Bacterial extracellular vesicles in the oral–gut axis: Roles in periodontitis and inflammatory bowel disease

Microbiological Research · 2026-04-23

Deletion of gltA attenuates virulence and confers immune protection against Salmonella Enteritidis

ScienceDB · 2026-04-27

Salmonella enterica serovar Enteritidis is the leading cause of foodborne diseases worldwide. The prevalence of multidrug-resistant strains has significantly increased the challenges of clinical treatment and public health risks. The tricarboxylic acid (TCA) cycle serves as the central hub of bacterial central carbon metabolism, and genes encoding its key enzymes are closely associated with the environmental adaptability and pathogenicity of bacteria. However, the biological function of gltA, the gene encoding citrate synthase—the rate-limiting enzyme initiating the TCA cycle—in S. Enteritidis, as well as its potential for use in attenuated vaccines, has not yet been systematically elucidated. In this study, the λ-Red homologous recombination technique was used to construct a gltA-deleted strain (ΔgltA) and its complement (ΔgltA+gltA) from S. Enteritidis strain C50336. We systematically evaluated the effects of gltA deletion on the basic biological characteristics, antimicrobial susceptibility, and environmental stress tolerance of the strains. The molecular mechanism underlying its regulation of virulence was elucidated by combining transcriptomics and quantitative real-time PCR (qRT-PCR), and the attenuation effect and immunoprotective efficacy of the deletion mutant were assessed using a mouse model. The results showed that gltA deletion did not affect the growth characteristics of the strain in nutrient-rich LB medium or nutrient-poor M9 minimal medium, but significantly reduced its motility and biofilm formation ability, inhibited the synthesis of core biofilm components Curli fimbriae and cellulose, and simultaneously markedly increased the susceptibility of the strain to 15 antimicrobial agents. Furthermore, the ΔgltA mutant exhibited significantly decreased tolerance to various extreme environments, including acidic, alkaline, oxidative stress, high temperature, and high osmolarity. Mouse infection studies revealed more than 10⁶-fold attenuated virulence in Kunming mice via intraperitoneal injection compared with the wild-type strain (wild-type LD₅₀ = 3.16 × 10³ CFU; no mortality was observed in mice challenged with 1 × 10⁹ CFU of the deletion mutant). The bacterial loads in the liver and spleen in vivo were significantly decreased, and the expression levels of 24 key virulence genes were comprehensively downregulated. Immunization and challenge experiments demonstrated that a single oral immunization with the ΔgltA mutant induced strong humoral and cellular immune responses in mice, providing 100% immunoprotection against lethal challenge with wild-type S. Enteritidis. This study demonstrates that gltA is a key functional gene regulating metabolic homeostasis, environmental adaptability, and pathogenicity in S. Enteritidis. The ΔgltA mutant displays displays promising immunoprotective efficacy, providing an ideal molecular target and candidate strain for the development of novel live attenuated vaccines against S. Enteritidis.

[Research advances of association between age at natural menopause and diabetes risk: evidence from prospective studies].

PubMed · 2025-08-10

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Abstract 4368327: Targeting PDE4B (Phosphodiesterase-4 Subtype B) alleviates sepsis-induced multiple organ dysfunction via inhibiting endothelial cells pyroptosis

Circulation · 2025-11-03

Introduction: Sepsis, a leading cause of mortality and critical illness globally, is a life-threatening condition due to dysregulated host immune response to infection, which may lead to multiple organ dysfunction. We previously reported that depletion of PDE4B, ameliorated myocardial ischemia-reperfusion injury, revealing a pivotal role of PDE4B in sterile inflammation. This study aimed to elucidate the role of PDE4B in sepsis. Approaches: PDE4B global knock-out (PDE4B -/- ), endothelial cell-specific (PDE4B EC-/- ) and myeloid cell-specific (PDE4B LYZ-/- ) PDE4B knock-out male mice and their littermate controls were induced to develop sepsis following cecal ligation and puncture (CLP) surgery. Animal survival was recorded for 7 days after CLP. Early pathological changes were assessed at 12h-post CLP by determining vascular permeability, echocardiography, plasma level of markers for liver and kidney injury (ALT, AST, CREA and BUN). Microcirculation was detected by laser Doppler flowmetry. Histology staining was performed on lung sections and lipopolysaccharide transfected isolated lung endothelial cells were used to delineate the mechanism of pyroptosis. Results: Deletion of PDE4B significantly improved the survival rate of septic mice (73% versus 31%). Meanwhile, PDE4B deletion markedly reduced organ injury, including reduced lung vascular permeability and myeloid cell infiltration, improved function of heart (LVEF: 40.2±6.0% versus 75.2±5.0%), liver and kidney, and increased hindlimb blood perfusion (48.46±9.08 versus 90.41±5.86). Strikingly, deficiency of endothelial cell (but not myeloid cell)-PDE4B protected against sepsis to an extent similar to global PDE4B knock-out (survival rate: PDE4B EC-/- 70% versus PDE4B LYZ-/- 30%). Mechanismly, sepsis induced extensive pyroptosis in lung tissue and PDE4B deletion essentially abolished the activation of gasdermin-D, the key executor of pyroptosis. Further in vitro study showed that PDE4B played a critical role in endothelial cells pyroptosis, in both transcription dependent and in-dependent manner. Conclusions: Endothelial cell PDE4B promotes pyroptosis, critically involving in sepsis induced multiple organ dysfunction. Selective inhibition of PDE4B represent a promising approch to sepsis treatment.

2127P Neoadjuvant low dose radiotherapy combined with tislelizumab and chemotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma (GAS-Jiangsu 01): A single-arm phase II trial

Annals of Oncology · 2025-09-01

MA10.03 Efficacy and Safety of Cadonilimab Plus Pulocimab in NSCLC Patients Who Progressed Following Prior Immunotherapy: A Phase 1b/2 Study

Journal of Thoracic Oncology · 2025-10-01

Bioreactor culture of Lessertia frutescens adventitious roots and their inhibitory effects on non-enzymatic glycation

Plant Cell Tissue and Organ Culture (PCTOC) · 2025-07-16

Molecular Landscape Remodeling Unravels the Cross-Links of Microplastics-Induced Lipidomic Fluctuations, Nutrient Disorders and Energy Disarrangements

Environment & Health · 2025-10-29 · 1 citations

Microplastics are emerging contaminants that pose health risks. They can cause hepatic lipid interventions, but the underlying mechanisms require investigation. This study assessed the retention of polypropylene microplastics in mouse liver and determined the intercorrelations between hepatic lipid fluctuations and transcriptomic changes. Microplastic-induced liver dysfunction was confirmed by the variations of transamination, cholesterol metabolism, biotransformation, and redox state. Chronic high-dose treatment induced distinct pathological changes, including regional fibrotic remodeling and ultrastructural mitochondrial abnormalities. Raman biospectra of liver slice proposed vital peaks of 1060, 1132, 1168, 1340, 1446, 1618, and 1670 cm–1, representing the liver biomolecule landscapes. Transcriptomic changes were mainly involved in mRNA transcription, multicellular organism development, various stimuli response, cell differentiation, and lipid metabolic process. Microplastic exposure dosage exerted more profound effects than exposure duration on gene expressions of oxidation–reduction process, signal transduction, and lipid metabolism. WGCNA analysis proposed 47 hub genes involved gene expression orchestration, cell fate monitor, and mitochondria translation modulation. Nine differentially expressed genes associated with lipid biomarkers were related to mitochondria transcription (Mrps12 and Mrpl53), cell differentiation (Bbc3, Lrrc15 and Gdf15), lipid catabolism (Etnppl and lipg) and tRNA methyltransferase (Trmt112), and Raman peak at 1670 cm–1 intimately connected with aggregated forms of protein. Our findings suggested that polypropylene microplastics could change the liver molecular landscape and induce lipid metabolism disorders and transcriptomic changes in mitochondrial protein translation and expression regulation, highlighting their significant consequences in nutrient and energy imbalance.

High cGAS-STING expression associates with improved efficacy of neoadjuvant chemo-immunotherapy in head and neck squamous cell carcinoma

Frontiers in Oncology · 2025-07-15

Purpose Neoadjuvant chemo-immunotherapy (NACI) has demonstrated significant clinical advantages in head and neck squamous cell carcinomas (HNSCC), while clinical responses vary in different patients. This study investigated the correlation between the cyclic GMP-AMP synthase (cGAS, CGAS ) and the stimulator of interferon genes (STING, STING1 ) expressions and the efficacy of NACI in HNSCC. Methods The correlation between CGAS and STING1 expressions and chemotherapy/immunotherapy drug sensitivity was analyzed using the GDSC and TCIA dataset. The study enrolled 38 HNSCC patients receiving NACI, with protein expressions of cGAS and STING evaluated via immunohistochemistry. The T cell abundance and tumor-T cell interactions in different CGAS and STING1 expression groups were analyzed using bulk RNA-seq and scRNA-seq data from open databases. Results The mRNA expressions of CGAS and STING1 were negatively correlated with the IC50 of docetaxel and positively correlated with the efficacy of anti-PD-1 treatment (p<0.05). In the real-world cohort, cGAS and STING expressions were both positively related to NACI efficacy (p<0.05). The mRNA expressions of CGAS and STING1 were positively correlated with the abundance of Act-CD4 ( CGAS : rho=0.416, p<2.21e-16; STING1 : rho=0.26, p=1.82e-09), Act-CD8 ( CGAS : rho=0.089, p=0.0425; STING1 : rho=0.303, p=1.98e-12), NKT cell ( CGAS : rho=0.255, p=0.3.78e-09; STING1 : rho=0.375, p=2.2e-6). Tumor cells with increased expression of CGAS or STING1 showed enhanced interactions with T cells. Conclusion This study confirms the positive correlation between cGAS and STING expressions and NACI efficacy, suggesting their role in immune activation and potential as biomarkers for predicting NACI efficacy in HNSCC.