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PubMed2026

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral® and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

Humans↗

PubMed2026

Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa causing infections in patients hospitalized in hematology, oncology, and transplant units from United States medical centres (2019-2024).

Immunosuppression increases the risks and severity of infections and is associated with a higher incidence of infection with multidrug-resistant (MDR) pathogens. We evaluated the antimicrobial susceptibility of Enterobacterales and Pseudomonas aeruginosa from patients hospitalized in hospital units where the frequency of immunosuppressed patients is very high. Bacterial isolates were consecutively collected (1/patient) from 75 US medical centres in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales (n = 2,407) and P. aeruginosa (n = 485) from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE) were screened for β-lactamases by whole genome sequencing. Enterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (19.9%) and P. aeruginosa were mainly from BSI (37.9%) and pneumonia (35.0%). Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against Enterobacterales (99.9-99.4% susceptible), including MDR isolates (99.6-98.1% susceptible), but only aztreonam-avibactam exhibited good activity against CRE (95.8% susceptible). Ceftolozane-tazobactam showed good activity against Escherichia coli (95.7% S) and Klebsiella pneumoniae (92.8% S), but limited activity against Enterobacter cloacae species complex (75.9% susceptible). All (100.0%) carbapenemase (CBase)-producing CRE isolates were aztreonam-avibactam-susceptible while 77.4% were ceftazidime-avibactam-susceptible and 67.7% were meropenem-vaborbactam-susceptible. The most common CBases were KPC (41.7%), NDM (12.5%), and OXA-48 types (10.4%). Metallo-β-lactamases represented 23.5% of CBases and were identified in 16.7% of CREs. The most active agents against P. aeruginosa were ceftazidime-avibactam (95.7% susceptible), ceftolozane-tazobactam (94.8% susceptible), and tobramycin (91.5% susceptible). Piperacillin-tazobactam and meropenem were active against 81.4% and 82.5% of P. aeruginosa, respectively, and aztreonam-avibactam inhibited 78.6% of P. aeruginosa at ≤8 mg/L.

Humans↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗

PubMed2026

Immunogenicity and safety of prophylactic HPV vaccines in people living with HIV: A systematic review and meta-analysis.

Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N = 1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian-Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9-99.1%; I2 = 89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1-97.7%; I2 = 95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7-98.6%; I2 = 66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5-99.1%; I2 = 95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4 > 350 cells/μL vs. 71.1% in those with CD4 ≤ 200 cells/μL (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.

Humans↗

PubMed2026

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans↗

PubMed2026

IgA Vasculitis with necrotizing arteritis: a multicenter retrospective study from the French Vasculitis Study Group and systematic review of the literature.

IgA vasculitis (IgAV) primarily affects small vessels, but rare cases with necrotizing arteritis (NA) raise questions about overlap with polyarteritis nodosa (PAN). To characterize IgAV with necrotizing arteritis (IgAV-NA) and compare its phenotype with classical IgAV and PAN. We performed a multicenter retrospective study combined with a systematic literature review (1990-2025). Patients fulfilled EULAR/PRINTO/PRES IgAV criteria, had pathological or imaging evidence of NA in small or medium arteries, and were ANCA-negative. Thirty patients were included (7 from databases, 23 from the literature). NA was confirmed by biopsy (n = 16) or vascular imaging (n = 14). Clinical features, treatments, remission, and mortality were compared with 257 adult IgAV and 196 PAN patients. Median age was 54.5 years. IgAV-NA was characterized by severe manifestations, including gastrointestinal bleeding, perforation, surgical abdomen, neuropathy, pancreatitis, and livedo. Compared with classical IgAV, IgAV-NA showed significantly higher rates of multi-organ involvement and mortality. Compared with PAN, IgAV-NA shared vascular complications but had less fever and neuropathy. Despite arterial involvement, patients did not fulfil PAN criteria. IgAV-NA represents a rare, severe IgAV phenotype with life-threatening complications rather than an IgAV-PAN overlap. Severe or atypical IgAV presentations should prompt vascular imaging and intensified immunosuppression.

Humans↗

PubMed2026

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans↗

PubMed2026

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans↗

PubMed2026

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96 h-LC50 of the agent was determined to be 0.81 mg/L, and exposure to 1.68 mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗

PubMed2026

Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans↗

PubMed2026

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8 Da), and herbicolin B (1138 Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5 mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5 mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea↗

PubMed2026

Cationic porphyrin covalent organic framework reinforced hydroxypropyl methylcellulose films for photodynamic-photothermal sterilization and food preservation.

Microbial contamination in food necessitates effective antimicrobial packaging. While cellulose-based packaging materials suffer from limited antimicrobial efficacy, lack of active functionality, and susceptibility to inducing microbial resistance. To address these challenges, this study synthesized a cationic porphyrin-based covalent organic framework (Por-ICOF) as a multimodal photosensitizer. Por-ICOF was uniformly dispersed via non-covalent interaction within hydroxypropyl methylcellulose (HPMC), creating an HPMC/Por-ICOF composite film. This integration enhanced mechanical strength (increased by 26%), hydrophobicity (WCA 71°), and gas barrier properties (OP reduced by 42%, WVP reduced by 36%). Under visible light, the HPMC/Por ICOF film superior absorption generated reactive oxygen species (ROS) and photothermal effects, inactivating 99.2% of Escherichia coli and 99.95% of Staphylococcus aureus within 20 min. The composite film exhibited excellent biocompatibility and effectively extended the shelf life of strawberries. This cationic modification strategy for cellulose-based films offers a novel avenue for the design of high-performance antimicrobial food packaging materials.

Food Preservation↗

PubMed2025

Impact of stromal maturity and proportion on prognosis and immune landscape in colorectal cancer.

BACKGROUND: Tumour microenvironment and cancer cells have constant interaction affecting cancer progression. Tumour-stroma ratio (TSR) in the tumour centre and desmoplastic reaction (DR) classification at the invasive margin are prognostic factors based on stroma evaluation on H&E slides. However, their combined value and immunological associations remain poorly defined. This study examines the prognostic and immunological value of TSR, DR, and their combination in two large colorectal cancer cohorts. METHODS: Two colorectal cancer cohorts (N = 1,876) were analyzed. We introduced a three-tiered Stromal Maturity and Proportion Score (SMAPS) based on the presence of high (>50%) TSR and myxoid stroma (immature DR classification). Alcian blue staining was used to further quantify myxoid stroma. Multiplex immunohistochemistry combined with digital image analyses, was utilized to study immune cell densities associated with SMAPS, TSR, DR, and Alcian blue intensity. RESULTS: In the study cohort (N = 1,100), SMAPS was a stronger predictor of cancer-specific mortality [HR for high (vs. low) SMAPS 2.01 (95% CI 1.47-2.75), p < 0.0001] compared to TSR [HR for stroma-high (vs. stroma-low) 1.49 (95% CI 1.15-1.93), p = 0.003] and DR classification [HR for immature (vs. mature) 1.84 (95% CI 1.39-2.45), p < 0.0001]. High SMAPS, stroma-high TSR, and immature DR correlated with lower densities of CD3+ T cells, B cells, M1-like macrophages, CD66B+ granulocytes, and mast cells. Alcian blue staining was associated with immature DR and corresponding immune cells. The validation cohort (N = 776) confirmed the association of SMAPS with survival and T cell densities. CONCLUSIONS: TSR and DR are independent prognostic factors for cancer-specific survival. SMAPS is a promising prognostic tool that integrates stromal maturity at the invasive margin and stromal proportion in the tumour centre. SMAPS has stronger prognostic value compared to TSR and DR classifications alone. A high stromal proportion and myxoid content are associated with an immunosuppressive microenvironment characterized by lower densities of antitumourigenic immune cells.

Humans↗

PubMed2026

Integrated assessment of biocontrol potential and genome analysis of endophytic Bacillus velezensis MGL-B1 against mango stem-end rot.

Mango stem-end rot is a globally significant postharvest disease that severely threatens the mango industry, primarily caused by Botryosphaeria dothidea. However, information on biocontrol agents targeting this pathogen in mango remains limited. In this study, we isolated and identified a strain of Bacillus velezensis MGL-B1 from mango leaf tissues for the first time, which exhibited broad-spectrum antifungal activity. Both in vitro and in vivo assays demonstrated that MGL-B1 effectively inhibited the growth of B. dothidea, with an in vivo biocontrol efficacy reaching 83.72 ± 5.10%, comparable to that of the commonly used chemical fungicide thiabendazole. Further mechanistic analysis revealed that MGL-B1 acts by directly disrupting the integrity of the pathogen's mycelial cell membrane. In addition, its released volatile organic compounds (VOCs) also displayed significant antifungal activity, with components such as 2-nonanone, 2-nonanol, and phenylethyl alcohol being confirmed to exert antifungal effects in in vitro fumigation assays. qPCR analysis showed that MGL-B1 treatment significantly upregulated the transcriptional levels of genes involved in plant-pathogen interaction, phenylpropanoid biosynthesis, and antioxidant defense pathways in mango fruits, with upregulation folds of 16.32, 37.19, and 75.93, respectively; meanwhile, the expression of browning-related genes such as polyphenol oxidase (PPO) was markedly suppressed. Whole-genome sequencing further revealed 14 biosynthetic gene clusters for antimicrobial compounds, including five unknown gene clusters. Collectively, B. velezensis MGL-B1 represents a promising biocandidate strain with multiple antifungal mechanisms and excellent control efficacy, providing a valuable resource for green and sustainable management of mango diseases.

Mangifera↗

PubMed2026

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗

PubMed2026

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50 mg/day) or metformin (1000 mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL∶HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD = 0.61 (0.02 to 1.21), p = 0.04; metformin: MD = 0.45 (0.07 to 0.83), p = 0.02], with no significant between-group difference in unadjusted analysis (p = 0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (β = -0.324, p = 0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (β = -1.209, p = 0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Humans↗