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461 papers

The yeast mitochondrial porin represses Snf1/AMP kinase signaling to attenuate viral replication.

Chau S et al. · Jul 1, 2026

Although fungi are broadly infected with mycoviruses, the antiviral mechanisms fungal cells use to oppose viral replication are not well understood. Here, we discover a new mitochondrially controlled signaling mechanism in the budding yeast Saccharomyces cerevisiae that limits replication of L-A, an RNA mycovirus that endemically infects this organism. We show that Por1, the mitochondrial voltage dependent anion channel, prevents hyper-replication of L-A in stationary phase cells that have exhausted media nutrients. By investigating known stationary phase regulators, we find that deletion of the AMP-activated kinase homolog SNF1 reverses hyper-replication of L-A observed in por1Δ cells. This epistatic relationship suggests that Por1 negatively regulates Snf1 in stationary phase cells and derepressed Snf1 promotes L-A hyper-replication. We confirm this model, first demonstrating that POR1 prevents the accumulation of activated Snf1 throughout stationary phase. By investigating Snf1 signaling targets, we show that this POR1-SNF1 regulatory mechanism acts in stationary phase cells to limit amino acid availability that sustain L-A replication. POR1-SNF1 signaling represents a novel physiological control mechanism to limit viral replication in a eukaryotic cell.

Biochemistry, Genetics and Molecular Biology

Assessment of allopurinol use in patients with chronic kidney disease and asymptomatic hyperuricemia: a retrospective cohort study.

Souza MELS et al. · Jul 1, 2026

Introduction Asymptomatic hyperuricemia (AH) is common in patients with chronic kidney disease (CKD) and has been identified as a modifiable condition. Addressing it could increase the possibilities for preventing and treating kidney injury. Objective To assess whether administering allopurinol to people with chronic kidney disease and asymptomatic hyperuricemia enhances kidney function and delays progression to kidney failure. Methods This is a retrospective cohort study with data collection from medical records at a specialized center from 2006 to 2020. Eighty people in stages 3 and 4 of CKD with AH were divided into two groups: 40 patients received allopurinol and 40 did not receive medication. Patients were followed for 24 months, with four consultations. Serum uric acid levels and creatinine-based estimated glomerular filtration rate (eGFRcr), estimated by the CKD-EPI formula, were compared within groups and between groups using mean, standard deviation, and analysis of variance (ANOVA). Results Eighty patients were included in the study. Comparing 40 patients with no treatment for hypertension with 40 patients receiving hypouricemic therapy (HUT) with allopurinol, it was observed that mean serum uric acid decreased at all review visits in the allopurinol group, and there was a significant increase in mean eGFRcr after starting allopurinol (p Conclusion Allopurinol was useful in reducing serum uric acid levels, improving kidney function, and delaying progression to kidney failure in patients with AH.

Medicine

Socio-Structural Factors as Predictors of Parents' Intentions to Enrol Their Children in Swimming Lessons.

Hamilton K et al. · Jul 1, 2026

Issue addressed Swimming lessons are an effective drowning prevention strategy, yet uptake remains socially patterned. Socio-structural factors such as parent age, sex and family income may shape parents' decisions to enrol their children in swimming lessons. According to the Theory of Planned Behaviour (TPB), people's beliefs, reflected in their attitudes, subjective norms and perceived control, drive health-related intentions. Socio-structural characteristics may therefore influence parents' intentions indirectly by shaping these underlying beliefs. This study examined an untested pathway, assessing whether socio-structural factors shape parents' beliefs and, in turn, their intentions to enrol children in swimming lessons. Methods Parents (N = 323) of primary school-aged children without prior formal lessons completed an online survey. Latent variable structural equation modelling in R (Lavaan) tested direct and indirect relationships between socio-structural factors, TPB constructs and intention. Results The model demonstrated good fit. Parent age predicted attitudes, subjective norms and perceived control. Sex directly predicted intention, while income predicted perceived control. All three TPB constructs significantly predicted intention, mediating the effects of age and income. The model explained 70% of variance in intention. Conclusions Parents' intention to enrol their children in swimming lessons is shaped indirectly by socio-structural characteristics through belief-based TPB constructs. This highlights the importance of integrating structural determinants into social cognition models to better understand inequities in preventive health behaviours. SO WHAT?: Strengthening positive attitudes, supportive social norms and parental confidence, while reducing financial and structural barriers to participation, may improve equitable access to swimming lessons and contribute to drowning prevention.

Medicine

Diagnostic performance of donor-derived cell-free DNA for acute rejection in kidney allograft biopsies.

Nakamura MR et al. · Jul 1, 2026

Objective To determine the performance of donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker for the diagnosis of acute rejection in for-cause kidney transplant biopsies. Methods This cross-sectional single-center study (between May 2021 and June 2022) included for-cause biopsies performed in kidney transplant recipients with acute graft dysfunction (AGD) or suboptimal graft function (SGF). dd-cfDNA levels were correlated with histological diagnosis according to the Banff 2022 classification. Results Among 492 biopsies, 80.7% were performed for AGD and 19.3% for SGF. The distribution of histological phenotypes was 10.2% (category 1), 6.5% (category 2), 6.9% (category 3), 7.9% (category 4), 33.3% (category 5), and 35.2% (category 6). The respective median dd-cfDNA values were 0.25% (IQR 0.16-0.46), 1.88% (IQR 0.92-5.11), 0.45% (IQR 0.26-0.63), 0.51% (IQR 0.34-1.11), 0.27% (IQR 0.15-0.45), and 0.38% (IQR 0.23-0.64). Category 2 presented a higher median dd-cfDNA compared with the other groups (p Conclusion In this cohort, dd-cfDNA showed moderate diagnostic performance for acute graft rejection and high negative predictive value. dd-cfDNA threshold diagnostic varied according to the type of for-cause biopsies (AGD or SGF).

Biochemistry, Genetics and Molecular Biology

Identification of diagnostic biomarkers for relapsing-remitting multiple sclerosis in plasma by mass spectrometry-based proteomics.

García-Silva VM et al. · Jul 1, 2026

In the absence of molecular biomarkers, the current diagnosis of multiple sclerosis is based on clinical assessment, neuroimaging, and detection of oligoclonal bands in cerebrospinal fluid. Early and rapid diagnosis using patient samples obtained by non-invasive methods would be a major advance in clinical management. We tested 5 different methods for preparation of the plasma proteome for liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. These were as follows: (1) single-pot, solid-phase-enhanced sample preparation (SP3), (2) iST and (3) ENRICH-iST of raw plasma, (4) SP3 of highly abundant-proteins depleted plasma (DEPL-SP3), and (5) SP3 of plasma extracellular vesicles (EV-SP3). DEPL-SP3 and EV-SP3 sample preparation workflows yielded the highest numbers of quantified plasma proteins. Using both methods, we analyzed the plasma proteome of 15 relapsing-remitting multiple sclerosis (RRMS) patients and 5 healthy controls. We found 54 and 35 regulated plasma proteins with DEPL-SP3 and EV-SP3 workflows, respectively. Among them, von Villebrand factor (VWF) was identified as a potential RRMS diagnostic biomarker. The use of sample preparation workflows for LC-MS/MS analysis that describe both the soluble and EV plasma proteomes might increase the likelihood of identifying new and robust RRMS biomarkers.

Biochemistry, Genetics and Molecular Biology

An Umbrella Review of Systematic Reviews of School-Based Nutrition Interventions to Determine Outcomes Used and Their Measurement Tools.

Olgacher D et al. · Jul 1, 2026

Context School-based nutrition interventions have the potential to promote dietary behaviors and other outcomes among children and adolescents. However, inconsistent reporting of outcomes and measurement tools limits evidence synthesis and the identification of effective intervention strategies. Objective This umbrella review aimed to synthesize the range of outcomes related to diet, health, well-being, and education reported in systematic reviews of school-based nutrition interventions, along with the measurement tools used. The findings will be used to inform the development of a Core Outcome Set (COS) to guide future evaluations in this field. Data sources We conducted a systematic search across 7 databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, PsycINFO, CINAHL, Web of Science, and Scopus) to identify systematic reviews published from January 2018 to December 2023. Data extraction Data on outcomes related to diet, health, well-being, and education were extracted from eligible systematic reviews. When available, information on outcome measurement tools was also extracted. Additional details were retrieved from primary studies referenced within systematic reviews as needed. Data analysis Ninety-eight systematic reviews, comprising 965 unique studies, were included. Outcomes were categorized into 4 domains: (1) "diet" (68.8%), subdivided into "dietary intake" and "diet-related cognitive/attitudinal behaviors"; (2) "physical health" (44.8%), subdivided into "body composition" and "clinical/biochemical measures"; (3) "social and emotional well-being and behavior" (9.2%); and (4) "education" (6.4%). Substantial heterogeneity was observed across outcome domains, subdomains, and measurement tools, which presents challenges for evidence synthesis and limits comparability across studies. Conclusions The findings of this review underscore the need for a stakeholder-informed, context-aware COS to standardize outcome reporting in school-based nutrition interventions. Such standardization is essential to improve the comparability of research findings, enhance evidence synthesis, and facilitate the translation of evidence into policy and practice. Subsequent phases of this work will involve diverse stakeholder engagement to finalize the COS and recommend appropriate tools for outcome measurement for evaluating school-based nutrition interventions. Systematic review registration PROSPERO registration No. CRD42022378746.

Medicine

Applying the Bow Tie Method to Evaluate Emerging Risk: The Case of Carbon Capture and Water Stress.

Weisner MJ et al. · Jul 1, 2026

Emerging environmental risks are often shaped not by a lack of knowledge alone, but by fragmented information across systems, disciplines, and levels of governance. This fragmentation limits the ability of local decision-makers to identify and respond effectively to rapidly developing technologies. This paper introduces a novel bow tie risk assessment framework as a practical tool for identifying and organizing these risks. By integrating engineering, environmental, and policy perspectives, the approach captures interactions across land use, water systems, and governance structures. We apply the framework to carbon capture, utilization, and storage (CCUS) development in Colorado. Analysis shows that tracking how CCS, CCU, and CCUS are defined and applied across institutions reveals gaps in accountability, coordination, and risk identification. These inconsistencies contribute to policy drift, obscure system-level impacts, and limit stakeholder engagement. The bow tie framework makes these gaps visible, drawing attention to risks that remain hidden within fragmented knowledge and governance systems. Findings from the Colorado case study indicate that current CCUS governance lacks consistent mechanisms to define, measure, and account for water use and impacts across institutions. The analysis highlights a critical gap in how water is conceptualized and measured, particularly where it may be permanently removed or altered through subsurface injection, storage, or disposal in ways that do not align with conventional distinctions between consumptive and non-consumptive use. The method provides a practical tool for local and regional governments to identify risks, engage broader stakeholders, and support coordinated, interdisciplinary, and adaptive decision-making.

Environmental Science

miR-19a-3p and miR-19b-3p Promote Microglia Activation Associated With Neuroinflammation.

Sahebdel F et al. · Jul 1, 2026

Neuroinflammation, driven by microglia activation and the production of pro-inflammatory cytokines, has been implicated in several neurological diseases and neuropathic pain. MicroRNAs (miRNAs) have emerged as important regulators of neuroinflammatory processes. Prior studies identified elevated levels of circulating miR-19a and miR-19b in individuals living with chronic pain following spinal cord injury (SCI). In this study, we wanted to determine whether miR-19a and miR-19b have a direct effect on microglia activation, specifically pro-inflammatory activation, associated with neuroinflammation. Microglia were activated by inflammatory stimuli in the presence of miR-19a or miR-19b mimics, and assessed for the expression of cytokines, chemokines, and effector molecules. The results show that miR-19a or miR-19b mimics increased the expression of pro-inflammatory cytokines, chemokines, and effector molecules in microglia. The results also showed decreased expression of suppressor of cytokine signaling (SOCS) proteins, namely SOCS1 and SOCS3, in activated microglia with miR-19a and miR-19b mimics. Additionally, enhanced signaling through the NFκB and Jak pathways was observed with increased NFkB-p65 and JAK1 phosphorylation in the presence of miR-19a and miR-19b mimics. Further results show that miR-19a and miR-19b inhibitors reversed these effects on activated microglia. Overall, our results demonstrate that miR-19a or miR-19b increased the expression of pro-inflammatory cytokines, chemokines, and effector molecules in activated microglia. These results indicate that miR-19a and miR-19b can enhance microglia activation and associated inflammatory responses, which may have implications for conditions associated with neuroinflammation.

Medicine

rTMS Over Dorsolateral Prefrontal Cortex Augments Dual-Task Training for Mobility, Balance and Cognition in Sub-Acute Stroke: A Randomized Controlled Trial.

Yang L et al. · Jul 1, 2026

Objective To evaluate the effects of adding repetitive transcranial magnetic stimulation (rTMS) to dorsolateral prefrontal cortex (DLPFC) with dual-task (DT) exercise on DT mobility, balance and cognitive performance in individuals with sub-acute stroke. Methods Thirty sub-acute stroke patients [age, mean (SD) = 59.2 (7.9) years] were randomly assigned to the experimental group (N = 15), or the sham stimulation group (N = 15). 5 Hz rTMS (90% resting motor threshold, 1200 pulses/session) or sham stimulation was applied to the ipsilesional DLPFC, 1 session/day, 5 days/week for 2 weeks, followed by dual-task training. Two mobility tests [10 m walking and timed-up-and-go (TUG) test] and two cognitive tasks (serial 3 subtractions and verbal fluency) were assessed separately [that is, single-task (ST) condition] and concurrently (i.e., DT condition) before and after the intervention. Results The experimental group had greater improvement in TUG time under both ST and DT conditions (p Discussion The 2-week rTMS to DLPFC combined with DT training augments DT walking performance, and improves balance and cognitive function in mild to moderate motor and cognitive impairment individuals with sub-acute stroke. Implications of physiotherapy practice This combined intervention is a feasible, effective strategy to improve real-world mobility in sub-acute stroke rehabilitation. Trial registration Chinese Clinical Trial Registry platform (www.chictr.org.cn), with the registration number ChiCTR2200066237.

Neuroscience

HIV Care Retention and Cost Analysis in Multi-Month ART Dispensing: A Randomized Controlled Trial in China.

Shang W et al. · Jul 1, 2026

Introduction Multi-month dispensing (MMD), as a differentiated service delivery model, can reduce the frequency of clinic visits, waiting time and travel costs for clinically stable people living with HIV. This study aimed to evaluate the impact of 6-month MMD of antiretroviral therapy (ART) on retention and conduct a cost analysis in China. Methods We conducted a randomized, non-blind, non-inferiority study from December 2022 to March 2023 at The First Hospital of China Medical University. Eligible participants were randomly assigned to a 3-month dispensing group (n = 789) or a 6-month dispensing group (n = 799) and followed up for 18 months. The proportion of patients continuing ART after 18 months, virological suppression rate ( Results A total of 1588 participants were included (median age 40.0 years, IQR 34.0-50.0; 94.8% male), with no significant between-group differences in demographic and clinical characteristics (all p>0.05). In the intention-to-treat analysis, treatment retention rates at 18 months were 94.9% (749/789) in the 3-month dispensing group and 94.2% (753/799) in the 6-month dispensing group. The risk difference (6-month minus 3-month) was -0.7% (95% CI -2.9% to 1.5%); non-inferiority was demonstrated as the lower bound of the 95% CI (-2.9%) exceeded the pre-specified margin of -5%. Viral suppression rates ( 2 = 0.0421, p = 0.8375). In terms of cost, the 6-month dispensing group had two fewer annual outpatient visits (3 vs. 5), with total treatment costs reduced by 27.7% (¥931.82 vs. ¥1288.85) and work value loss decreased by 16.7% (¥174.20 vs. ¥209.04 yearly). Conclusions Six-month MMD of ART did not reduce treatment retention; instead, it decreased patients' clinic visit costs, thereby meeting cost-effectiveness criteria. Clinical trial number ChiCTR2200066438.

Medicine