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Norgestrel drives mitochondrial collapse and plasma membrane impairment in Pacific oyster (Crassostrea gigas) sperm by triggering premature acrosome reaction.

The toxic mechanisms of norgestrel (NGT), an emerging marine pollutant, on the sperm from externally fertilized invertebrates remain elusive. This study employed an integrated physiological and multi-omics framework to elucidate how NGT (10 and 1000 ng/L) disrupts acrosome reaction (AR) signaling machinery, thereby impairing the functional integrity of Pacific oyster (Crassostrea gigas, also known as Magallana gigas) sperm. Exposure to NGT triggered a significant, dose-dependent premature AR, characterized by elevated acrosin activity and a loss of acrosomal integrity. Multi-omics integration supports a model in which this premature exocytosis is linked to signaling disturbances, including disruption of calcium signaling and reduced transcript abundance of calmodulin (CaM) and the primary recognition protein zonadhesin (Zan). This signaling interference induced an premature AR, subsequently driving a cascade of bioenergetic and structural failures. At the mitochondrial level, NGT induced abnormal mitochondrial permeability transition pore (mPTP) opening and elevated the transcript levels of antioxidant defense genes (e.g., peroxiredoxin-5, PRDX5). These alterations indicate the occurrence of mitochondrial collapse. Concurrently, scanning electron microscopy verified localized plasma membrane wrinkling and pore formation in sperm. In addition, NGT exposure decreased the transcript abundance of cytoskeleton-related genes, including solute carrier family 26 member 6 (SLC26A6), actin (ACT), and tubulin polymerization promoting protein family member 3 (TPPP3). These molecular changes further disrupted membrane phospholipid homeostasis, as represented by altered glycerophospholipid metabolism. At the same time, cumulative cellular stress was associated with decreased transcript abundance of cytoprotective factors (e.g., baculoviral IAP repeat-containing proteins, birc2) and changes in apoptosis-related genes consistent with activation of a caspase-8-mediated apoptotic programme. In conclusion, NGT, as a representative synthetic progestin, exerts reproductive toxicity by interfering with signaling mediators to induce premature AR, which subsequently exhausts metabolic energy and triggers plasma membrane impairment. These findings provide a critical mechanistic basis for the aquatic ecological risk assessment of synthetic progestins.

Animals

Clinical Outcomes and Genomic Epidemiology of Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Keratitis.

PURPOSE: To characterize the clinical features, management, antimicrobial resistance patterns, and genomic epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) keratitis at two North American centers. DESIGN: Retrospective interventional case series combined with laboratory investigation PARTICIPANTS: Seventy eyes of 67 patients presenting laboratory-confirmed MRSA keratitis were included METHODS: We performed a multicenter retrospective case series of patients with culture-proven MRSA keratitis treated between 2005 and 2022. Demographic and clinical data were collected. Antimicrobial susceptibility testing was conducted, and multidrug resistance (MDR) was defined as resistance to ≥3 antibiotic classes. A subset of isolates underwent whole-genome sequencing with core genome multilocus sequence typing. Vancomycin susceptibility, heteroresistance screening, and tolerance testing were performed on available isolates. MAIN OUTCOME MEASURES: Antimicrobial susceptibility and multidrug resistance rates, vancomycin phenotypic profiles, MRSA genotypic distribution, and final best-corrected visual acuity RESULTS: Median age was 63.5 years, and 61.4% were female. Ocular surface disease (67.7%) and prior ocular surgery (65.2%) were common. Only 25.4% had significant healthcare exposure in the preceding year. Most isolates (85.7%) were MDR. Fluoroquinolone susceptibility was low (moxifloxacin 19.7%). All isolates were susceptible to vancomycin (MIC₉₀ 2 µg/mL), and no vancomycin-intermediate, heteroresistant, or tolerant phenotypes were identified. Whole genome sequencing (n = 41) demonstrated predominance of clonal complexes 5 (68.3%) and 8 (29.2%). Visual outcomes were poor, with most patients (85.2%) having a final visual acuity worse than 20/60 among those with follow-up. CONCLUSIONS: MRSA keratitis is associated with high rates of multidrug resistance and poor visual outcomes despite guideline-based therapy. Infections were predominantly caused by CC5 MDR strains despite limited recent healthcare exposure. These findings highlight the persistence of highly resistant MRSA lineages in community-associated corneal infection and underscore the need for ongoing antimicrobial surveillance and optimized treatment strategies.

Humans

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg &#xd7; 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age &#x2264;50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article

The role of psychological resilience in the relationship between complex post-traumatic stress disorder symptom severity and functioning impairment in mental health support-seeking Australian defence force veterans: A cross-sectional study.

OBJECTIVE: Military veterans have high rates of mental health conditions; complex post-traumatic stress disorder may be the most functionally impaired trauma diagnosis in this patient group. Psychological resilience acts as a protective factor for mental health. Still, it is unclear how this may influence relationships between the two main symptom clusters of complex post-traumatic stress disorder and functioning impairment in veterans. Therefore, we investigated the relationships between psychological resilience, trauma symptom severity, trauma exposure and work/social functional impairment among Australian Defence Force veterans. METHODS: Cross-sectional survey including 148 mental health support-seeking former-serving Australian Defence Force veterans in primary care. Relationships between variables were explored using correlations, mean difference tests and mediation analysis to examine the role of resilience in the relationship between complex post-traumatic stress disorder symptoms and functional impairment. RESULTS: Resilience showed significant negative correlations with functioning impairment. The number of traumas showed weak positive correlations with disturbances in self-organisation symptoms, post-traumatic stress disorder symptoms and functional impairment. The complex post-traumatic stress disorder group had significantly lower resilience and functioning than those with no diagnosis. After controlling for the number of trauma exposures, resilience partially mediated the association between post-traumatic stress disorder symptoms and functioning (indirect effect&#x2009;=&#x2009;0.141, p&#x2009;<&#x2009;0.05), and partially mediated the association between disturbances in self-organisation symptoms and functioning (indirect effect&#x2009;=&#x2009;0.157, p&#x2009;<&#x2009;0.05). CONCLUSIONS: Psychological resilience was associated with better functioning in veterans regardless of trauma diagnosis. Resilience also partially mediates the relationship between disturbances in self-organisation/post-traumatic stress disorder symptoms and functioning in those with International Classification of Diseases, 11th Revision, complex post-traumatic stress disorder, indicating it is an important intervention target in Australian Defence Force veterans with polytrauma.

Humans

Substance use and co-occurring mental health conditions among adolescents and young adults in North America: a systematic review.

BACKGROUND: Substance use and co-occurring mental health conditions are common among adolescents and young adults and represent an important clinical and public health concern in North America. Trauma exposure, psychiatric symptoms, and social adversity frequently co-occur with substance-related problems in this population. This systematic review aimed to synthesize evidence on prevalence patterns, associated clinical and psychosocial factors, and care-related implications described in the literature on adolescents and young adults with substance use and co-occurring mental health conditions. METHODS: This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024581685). A systematic search was conducted in MEDLINE (Ovid), Embase, PsycINFO, and Google Scholar. Eligible studies examined adolescents and young adults (&#x2264;&#x2009;25 years) in North America. A combination of subject headings, keywords, and synonyms for the concepts "adolescents," "young adults," "substance use disorders," and "co-occurring mental health conditions" was used. Of 1,882 records identified, 29 studies met the inclusion criteria. Given the heterogeneity of the literature, findings were synthesized narratively. RESULTS: The included studies showed heterogeneity in population, setting, denominator, and ascertainment method. Across the literature, depressive, anxiety-related, trauma-related, and externalizing mental health presentations were frequently reported alongside substance-related problems in adolescents and young adults. Trauma exposure, adverse childhood experiences, and broader social adversity were also commonly reported in association with substance-related problems across studies. Care-related implications were more limited and were largely derived as future directions mentioned across studies rather than direct evaluations of youth-specific service models. CONCLUSION: Co-occurring mental health and substance-related problems were frequently reported among adolescents and young adults in high-risk and service-engaged populations in North America. Trauma and social adversity were prominent across the reviewed literature, while direct evidence for evaluated, integrated, youth-specific care models remains limited. These findings support the relevance of developmentally appropriate, integrated, and trauma-informed approaches to care and highlight the need for further research directly evaluating improved service delivery models for this population. CLINICAL TRIAL NUMBER: Not applicable.

Humans

Alternative genetic codes in bacteria and archaea identified with a fast k-mer-based algorithm.

The genetic code is conserved across all domains of life and is often described as universal. Nevertheless, many exceptions to the "universal" code have now been documented, most of these through manual or semiautomated inspection of highly conserved genes. Modern bioinformatics tools improved our ability to find alternative genetic codes but remain computationally expensive, preventing widespread use on thousands of new species identified by sequencing environmental samples. Here, I report a >100-fold accelerated method for inferring the genetic code directly from assembled genomes and apply it to thousands of previously uncharacterized assemblies from archaea and bacteria. I describe three candidate genetic code variations, one of which, an alternative genetic code used by a family of Asgard archaea, is a unique example of sense codon reassignments for this domain. Identifying genetic code variations is important for understanding evolution of the standard code and improving accuracy of protein databases and open reading frame identification.

Genetic Code

Safety, tolerability, pharmacokinetics, and pharmacodynamics of oral JMKX003002 in Chinese healthy participants: a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food-effect phase I clinical trial.

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharma-codynamics (PD) of the sodium-hydrogen exchanger 3 (NHE3) inhibitor JMKX003002 in Chinese healthy participants. PATIENTS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study included a single-ascending dose (SAD) study with seven cohorts (1&#x2009;mg [n&#x2009;=&#x2009;4] and 5, 20, 50, 75, 100, or 125&#x2009;mg [n&#x2009;=&#x2009;8]), a food-effect (FE) study with six sequence groups (25&#x2009;mg twice daily, n&#x2009;=&#x2009;4), and a multiple-ascending dose (MAD) study with two cohorts (10&#x2009;mg or 20&#x2009;mg twice daily, n&#x2009;=&#x2009;10). RESULTS: JMKX003002 was well-tolerated, with mostly mild treatment-related adverse events. One Grade 3 diarrhoea occurred in each of the 50&#x2009;mg and 125&#x2009;mg groups. No serious adverse events were reported, and no participants discontinued or withdrew due to treatment-emergent adverse events. Most plasma samples were below the limit of quantification (0.2&#x2009;ng/mL), with only transient detection of low concentrations, indicating low systemic exposure. JMKX003002 was primarily excreted in&#xa0;stool (79.9% recovered) and was undetectable in urine. The PD results consistently showed decreased urinary sodium and phosphorus, along with increased stool sodium and phosphorus, compared to baseline across all three studies. One day after discontinuation, stool sodium and phosphorus remained elevated relative to baseline in the MAD study. Mixed-effects model analysis in the FE study demonstrated significant food effect on stool sodium and phosphorus excretion. CONCLUSION: JMKX003002 exhibited favorable safety and tolerability with minimal systemic exposure. It effectively increased sodium and phosphorus excretion in stool. These promising findings warrant further investigation of JMKX003002 to evaluate its clinical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070473). Registered on April 13, 2023; prospectively registered.

Adult

Candidate biomarkers for early Giardia duodenalis infection revealed by time-resolved secretome proteomics.

Giardia duodenalis is a zoonotic protozoan parasite that causes giardiasis in humans and other mammals. Early diagnosis remains challenging because current diagnostic methods, including microscopy and enzyme-linked immunosorbent assays (ELISAs), primarily detect established infections. Consequently, a critical diagnostic gap exists during the early stage of infection within the first 2-48&#xa0;h following exposure. To address this limitation, we characterized the proteins released by in vitro-cultured G. duodenalis trophozoites under serum-free conditions and evaluated their potential as early diagnostic biomarkers. Proteomic analysis of culture supernatants collected during early trophozoite incubation identified 31,773 peptides corresponding to 2504 quantifiable proteins. Temporal profiling showed distinct secretion patterns, including proteins that peaked during the early stage, progressively accumulated over time, or remained persistently abundant throughout the incubation period. Based on their secretion characteristics and predicted immunogenic properties, five candidate biomarkers were selected for further evaluation. Polyclonal antibodies raised against selected candidates successfully detected the corresponding proteins in serum-free culture supernatants, providing preliminary evidence for their potential utility as early-stage diagnostic targets. These findings identify stage-associated candidate proteins that may serve as a resource for future early giardiasis diagnostic development, provide a valuable resource for investigating host-parasite interactions, and establish a foundation for future diagnostic assay development. However, further validation in clinical and biological samples is required to confirm their diagnostic applicability. SIGNIFICANCE: Giardiasis, caused by Giardia duodenalis, is a major diarrheal disease worldwide. Although enzyme-linked immunosorbent assays (ELISAs) provide rapid detection, their diagnostic utility is limited by the lack of biomarkers capable of identifying infection during its earliest stages, creating a critical gap in the detection of active infection within 2-48&#xa0;h following exposure. Using data-independent acquisition proteomics, this study provides a time-resolved characterization of proteins released by G. duodenalis trophozoites into serum-free culture supernatants. Our findings reveal temporal secretion dynamics of protein secretion and identify candidate biomarkers with potential utility for the development of early-stage diagnostic assays pending rigorous biological and clinical validation. In addition, this proteomic resource provides a foundation for investigating host-parasite interactions and may facilitate the development of future point-of-care diagnostic strategies.

Giardiasis

The Effects of Intermittent Hypoxic Training Strategies on Maximal Oxygen Uptake in Healthy Humans: A Meta-analysis with Meta-regression.

BACKGROUND: Intermittent hypoxic training aims to enhance exercise performance and health, commonly assessed through maximal oxygen uptake (VO2max). Currently applied methods are live-high train-low (LHTL), live-low train-high (LLTH) and passive hypoxic conditioning (PHC). However, within these methods, numerous modes of application exist, and effectiveness is debated. OBJECTIVE: To determine the effect of LHTL, LLTH and PHC on VO2max in healthy participants, and identify factors associated with the amplitude of change in VO2max. METHODS: We conducted a systematic review with random-effects meta-analysis and meta-regression. Studies were identified through PubMed, EMBASE and Web of Science. We included controlled studies, calculating between-group standardised mean differences. Athlete and non-athlete populations were analysed separately. RoB2 was used to assess study quality and publication bias was investigated with funnel plots and the Egger's test. RESULTS: Of the 5244 identified studies, 62 were included for analysis, resulting in a sample size of 1332 participants (610 athletes, 722 non-athletes). LHTL increased VO2max significantly more than control in athletes (mean difference [MD]&#x2009;=&#x2009;2.17; 95% CI&#x2009;=&#x2009;0.77, 3.56) but not in non-athletes (MD&#x2009;=&#x2009;3.1; 95% CI&#x2009;=&#x2009;&#x2009;-&#x2009;0.23, 6.43). LLTH did not increase VO2max significantly more than control in athletes (MD&#x2009;=&#x2009;0.89; 95% CI&#x2009;=&#x2009;&#x2009;-&#x2009;0.27, 2.05) but it did in non-athletes (MD&#x2009;=&#x2009;1.70; 95% CI&#x2009;=&#x2009;0.85, 2.54). PHC did not increase VO2max significantly more than control in athletes (MD&#x2009;=&#x2009;&#x2009;-&#x2009;1.07; 95% CI&#x2009;=&#x2009;&#x2009;-&#x2009;3.51, 1.37) but it did in non-athletes (MD&#x2009;=&#x2009;2.26; 95% CI&#x2009;=&#x2009;1.00, 3.52). Multivariate meta-regressions identified the severity, duration, and frequency of hypoxic exposure to be significantly associated with the change in VO2max. CONCLUSIONS: LHTL showed a significant effect on VO2max in athletic populations while LLTH and PHC showed a significant effect on VO2max in non-athletic populations only. Future studies should target investigating which characteristics (e.g. severity, duration) of the hypoxic exposure are most beneficial.

Journal Article

Modelling the effects of biological intervention in a dynamical gene network.

Cellular response to environmental and internal signals can be modeled by dynamical gene regulatory networks (GRN). In the literature, three main classes of gene network models can be distinguished: (1) non-quantitative (or data-based) models which do not describe the probability distribution of gene expressions; (2) quantitative models which fully describe the probability distribution of all genes co-expression; and (3) mechanistic models which allow for a causal interpretation of gene interactions. We propose two rigorous frameworks to model gene alteration in a dynamical GRN, depending on whether the network model is quantitative or mechanistic. We explain how these models can be used for design of experiment, or, if additional alteration data are available, for validation purposes or to improve the parameter estimation of the original model. We apply these methods to the Gaussian graphical model, which is quantitative but non-mechanistic, and to mechanistic models of Bayesian networks and penalized linear regression.

Gene Regulatory Networks

Sex modifies the association of high-altitude hypoxia with poor sleep quality and depression in school-age children and adolescents.

BACKGROUND: While chronic exposure to high-altitude hypoxia is known to impair sleep and mental health, whether these effects are sex-dependent remains unclear. This study addresses a critical gap by investigating how sex modifies the association between high-altitude hypoxia and risks of poor sleep quality, depressive symptoms, and their co-occurrence in children and adolescents. METHODS: In this cross-sectional study (March-May 2024), we enrolled 1,345 long-term residents of the Shannan Tibet Autonomous Prefecture (altitude: 3,650-4,800&#xa0;m) and 2,909 age-matched controls from low-altitude plains (Anhui Province, China). Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Montgomery-Asberg Depression Rating Scale (MADRS), respectively. Sex-stratified analyses and interaction metrics (RERI/AP/SI) were employed to evaluate additive and multiplicative effects. RESULTS: High-altitude residents exhibited significantly higher prevalence of poor sleep (24.2% vs. 18.7%, P&#x2009;<&#x2009;0.001), depression (23.6% vs. 15.3%, P&#x2009;<&#x2009;0.001), and their co-occurrence (12.6% vs. 8.6%, P&#x2009;<&#x2009;0.001) compared to low-altitude controls. A significant negative additive interaction (RERI&#x2009;=&#x2009;-&#x2009;0.78, 95% CI: -1.35 to -&#x2009;0.3; P&#x2009;<&#x2009;0.001) indicated that sex modifies the altitude-outcome association. Specifically: (1) high-altitude residence significantly increased poor sleep risk in males (OR&#x2009;=&#x2009;1.60, 95% CI: 1.26-2.03) but not in females (OR&#x2009;=&#x2009;1.39, 95% CI: 1.07-1.79); and (2) the expected female predominance in poor sleep observed in the plain region (OR&#x2009;=&#x2009;1.452, 95% CI: 1.191-1.769) disappeared in the plateau region (OR&#x2009;=&#x2009;0.865, 95% CI: 0.667-1.121). Similar patterns were independently replicated for depressive symptoms. These findings confirm that high-altitude exposure differentially increases risk in males rather than protecting females. CONCLUSION: Males show marked vulnerability to high-altitude-associated sleep and mood impairments, while females demonstrate resilience. Sex-tailored interventions for high-altitude populations, particularly targeting male adolescents, are urgently needed.

Humans

Pilot Distractions and Interruptions in Airlines: Ranking of Sources by Analytic Hierarchy Process.

ObjectiveThis work establishes a methodological framework for sources of pilot distraction and interruptions in a structured model that can be used as a tool for cockpit design/procedure assessment.BackgroundPilots must complete complex tasks, and distractions can impair performance and lead to errors that can cause aircraft accidents. Although various cockpit distractors are examined individually, there is no integrated approach.MethodDistraction and interruption sources were identified through a literature review and confirmed/extended by interviews with airline pilots. Associated weights were determined through pairwise comparisons, yielding a hierarchical model using the Analytic Hierarchy Process.Results26 sources of pilot distraction and interruptions were quantified and categorized into four categories: communication, head-down time, responding to abnormal conditions & unexpected situations, and searching for traffic.ConclusionA taxonomic structure for assessment is achieved with the top 5 sources identified as communications, technical interruptions, experience in type, environmental factors, operational irregularities, and airspace high terrain, accounting for 63.07%.ApplicationThe structured system is a flexible assessment scale that provides a taxonomic framework for airline risk management, supports future research, and cockpit design efforts.

Humans

Hand Pain and Sensory Deficits: Carpal Tunnel Syndrome: 2026 Revision. Using the Evidence to Guide Musculoskeletal Rehabilitation Practice.

SYNOPSIS: Carpal tunnel syndrome is common in women, manual laborers, and during pregnancy; it is often associated with medical conditions such as obesity and diabetes. The musculoskeletal rehabilitation clinician's approach to managing hand pain and sensory deficits associated with carpal tunnel syndrome should include prescribing a neutral-positioned wrist orthosis plus instructing the patient on how to modify activities, adjust ergonomics, and reduce exposure to risk factors. Here, we present for clinicians the most up-to-date information to guide their work in managing hand pain and sensory deficits associated with carpal tunnel syndrome. J Orthop Sports Phys Ther 2026;56(9):622-623. doi:10.2519/jospt.2026.0502.

Humans

Control of foreign DNA: emerging roles of xenogeneic silencers.

Bacteria continuously acquire foreign DNA through horizontal gene transfer, yet its successful integration depends on regulatory mechanisms that balance genome protection with evolutionary innovation. Xenogeneic silencers are central to this process: they preferentially bind AT-rich DNA, a common feature of many horizontally acquired genetic elements, and repress its transcription. Recent studies, however, reveal a much broader regulatory repertoire. Beyond transcriptional repression, these proteins contribute to chromosome organization by forming higher-order nucleoprotein complexes and phase-separated condensates that shape bacterial nucleoid architecture. Furthermore, they play roles in regulating bacteriophage infection cycles, including mechanisms by which phages hijack host silencing activities for their own benefit. Their extensive regulatory reach, spanning virulence genes, biofilm formation, specialized metabolite production, and mobile genetic elements (MGEs), underscores their central role in connecting environmental signals, including fluctuations in the second messenger c-di-GMP, with gene expression, and genome organization. The diversification of xenogeneic silencers across bacterial chromosomes, plasmids, phages, and other MGEs highlights their evolutionary significance. Together, these recent findings position xenogeneic silencers as dynamic regulatory modules that shape the fate of foreign DNA across the horizontal gene transfer network.

Gene Transfer, Horizontal

Evaluation of the effects of domestic tomato processing on biopesticide residue using natural deep eutectic solvents (NADES) extractions.

The present study evaluated the fate of fourteen botanical biopesticides in processed tomato samples. Various processing methods were employed, including washing, dehydration, and the preparation of juice and sauce. The extraction was performed using more sustainable techniques, aimed at minimizing the environmental impact of conventional organic solvents by substituting them with natural deep eutectic solvents (NADES). Solid-liquid extraction (SLE) and dispersive liquid-liquid microextraction with solidification of floating organic drop (DLLME-SFOD) were utilized for solid and liquid tomato samples, respectively. The NADES used was choline chloride:2,3-butanediol (ChClBt) at a 1:4&#xa0;molar ratio for both techniques, resulting in recovery values ranging from 69.2 to 106.2% for SLE, and extraction efficiencies reaching up to 46.2% for DLLME-SFOD. The impact of these processes was evaluated employing the processing factor (PF), yielding PF values of less than 1 in all cases. Compounds as pyrethrins, azadirachtin, and rotenone persisted after processing, posing a potential consumer risk.

Solanum lycopersicum

PGPR inoculation and growth enhancement of crops cultivated in hydroponic systems.

Plant growth-promoting rhizobacteria (PGPR) are ubiquitous rhizosphere microorganisms that promote plant health through various mechanisms. Although the study of PGPR inoculants in soil has been done for ages, their application in hydroponic systems has received relatively limited attention. This review identifies PGPR inoculants that are commonly used in hydroponics, methods of application, and their effects on plant growth and nutrient use efficiency. Literature shows that PGPR inoculants improve plant performance in controlled hydroponic systems through the production of growth-stimulating substances, nitrogen fixation, and improved nutrient acquisition. However, the plant growth responses are highly variable depending on the composition of nutrient solutions, environmental factors, crop and microbe species, and the type of hydroponic system. The review identifies various challenges of PGPR inoculation in hydroponic systems and future research directions to address the current gaps. Generally, the productivity of hydroponic systems can be enhanced through advanced inoculation strategies and the development of suitable carrier materials to improve inoculant survival, viability, and functions. Emphasis should also be placed on designing system-specific microbial consortia and Synthetic communities that are tailored to the unique ecological conditions of hydroponic systems.

Hydroponics

Developmental roles of LSD1/KDM1A-like (LDL) proteins in plants.

LYSINE-SPECIFIC DEMETHYLASE 1-like (LDL) proteins are conserved FAD-dependent amine oxidases that serve as pivotal regulators in plants. While animal systems typically rely on a single LSD1/KDM1A enzyme, the Arabidopsis thaliana genome encodes an expanded family of LDL homologues (FLD, LDL1, LDL2, and LDL3), resulting in substantial subfunctionalization and specialized recruitment mechanisms. This review explores the diverse developmental roles of plant LDLs, ranging from flowering time and circadian clock regulation to heterochromatin maintenance and epigenetic regulation. We discuss the redundant roles of FLD, LDL1, and LDL2 in repressing the floral repressor FLC and their nonredundant specialized function within the CCA1/LHY-TOC1 circadian feedback loop. A central focus of our review is the emerging mechanism of transcription-coupled demethylation, in which LDLs associate with the phosphorylated C-terminal domain of RNA polymerase II to modify chromatin cotranscriptionally within gene bodies. By integrating findings from Arabidopsis thaliana and crops such as tomato and soybean, we illustrate how the diversified LDL-mediated regulatory toolkit facilitates precise, gene-specific regulation. Ultimately, the LDL family represents a cornerstone of the sophisticated epigenetic strategies that regulate plant phenotypic plasticity in response to developmental and environmental cues.

Circadian clock