatty acid desaturases are key enzymes in the biosynthesis of n-3 polyunsaturated fatty acids (PUFAs) via conversion of n-6 polyunsaturates to their n-3 counterparts. In this study, we reported the characterization and molecular docking of Δ17 desaturases from Rhizophagus irregularis and Octopus bimaculoides. These two new desaturase genes were screened using the known Δ17 desaturase gene (oPaFADS17) from Pythium aphanidermatum as a template. Analysis of their genes revealed that the sequences of oRiFADS17 and oObFADS17 contained the typical His-rich motifs (one HXXXH and two HXXHH). They were then expressed in Saccharomyces cerevisiae INVSc1 to examine their activities and substrate preferences. Our results show that the two candidate n-3 desaturases possess a strong Δ17 desaturase activity, exhibiting remarkable increase in desaturation activity on C20 fatty acids compared to C18 fatty acids. To the best of our knowledge, oRiFADS17 desaturase has greater (3-4 fold) catalytic activity for C18 substrates than other reported Δ17 desaturases and oObFADS17 is the first reported Δ17 desaturase in sea mollusks. Characterization of these two new desaturases will be of greater value for genetic engineering in industrial production of eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3). Due to lack of crystal structure information about n-3 desaturases, for the first time, the view of their predicted structures, binding pockets and substrate tunnels was clearly observed based on molecular docking. This will contribute to strengthening our understanding of the structure-function relationships of n-3 fatty acid desaturases.

Immunoglobulin A (IgA), as the most secreted immunoglobulin in the intestine, plays an irreplaceable role in mucosal immunity regulation. Previous studies have indicated that Lactobacillus showed strain specificity in stimulating the secretion of IgA through intestinal mucosal lymphocytes. The reason for this phenomenon is not clear. The current studies have been aimed at exploring the effect of a strain on the secretion of IgA in the host's intestine, but the mechanism behind it has not been seriously studied. Based on this, we selected five strains of Lactobacillus fermentum isolated from different individuals to determine whether there are intraspecific differences in stimulating the secretion of IgA from the intestinal mucosa. It was found that IgA concentrations in different intestinal segments and faeces induced by L. fermentum were different. 12-1 and X6L1 strains increased the secretion of IgA by the intestine significantly. In addition, different strains of L. fermentum were also proven to have different effects on the host gut microbiota but no significant effects on IgA-coated microbiota. Besides, it was speculated that different strains of L. fermentum may act on different pathways to stimulate IgA in a non-inflammatory manner. By explaining the differences of IgA secretion in the host's intestine tract stimulated by different strains of L. fermentum, it is expected to provide a theoretical basis for the stimulation of intestinal secretion of IgA by Lactobacillus and a new direction for exploring the relationship between Lactobacillus and human immunity.

Inflammatory bowel disease (IBD) is a worldwide chronic intestinal inflammatory immune-related disease. In this study, mice with dextran sulfate sodium (DSS)-induced colitis were used to evaluate the effect of Lactobacillus acidophilus on colitis. The results revealed that L. acidophilus CCFM137 and FAHWH11L56 show potential for relieving colitis symptoms, while L. acidophilus FGSYC48L79 did not show a protective effect. Moreover, L. acidophilus NCFM and FAHWH11L56 showed similar effects on various indicators of DSS-induced colitis, increasing the IL-10 and IL-17 in the colon, and modifying the CCL2/CCR2 axis and CCL3/CCR1 axis. For L. acidophilus CCFM137, its effects on colitis were different from the above two strains. Moreover, L. acidophilus FGSYC48L79 had negative effects on colitis by increasing the abundance of harmful bacteria in the gut microbiota and may promote the signaling of chemokines and their receptors. This may be related to its special genome compared to the other strains.

The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations and perform precisely targeted modulation for obese individuals.

Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. COX-2, MPO, and iNOS activities and the inflammatory cytokines' expressions were determined to demonstrate the inhibition inflammation by GLE. Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways.

The sealing ring of the external floating roof tank is prone to petroleum gas leakage due to material aging and oil corrosion. Petroleum gas leakage and diffusion easily accumulate above the floating deck. When it is within the explosion limit range, there will be the risk of explosion and fire. To deal with the explosion accident of storage tank caused by the concentration distribution of petroleum gas leakage for the sealing ring, and to study the influence of petroleum gas diffusion and concentration distribution after sealing ring leakage on the control area above the floating deck in the tank farm environment, this paper established numerical models of sealing ring leakage under different liquid level heights for 10 × 104 m3 external floating roof tank. Through numerical calculation, it is found that the diffusion concentration of petroleum gas is related to the wind speed, the range of the control area above the floating deck, and leakage when sealing rings leak at different liquid levels. Through dimensionless analysis, the functional relationship of gas leakage diffusion concentration distribution under different liquid level heights of external floating roof tank sealing rings is verified by numerical calculation results. The results show that the numerical results are consistent with those predicted by the formula.

We present Richardson-Lucy network (RLN), a fast and lightweight deep learning method for three-dimensional fluorescence microscopy deconvolution. RLN combines the traditional Richardson-Lucy iteration with a fully convolutional network structure, establishing a connection to the image formation process and thereby improving network performance. Containing only roughly 16,000 parameters, RLN enables four- to 50-fold faster processing than purely data-driven networks with many more parameters. By visual and quantitative analysis, we show that RLN provides better deconvolution, better generalizability and fewer artifacts than other networks, especially along the axial dimension. RLN outperforms classic Richardson-Lucy deconvolution on volumes contaminated with severe out of focus fluorescence or noise and provides four- to sixfold faster reconstructions of large, cleared-tissue datasets than classic multi-view pipelines. We demonstrate RLN's performance on cells, tissues and embryos imaged with widefield-, light-sheet-, confocal- and super-resolution microscopy.

Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Gene Expression Omnibus database and StarBase were used to predict important regulatory pathways related to HCC. Then, the expression of KDM5B and microRNA-448 (miR-448) in HCC tissues was detected by RT-qPCR and Western blot analysis. The correlation between KDM5B and miR-448 expression was analysed by Pearson's correlation coefficient and ChIP experiments, and the targeting of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) by miR-448 was examined by luciferase assay. Additionally, the effect of KDM5B on the proliferation, migration, invasion and apoptosis as well as tumorigenicity of transfected cells was assessed using ectopic expression and depletion experiments. KDM5B was highly expressed in HCC cells and was inversely related to miR-448 expression. KDM5B demethylated H3K4me3 on the miR-448 promoter and thereby inhibited the expression of miR-448, which in turn targeted YTHDF3 and integrin subunit alpha 6 (ITGA6) to promote the malignant phenotype of HCC. Moreover, KDM5B accelerated HCC progression in nude mice via the miR-448/YTHDF3/ITGA6 axis. Our study uncovered that KDM5B regulates the YTHDF3/ITGA6 axis by inhibiting the expression of miR-448 to promote the occurrence of HCC.

Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa.

The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut-brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.

Background: Long non-coding RNAs (lncRNAs) play an important role in the immune processes of glioma. Immune related lncRNAs (IRlncRs) may be a critical prognosis in patients with glioma. The current study aimed to construct a glioma immune-related prognosis model by IRlncRs. Methods: Transcriptome RNA-sequencing data of glioma were obtained from The Cancer Genome Atlas (TCGA) and an immune‑related risk score (IRRS) model was constructed by Lasso and multivariate Cox regression analysis. Receiver Operating Characteristic (ROC) curves were used to assess the sensitivity and specificity of the prognosis on IRRS. A predictive nomogram and a time-dependent ROC curve was performed in training and validation cohort. We explored the relationships between survival‑related IRlncRs (sIRlncRs) and clinicopathologic parameters. Functional annotation of the sIRlncRs was investigated by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The relationships between IRRS model and immune cell infiltration and co-expression network analysis among the sIRlncRs were performed for molecular mechanism study. Results: A total of 10 sIRlncRs were enrolled to build IRRS model. The IRRS was identified as an independent prognostic factor and correlated with the overall survival (AUC =0.880). The nomogram was constructed successfully with IRRS, age and grade as variables. Immune cell infiltration analysis indicated that B cells, neutrophil, dendritic and macrophage cells were positively correlated with IRRS. PCA and GSEA illustrated that the lncRNA signature enrolled the IRRS model was closely related to immune status. Additionally, co-expression network showed that there was a strong correlation between 10 sIRlncRs at the transcriptional level. Conclusion: We successfully constructed a remarkable clinical model of sIRlncRs with potential prognostic value for glioma patients, which provides an insight into immunological research and treatment strategies of glioma.

Metabolic disturbance may be implicated in the pathogenesis of autism. This study aimed to investigate the gut metabolomic profiles of autistic children and to analyze potential interaction between gut metabolites with autistic symptoms and neurodevelopment levels. We involved 120 autistic and 60 neurotypical children. Autistic symptoms and neurodevelopment levels were assessed. Fecal samples were analyzed using untargeted liquid chromatography-tandem mass spectrometry methods. Our results showed the metabolic disturbances of autistic children involved in multiple vitamin and amino acid metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine-methionine metabolism, and vitamin digestion and absorption. Differential gut metabolites were correlated to autistic symptoms and neurodevelopment levels. Our findings improved the understanding of the perturbations of metabolome networks in autism.

Following fertilization, cortical granules exocytose ovastacin, a metalloendopeptidase that cleaves ZP2 in the zona pellucida surrounding mouse eggs to prevent additional sperm binding. Using high- and super-resolution imaging with ovastacinmCherry as a fluorescent marker, we characterize cortical granule dynamics at single granule resolution in transgenic mouse eggs. Newly-developed imaging protocols provide an unprecedented view of vesicular dynamics near the plasma membrane in mouse eggs. We discover that cortical granule anchoring in the cortex is dependent on maternal MATER and document that myosin IIA is required for biphasic trafficking to the plasma membrane. We observe local clearance of cortical actin during exocytosis and determine that pharmacologic or genetic disruption of trafficking to the plasma membrane impairs secretion of cortical granules and results in polyspermy. Thus, the regulation of cortical granule dynamics at the cortex-plasma membrane interface is critical for exocytosis and the post-fertilization block to sperm binding that ensures monospermic fertilization.