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PubMed2026

Direct background subtraction LC-MS/MS assay for human plasma progesterone: Full validation and comparative application.

OBJECTIVE: To develop and validate a liquid chromatography-tandem mass spectrometry method based on direct background subtraction for the quantification of endogenous progesterone in human plasma. METHODS: Protein precipitation was used for sample preparation with deuterated progesterone as the internal standard. Chromatographic separation was performed on an ACQUITY C18 column using gradient elution with 0.1% formic acid in water and acetonitrile at a flow rate of 0.3 mL/min. Mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Instead of using analyte-stripped matrix or surrogate matrix, authentic plasma was directly used for all validation experiments. Quantitation was achieved by subtracting the background signal, and results were compared with those from the classical method using stripped matrix. RESULTS: Excellent linearity was achieved over 0.1-100 ng/mL (R2 ≥ 0.99). Precision, accuracy, recovery, matrix effect, and stability all met FDA and ICH M10 acceptance criteria. Compared with the classical method, the bias in Cmax and AUC0-t was within ±15%, indicating no significant difference between the two methods. CONCLUSION: The direct background subtraction method avoids laborious preparation of blank matrix, eliminates matrix effect discrepancies, and is simple, efficient, and low-cost. It can serve as a general strategy for endogenous substance determination.

Humans↗

PubMed2026

Forensic taphonomy in fluvial water: A systematic review.

Human remains are frequently recovered from fluvial (lotic) water environments. Rivers, streams, canals and other flowing water bodies pose distinct challenges in forensic practice, particularly due to their current. Compared to other aquatic contexts, fluviatile taphonomy is underrepresented in the forensic literature and the last comprehensive summary was written over a decade ago. Therefore, a systematic review was performed to collect and summarise the current knowledge in forensics about fluvial taphonomy, including decomposition of remains, transport characteristics, search, postmortem submersion interval (PMSI) estimation, taphonomic alterations, and differences to other water bodies. 92 reports met the inclusion criteria for this review, most of them showed a moderate risk of bias. Their main findings were summarised and two major challenges identified. First, predictions about fluvial transport of human bodies pose a tremendous issue in forensic practice, leading to later detection and lower recovery rate of remains, complicating various subsequent analyses. Second, PMSI estimations are difficult particularly due to variable environmental conditions in fluviatile systems. Recommendations for future research in the area of fluvial forensic taphonomy include that case-related data such as the detailed decomposition state and river characteristics need to be made available. More standardised research protocols are required for a facilitated comparison between studies, environments and regions. This review provides forensic practitioners with a comprehensive, updated resource for the investigation of fluvial remains. It also guides future research towards a more efficient practice to build the basis for a broader, more robust and comprehensive synthesis, subsequently supporting analyses in forensic casework.

Humans↗

PubMed2026

Comprehensive identification and evolutionary analysis of the Wnt gene family in bivalves: Insights into the larval development of the noble scallop Chlamys nobilis.

The Wnt gene family regulates fundamental developmental processes in metazoans, but its evolutionary composition and developmental deployment in bivalves remain largely unresolved. Here, we performed a comparative genomic analysis of Wnt genes in 19 bivalve species and examined developmental expression profiles in the noble scallop Chlamys nobilis, with Crassostrea gigas and Chlamys farreri used for cross-species comparison. A total of 235 Wnt genes were identified and assigned to 12 subfamilies. No reliable Wnt3 ortholog was detected in any analyzed bivalve, supporting the view that Wnt3 loss occurred early during lophotrochozoan evolution rather than representing a lineage-specific absence. Most Wnt proteins retained the conserved WNT domain, indicating strong structural conservation, whereas lineage-specific copy-number variation and gene loss were observed among species. C. farreri and C. gigas each retained 12 Wnt genes and lacked Wnt3, whereas C. nobilis lacked Wnt3, Wnt7, and Wnt16. Developmental transcriptome analysis and RT-qPCR revealed clear stage-specific expression patterns. In C. gigas, Wnt2/10/A were highly expressed during earlydevelopment and peaked around the D-shaped larval stage, while Wnt8 and Wnt11 showed distinct stage-specific peaks. By contrast, Wnt1/5/6/9 were more active during later larval development or juvenile formation. These results provide a comparative framework for bivalve Wnt evolution and identify candidate Wnt genes potentially involved in larval development and aquaculture-relevant developmental transitions.

Animals↗

PubMed2026

Pharmacokinetic Differences Between Fast-Acting, Standard, and Placebo Cannabis Edibles.

INTRODUCTION: Edibles have become the second-most used cannabis product in legal U.S. states, wherein 64% of cannabis consumers reported using edibles within the past year. Among expansions to the legal cannabis industry are the newly marketed "fast-acting" edible compounds, which may address many of the issues associated with edible use related to overdose and dose management. The study hypotheses were that fast-acting edibles would reach peak concentration significantly faster than standard edibles and placebo edibles. MATERIALS AND METHODS: Twenty participants completed three arms within-subjects designed study to test hypotheses. The three arms were ingestion of a (1) fast-acting edible, (2) a standard edible, and (3) a Δ9-tetrahydrocannabinol (THC) terpene-derived placebo edible that was indistinguishable from the two THC-containing edibles. Blood plasma was analyzed for the presence of THC and THC analytes. The pharmacokinetic parameters tested were time to max concentration (Tmax), maximum concentration (Cmax), terminal half-life (t1/2), and area under the curve (AUC). RESULTS: Results supported study hypotheses in that Tmax was significantly faster for the fast-acting edible, observed 30 min post-ingestion and, on average, 30 min earlier than the Tmax for the standard edible. There were no significant differences between the fast-acting and standard edibles on Cmax, t1/2, and AUC; however, both the fast-acting and standard edibles were significantly different compared with the placebo across all pharmacokinetic parameters. DISCUSSION: The results indicate that the microencapsulation technology used to create the fast-acting edible enabled analyte concentrations to peak significantly faster compared to the standard and placebo edibles.

Humans↗

PubMed2026

Methyltransferase 3 promotes v-set and transmembrane domain-containing 2-like protein expression to intensify ferroptosis-mediated prostate adenocarcinoma progression through the m6A methylation modification.

BACKGROUND: Prostate adenocarcinoma (PRAD) is a common malignancy with high incidence in men. The role of v-set and transmembrane domain-containing 2-like protein (VSTM2L) in PRAD remains largely unreported. METHODS: Gene expression was analyzed using The Cancer Genome Atlas (TCGA), the Tumor Immune Estimation Resource (TIMER) 2.0, and the University of Alabama at Birmingham CANcer data analysis Portal (UALCAN) databases, and validated by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining. Apoptosis and mitochondrial membrane potential were examined by flow cytometry. Intracellular iron, Fe2+, and reactive oxygen species (ROS) levels were measured using commercial kits and flow cytometry. The role of VSTM2L in tumor growth was evaluated using xenograft mouse models, with protein expression in tumors evaluated by immunohistochemistry (IHC). The N6-methyladenosine (m6A) modification sites on VSTM2L mRNA were predicted using the sequence-based RNA adenosine methylation site predictor (SRAMP) website. The interaction between methyltransferase 3 (METTL3) and VSTM2L was confirmed by methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assay. Correlation analysis was performed using the TCGA database. RESULTS: VSTM2L was overexpressed in PRAD tissues and cell lines. Silencing VSTM2L inhibited PRAD cell proliferation, promoted apoptosis, and enhanced ferroptosis and oxidative stress in vitro. Consistently, VSTM2L knockdown suppressed tumor growth in vivo. Mechanically, METTL3 mediated m6A methylation to stabilize VSTM2L mRNA. Furthermore, METTL3 promoted proliferation and inhibited apoptosis, ferroptosis, and oxidative stress in PRAD cells via a VSTM2L-dependent manner. CONCLUSION: METTL3 promotes PRAD progression by stabilizing VSTM2L expression through m6A methylation, thereby inhibiting ferroptosis. This study establishes a direct link between RNA methylation and ferroptosis in PRAD, revealing the METTL3/VSTM2L axis as a novel regulatory pathway and a potential therapeutic target.

Male↗

PubMed2026

Ribosome stalling position, spacing, and A-site occupancy impact translation and cotranslational mRNA decay in plants.

Ribosomes can pause during mRNA translation, but what causes pausing, how pauses affect protein production, and whether they trigger cotranslational mRNA decay are poorly understood in plants. Here, we investigate the causes and consequences of ribosome pausing in Arabidopsis and maize. This is accomplished by sizing, mapping, and quantifying footprints of individual ribosomes (monosomes) and closely spaced ribosome pairs (disomes) at single-codon resolution on open reading frames (ORFs). Ribosome footprinting was combined with 5'P-degradome-seq to examine the coincidence of pausing with cotranslational decay under control conditions and brief hypoxia in Arabidopsis. The data resolve two monosome conformations and three disome configurations. These include monosomes with a vacant or occupied A-site and disomes that have collided or are separated by one or two codons. Pausing is prevalent at initiation, termination, and di-Proline codons. Di-Proline pauses do not trigger cotranslational decay but appear important in cotranslational protein processing. Brief hypoxia induces stalling of A-site vacant ribosomes at Aspartate codons, often coinciding with 5'P peaks, indicating that rate-limiting decoding can trigger cotranslational mRNA decay. Notably, actively transcribed and translated hypoxia-response mRNAs accumulate 1- to 2-codon-separated disomes and are actively degraded. Comparative analysis of footprints in the two species reveals ribosome conformations and codon-specific pausing can be conserved or lineage-specific, as exemplified by pausing at di-Prolines and on Conserved Peptide upstream ORFs. In sum, the stalling of ribosomes at specific codons, coupled with ribosome A-site occupancy and disome spacing, modulates protein production and cotranslational mRNA decay in plants.

Ribosomes↗

PubMed2026

Genome-Wide Characterization of β-Glucosidase (TaBGLU) Genes in Bread Wheat and Their Expression Under Drought, Cold, and Combined Stress.

Glycoside hydrolase 1 (GH1) β-glucosidases were known to activate hormone conjugates and defense metabolites, yet their genomic organization and stress-response dynamics in wheat remained incompletely defined. We therefore performed an integrated characterization of TaBGLUs spanning phylogeny, gene structure and conserved motifs, subcellular localization, promoter cis-elements, Gene Ontology enrichment, protein-protein interaction networks, and targeted expression profiling. Wheat TaBGLUs partitioned into well-supported clades that shared canonical GH1 catalytic residues and a largely conserved motif scaffold. Subcellular localization predictions indicated predominant nuclear and chloroplast targeting, with a smaller cohort directed to secretory or endomembrane compartments. Promoters were enriched for light-responsive, hormone-related (ABA, JA/SA, auxin, GA) and stress-associated (MYB/WRKY, heat, low temperature) cis-elements, and functional annotations were consistent with roles in carbohydrate and cell-wall metabolism, hormone homeostasis, and defense. Network analysis revealed a densely connected TaBGLU submodule embedded within broader carbohydrate and defense interaction networks, suggesting coordinated or cooperative functions. Expression profiling under cold, drought, and combined drought and cold demonstrated broad stress inducibility, with early activation detected by 6 h, cold-responsive maxima typically at 12 h, drought-responsive peaks predominating at 24 h, and combined stress eliciting both earlier and more sustained expression maxima between 12-24 h. Representative strongly responsive genes included TaBGLU20, TaBGLU44, TaBGLU6, and TaBGLU23, which showed pronounced late induction under combined stress, TaBGLU30, which exhibited an earlier combined-stress peak, and TaBGLU12, which displayed a marked late drought-specific response. Taken together, this integrated genomic, regulatory, and expression atlas refined the wheat BGLU repertoire relative to previous gene model inventories, highlighted candidate TaBGLUs with central network positions and strong stress inducibility, and provided concrete entry points for functional validation and breeding for improved stress resilience.

Triticum↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Transforming Curcuma longa leaf waste into cellulose scaffolds.

The constant dearth of transplantable tissues and organs in India required the development of substitute biomaterials for tissue engineering. Plant-based decellularized scaffolds have become attractive options because of their abundance, ethical acceptability, architectural diversity, and lower risks of zoonotic transmission. Curcuma longa leaves were investigated in this study as a possible source of cellulose-based scaffolding for use in biomedical applications. After cuticle removal, an immersion decellularization technique utilizing sodium dodecyl sulphate (SDS) and triton-X-100 was developed to successfully remove cellular and nuclear material while maintaining leaf parenchyma architecture. Histology, DAPI staining, scanning electron microscopy, and a notable decrease in leftover DNA content all demonstrated efficient decellularization. When contrasted with native leaves, the resultant decellularized C. longa leaf scaffolds showed significant increase in porosity, water vapor transmission rate and swelling percent, and significantly lower contact angle with an optimum surface roughness promoting cell adhesion. Mechanical test manifest higher tensile strength with decreased stiffness. Fourier transform infrared spectra of leaf scaffold reveals persistence of different components except cuticle but the intensity of different peaks was decreased. The leaf scaffolds showed superior hemocompatibility and excellent compatibility with Madin-Darby canine kidney cells (MDCK) which is demonstrated by cell attachment and proliferation. MTT assay of seeded scaffold showed significantly higher metabolically active cell. In vivo subcutaneous implantation of decellularized scaffolds showed host tissue incorporation, accumulation of collagen, and neovascularization. C. longa leaf scaffolds can be utilized as cost effective and sustainable biomaterials for soft tissue engineering and regenerative medicine.

Curcuma↗

PubMed2026

Evolution of Candidaemia and azole resistance in Italy: A multicentre retrospective study.

PURPOSE: Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. METHODS: This retrospective multicentre study (2015-2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. RESULTS: 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020-2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4%), followed by C. parapsilosis (24.7%), C. glabrata (11.8%), and C. tropicalis (11.4%). Echinocandin resistance remained low (< 2% for C. albicans and C. glabrata), whereas azole resistance increased markedly, particularly in C. parapsilosis, reaching fluconazole resistance rates of 25.6% in 2022. CONCLUSIONS: Candidaemia increased during the 9-year study period in Italy, particularly in the COVID-19 pandemic, in medical wards and ICU. Emerged a growing azole resistance, underscoring the need for enhanced surveillance and informed empirical treatment strategies.

Candida species etiology↗

PubMed2026

Assessment of Genetic Diversity and Population Structure on Azadirachta indica A. Juss. in an Urban Metropolitan: Ahmedabad, India.

Azadirachta indica (A. indica) A. Juss., commonly known as Neem, is a valuable multipurpose tree with profound medicinal properties and socioeconomic importance, widely recognized since ancient Ayurvedic times. Despite its prominence, knowledge about its genetic diversity within the metropolitan area of Ahmedabad is limited. This study marks the first in-depth exploration of the genetic diversity and population structure of A. indica in Ahmedabad. The authenticity of the species was validated through DNA barcoding, and a Geographical Information System (GIS) was used to collect the samples. A total of 35 A. indica accessions were analyzed using five Inter Simple Sequence Repeat (ISSR) primers. Genetic diversity and population structure were evaluated using Inter Simple Sequence Repeat (ISSR) markers through polymorphism assessment, clustering, ordination, and Bayesian population structure analyses. ISSRs revealed a high level of polymorphism (75.66%), indicating substantial genetic variability among accessions. An analysis of genetic diversity indices revealed low to moderate diversity (Hs = 0.14, Ht = 0.217, I = 0.217). Analysis of Molecular Variance (AMOVA) analysis depicted 81% variation within the population and 19% among the population. Low to moderate genetic differentiation (Gst = 0.319) and moderate gene flow (Nm = 1.06) indicated that urban development has not hindered gene flow among populations. Mantel's test revealed a weak but significant correlation between genetic and geographic distances, suggesting limited isolation by distance. The estimated ΔK using STRUCTURE exhibited two subpopulations, representing two gene pools for A. indica accessions (K = 2). Collectively, these patterns indicate that urbanization has not severely disrupted genetic connectivity in A. indica, reflecting its resilience and adaptive potential in a metropolitan environment. These findings provide pivotal knowledge for further understanding the genetic diversity and population structure of A. indica in one of the fastest-growing cities in India, which can be utilized for new breeding programmes, sustainable development and future conservation strategies around the globe.

India↗

PubMed2026

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt‑tolerant rootstock for pear, but its salt‑tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co‑expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss‑of‑function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival‑first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker‑assisted breeding of salt‑tolerant pear cultivars.

Salt Stress↗

PubMed2026

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals↗

PubMed2026

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans↗

PubMed2026

Autodissemination stations suppress Aedes notoscriptus mosquitoes and reduce Buruli ulcer risk in urban Australia: a randomized controlled field trial.

Aedes notoscriptus are mosquito vectors implicated in transmission of Mycobacterium ulcerans. This bacterium causes a destructive infection of skin and soft tissue called Buruli ulcer. Here we ran a randomized controlled trial in an urban Buruli ulcer endemic area in Melbourne, Australia to test whether autodissemination mosquito control stations, containing pyriproxyfen (larvicide) and Beauveria bassiana (entomopathogenic fungus), suppress Ae. notoscriptus populations. Six geographic areas each received 100 autodissemination stations for 8 weeks, and six control areas received no stations between 25 January 2024 and 21 March 2024. The primary outcome measure was mosquito population numbers. After the trial, there was a 70% average reduction in mosquito egg counts among the six intervention areas compared to control areas (P = 0.0076). In an ad hoc analysis, we then explored human Buruli ulcer notifications in treatment and control areas. After accounting for the 4.8-month mean incubation period, there was an 83% reduction in infection likelihood coinciding with peak intervention effect (intervention zones 1 case, control zones 6 cases, incidence ratio rate 0.167, 95% CI 0.0026-1.054, P = 0.047). The effect was not observed during the same time period in the year previous or following 2024, when no interventions were undertaken. A strong correlation (R2 = 0.85) was observed between decreased disease risk and mosquito suppression. These data show that autodissemination traps can effectively lower urban mosquito populations and reduce the threat of Buruli ulcer in humans.

Animals↗

PubMed2026

Effects of free-weight resistance training based on hexagonal barbell deadlift in older women: A 24-week randomized controlled trial.

PURPOSE: This randomized controlled trial examined effects of a 24-week hexagonal barbell deadlift (HBDL)-based free-weight resistance training program on body composition, trunk muscle function, and functional performance in older women. METHODS: Thirty-two women (67.6 ± 6.3 years) were randomly assigned to an HBDL group (DG, n = 16) or control group (CG, n = 16). DG trained twice weekly for 24 weeks under supervision. Primary outcomes were body composition and isokinetic trunk peak torque and average power at 60°/s and 120°/s. Secondary outcomes were isokinetic knee function, mobility, and maximal isotonic strength. Between-group differences after the intervention were examined by analysis of covariance (α = 0.05). RESULTS: After intervention, DG showed greater trunk lean mass (+0.4 kg vs. -0.2 kg, p = 0.006) than CG, and reductions in body fat percentage (-1.4% vs. +0.3%, p = 0.003), total fat mass (-1.1 kg vs. +0.3 kg, p = 0.013), and regional fat mass (trunk, gluteal, thigh; all p < 0.05). Trunk extensor peak torque at 60°/s (+26.0% vs. -6.3%, p < 0.001) and average power at 60°/s (+38.1% vs. -7.6%, p < 0.001) and 120°/s (+33.2% vs. +0.1%, p = 0.002) improved significantly. DG also showed better eyes-closed static balance and 6-min walk performance (both p < 0.05). Whole-body lean mass and lower-limb isokinetic strength did not differ between groups. Attendance was 89.6% with no adverse events. CONCLUSION: HBDL-based free-weight resistance training is a safe, feasible, and effective strategy to improve body composition, trunk extensor function, and mobility in older women.

Humans↗

PubMed2026

A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.

PURPOSE: Survival for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains low with <20% immunotherapy response. Metformin increases tumor-infiltrating CD8+ T and natural killer (NK) cells, which harbor PD-1. In this phase II clinical trial (NCT04414540), we combined metformin and pembrolizumab to evaluate the overall response rate (ORR) in R/M HNSCC and assess NK-cell activity. PATIENTS AND METHODS: Eligible patients were randomized 1:1 into two arms: (i) metformin extended-release (ER) dose escalation to 2,000 mg over 14 days followed by combination with pembrolizumab 200 mg every 3 weeks or (ii) pembrolizumab 200 mg every 3 weeks followed by combination with metformin ER 2,000 mg daily. The primary endpoint was ORR per RECIST 1.1. Nineteen evaluable patients were planned to estimate the proportion of approximately 32% ORR. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0. The distribution, activation, and cytotoxic function of NK cells were analyzed via flow cytometry. RESULTS: Twenty-one patients were enrolled; 76% were male, 52% were smokers, and the median age was 64 years. Ten patients had oropharyngeal tumors, of which nine were p16+. Eighteen patients were evaluable for response, including four complete and five partial responses for an ORR of 50% [95% confidence interval (29-71)]. Combination therapy was well tolerated with no unexpected adverse events (AE). Five grade 3 AEs occurred: nausea, diarrhea, fatigue, and weight loss. Metformin led to increased peripheral NK-cell maturation and cytotoxic ability. CONCLUSIONS: The combination of metformin and pembrolizumab was well tolerated with mild gastrointestinal AEs and promising activity, warranting further investigation in a randomized trial.

Humans↗

PubMed2026

Optimizing physical activity bouts to interrupt sedentary behaviour for cardiometabolic health: a systematic review and meta-analyses of randomized controlled trials.

AIMS: Chronic diseases such as type 2 diabetes mellitus and cardiovascular diseases are leading causes of mortality worldwide, with sedentary behaviour (SB) and physical inactivity recognized as major interrelated risk factors. Prolonged SB, particularly when combined with insufficient physical activity, adversely affects cardiometabolic health. This systematic review aimed to evaluate which characteristics of physical activity (PA) bouts, in terms of frequency, duration, and intensity, are associated with improvements in cardiometabolic outcomes. METHODS AND RESULTS: Studies assessing physical activity interventions compared with sedentary control conditions were included. Eligible studies involved adults aged 18-65 years, with or without cardiometabolic conditions. PubMed, Cochrane Central, Embase, and Web of Science were searched to February 2025. Random-effects models were used to calculate pooled standardized mean differences (SMD) with 95% confidence interval (CI). Subgroup and meta-regression analyses explored potential moderators. A total of 144 studies (247 intervention arms; 2216 participants) were included. Frequent PA bouts reduced blood glucose [SMD -0.22 (95% CI -0.27 to -0.16)]. Longer and/or more intense PA bouts decreased triglycerides [SMD -0.27 (-0.34 to -0.19)], with significant duration × intensity interactions for glucose (P = 0.032) and triglycerides (P < 0.001). Moderate-to-vigorous PA bouts improved endothelial function [flow-mediated dilation SMD 0.88 (0.47-2.24); shear rate SMD 0.54 (0.31-0.78)]. PA bouts also lowered insulin [SMD -0.26 (-0.32 to -0.19)], systolic BP [SMD -0.29 (-0.39 to -0.19)], and diastolic BP [SMD -0.16 (-0.26 to -0.05)]. CONCLUSION: In acute experimental settings, glucose regulation appears to benefit more from frequent PA bouts, while triglyceride responses are more closely related to greater duration and/or intensity. Blood pressure shows favourable acute responses across PA types, whereas higher PA intensity is associated with improved endothelial function. Tailoring strategies to interrupt SB with PA bouts may help inform approaches to improve cardiometabolic health.

Humans↗