Prevotella copri Improves Selenium Deposition and Meat Quality in the longissimus dorsi Muscle of Fattening Pigs.

Selenium is among the important trace elements that influence the quality of meat. Although it has been established that the gut microbiota is closely associated with selenium metabolism, it has yet to be determined whether these microbes influence the accumulation of selenium in muscles. To identify gut microbiota that potentially influence the deposition of selenium in muscles, we compared the colonic microbial composition of pigs characterized by high and low contents of selenium in the longissimus dorsi muscle and accordingly detected a higher abundance of the bacterium Prevotella copri (P. copri) in pigs with a higher muscle selenium content. To verify the effect of P. copri, 16 pigs weighing approximately 61 kg were fed either a basal diet or a basal diet supplemented with P. copri (1.0 × 1010 CFU/kg feed) for 45 days. The results revealed significant increases in the contents of selenium and selenoprotein in the serum and longissimus dorsi muscle of fattening pigs fed the P. copri-supplemented diet. Moreover, supplementing the feed of pigs with P. copri was observed to promote significant improvement in the antioxidant capacity and quality of meat, including drip loss, pH, and meat color. In conclusion, our findings in this study indicate that P. copri has potential utility as a dietary supplement for improving the selenium status and meat quality in fattening pigs.

The relationship between dietary live microbe intake and overactive bladder among American adults: a cross-sectional study from NHANES 2007-2018.

OBJECTIVE: The underlying mechanisms of Overactive Bladder (OAB) remain unclear. This research is designed to investigate the correlation between the intake of dietary live microorganisms and OAB. METHODS: This analysis encompasses a cross-sectional study of broad population information gathered from the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2007 to 2018. Participants were categorized into three groups-low, medium, and high-according to their consumption of dietary live microorganisms, as per the Sanders Dietary Active Microbiota Classification System. We utilized a weighted logistic regression model, restricted cubic spline (RCS), and subgroup analyses to investigate the relationship between dietary live microorganism intake and OAB. RESULTS: This research encompassed 16,795 subjects. The incidence of OAB was reduced in the group consuming a high amount of live dietary microbes compared to the groups with low and medium intake of such microbes. After detailed adjustments for covariates, analysis revealed that participants in the high live dietary microbe group had notably reduced odds of OAB compared to those in the low live dietary microbe group (OR: 0.84, 95% CI: 0.71-0.99, p = 0.03). RCS analysis indicated a nonlinear correlation between high dietary active microbiota intake and the incidence of OAB. CONCLUSION: This research emphasizes the potential advantages of a high dietary intake of active microbiota for preventing OAB. These findings support incorporating active microbiota into dietary guidelines, demonstrating their connection with a decreased incidence of OAB.

Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.

Background: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI). Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index). Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI. Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

Effects of different energy levels in low-protein diet on liver lipid metabolism in the late-phase laying hens through the gut-liver axis.

BACKGROUND: The energy/protein imbalance in a low-protein diet induces lipid metabolism disorders in late-phase laying hens. Reducing energy levels in the low-protein diet to adjust the energy-to-protein ratio may improve fat deposition, but this also decreases the laying performance of hens. This study investigated the mechanism by which different energy levels in the low-protein diet influences liver lipid metabolism in late-phase laying hens through the enterohepatic axis to guide feed optimization and nutrition strategies. A total of 288 laying hens were randomly allocated to the normal-energy and normal-protein diet group (positive control: CK) or 1 of 3 groups: low-energy and low-protein diet (LL), normal-energy and low-protein diet (NL), and high-energy and low-protein diet (HL) groups. The energy-to-protein ratios of the CK, LL, NL, and HL diets were 0.67, 0.74, 0.77, and 0.80, respectively. RESULTS: Compared with the CK group, egg quality deteriorated with increasing energy intake in late-phase laying hens fed low-protein diet. Hens fed LL, NL, and HL diets had significantly higher triglyceride, total cholesterol, acetyl-CoA carboxylase, and fatty acid synthase levels, but significantly lower hepatic lipase levels compared with the CK group. Liver transcriptome sequencing revealed that genes involved in fatty acid beta-oxidation (ACOX1, HADHA, EHHADH, and ACAA1) were downregulated, whereas genes related to fatty acid synthesis (SCD, FASN, and ACACA) were upregulated in LL group compared with the CK group. Comparison of the cecal microbiome showed that in hens fed an LL diet, Lactobacillus and Desulfovibrio were enriched, whereas riboflavin metabolism was suppressed. Cecal metabolites that were most significantly affected by the LL diet included several vitamins, such as riboflavin (vitamin B2), pantethine (vitamin B5 derivative), pyridoxine (vitamin B6), and 4-pyridoxic acid. CONCLUSION: A lipid metabolism disorder due to deficiencies of vitamin B2 and pantethine originating from the metabolism of the cecal microbiome may be the underlying reason for fat accumulation in the liver of late-phase laying hens fed an LL diet. Based on the present study, we propose that targeting vitamin B2 and pantethine (vitamin B5 derivative) might be an effective strategy for improving lipid metabolism in late-phase laying hens fed a low-protein diet.

Metabolomics reveals altered metabolites in cirrhotic patients with severe portal hypertension in Tibetan population.

Background: Portal hypertension (PHT) presents a challenging issue of liver cirrhosis. This study aims to identify novel biomarkers for severe PHT (SPHT) and explore the pathophysiological mechanisms underlying PHT progression. Methods: Twenty-three Tibetan cirrhotic patients who underwent hepatic venous pressure gradient (HVPG) measurement were included. Eleven patients had an HVPG between 5 mmHg and 15 mmHg (MPHT), while 12 had an HVPG ≥16 mmHg (SPHT). Peripheral sera were analyzed using liquid chromatograph-mass spectrometer for metabolomic assessment. An additional 14 patients were recruited for validation of metabolites. Results: Seven hundred forty-five metabolites were detected and significant differences in metabolomics between MPHT and SPHT patients were observed. Employing a threshold of p < 0.05 and a variable importance in projection score >1, 153 differential metabolites were identified. A significant number of these metabolites were lipids and lipid-like molecules. Pisumionoside and N-decanoylglycine (N-DG) exhibited the highest area under the curve (AUC) values (0.947 and 0.9091, respectively). Additional differential metabolites with AUC >0.8 included 6-(4-ethyl-2-methoxyphenoxy)-3,4,5-trihydroxyoxane-2-carboxylic acid, sphinganine 1-phosphate, 4-hydroxytriazolam, 4,5-dihydroorotic acid, 6-hydroxy-1H-indole-3-acetamide, 7alpha-(thiomethyl)spironolactone, 6-deoxohomodolichosterone, glutaminylisoleucine, taurocholic acid 3-sulfate, and Phe Ser. Enzyme-linked immunosorbent assay further confirmed elevated levels of sphinganine 1-phosphate, N-DG, and serotonin in SPHT patients. Significant disruptions in linoleic acid, amino acid, sphingolipid metabolisms, and the citrate cycle were observed in SPHT patients. Conclusion: Pisumionoside and N-DG are identified as promising biomarkers for SPHT. The progression of PHT may be associated with disturbances in lipid, linoleic acid, and amino acid metabolisms, as well as alterations in the citrate cycle.

Light-emitting probes for in situ sensing of plant information.

Monitoring plant physiological information for gaining a comprehensive understanding of plant growth and stress responses contributes to safeguarding plant health. Light-emitting probes - in terms of small-molecule, nanomaterials-based, and genetically protein-based probes - can be introduced into plants through foliar and root treatment or genetic transformation. These probes offer exciting opportunities for sensitive and in situ monitoring of dynamic plant chemical information - for example, reactive oxygen species (ROS), calcium ions, phytohormones - with spatiotemporal resolution. In this review we explore the sensing mechanisms of these light-emitting probes and their applications in monitoring various chemical information in plants in situ. These probes can be used as part of a sentinel plant approach to provide stress warning in the field or to explore plant signaling pathways.

ALKBH5-mediated N6-methyladenosine modification of HO-1 mRNA regulates ferroptosis in cobalt-induced neurodegenerative damage.

The utilization of Cobalt (Co) has surged due to it is critical role in renewable energy technologies and other high-tech applications. Concurrently, the potential health risks associated with Co exposure have raised concerns. Previous studies, including our own, have shown that Co can impair learn and memory functions as an epigenetic hazard, even at low concentrations. In this study, we explore the mechanisms of Co-induced ferroptosis in neurodegenerative damage both in vivo and in vitro, focusing on the epigenetic regulation by N6-methyladenosine (m6A) demethylase alkB homolog 5 (ALKBH5). We identify heme oxygenase-1 (HO-1) as a direct target gene of ALKBH5, playing a crucial role in mitigating Co-induced ferroptosis. ALKBH5 deficiency affects the post-transcriptional regulation of HO-1 through m6A modification, which in turn influences mRNA's stability, intracellular distribution, and alternative splicing, thereby enhancing susceptibility to Co-induced ferroptosis. Additionally, we discuss the potential involvement of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in regulating alternative splicing of HO-1 mRNA, potentially mediated by m6A modifications. This study provides new epigenetic insights into the post-transcriptional regulatory mechanisms involved in Co-induced ferroptosis and highlights the broader implications of environmental hazards in neurodegenerative damage.

Charcot arthropathy of the knee accompanied by tethered cord syndrome and lumbosacral fur sinus.

Charcot arthropathy is a rare disease in clinic, which is easy to be misdiagnosed and delayed diagnosis. Imaging examination plays a key role in the diagnosis of Charcot arthropathy. It is important to improve the early diagnosis rate and strive for early treatment to improve the quality of life of these patients. Here we reported a rare case of charcot knee (CK) accompanied by tethered cord syndrome and lumbosacral fur sinus, who presented with joint destruction, joint deformity and multiple free bodies and received joint free bodies removal and joint replacement surgery with acceptable short and midterm follow-up results.

Disinfection-residual bacteria (DRB) after chlorine dioxide treatment: Microbial community structure, regrowth potential, and secretion characteristics.

This study investigates the effects of chlorine dioxide (ClO2) disinfection on the community structure, regrowth potential, and metabolic product secretion of disinfection-residual bacteria (DRB) in secondary effluent (SE), denitrification filter effluent (DFE), and ultrafiltration effluent (UE). Results show that ClO2 effectively reduces bacteria in SE and UE, achieving log removal values exceeding 3 at 1 mg/L within 30 min. A salient positive correlation (R2 > 0.95) exists between changes in total fluorescence intensity and disinfection efficacy. Post-treatment, Acinetobacter abundance increased in SE, while Pseudomonas decreased in DFE and UE. At lower ClO2 concentrations, Staphylococcus, Mycobacterium, Aeromonas, and Lactobacillus increased in DFE, but decreased at higher concentrations. After storage, bacterial counts in disinfected samples exceeded those in the control group, surpassing 105 CFU/mL. Despite an initial decline, species richness and evenness partially recovered but remained lower than control levels. Culturing DRB for 72 h showed elevated extracellular polymeric substances (EPS) secretion, quantified as total organic carbon (TOC), ranging from 5 to 27 mg/L, with significantly higher EPS in the disinfection group. Parallel factor analysis with self-organizing maps (PARAFAC-SOM) effectively differentiated water sample types and EPS fluorescent substances, underscoring the potential of three-dimensional fluorescence as an indirect measure of ClO2 disinfection efficacy.

Synergistic ferrate(VI) and chlorine for reclaimed water disinfection: Microbial control and chlorine decay mitigation.

Chlorination is the most widely used disinfection technology due to its simplicity and continuous disinfection ability. However, the drawbacks of disinfection by-products and chlorine-resistant bacteria have gained increasing attention. Nowadays, ferrate (Fe(VI)) is a multifunctional and environmentally friendly agent which has great potential in wastewater reclamation and reuse. This study investigated synergistic Fe(VI) and chlorine technology for reclaimed water disinfection in terms of microbial control and chlorine decay mitigation. Specifically, synergistic disinfection significantly improved the inactivation efficiency on total coliform, Escherichia coli and heterotrophic bacteria compared to sole chlorination. Synergistic disinfection also exhibited superior performance on controlling the relative abundance of chlorine-resistant bacteria and pathogenic bacteria. In addition, the decay rate of residual chlorine was relatively lower after Fe(VI) pretreatment, which was beneficial for microbial control during the reclaimed water distribution process. Technical and economic analyses revealed that synergistic Fe(VI) and chlorine disinfection was suitable and feasible. Results of this study are believed to provide useful information and alternative options on the optimization of reclaimed water disinfection.

CT-guided iodine-125 brachytherapy is an effective palliative treatment for the right lower paratracheal lymph nodes metastasis previously treatment failure.

PURPOSE: This study aimed to evaluate the effectiveness and safety of iodine-125 brachytherapy as a treatment for right lower paratracheal lymph node metastasis following unsuccessful prior therapies. METHODS: A retrospective review of patients who underwent iodine-125 brachytherapy for right lower paratracheal lymph node metastasis was conducted. The study included 24 patients who met the predefined criteria. Iodine-125 seeds were implanted under CT guidance, and treatment planning was performed using a treatment planning system. The primary endpoint was the objective response rate (ORR), while overall survival (OS) and complications were secondary endpoints. RESULTS: The ORR was 87.5%, with 4 patients achieving complete response (CR) and 17 patients achieving partial response (PR). The mean diameter of metastatic lymph nodes significantly reduced from 40.21 ± 6.66 mm before treatment to 12.25 ± 9.27 mm at the last follow-up (p < 0.001). The median OS was 14.70 months, with 1-year and 2-year survival rates of 78.9% and 20.9%, respectively. Clinical symptoms significantly improved, as indicated by increased Karnofsky Performance Score (KPS) scores. Complications were manageable, with no procedure-related deaths. CONCLUSION: Iodine-125 brachytherapy demonstrated promising efficacy and safety as an alternative treatment for right lower paratracheal lymph node metastasis after unsuccessful prior therapies.

Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma.

BACKGROUND: The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC. AIM: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment. METHODS: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry. RESULTS: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC. CONCLUSION: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.

Topic Modeling Analysis of Chinese Medicine Literature on Gastroesophageal Reflux Disease: Insights into Potential Treatment.

OBJECTIVE: To analyze Chinese medicine (CM) prescriptions for gastroesophageal reflux disease (GERD), we model topics on GERD-related classical CM literature, providing insights into the potential treatment. METHODS: Clinical guidelines were used to identify symptom terms for GERD, and CM literature from the database "Imedbooks" was retrieved for related prescriptions and their corresponding sources, indications, and other information. BERTopic was applied to identify the main topics and visualize the data. RESULTS: A total of 36,207 entries are queried and 1,938 valid entries were acquired after manually filtering. Eight topics were identified by BERTopic, including digestion function abate, stomach flu, respiratory-related symptoms, gastric dysfunction, regurgitation and gastrointestinal dysfunction in pediatric patients, vomiting, stroke and alcohol accumulation are associated with the risk of GERD, vomiting and its causes, regurgitation, epigastric pain, and symptoms of heartburn. CONCLUSIONS: Topic modeling provides an unbiased analysis of classical CM literature on GERD in a time-efficient and scale-efficient manner. Based on this analysis, we present a range of treatment options for relieving symptoms, including herbal remedies and non-pharmacological interventions such as acupuncture and dietary therapy.

Excess multi-cause mortality linked to influenza virus infection in China, 2012-2021: a population-based study.

Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

Elucidation of the Biosynthesis of Griseoluteic Acid in Streptomyces griseoluteus P510.

Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in agriculture, medicine, and industry. Griseoluteic acid is a cytotoxic compound secreted by Streptomyces griseoluteus P510, displaying potential medical applications. However, the biosynthetic pathway of griseoluteic acid has not been elucidated, limiting its development and application. In this study, a conserved phenazine biosynthetic gene cluster of S. griseoluteus P510 was identified through genomic analysis. Subsequently, its was confirmed that the four essential modification enzymes SgpH, SgpI, SgpK, and SgpL convert phenazine-1,6-dicarboxylic acid into griseoluteic acid by heterologous expression in Escherichia coli. Moreover, the biosynthetic pathway of griseoluteic acid was established in Pseudomonas chlororaphis characterized by a high growth rate and synthesis efficiency of phenazines, laying the foundation for the efficient production of griseoluteic acid.

Involvement of autophagy in mesaconitine-induced neurotoxicity in HT22 cells revealed through integrated transcriptomic, proteomic, and m6A epitranscriptomic profiling.

Background: Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb Aconitum carmichaelii, is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. Methods: HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both in vitro and in vivo, employing multi-omics techniques to explore the potential mechanisms of toxicity. Results: Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Conclusion: Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.

Sulforaphane Inhibits Oxidative Stress and May Exert Anti-Pyroptotic Effects by Modulating NRF2/NLRP3 Signaling Pathway in Mycobacterium tuberculosis-Infected Macrophages.

Sulforaphane (SFN) is a natural isothiocyanate derived from cruciferous vegetables such as broccoli, Brussels sprouts, and cabbage. SFN plays a crucial role in maintaining redox homeostasis by interacting with the active cysteine residues of Keap1, leading to the dissociation and activation of NRF2 in various diseases. In this study, our objective was to investigate the impact of SFN on oxidative stress and pyroptosis in Mycobacterium tuberculosis (Mtb)-infected macrophages. Our findings demonstrated that Mtb infection significantly increased the production of iNOS and ROS, indicating the induction of oxidative stress in macrophages. However, treatment with SFN effectively suppressed the expression of iNOS and COX-2 and reduced MDA and ROS levels, while enhancing GSH content as well as upregulating NRF2, HO-1, and NQO-1 expression in Mtb-infected RAW264.7 macrophages and primary peritoneal macrophages from WT mice. These results suggest that SFN mitigates oxidative stress by activating the NRF2 signaling pathway in Mtb-infected macrophages. Furthermore, excessive ROS production activates the NLRP3 signaling pathway, thereby promoting pyroptosis onset. Further investigations revealed that SFN effectively suppressed the expression of NLRP3, Caspase-1, and GSDMD, IL-1ß, and IL-18 levels, as well as the production of LDH, suggesting that it may exhibit anti-pyroptotic effects through activation of the NRF2 signaling pathway and reductions in ROS production during Mtb infection. Moreover, we observed that SFN also inhibited the expression of NLRP3, ASC, Caspase1, and IL-1ß along with LDH production in Mtb-infected primary peritoneal macrophages from NFR2-/- mice. This indicates that SFN can directly suppress NLRP3 activation and possibly inhibit pyroptosis initiation in an NRF2-independent manner. In summary, our findings demonstrate that SFN exerts its inhibitory effects on oxidative stress by activating the NRF2 signaling pathway in Mtb-infected macrophages, while it may simultaneously exert anti-pyroptotic properties through both NRF2-dependent and independent mechanisms targeting the NLRP3 signaling pathway.

Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing.

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern. Microcystin-leucine arginine (MC-LR) is a well-established toxin produced by cyanobacterial blooms, which is widely distributed in eutrophic waters. MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals. However, the underlying mechanisms of MC-LR-induced liver toxicity are unclear. Herein, we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice. We established the first single-cell atlas of mouse livers in response to MC-LR. Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treated with MC-LR are highly heterogeneous. Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3, which potentially contributed to hepatocyte apoptosis in response to MC-LR. Moreover, MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes. Furthermore, the MC-LR increased several subtypes of CD8+ T cells with highly expressed multiple cytokines and chemokines. Overall, apart from directly inducing hepatocytes apoptosis, MC-LR activated proinflammatory Kupffer cell and CD8+ T cells, and their interaction may constitute a hostile microenvironment that contributes to liver injury. Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

Vitamin D supplementation for cardiometabolic risk markers in pregnant women based on the gestational diabetes mellitus or obesity status : a randomized clinical trial.

PURPOSE: Women with gestational diabetes mellitus (GDM) or obesity are vulnerable to impaired gestational cardiovascular health (CVH) and cardiovascular disease (CVD) in the future. It is unclear if prenatal vitamin D supplementation improves gestational CVH, especially in women at high risk for developing CVD. Our goal was to find out if vitamin D supplementation could protect against gestational CVH, including the women with GDM or obesity. DESIGN: We randomly assigned women with a serum 25(OH)D concentration < 75 nmol/L to receive 1600 IU/d (intervention group) or 400 IU/d (control group) of vitamin D3 for two months at 24-28 weeks' gestation. The primary outcome was gestational CVH marks (lipids, inflammatory cytokines, endothelial function). RESULTS: There were 1537 participants divided into the intervention (N = 766) and control groups (N = 771). No baseline differences existed among study groups in CVH markers. At the two-month visit, the intervention group's HDL-C levels (2.01 ± 0.39 VS 1.96 ± 0.39 mmol/L) were significantly higher than those of the control group, while the hs-CRP levels were significantly lower (3.28 ± 2.02 VS 3.64 ± 2.42 mg/L). Subgroup analysis found that HDL-C, TC, hs-CRP, E-Selectin, and SBP were improved in the intervention group among women with GDM or overweight/obesity, and the improvement was not found in women without GDM or overweight/obesity. Vitamin D supplementation significantly decreased the mean triglyceride-glucose index at the two-month visit in women with GDM. CONCLUSIONS: Vitamin D supplementation at mid-gestation might optimize the gestational CVH status for pregnant women, particularly the women with GDM or obesity, which is advantageous for later-life primary prevention of CVD. CLINICAL TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100051914, 10/9/2021, Prospective registered, https://www.chictr.org.cn/showproj.aspx?proj=134700 ).

[Analysis of Regional Differences in Cadmium Ecological Risk in Surface Waters of the Yangtze River Basin].

This study primarily focused on the regional disparities in both water quality criteria and ecological risks attributed to cadmium presence within the surface waters of the Yangtze River Basin. In the initial phase, the long-term water quality criteria for cadmium were recalibrated in accordance with the guidelines outlined in China's "Water Quality Criteria for Freshwater Aquatic Organisms-Cadmium," accounting for the prevalent hardness distribution within the Yangtze River Basin's surface water. Subsequently, a more refined revision was undertaken considering the specific characteristics of the species residing within the Yangtze River Basin. This undertaking led to a comprehensive interpretation of the regional variations in both the distribution of long-term water quality criteria values and the risk quotient distribution of cadmium throughout the Yangtze River Basin. The incorporation of hardness and species-specific attributes resulted in a revised range of long-term water quality criteria for cadmium across different urban locales within the Yangtze River Basin. Notably, the recalibrated values ranged from 0.08 µg·L-1 as the lowest threshold to 0.75 µg·L-1 as the upper limit, signifying a tenfold differentiation. Correspondingly, the urban average annual risk quotient associated with cadmium exposure demonstrated a variation from 0.035 to 1.12, marking a significant 32-fold discrepancy between the lowest and highest values. It is essential to highlight that regions of paramount importance, such as the confluence area connecting the upper and middle stretches of the Yangtze River Basin and the intricate Dongting Lake system, exhibited noteworthy ecological risks attributed to cadmium presence. Consequently, further in-depth investigations into these critical regions are imperative for a comprehensive understanding of the associated risks.