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PubMed2026

Marginal fit and five-year outcomes of posterior monolithic zirconia restorations: A randomized paired and observational clinical study.

OBJECTIVES: The aim of this study was to evaluate the marginal fit and five-year clinical performance of posterior 5 mol% yttria-partially stabilized zirconia restorations. A randomized paired comparison with lithium disilicate crowns was performed for marginal fit. METHODS: A total of 65 posterior restorations were placed in 38 patients, including 32 zirconia crowns, 17 lithium disilicate crowns, and 16 zirconia partial coverage restorations. In the randomized paired comparison, 17 patients received one lithium disilicate crown and one zirconia crown. Additional zirconia crowns (n=15) and zirconia partial coverage restorations (n=16) were included in a prospective observational cohort. The primary outcome was marginal fit within the randomized cohort. Marginal and internal fit were assessed using the replica technique. Marginal and internal gap values were compared using the Wilcoxon signed-rank test; clinical outcomes were analyzed descriptively, and Kaplan-Meier estimates were calculated for survival and complication-free survival. Clinical performance was assessed using CDA criteria, periodontal parameters, complication recording, and patient-reported outcomes. Clinical examinations were performed at baseline and at 12, 24, 36, 48, and 60 months. RESULTS: Mean marginal gap values at the crown margin were 46 ±33 µm for lithium disilicate crowns and 50 ±32 µm for zirconia crowns (p>0.05). No restoration required replacement, resulting in 100% restoration survival after a median follow-up of 60 months (range: 57-64 months). Most complications were biological or functional, including endodontic, periodontal, occlusal, and proximal-contact-related events. One zirconia partial coverage restoration exhibited a small ceramic fracture managed by polishing. The Kaplan-Meier probability of complication-free survival was 76.4% for zirconia crowns, 66.7% for lithium disilicate crowns, and 87.5% for zirconia partial coverage restorations. CONCLUSIONS: In the randomized paired comparison, 5 mol% yttria-partially stabilized zirconia crowns showed marginal gap values similar to lithium disilicate crowns. All restorations remained in situ during the observation period. Lower complication-free survival was mainly related to biological and functional events and should be interpreted separately from restoration survival. CLINICAL SIGNIFICANCE: Clinical evidence for posterior 5 mol% yttria-partially stabilized zirconia restorations remains limited. This study provides mid-term clinical data on crowns and partial coverage restorations. In the randomized full-crown comparison, marginal fit was similar to that of lithium disilicate crowns, supporting the clinical consideration of monolithic zirconia restorations for posterior teeth.

Humans↗

PubMed2026

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3 mg g-1 for myricetin and 112.1 mg g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08 mg g-1, respectively. Moreover, the affinity constants (KL = 0.760-0.950 L mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59 ng mL-1 and limits of quantification (LOQs) of 1.10-1.96 ng mL-1, and excellent linearity over the concentration range of 5.0-5500 ng mL-1 (R2 > 0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids↗

PubMed2026

A horizontally acquired gene mediates insect cocoon pigmentation in the eri silkmoth, Samia ricini.

Holometabolous insects make cocoons during larval-pupal metamorphosis to protect the pupal phase. The materials used for cocoon construction vary widely. Lepidopteran insects typically secrete silk to form cocoons, which display diverse colors. The eri silkworm, Samia cynthia ricini, is an economically important domesticated species that mostly produces white cocoons, with some varieties producing red cocoons. The enzyme kynureninase (KYNU), acquired from bacteria by horizontal gene transfer, has previously been implicated in insect coloration, while the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been identified as a red pigment. However, exactly how KYNU is involved in cocoon pigmentation remains unclear. Here, we report that a horizontally transferred bacterial gene encoding KYNU regulates red cocoon formation. Metabolomic analysis revealed a high accumulation of 3-HAA in red cocoons, confirming its role as the primary pigment and associating the coloration with tryptophan metabolism. Quantitative real-time polymerase chain reaction (qPCR) analysis indicated that SrKYNU is highly expressed in the silk glands and significantly downregulated in the red cocoon strain compared to the white cocoon strain. Genomic sequencing identified a 141 bp deletion in the upstream regulatory region of KYNU in the red cocoon strain compared to the white cocoon strain. Dual-luciferase assays confirmed that this deletion significantly reduced promoter activity. CRISPR/Cas9 knockout of SrKYNU in the white-cocoon strain resulted in mutants producing red cocoons with elevated 3-HAA content. These findings reveal that the horizontally transferred gene SrKYNU exhibits tissue-specific expression and regulates cocoon coloration in S. ricini, illustrating that horizontal gene transfer can play an important role in regulating an insect physiological process.

Animals↗

PubMed2026

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p < 0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (ΔNeff), landscape geometry (ΔEvar and ΔGmag), and dominant low-energy attractor organization (ΔLow mass and ΔLow area) showed significant monotonic trends (p < 0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r| = 0.353-0.423, p = 0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r| = 0.333-0.455, p = 0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans↗

PubMed2026

Comparative analysis of lipopolysaccharide lipid A structure and its biosynthetic genes in the plant-associated bacteria Brucella cytisi and Brucella lupini.

The genus Brucella comprises important human and animal pathogens, as well as numerous environmental and symbiotic species. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, plays a crucial role in bacterial physiology and host interactions. In this study, the structures of lipid A, the hydrophobic anchor of lipopolysaccharide, isolated from two plant-associated strains, Brucella cytisi ESC1ᵀ and Brucella lupini LUP21ᵀ, were presented. Lipid A preparations were structurally characterized using chemical methods, MALDI-TOF mass spectrometry, and nuclear magnetic resonance spectroscopy. The obtained results indicated that both lipid A molecules have almost identical structures. Their sugar backbones consist exclusively of 2,3-diamino-2,3-dideoxy-d-glucose (d-GlcpN3N). Phosphate residues were connected to distal and proximal GlcpN3N in approximately half of the lipid A molecules. Fatty acid analysis revealed the presence of C14:0 (3-OH), C16:0 (3-OH), and traces of C18:0 (3-OH). All of these were primary fatty substituents of the sugar backbone and were amide-linked residues. Lactobacillic acid C19:0cyc and 27-hydroxyoctacosanoic acid (C28:0 (27-OH)) were found as ester-linked secondary acyl residues. In turn, C28:0 (27-OH) was partly esterified by a 3-hydroxybutyroyl residue. Two unsubstituted 3-hydroxyfatty acids were linked exclusively to the proximal d-GlcpN3N residue. It was pointed out that sequences of putative genes encoding enzymes required for lipid A biosynthesis and genes encoding specific enzymes involved in structural modifications of lipid A occurring in the genomes of both bacterial species are almost identical. The high sequence similarity of these proteins reflects the observed similarities in the lipid A structures in both investigated Brucella species.

Brucella↗

PubMed2026

Occupationally relevant vibrations and the brain: frequency-dependent proteomics signatures in a rat model.

INTRODUCTION: Occupational exposure to whole-body vibration (WBV), particularly in agricultural environments, has been associated with adverse cognitive and physiological effects. This study examined the neurophysiological impact of WBV in a rat model at 4 Hz and 30 Hz, frequencies representative of off-road and on-road vehicle operation. METHODOLOGY: Forty-four Sprague-Dawley rats were assigned to control (0 Hz), low-frequency (4 Hz), or high-frequency (30 Hz) vibration conditions. After three days of exposure, brain tissues were collected and analyzed using mass spectrometry-based proteomics to identify differentially expressed proteins. RESULTS: Proteomic profiling revealed distinct, frequency-dependent alterations in brain protein expression. Compared with controls, 32 cognition-related proteins were differentially regulated at 4 Hz and 29 at 30 Hz, with 13 differing between the two vibration conditions. Principal component analysis showed clear separation among groups, indicating unique proteomic signatures for each exposure frequency. Functional enrichment and protein-protein interaction analyses demonstrated involvement of synaptic plasticity, cytoskeletal organization, calcium regulation, and neurotransmitter release. Exposure to 4 Hz was associated with the upregulation of proteins involved in calcium homeostasis and synaptic integrity, suggesting potential disruption of cognitive processes. In contrast, 30 Hz increased the expression of proteins related to axonal guidance and neuroprotection, indicating a less clearly adverse response that may reflect adaptive or potentially beneficial effects. DISCUSSION: These findings provide new insight into biological mechanisms underlying WBV-induced cognitive changes and underscore the importance of vibration frequency in shaping neurophysiological outcomes. They also establish a foundation for future studies integrating proteomics with behavioural assessments in animals and humans.

Animals↗

PubMed2026

Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N≈1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age↗

PubMed2026

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans↗

PubMed2026

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans↗

PubMed2026

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4 days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15 kcal kg FFM-1 day-1) and maintaining energy availability at 45 kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and β-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, β-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40% ± 14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male↗

PubMed2026

Metabolomic Responses to Oral Glucose Tolerance Test and Hyperinsulinemic-euglycemic Clamp in CKD.

BACKGROUND: The oral glucose tolerance test (OGTT) captures integrated physiological responses involving intestinal glucose absorption, incretin signaling, and endogenous insulin secretion, whereas the hyperinsulinemic-euglycemic clamp (clamp) isolates insulin-mediated glucose uptake. Comparing plasma metabolomic responses to these two challenges may identify processes specific to intestinal nutrient delivery and how they vary in CKD. METHODS: Targeted plasma metabolomics was performed in 59 adults without diabetes (39 with CKD [eGFR <60 mL/min/1.73 m2] and 20 controls) from the Study of Glucose and Insulin in Renal Disease (SUGAR). Each participant underwent a 75-g OGTT and clamp approximately one week apart. Eighty-eight plasma metabolites were quantified at fasting and during each challenge. Metabolite levels were log-transformed and normalized using Systematic Error Removal Using Random Forest (SERRF). Metabolites were classified using adjusted regression slopes relating OGTT and clamp responses. RESULTS: The mean (SD) age and eGFR were 64 (13) years and 54 (26) mL/min/1.73 m2, respectively, and 41% were female. In the overall cohort, OGTT and clamp induced broad plasma metabolic changes, with 63 (72%) and 76 (86%) metabolites significantly altered from fasting, respectively. Seventy-three metabolites (83%) demonstrated a significant relationship between OGTT and clamp responses. Of these, 22 (25%) exhibited true concordance and 51 (58%) demonstrated similar directional changes but differed in magnitude. A total of 15 (17%) metabolites were discordant or non-corresponding, of which only three were discordant. The non-corresponding metabolites were enriched in amino acid metabolism. Eleven metabolites (13%) demonstrated differential responses between OGTT and clamp by CKD status, involving amino acid and glucose metabolism pathways. CONCLUSIONS: Metabolomic responses to OGTT and clamp were largely directionally concordant but differed in magnitude, with attenuation during OGTT. Discordant metabolites were rare, while non-corresponding metabolites were confined to amino acid pathways. CKD modified OGTT-clamp correspondence for metabolites involved in amino acid and glycolytic metabolism.

Journal Article↗

PubMed2026

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantification of twenty-five steroids in equine serum.

Steroids are potential biomarkers for monitoring equine pregnancy. However, immunoassays currently used for their quantification suffer from cross-reactivity and limited specificity, thus requiring more accurate methods. This study reports the development and validation of a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 25 steroids covering the main biosynthetic pathways of progestogens, corticosteroids, androgens, and estrogens. Steroids were extracted by protein precipitation followed by evaporation, derivatization, and reconstitution before LC-MS/MS analysis. A surrogate matrix was used for calibration and validation to avoid endogenous interference. Validation was performed according to and partly adapted from Clinical and Laboratory Standards Institute guidelines (CLSI), including linearity, trueness, precision, limits of detection and quantification, measurement uncertainty, recovery, matrix effects, carryover, selectivity, and stability. Calibration curves were fitted using the best-performing weighted linear or quadratic regression model, yielding excellent linearity (R2 > 0.990), trueness between -9.0% and 2.3%, and intra- and inter-day precision <6.3%. Lower limits of quantification ranged from 2.07 to 2250 pg/mL depending on physiological analytes concentration. Extraction recovery averaged 24.3-114.9%, matrix effects were acceptable, and accuracy ranged from 94.4% to 98.9%. No carryover or interferences were detected. Measurement uncertainty remained <15%. This study presents the first LC-MS/MS method partially validated per CLSI criteria for the quantification of 24 steroids in equine serum. The method offers a sensitive and specific alternative to immunoassays and provides a robust tool for equine steroid profiling with potential applications in pregnancy monitoring, placentitis diagnosis, and fetal sex determination.

Animals↗

PubMed2026

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin↗

PubMed2026

Durability and Safety of Imeglimin as an Add-On to DPP-4 Inhibitors in Japanese Type 2 Diabetes: The 104-Week FAMILIAR Trial.

AIMS: To evaluate the long-term efficacy and safety of imeglimin added to dipeptidyl peptidase-4 (DPP-4) inhibitors in Japanese patients with type 2 diabetes, focusing on glycemic durability and safety in elderly patients over 104 weeks. MATERIALS AND METHODS: This multicenter, randomized, placebo-controlled trial comprised a 24-week double-blind phase (imeglimin 1000 mg or placebo twice daily) followed by an 80-week open-label extension in which all patients received imeglimin. Eligible patients had inadequate glycemic control despite DPP-4 inhibitor monotherapy. The main assessment measured HbA1c changes from baseline to week 104. Secondary assessments included meal tolerance tests (MTT) for evaluating physiological changes in β-cell function and insulin resistance and safety monitoring. RESULTS: Of 117 randomized patients, 81 completed 104 weeks. In the early-start group that received imeglimin from week 0, the significant HbA1c reduction observed at week 24 (-0.65%) was maintained through week 104 (-0.55%; p < 0.001 vs. baseline). The delayed-start group that switched to imeglimin at week 24 achieved similar glycemic control thereafter. Elderly patients (≥ 65 years) in the early-start group maintained stable HbA1c reduction (-0.58%) without hypoglycemic events over 2 years. MTT analysis in the early-start group showed sustained improvements in glucose AUC and insulin sensitivity without unnecessary insulin secretion over time. CONCLUSIONS: Imeglimin added to DPP-4 inhibitors appeared to improve glycemic control for 104 weeks, without clear attenuation. The combination was well-tolerated with a low risk of hypoglycemia even in elderly patients. The long-term effect may be associated with improvements in insulin sensitivity. TRIAL REGISTRATION: jRCTs061210082.

Humans↗

PubMed2026

Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (β: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (β: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (β: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (β: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (β: 0.020 for anticipated discrimination; β: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (β: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans↗

PubMed2026

A Pilot Study: Developing a Lactating Dairy Goat Model to Study Staphylococcus aureus Mastitis in Women.

INTRODUCTION: Lactational mastitis is common in lactating women, with Staphylococcus aureus as the most commonly isolated agent associated with infectious lactational mastitis. Currently, there are no evidence-based guidelines for antimicrobial treatment due to barriers in obtaining pharmacokinetic data from lactating women. To overcome this barrier, a suitable large animal model is needed. Goats are an ideal translational model for human mastitis due to their anatomical and physiological similarity to humans. The objective of this pilot study was to assess if goats would develop clinical mastitis following intramammary inoculation with a clinical human isolate of S. aureus with the goal of establishing an alternative in vivo model for future research. The hypothesis was that the infected mammary gland half would show similar clinical signs to women with mastitis and demonstrate a similar local immune response when compared to the control mammary gland half. METHODS: One half of the mammary gland of two healthy lactating does was inoculated with a clinical human isolate of S. aureus. The other half of the mammary gland was sham inoculated with sterile buffered saline. Physical examinations, mammary gland assessments, and sterile milk samples were collected every 12 hours post inoculation. At 96 hours post inoculation, the goats were euthanized, and the mammary glands were examined for pathological changes. RESULTS: Goats did not develop systemic signs of disease following inoculation. Focal infected mammary gland changes included warmth, swelling, redness, discoloration, and reduced milk production; the other mammary gland half remained normal throughout the study period. S. aureus was enumerated from only the infected mammary gland half. The microscopic findings of the infected half showed neutrophilic inflammation and cell necrosis consistent with acute mastitis. DISCUSSION: This pilot study demonstrated lactating does can develop clinical signs like those observed in women. Goats have the potential to be a promising animal model to study infectious lactational mastitis.

Animals↗

PubMed2026

Analgesic effect of premixed nitrous oxide in postoperative rehabilitation for ankle fractures: a randomized controlled trial.

INTRODUCTION: The global incidence of ankle fractures is on the rise, effective postoperative rehabilitation is a crucial aspect of surgical management. However, the occurrence of severe pain during the rehabilitation continues to pose a substantial clinical challenge. METHODS: The study utilizes a dual-arm, single-center, double-blind, randomized controlled trial design. A total of 100 participants were enrolled. Participants included patients experiencing acute pain (self-reported pain score ≥4) who underwent postoperative rehabilitation for ankle fractures. Participants undergoing rehabilitation training were randomized to receive either 65% nitrous oxide or 100% oxygen. The primary outcome measured was the pain score, while secondary outcomes encompassed anxiety scores, physiological indices, side effects, patient and therapist satisfaction, acceptance, and residual pain. RESULTS: Pain scores were found to be significantly lower in the nitrous oxide group than in the oxygen group (T1: median difference -3.0, [95% CI -3.4 to -2.6]; p < 0.001; T2: median difference -2.0, [95% CI -2.8 to -1.2]; p < 0.001). Compared with the oxygen group, both therapists (p < 0.001) and participants (p < 0.001) in the nitrous oxide group reported significantly higher satisfaction levels. Acceptance rate showed significant intergroup differences (p < 0.001). No severe adverse effects were observed in either group. Anxiety scores between the two groups did not show a significant difference (p = 0.31, η2 = 0.027). CONCLUSION: The safety and analgesic profile of nitrous oxide renders it a suitable option for pain management in postoperative ankle fractures rehabilitation, thus providing a safe and easily manageable alternative to the current available strategies. CLINICAL TRIAL REGISTRATION: We have registered at https://www.chictr.org.cn and the registration number is: ChiCTR2400089379.

Humans↗

PubMed2026

Effects of blood flow restriction training combined with resistance training on lower-limb strength and sport-specific performance in athletes: a systematic review and meta-analysis.

BACKGROUND: In contemporary sports science, athletes and coaches continuously explore strategies to reduce training load and injury risk while increasing muscular strength and sport-specific performance. This meta-analysis evaluated the effects of blood flow restriction training (BFRT) combined with resistance training (RT) on lower-limb muscle strength and sport-specific performance in athletes. METHODS: Relevant randomized controlled trials (RCTs) were systematically searched across major databases (e.g. PubMed, Web of Science, Cochrane, CNKI, Wanfang Data, and Embase) from inception until November 2024. Two independent reviewers carefully assessed the studies. Data analysis was carried out using RevMan 5.4 software, which included heterogeneity testing, meta-analysis, subgroup analysis, and assessment of publication bias. RESULTS: Ten RCTs (181 athletes; 91 in the BFRT and RT group, 90 in the control group) were included. Outcomes determined BFRT combined with RT yielded notable enhancements in lower-limb muscle strength (SMD = 1.09, 95% CI [0.52, 1.66], p < 0.05) and muscle hypertrophy (MD = 1.09, 95% CI [0.10, 2.09], p < 0.05) compared to control training. However, no significant improvement in sport-specific performance was found (SMD = 0.11, 95% CI [-0.18, 0.40], p = 0.46). Substantial heterogeneity was observed for strength outcomes (I2 = 75%), whereas low heterogeneity was observed for sport-specific performance and hypertrophy outcomes (I2 = 0%). No evidence of significant publication bias was detected. CONCLUSION: BFRT combined with RT appears to provide effective augmentation of lower-limb muscle strength and hypertrophy in athletes compared to RT or conventional training alone. It may be prudent to integrate this approach systematically into training cycles to optimize physiological muscle stimulation and training outcomes, despite not directly improving sport-specific performance.

Humans↗