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PubMed2026

Bioprospecting microbial genomes to expand the biocatalytic toolbox of rubber oxygenases.

A set of rubber oxygenases was discovered through phylogenetic analysis and AI-based structural modeling of complexes of the putative enzymes with a substrate mimicking cis-1,4-polyisoprene. Sixteen candidate proteins were selected from thermophilic microorganisms, all sequence-related to the Latex clearing protein from Streptomyces sp. K30 (LcpK30). Sequence truncation and solubility tags were then evaluated to enhance protein expression, with the SUMO tag proving to be the most effective. Including LcpK30, nine heme-containing oxygenases were successfully expressed in E. coli NEB 10-beta cells, purified (35-157 mg L-1 yield) and characterized. Steady-state kinetics revealed significant rubber latex-degrading properties for six of them, with the truncated SUMO-fused LcpK30 (SUMO-LcpK30T) showing activity in agreement with literature. Notably, the catalytic efficiencies of all the expressed homologs lay within one order of magnitude and the oxygenase from Thermomonospora echinospora was found to be particularly promising in terms of activity, especially at high latex concentrations (more than 1% w/v). The analysis of reaction mixtures by both HPLC and HPLC-MS confirmed the oxidation of cis-1,4-polyisoprene to form the expected isoprenoid oligomers (n = 2-12), whose distribution was consistent with the usual endo-type cleavage pattern in all but one case. This bioprospecting effort afforded a platform of new rubber-degrading enzymes with diverse efficiencies and product profiles, capable of adapting to targeted applications.

Oxygenases↗

PubMed2026

A systematic review of qualitative research on HIV and food insecurity in high-income countries.

OBJECTIVES: Food insecurity leads to adverse health outcomes in people living with HIV, including obesity, poor mental health and viral non-suppression. Qualitative studies in low- and middle-income countries have described the impact of food insecurity on medication adherence. However, limited qualitative research exists on the lived experiences of food insecurity among people living with HIV in high-income countries (HICs). We aimed to synthesize qualitative literature on food insecurity among people living with HIV in HICs. DESIGN: Systematic review and textual narrative synthesis. METHODS: We searched MEDLINE, CINAHL, Scopus, Embase, and PsycINFO, extracting data from included articles on a standardized form in Covidence. We synthesized literature using a textual narrative approach. We conducted quality appraisal (Critical Appraisal Skills Programme Qualitative Studies Checklist) and graded certainty of findings (GRADE-CERQual). RESULTS: We reviewed 2772 articles, reduced to 940 after deduplication, with 12 articles included after full text screening. Included articles reported on studies conducted in the United States ( n  = 7), and Canada ( n  = 5). We identified three key themes, each with their own sub-themes: the role of structural inequalities in shaping and navigating food insecurity; the impacts of food insecurity on health and wellbeing; and the labour of acquiring of food. CONCLUSIONS: Our review highlights the syndemic nature of food insecurity and HIV; intersecting experiences of multiple structural hardships constellate and interact synergistically to amplify poor health outcomes. Interventions should address the multiple and reinforcing social and structural conditions that shape food insecurity among people living with HIV.

Humans↗

PubMed2026

Female genital mutilation knowledge, attitudes and training needs among health professionals in non-practicing countries: A literature review.

BACKGROUND: With increasing globalization and migration, the number of women affected by female genital mutilation who reside in countries where the practice is not traditionally performed is constantly increasing. Healthcare providers in these settings are required to address the complex health needs of this vulnerable population. We aimed to synthesize recent literature on their knowledge, preparedness, and educational background. METHODS: We conducted a systematic review across PubMed, Scopus and Embase, identifying papers published from January 2015 onwards, examining providers' knowledge, education and attitudes toward female genital mutilation in non-practicing countries. Both quantitative and qualitative observational studies were eligible. Given heterogeneity in study populations, outcome definitions, and assessment tools, findings were synthesized narratively. The review protocol was registered with the International Prospective Register of Systematic Reviews (CRD420251044761). FINDINGS: 1046 records were screened by title and abstract, and 140 full-text articles were assessed for eligibility. 31 studies met the inclusion criteria (23 quantitative, 8 qualitative). Many providers reported clinical experience with women affected by female genital mutilation, yet substantial variability was observed in knowledge, training, and attitudes. Gaps were particularly evident regarding legislation, World Health Organization classification, clinical guidelines, referral pathways, workplace protocols. Midwives and younger professionals tended to demonstrate higher knowledge levels. Training exposure ranged from 5% to 91%, and many participants perceived it as insufficient. Qualitative findings echoed these patterns, highlighting challenges in female genital mutilation classification, legal awareness, documentation systems, the impact of providers' cultural beliefs on care delivery. CONCLUSION: Considerable efforts are needed to equip healthcare providers to deliver high-quality, culturally competent care to women affected by female genital mutilation. Research should develop validated tools to assess preparedness, adopt mixed-methods strategies to capture patient and provider perspectives, and guide standardized, up-to-date training programs, strengthening knowledge in managing female genital mutilation.

Humans↗

PubMed2026

Potential Links Between Physiological and Perceptual Strain in High Heat Stress.

The physiological strain index (PhSI) is widely used to quantify thermoregulatory and cardiovascular strain during heat stress. However, direct physiological measurements may not always be feasible in occupational or athletic settings. Therefore, this study aimed to examine the relationship and agreement between perceptual strain and integrated physiological strain indices during high heat stress. Ten healthy, physically active, non-heat-acclimated males (29 (7) yr; 1.79 (0.11) m; 77.4 (9.3) kg) completed two randomized crossover exercise trials in hot-dry (HD) and warm-humid (WH) environments with equivalent wet-bulb globe temperatures. Heart rate, rectal temperature, skin temperature, rating of perceived exertion, and thermal sensation were measured at baseline and every 15 minutes during 60 minutes of cycling. Physiological strain index (PhSI), adaptive physiological strain index (aPhSI), and perceptual strain index (PeSI) were calculated using validated equations. Repeated-measures correlation analyses demonstrated very strong associations between PeSI and both PhSI and aPhSI under HD (Rrm = 0.940-0.943) and WH (Rrm = 0.980-0.982; all p < 0.001). Receiver operating characteristic analyses demonstrated good-to-excellent discrimination of physiological strain by PeSI (AUC = 0.895-0.969). Mixed-effects analyses showed that higher PeSI values were associated with increased PhSI (β = 1.325, p < 0.001) and aPhSI (β = 1.459, p < 0.001). However, Bland-Altman analyses demonstrated relatively small mean biases (0.4-0.9 AU) but wide limits of agreement (-2.8 to 4.2 AU), indicating that PeSI and physiological strain indices are not interchangeable. These findings suggest that PeSI may serve as a practical adjunctive or screening indicator of physiological strain when direct physiological measurements are unavailable.

Humans↗

PubMed2026

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H₂O₂-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans↗

PubMed2026

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P = .056). Multivariable regression analysis confirmed this (RR = 2.1, 95% CI: 1.5-3.1; P < .001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P = .316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans↗

PubMed2026

Effects of automated massage chair therapy on mental health and physical health: A comprehensive study.

BACKGROUND AND OBJECTIVE: Automated massage chair therapy is a non-pharmacological intervention widely believed to enhance wellness, yet evidence regarding its effects remains limited. This 3-part study evaluated the effects of automated massage chair therapy on mental and physical health. METHODS: In Part 1, 20 moderately stressed students were randomized to receive a 20-minute automated massage chair therapy session followed by a 20-minute control session, or vice versa, with a 48-hour washout period. Blood pressure (BP), heart rate (HR), electroencephalogram (EEG), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale (VAS) were measured. In Part 2, 20 hypertensive hospital staff received three 20-minute automated massage chair therapy sessions on alternate days. BP, HR, and skin blood flow (SBF) were measured. In Part 3, 20 hospital staff with chronic low back pain received three 20-minute automated massage chair therapy sessions on alternate days. Electromyogram (EMG) and VAS were measured. RESULTS: Automated massage chair therapy significantly reduced diastolic blood pressure (DBP), HR, stress, and anxiety among moderately stressed students. In hospital staff with hypertension, SBF did not change significantly, whereas BP and HR decreased significantly after automated massage chair therapy. In hospital staff with chronic low back pain, low back function improved, and pain was significantly reduced after automated massage chair therapy. CONCLUSION: These findings indicate that automated massage chair therapy may help reduce stress, lower blood pressure, and alleviate low back pain.

Humans↗

PubMed2026

Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies.

BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged ≥ 50 years (n = 7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g = 1.60, 95% CI: 0.95-2.25) and 8-OHdG (g = 2.64, 95% CI: 2.13-3.14) were markedly elevated (p < 0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g = 5.24). In PD, 8-OHdG was moderately elevated (g = 0.78, 95% CI: 0.18-1.39; p = 0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g = 0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.

Humans↗

PubMed2026

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗

PubMed2026

Integrated physiological and transcriptomic analyses reveal coordinated gill responses to heat stress in pikeperch (Sander lucioperca).

Climate change-driven warming of aquatic environments has made thermal stress an increasingly important factor influencing fish physiological homeostasis. Given their central roles in respiration and osmoregulation, gills are particularly responsive to variations in ambient temperature. Histological examination, physiological measurements, and transcriptome profiling were integrated to investigate the mechanisms associated with heat stress-induced gill injury in pikeperch (Sander lucioperca). Histological analysis revealed that exposure to 29 °C directly caused structural damage to the gills of pikeperch. Oxidative status was evaluated by measuring malondialdehyde (MDA) levels and the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). MDA accumulation was significantly enhanced under heat stress, while antioxidant enzyme activities (SOD, POD, and CAT) displayed a transient increase followed by a subsequent decline. Transcriptome profiling showed marked enrichment of the protein processing in endoplasmic reticulum pathway after heat stress, suggesting activation of endoplasmic reticulum (ER) stress in pikeperch gills. With increasing stress duration, the unfolded protein response (UPR) appeared unable to re-establish ER homeostasis, shifting ire1 and atf6 toward a pro-apoptotic state. Protein-protein interaction (PPI) analysis further highlighted hub genes potentially involved in heat stress-induced ER stress and apoptosis. TUNEL staining and western blotting collectively confirmed that heat stress triggered apoptosis in pikeperch gill tissue. Overall, this study provides new insights into the physiological and molecular responses of pikeperch gills to heat stress and enhances our understanding of thermal stress adaptation in cold-water aquaculture species under climate change.

Animals↗

PubMed2026

Changes in sexual behavior among women in studies evaluating the dapivirine vaginal ring for HIV prevention.

BACKGROUND: Access to novel HIV prevention technologies often raise concerns of risk compensation. This analysis examined changes in the sexual behaviors of MTN 020/ASPIRE participants, a placebo controlled randomized control trial, who subsequently enrolled in MTN-025/HOPE, an open-label extension using the dapivirine vaginal ring. METHODS: Both studies enrolled healthy, sexually active, HIV-negative women from Malawi, South Africa, Uganda and Zimbabwe. Longitudinal data on participants' sexual behaviors, specifically sex with a nonprimary partner (past 3 months), and use of male or female condoms at the last vaginal sex act were compared between ASPIRE and HOPE. Conditional and mixed ordinal logistic regression models evaluated associations between study and sexual behaviors at enrollment, and quarterly over the first 12 months. RESULTS: Of the 2629 individuals enrolled in ASPIRE, 1456 (55%) participated in HOPE. At enrollment, the proportion of participants who reported sex with a nonprimary partner and condom use at last vaginal sex act did not differ by study. Across all quarterly follow-up visits, sex with a nonprimary partner was more common in HOPE (13.9-18.7%) than ASPIRE (10.7-12.6%); adjusted OR 1.47, 95% CI 1.24-1.75, P < 0.001. There was no difference in condom use at the last vaginal act across all quarterly follow-up visits between ASPIRE (36.5-42.7%) and HOPE (43.6-46.7%); adjusted OR 1.05, 95% CI 0.94-1.18. CONCLUSION: More women reported sex with nonprimary partners in HOPE, with little change in condom use over time between the two studies. Understanding behavior changes during PrEP use allows for tailored, holistic reproductive health programming.

Humans↗

PubMed2026

Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings.

Acute physical fatigue can impair cognitive control, yet its underlying neurochemical mechanisms remain unclear. This study investigated whether catecholaminergic modulation influences behavioral and neural markers of inhibitory control following physical fatigue. Eighteen healthy, recreationally active adults (9 males, 9 females; 23.4 ± 2.2 years) completed a randomized, triple-blind, placebo-controlled crossover study. On separate visits, participants received methylphenidate (MPH; 20 mg; a dopamine and noradrenaline reuptake inhibitor), reboxetine (REB; 8 mg; a noradrenaline reuptake inhibitor), or placebo. Physical fatigue was induced by repeated bilateral leg extensions to task failure. Cognitive performance was assessed before and after physical fatigue using a Go/No-Go task with electroencephalographic recording. Behavioral outcomes included reaction time and accuracy, while event-related potentials measured neural stages of response execution and inhibition (N2 and P3). Mixed-effects models were used for statistical analysis. For No-Go trials, a significant MPH × Time interaction was observed for accuracy (p = 0.008), with improved post-fatigue performance following MPH administration (p = 0.048). At the neural level, MPH was associated with shorter fronto-central No-Go N2 latency (p = 0.038) and altered fatigue-related changes in No-Go P3 latency (p = 0.047). REB did not produce comparable behavioral or neural effects. These findings provide pharmacological evidence that catecholaminergic mechanisms contribute to inhibitory control following physical fatigue. The differential effects of MPH and REB suggest that selective noradrenergic enhancement alone is insufficient to maintain inhibitory control following physical fatigue. Instead, the findings implicate broader dopaminergic and noradrenergic mechanisms, potentially involving alterations in the temporal dynamics of inhibitory processing. TRIAL REGISTRATION: (G095422N and identifier NCT05880342).

Adult↗

PubMed2025

Effectiveness of physical activity intervention for depression, anxiety and comorbid symptoms during the perinatal period among Chinese primiparas.

BACKGROUND: To examine the effectiveness of a physical activity (PA) programme incorporating partner support and enjoyment in preventing perinatal depression, anxiety, and comorbid anxiety and depression (CAD) among Chinese primiparas. METHODS: A total of 120 eligible primiparas were randomised into intervention or control groups. The intervention group received the 13-week PA programme and the control group received the usual care. The outcomes were depression, anxiety, and CAD assessed at baseline, post-intervention, and 6 weeks after delivery. Differences were examined using generalised linear mixed models with intention-to-treat. RESULTS: A significant group × time interaction was observed for depression score, anxiety score, anxiety incidence, and CAD incidence (all p < 0.05). However, no significant interaction was found for depression incidence. Compared to the control, the intervention substantially reduced the scores of depression (MD: -2.67 (-4.16 to -1.17); -2.63 (-4.15 to -1.11)) and anxiety (MD: -4.95 (-9.23 to -0.67); -7.33 (-11.85 to -2.82)), as well as the rates of depression (OR: 0.40 (0.18 to 0.85); 0.44 (0.21 to 0.93)) and CAD (OR: 0.35 (0.14 to 0.87); 0.26 (0.11 to 0.62)) at post-intervention and 6-week postpartum. Notably, anxiety incidence showed significant reduction only at 6-week postpartum (OR: 0.34 (0.16 to 0.74)) (all p < 0.05). Within the intervention group, no significant changes occurred in most outcomes from baseline to post-intervention and 6-week postpartum, except depression scores (MD:-1.60 (-2.79 to -0.41); -1.23 (-2.44 to -0.03); p < 0.05). CONCLUSIONS: The PA programme (including partner support and enjoyment) may be effective in reducing perinatal depression, anxiety and CAD among primiparas.

Adult↗

PubMed2026

Cognitive-behavioral therapy for post COVID-19 condition: A pilot randomized controlled trial.

BACKGROUND: The post COVID-19 condition (PCC) is a disabling condition with urgent need for effective treatments. This pilot randomized controlled trial examined the feasibility and efficacy of a cognitive-behavioral therapy (CBT) for PCC in a parallel-group design. METHODS: N = 53 individuals with PCC were randomized to CBT (n = 27) or 16-week wait-list control (WLC) condition (n = 26). One participant allocated to WLC was excluded after randomization, resulting in an intention-to-treat (ITT) sample of N = 52 participants (CBT: n = 27, age: M = 48.59, SD = 11.52, 77.8% female; WLC: n = 25, Age: M = 48.44, SD = 9.81, 60% female). CBT comprised eight group and five individual sessions addressing cognitive and behavioral factors of symptom maintenance (treatment duration if completed: M = 14 weeks, SD = 1 week). Primary outcomes included fatigue (FSS), overall somatic symptom burden (PHQ-15), and respiratory and cardiovascular symptoms (SBQ™-LC "Breathing" and "Circulation"), assessed at pre-, post-assessment, and follow-up. RESULTS: Participants receiving CBT showed a significant medium-sized reduction in fatigue directly after treatment compared to the WLC condition (d = -0.58, p = .045), whereas the WLC group showed a significant increase in overall somatic symptoms (d = 0.60, p = .027). Results for respiratory symptoms were mixed, showing inconsistent patterns across analyses. Retrospectively assessed feasibility and treatment satisfaction were good, with few adverse effects reported. CONCLUSIONS: This pilot trial suggests the feasibility and preliminary efficacy of CBT for PCC. Larger RCTs with active control groups should confirm these findings.

Humans↗

PubMed2026

Association of hydroxyurea use and sickle cell retinopathy: A systematic review and meta-analysis.

Hydroxyurea (HU) is prescribed to reduce systemic complications of sickle cell disease; however, its association with sickle cell retinopathy (SCR) remains unclear. This meta-analysis (PROSPERO: CRD420251079006) evaluates the pooled association between HU use and SCR. In the primary analysis, HU use was not associated with a statistically significant reduction in SCR (OR = 0.90, 95% CI [0.41, 1.97], p = 0.79; I² = 77%). In a prespecified leave-one-out analysis, exclusion of the outlier study did not produce a statistically significant association, although the estimate shifted toward a stronger protective effect with reduced heterogeneity (OR = 0.70, 95% CI [0.39, 1.27], p = 0.25; I² = 67%). In a subgroup analysis excluding high-risk-of-bias studies, HU use was also not associated with a statistically significant reduction in SCR (OR = 0.84, 95% CI [0.39, 1.82], p = 0.66; I² = 77%). In post hoc analyses, HU use was not associated with a statistically significant reduction in SCR in non-adult populations (OR = 1.14, 95% CI [0.43, 3.05], p = 0.79; I² = 81%) or genotype-restricted analyses (OR = 1.22, 95% CI [0.81, 1.84], p = 0.35; I² = 0%). In post hoc analyses restricting studies to retinopathy phenotype, however, HU was associated with statistically significant lower odds of non-proliferative SCR (OR = 0.73, 95% CI [0.54, 0.98], p = 0.04; I² = 0%) and proliferative SCR (OR = 0.24, 95% CI [0.09, 0.60], p = 0.002; I² = 12%). Very low-certainty evidence suggests mixed associations between HU and SCR. Prospective studies are needed to clarify its role in SCR prevention.

Humans↗

PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗

PubMed2026

Acetylcholine signaling regulates osmotic stress adaptation in the phytopathogen Dickeya solani.

Plants impose strong selective pressures that shape both the composition and functional potential of plant microbiomes. The adaptation of plant-associated bacteria to their hosts relies on an extensive repertoire of signal transduction systems that sense plant-derived molecules and dynamically adjust bacterial physiology and metabolism within the holobiont. These signals include key plant signaling compounds that regulate processes essential for plant-microbe interactions. Among them, acetylcholine is emerging as an important signaling molecule in both plants and bacteria. Here, we demonstrate that acetylcholine regulates the expression of the osmotic stress response betIBA gene cluster in the important phytopathogen Dickeya solani, where it plays an important role in osmoprotection. We show that the TetR-family transcriptional regulator associated with this pathway, BetIDs, recognizes acetylcholine as well as choline and trimethylamine. These three ligands differentially induce betIBA transcription in a manner that correlates with their binding affinities. Ligand binding does not affect BetIDs binding to the bet promoter or its oligomeric state. Instead, it induces pronounced changes in the secondary structure of BetIDs, with the magnitude of these conformational changes being ligand-dependent. We further show that quorum sensing modulates osmotic stress tolerance in D. solani by regulating the expression of the Bet pathway. The Bet system is required for the full virulence of D. solani, particularly in chemically complex plant tissues. Phylogenetic analyses reveal that the BetIBA system is widely distributed among plant-associated Pseudomonadota, collectively supporting its importance for bacterial survival and adaptation in plant-related environments.

Osmotic Pressure↗

PubMed2026

BMT4me En Español: Multisite Feasibility and Usability Testing of a Spanish-Language mHealth Adherence Support App for Spanish-Speaking Caregivers of Children After Hematopoietic Stem Cell Transplantation and Cancer Treatment.

BACKGROUND: Medication nonadherence during the first 100 days after pediatric hematopoietic stem cell transplantation (HSCT) and during oncology treatment increases risk for complications. BMT4me is a caregiver-facing mobile health (mHealth) application providing medication reminders, symptom tracking, and note-taking features to support medication management. Spanish-speaking caregivers are frequently excluded from digital adherence interventions due to the lack of language-accessible tools. PROCEDURE: We conducted a multisite, mixed-methods usability testing of a Spanish-language version of BMT4me ("BMT4me en Español") with Spanish-speaking caregivers of children (ages 2-17 years) post-HSCT or with an oncology diagnosis on active treatment. Caregivers completed a facilitated, three-step usability session (unobtrusive observation, interactive observation, and debriefing), followed by a semi-structured interview, and then completed the system usability scale (SUS). Quantitative outcomes were summarized descriptively; qualitative data were analyzed using content analysis with constant comparison. RESULTS: Fifteen participants enrolled at each site for a total of 30 participants. Across both sites, the recruitment rate was 91%. All participants completed all parts of the study. The SUS score (M = 80.09; SD = 17.35) was above average (>68). Two key qualitative themes emerged: (1) the perceived positive impact of BMT4me on managing a serious illness and (2) the acceptance and sociocultural relevance of BMT4me for Spanish-speaking families. Caregivers also shared suggestions to add educational content and multiuser functionalities to BMT4me. CONCLUSIONS: The acceptance and perceived positive impact of the Spanish BMT4me app indicates that socioculturally relevant, Spanish mHealth interventions have strong potential to support Spanish-speaking caregivers in pediatric oncology and HSCT settings. CLINICAL TRIALS NCT: NCT06361173.

Adolescent↗