Dihydroartemisinin Modulates Enteric Glial Cell Heterogeneity to Alleviate Colitis.

The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100ß)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100ß+ EGCs while promoting the differentiation of GFAP+/S100ß+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100ß+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.

Application of plant-derived products as adjuvants for immune activation and vaccine development.

Vaccines are one of the most important means to prevent and control the epidemic of infectious diseases. Commercial vaccines not only include corresponding antigens, but also need vaccine adjuvants. Immune adjuvants play an increasingly important role in the research, development and manufacture of vaccines. Adjuvants combined with antigens can improve the stability, safety and immune efficiency of vaccines. Some substances that can enhance the immune response have been found in nature(mainly plants) and used as adjuvants in vaccines to improve the immune effect of vaccines. These plant-derived immune adjuvants often have the advantages of low toxicity, high stability, low price, etc., providing more possibilities for vaccine development. We summarized and analyzed the advantages, application research, particulate delivery systems, existing problems and future research focus of botanical adjuvant. It is hoped to provide new ideas for the research and development of immune adjuvants in the future.

Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.

Complex heterozygous mutations in hereditary spherocytosis: A case report.

BACKGROUND: The aim of this study was to investigate the complex heterozygous mutations of ANK1 and SPTA1 in the same individual and improve our understanding of hereditary spherocytosis (HS) in children. We also hope to promote the application of gene detection technology in children with HS, with the goals of identifying more related gene mutations, supporting the acquisition of improved molecular genetic information to further reveal the pathogenesis of HS in children, and providing important guidance for the diagnosis, treatment, and prevention of HS in children. CASE SUMMARY: A 1-year and 5-month-old patient presented jaundice during the neonatal period, mild anemia 8 months later, splenic enlargement at 1 year and 5 months, and brittle red blood cell permeability. Genetic testing was performed on the patient, their parents, and sister. Swiss Model software was used to predict the protein structure of complex heterozygous mutations in ANK1 and SPTA1. Genetic testing revealed that the patient harbored a new mutation in the ANK1 gene from the father and a mutation in the SPTA1 gene from the mother. Combined with the clinical symptoms of the children, it is suggested that the newly discovered complex heterozygous mutations of ANK1 and SPTA1 may be the cause, providing important guidance for revealing the pathogenesis, diagnosis, treatment, and promotion of gene detection technology in children with HS. CONCLUSION: This case involves an unreported complex heterozygous mutation of ANK1 and SPTA1, which provides a reference for exploring HS.

Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

M2 Macrophage Classification of Colorectal Cancer Reveals Intrinsic Connections with Metabolism Reprogramming and Clinical Characteristics.

Introduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored. Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework. Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk. Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations.

Rupture risk of intracranial aneurysms: Comparison between small ruptured intracranial aneurysms and large unruptured intracranial aneurysms.

To compare the differences in clinical and morphological features between small ruptured intracranial aneurysms and large unruptured intracranial aneurysms to evaluate the risk factors for the rupture of IAs. The clinical data of 189 consecutive patients with 193 IAs were reviewed. The patients and IAs were divided into ruptured (<5 mm) and unruptured groups (>10 mm). The characteristics of the patients and the intracranial aneurysms (IAs) were compared between the 2 groups, and the risk factors for rupture of IAs were assessed using multiple logistic regression. Patient age (odds ratio [OR], 0.955), IA located at the internal carotid artery (ICA, OR, 0.202), irregular shape (OR, 0.083) and parent vessel diameter (OR, 0.426) were negatively correlated with the risk of IA rupture. IAs located at bifurcations (OR, 6.766) were positively correlated with the risk of IA rupture. In addition to the size of the IAs, regardless of IAs shape, other factors, such as younger age (<63.5 years), location at a bifurcation, IAs located at the ICA and a small parent vessel diameter (<3.25 mm), can influence the risk of IA rupture.

Effect of Flammulina velutipes polysaccharide on mitochondrial apoptosis in lung adenocarcinoma A549 cells.

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells.

Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC.

Aberrant cell proliferation is a hallmark of cancer, including breast cancer. Here, we show that USP27X is required for cell proliferation and tumorigenesis in breast cancer. We identify a PIM2-USP27X regulator of MYC signaling axis whose activity is an important contributor to the tumor biology of breast cancer. PIM2 phosphorylates USP27X, and promotes its deubiquitylation activity for MYC, which promotes its protein stability and leads to increase HK2-mediated aerobic glycolysis in breast cancer. Moreover, the PIM2-USP27X-MYC axis is also validated in PIM2-knockout mice. Taken together, these findings show a PIM2-USP27X-MYC signaling axis as a new potential target for breast cancer treatment.

Revitalizing gut barrier integrity: miR-192-5p's role in enhancing autophagy via Rictor in enteritis.

BACKGROUND: Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. METHODS: A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also employed. RESULTS: Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. CONCLUSION: Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in enteritis patients.

Cultivation of novel Atribacterota from oil well provides new insight into their diversity, ecology, and evolution in anoxic, carbon-rich environments.

BACKGROUND: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. RESULTS: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. CONCLUSION: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract.

Sex- and age-specific associations of serum essential elements with diabetes among the Chinese adults: a community-based cross-sectional study.

BACKGROUND: Although several studies have found the relationship between essential elements and diabetes, the studies about the association of essential elements with diabetes diagnosed according to an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) in a sex- and age-specific manner were limited. To investigate the linear and nonlinear relationship of five essential elements including iron (Fe), copper (Cu), Zinc (Zn), magnesium (Mg), and calcium (Ca) with diabetes, fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PPG), and HbA1c and to evaluate the sex- and age-specific heterogeneities in these relationships. METHODS: A total of 8392 community-dwelling adults were recruited to complete a questionnaire and undergo checkups of anthropometric parameters and serum levels of five metals (Fe, Cu, Zn, Mg, and Ca). The multivariable logistic and linear regression, the restricted cubic spline (RCS) analysis, and subgroup analysis were applied to find the associations between the essential elements and the prevalence of diabetes as well as FPG, PPG, and HbA1c. RESULTS: In the multivariable logistic regression and multivariable linear regression, serum Cu was positively associated with FPG, PPG, and HbA1c while serum Mg was significantly inversely correlated with FPG, PPG, HbA1c, and diabetes (all P < 0.001). In the RCS analysis, the non-linear relationship of Cu and diabetes (P < 0.001) was found. In the subgroup analysis, stronger positive associations of Cu with diabetes (P for interaction = 0.027) and PPG (P for interaction = 0.002) were found in younger women. CONCLUSIONS: These findings may lead to more appropriate approaches to essential elements supplementation in people with diabetes of different ages and sexes. However, more prospective cohort and experimental studies are needed to probe the possible mechanism of sex- and age-specific associations between serum essential elements and diabetes.

Construct a Magnetic Pt/Ru Alloy Peroxidase Mimic As a Reusable and Cost-Effective "Signal-Off" Sensing Platform for Sensitive and Wide-Linear-Range Assay.

"Signal-off" nanozyme sensing platforms are usually employed to detect analytes (e.g., ascorbic acid (AA) and alkaline phosphatase (ALP)), which are mostly based on oxidase (OXD) nanozymes. However, their drawbacks, like dissolved oxygen-dependent catalysis capability, relatively low enzyme activity, limited amount, and kind, may not favor sensing platforms' optimization. Meanwhile, with the need for sustainable development, a reusable "signal-off" sensing platform is essential for cutting down the cost of the assay, but it is rarely developed in previous studies. Magnetic peroxidase (POD) nanozymes potentially make up the deficiencies and become reusable and better "signal-off" sensing platforms. As a proof of concept, we first construct Fe3O4@polydopamine-supported Pt/Ru alloy nanoparticles (IOP@Pt/Ru) without stabilizers. IOP@Pt/Ru shows high POD activity with Vmax of 83.24 × 10-8 M·s-1 for 3,3',5,5'-Tetramethylbenzidine (TMB) oxidation. Meanwhile, its oxidation rate for TMB is slower than the reduction of oxidized TMB by reducers, favorable for a more significant detection signal. On the other hand, IOP@Pt/Ru possesses great magnet-responsive capability, making itself be recycled and reused for at least 15-round catalysis. When applying IOP@Pt/Ru for AA (ALP) detection, it performs better detectable adaptability, with a linear range of 0.01-0.2 mM (0.1-100 U/L) and a limit of detection of 0.01 mM (0.05 U/L), superior to most of OXD nanozyme-based ALP sensing platform. Finally, IOP@Pt/Ru's reusable assay was demonstrated in real blood samples for ALP assay, which has never been explored in previous studies. Overall, this study develops a reusable "signal-off" nanozyme sensing platform with superior assay capabilities than traditional OXD nanozymes, paves a new way to optimize nanozyme-based "signal-off" sensing platforms, and provides an idea for constructing inexpensive and sustainable sensing platforms.

Functional characterization of polyphenol oxidase OfPPO2 supports its involvement in parallel biosynthetic pathways of acteoside.

Acteoside is a bioactive phenylethanoid glycoside widely distributed throughout the plant kingdom. Because of its two catechol moieties, acteoside displays a variety of beneficial activities. The biosynthetic pathway of acteoside has been largely elucidated, but the assembly logic of two catechol moieties in acteoside remains unclear. Here, we identified a novel polyphenol oxidase OfPPO2 from Osmanthus fragrans, which could hydroxylate various monophenolic substrates, including tyrosine, tyrosol, tyramine, 4-hydroxyphenylacetaldehyde, salidroside, and osmanthuside A, leading to the formation of corresponding catechol-containing intermediates for acteoside biosynthesis. OfPPO2 could also convert osmanthuside B into acteoside, creating catechol moieties directly via post-modification of the acteoside skeleton. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and subcellular localization assay further support the involvement of OfPPO2 in acteoside biosynthesis in planta. These findings suggest that the biosynthesis of acteoside in O. fragrans may follow "parallel routes" rather than the conventionally considered linear route. In support of this hypothesis, the glycosyltransferase OfUGT and the acyltransferase OfAT could direct the flux of diphenolic intermediates generated by OfPPO2 into acteoside. Significantly, OfPPO2 and its orthologs constitute a functionally conserved enzyme family that evolved independently from other known biosynthetic enzymes of acteoside, implying that the substrate promiscuity of this PPO family may offer acteoside-producing plants alternative ways to synthesize acteoside. Overall, this work expands our understanding of parallel pathways plants may employ to efficiently synthesize acteoside, a strategy that may contribute to plants' adaptation to environmental challenges.

Tobacco exposure and alcohol drinking prevalence and associations with hypertension in rural southwest China: A cross-sectional study.

INTRODUCTION: This study examined the prevalence of tobacco exposure and drinking and ascertained the relationships between tobacco exposure, alcohol drinking, concurrent smoking and drinking, and hypertension in rural southwestern China. METHODS: Data were collected from a cross-sectional health interview and examination survey, which included 7572 adults aged ≥35 years, in rural China. Participant demographic characteristics, smoking habits, exposure to secondhand smoke (SHS), and alcohol drinking habits were obtained using a standard questionnaire. Blood pressure (BP), height, weight, and waist circumference were measured for each participant. RESULTS: The overall prevalence of smoking, SHS exposure, drinking, concurrent smoking and drinking, concurrent exposure to SHS and drinking, and hypertension was 37.7%, 27.4%, 16.2%, 12.6%, 1.6%, and 41.3%, respectively. Males had a significantly higher prevalence of smoking (74.1% vs 2.2%, p<0.01), drinking (31.1% vs 1.7%, p<0.01), and concurrent smoking and drinking than females (25.3% vs 0.3%, p<0.01). However, females had a higher prevalence of SHS exposure than males (30.2% vs 20.6%, p<0.01). Ethnic minorities had a higher prevalence of SHS exposure, drinking, and concurrent smoking and drinking, than Han participants (p<0.01). Participants with a higher education level had a higher prevalence of smoking, drinking, and concurrent smoking and drinking than their counterparts (p<0.01). In contrast, participants with a lower education level had a higher prevalence of SHS exposure than their counterparts (p<0.01). Multivariate logistic regression analysis found that smokers (AOR=1.31; 95% CI: 1.13-1.51), individuals exposed to SHS (AOR=1.24; 95% CI: 1.11-1.43), drinkers (AOR=1.31; 95%: CI: 1.15-1.50), and concurrent smokers and drinkers (AOR=1.45; 95% CI: 1.25-1.67) all had a higher probability of having hypertension (p<0.01). Additionally, concurrent smoking and drinking had the strongest association with the prevalence of hypertension (AOR=1.45; 95% CI: 1.25-1.67; p<0.01). CONCLUSIONS: Socioeconomic factors play an important role in influencing the prevalence of smoking, exposure to SHS, and drinking in rural southwest China. Interventions to prevent and reduce hypertension should, in particular, focus on smokers, individuals exposed to SHS, drinkers, and, in particular, concurrent smokers and drinkers.

Multi-omics insights into the function and evolution of sodium benzoate biodegradation pathway in Benzoatithermus flavus gen. nov., sp. nov. from hot spring.

Biodegradation stands as an eco-friendly and effective approach for organic contaminant remediation. However, research on microorganisms degrading sodium benzoate contaminants in extreme environments remains limited. In this study, we report to display the isolation of a novel hot spring enriched cultures with sodium benzoate (400 mg/L) as the sole carbon source. The results revealed that the phylum Pseudomonadota was the potential sodium benzoate degrader and a novel genus within the family Geminicoccaceae of this phylum. The isolated strain was named Benzoatithermus flavus SYSU G07066T and was isolated from HNT-2 hot spring samples. Genomic analysis revealed that SYSU G07066T carried benABC genes and physiological experiments indicated the ability to utilize sodium benzoate as a sole carbon source for growth, which was further confirmed by transcriptomic data with expression of benABC. Phylogenetic analysis suggested that Horizontal Gene Transfer (HGT) plays a significant role in acquiring sodium benzoate degradation capability among prokaryotes, and SYSU G07066T might have acquired benABC genes through HGT from the family Acetobacteraceae. The discovery of the first microorganism with sodium benzoate degradation function from a hot spring enhances our understanding of the diverse functions within the family Geminicoccaceae. This study unearths the first novel genus capable of efficiently degrading sodium benzoate and its evolution history at high temperatures, holding promising industrial applications, and provides a new perspective for further exploring the application potential of hot spring "microbial dark matter".

Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Nontarget and suspect screening reveals the presence of multiple plastic-related compounds in polar bear, killer whale, narwhal and long-finned pilot whale blubber from East Greenland.

The monitoring of legacy contaminants in sentinel northern marine mammals has revealed some of the highest concentrations globally. However, investigations into the presence of chemicals of emerging Arctic concern (CEACs) and other lesser-known chemicals are rarely conducted, if at all. Here, we used a nontarget/suspect approach to screen for thousands of different chemicals, including many CEACs and plastic-related compounds (PRCs) in blubber/adipose from killer whales (Orcinus orca), narwhals (Monodon monoceros), long-finned pilot whales (Globicephala melas), and polar bears (Ursus maritimus) in East Greenland. 138 compounds were tentatively identified mostly as PRCs, and four were confirmed using authentic standards: di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), di(2-propylheptyl) phthalate (DPHP), and one antioxidant (Irganox 1010). Three other PRCs, a nonylphenol isomer, 2,6-di-tert-butylphenol, and dioctyl sebacate, exhibited fragmentation patterns matching those in library databases. While phthalates were only above detection limits in some polar bear and narwhal, Irganox 1010, nonylphenol, and 2,6-di-tert-butylphenol were detected in >50% of all samples. This study represents the first application of a nontarget/suspect screening approach in Arctic cetaceans, leading to the identification of multiple PRCs in their blubber. Further nontarget analyses are warranted to comprehensively characterize the extent of CEAC and PRC contamination within Arctic marine food webs.

Induced production of defensive secondary metabolites from Aspergillus fumigatiaffinis by co-culture with Aspergillus alabamensis.

Seven previously undescribed compounds, including four diketomorpholine alkaloids (1‒4), one indole diketopiperazine alkaloid (9), one chromone (10), and one benzoic acid derivative (13), and nine known compounds (5-8, 11, 12, and 14-16) were isolated from two different fungal sources. Nine of these metabolites (1-9) were obtained from a seagrass-derived Aspergillus alabamensis SYSU-6778, while the others were obtained from a mixed culture of A. alabamensis SYSU-6778 and a co-isolated fungus A. fumigatiaffinis SYSU-6786. The chemical structures of the compounds were deduced via spectroscopic techniques (including HRESIMS, 1D and 2D NMR), chemical reactions, and ECD calculations. It is worth noting that compound 10 was identified as a defensive secondary metabolite of strain SYSU-6786, produced through the induction of compound 8 under co-culture conditions. Compounds 3 and 4 possessed a naturally rare isotryptophan core. Moreover, compounds 1 and 2 exhibited potent inhibitory activities against fish pathogenic bacterium Edwardsiella ictalurid, with minimum inhibitory concentration values of 10.0 µg/mL for both compounds.

Causal association between BMI and polycystic ovarian syndrome: Bidirectional two-sample Mendelian randomization study.

OBJECTIVE: The study aimed to explore the causal effect of body mass index (BMI) on polycystic ovarian syndrome (PCOS). METHODS: Genome-wide association data for BMI and PCOS were sourced from the Mendelian randomization (MR) base platform. Significantly associated single nucleotide polymorphisms (SNPs) for BMI served as instrumental variables in bidirectional two-sample MR analyses to investigate the causal relationship between BMI and PCOS. Analytical techniques utilized encompassed the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression. RESULTS: We identified 427 SNPs significantly associated with BMI (P < 5 × 10-8; linkage disequilibrium r2 < 0.001). Various methods consistently revealed a positive association between BMI and PCOS (IVW: odds ratio (OR) 2.027, 95% confidence interval (CI) 1.599-2.596; weighted median estimator: OR 2.368, 95% CI 1.653-3.392; MR-Egger Method: OR 3.610, 95% CI 1.795-7.263), indicating that higher BMI correlates with an increased risk of PCOS. Additionally, we observed a causal effect of genetic predisposition to PCOS on BMI (IVW: OR 1.020, 95% CI (1.019-1.022); weighted median estimator: OR 1.017, 95% CI (1.015-1.019); MR-Egger Method: OR 1.000, 95% CI (0.995-1.005)). CONCLUSION: The MR analysis furnished compelling evidence suggesting a causal relationship between elevated BMI and the risk of PCOS, as well as indicating that the severity of PCOS may contribute to elevated BMI levels.