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PubMed2026

A randomized trial of omega-3 fatty acids plus inositol versus N-acetylcysteine for the treatment of depression and mania in emotionally dysregulated youth age 5-17 with and without autism traits.

The aim of this study was to assess the effectiveness of the nutraceutical treatments combined omega-3 fatty acid plus inositol (O3I) versus N-acetylcysteine (NAC) in children and adolescents with emotional dysregulation and the impact of the co-occurrence of autism traits (AT). Participants were male and female children (5-17) with emotional dysregulation and the presence/absence of AT, as defined by Child Behavior Checklist score, randomized to receive open-label O3I (1020 mg EPA and 1000-2000 mg Inositol) or NAC (1800-2700 mg) daily for 6 weeks. Clinicians measured severity and improvement of depression and mania with the NIMH Clinical Global Improvement Scale (CGI). Parents completed Parent-Youth Mania Rating Scale (P-YMRS) and Children's Depression Inventory (CDI). Both O3I and NAC resulted in modest improvements in mania and depression and did not differ significantly in between group comparison in their effectiveness. Participants taking O3I, but not NAC, demonstrated statistically significant within group improvement in depression per CDI. Participants taking NAC had a greater decrease in P-YMRS scores versus O3I, but the difference did not reach statistical significance. In the presence of AT, NAC was more effective than O3I for mania but not for depression. Further, participants taking NAC, but not O3I, demonstrated significant within group improvement in SRS and BRIEF scores. These results suggest that O3I and NAC may be beneficial for mania and depression in youth, with trends towards O3I more effective for depression and NAC more effective for mania. The presence of AT in youth with emotional dysregulation may moderate the impact of NAC.

Humans↗

PubMed2026

Bypassing the emergency department for testicular torsion.

BACKGROUND: Testicular torsion is a time-sensitive urologic emergency that can result in testicular ischemia, atrophy, and loss if detorsion is delayed. Patients transferred from outside hospitals oftentimes experience prolonged ischemia due to repetitive assessments in the receiving emergency department (ED) and lengthy interhospital transfers. To address these delays, our institution created a pathway allowing patients with a confirmed diagnosis of testicular torsion to bypass the ED and proceed directly to the OR. OBJECTIVE: To evaluate the efficacy of an emergency department bypass pathway on time to surgical intervention and testicular salvage rates for patients transferred from outside hospitals with confirmed testicular torsion. STUDY DESIGN: Following one year of pathway implementation and institutional review board approval, a retrospective chart review was performed. Patients aged 12-18 years that were transferred from outside hospitals for confirmed testicular torsion were included in the pathway. A pre-pathway cohort (January 2022-December 2022) of patients with ED management was compared to a post-pathway cohort (August 2023-September 2024) of patients managed via direct OR transfer. Comparisons included patient age, mean time from ED registration to surgery start, orchiectomy rates, testicular atrophy rates at follow-up, and overall length of follow-up. T-tests and Fisher's exact tests were used for statistical analysis. RESULTS: 71 patients were included. Mean time from registration to OR start was significantly shortened in the post-pathway cohort compared to the pre-pathway cohort (70 min vs. 23 min, p < 0.0001). This represents a 67% decrease in time to surgery. Post-pathway patients were significantly older than pre-pathway patients (15 years vs. 13 years, p = 0.0025). Orchiectomy rates did not significantly differ between the two groups (14% post-pathway and 28% pre-pathway, p = 0.2454). Similarly, no significant difference was observed for testicular atrophy at follow-up (17% post-pathway and 15% pre-pathway, p = 1.0). Mean length of follow-up was insignificant (90 days for post-pathway and 76 days for pre-pathway, p = 0.6605). DISCUSSION: Direct transfer to the OR with ED bypass significantly reduced time to surgical detorsion. Other variables such as orchiectomy and testicular atrophy rates were not significantly impacted. Patient-limited factors may have influenced outcomes, such as delays in symptom recognition and time to initial care. CONCLUSION: An ED bypass pathway for transferred patients with testicular torsion was highly effective at reducing time to surgical intervention. Although testicular salvage rates were not significantly affected, reducing ischemia time is clinically important and encourages pathway refinement and broader use.

Humans↗

PubMed2026

Molecular characterization of 16 MAPK genes in silver carp (Hypophthalmichthys molitrix) and the differences of their mRNA expression between Qiandao Lake and Taihu Lake.

Mitogen-activated protein kinase (MAPK), a serine-threonine protein kinase, is involved in a variety of stress-induced responses and also plays an important regulatory role in cell metabolism. In the study the open reading frames (ORFs) of 16 MAPK genes in silver carp (Hypophthalmichthys molitrix) were obtained and verified, with the evaluations of their taxonomy, structures, conserved motifs, and evolutionary linkages. And the expression patterns of these genes in the silver carp from Qiandao Lake and Taihu Lake were explored for better understanding the response of MAPK genes to different water environment. MAPK genes of silver carp were divided into three subfamilies, including extracellular signal-regulated kinase (ERK) subfamily, p38 subfamily and C-Jun N-terminal kinase (JNK) subfamily. All these genes possessed similar structures and conserved motifs of MAPK family. Realtime qPCR revealed that the expression patterns of 10 MAPK genes (ScMAPK1, ScMAPK3, ScMAPK4, ScMAPK7, ScMAPK15, ScMAPK8a, ScMAPK8b, ScMAPK9, ScMAPK10 and ScMAPK11) in head kidney, spleen and gill of silver carp in Taihu Lake and Qiandao Lake were different. These findings provide a basis for further research on the function of MAPK in silver carp.

Animals↗

PubMed2026

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans↗

PubMed2026

Diving Deeper Into Mechanisms of Acrylamide-Induced Toxicity: RNA Sequencing Reveals Transcriptomic Alteration and Retrotransposon Expression in Drosophila melanogaster.

Given the inevitability of human and animal exposure to acrylamide, there is increasing concern regarding its potential health risks. While a number of molecular mechanisms have been proposed, the complexity of acrylamide toxicological pathways and interactions remains incompletely characterized. In this study, we employed a transcriptomic approach to investigate the transcriptional responses of Drosophila melanogaster following exposure to acrylamide (100 mg/kg). Our analysis identified 634 differentially expressed genes (DEGs), with 362 upregulated and 272 downregulated. Functional analysis revealed these DEGs are enriched in pathways related to reproduction, detoxification, cellular and metabolic processes, signaling, synaptic formation and organization. Notably, acrylamide exposure upregulated the expression of tau and beta-amyloid protein precursor-like genes, both implicated in Alzheimer's disease pathology. An aversive memory test further demonstrated that acrylamide impaired the short-term memory of treated flies. Additionally, acrylamide-induced toxicity altered the expression of nine long terminal repeat retrotransposons, belonging to the gypsy and pao superfamilies. By exploring the potential role of transposable element activity in acrylamide-mediated toxicity, this study provides novel insights into the molecular mechanisms underlying its effects. Collectively, these findings offer a more comprehensive understanding of the mechanisms and pathways associated with the toxic action and detoxification of acrylamide in D. melanogaster.

Animals↗

PubMed2026

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans↗

PubMed2026

Effects of adjunctive bifrontal tDCS on depressive symptoms and cognitive performance in major depressive disorder: A randomized, double-blind, sham-controlled crossover pilot study.

BACKGROUND: Evidence for antidepressant effects of transcranial direct current stimulation (tDCS) in major depressive disorder (MDD) is heterogeneous, and cognitive effects remain uncertain. We compared depressive symptoms and DSST performance during active and sham bifrontal tDCS in medicated outpatients with MDD and baseline HAMD-17 ≥ 15. METHODS: In this randomized, double-blind, sham-controlled crossover pilot trial, adults with MDD and inadequate response to an adequate antidepressant trial were assigned to active→sham or sham→active tDCS sequences while continuing antidepressants. Each period comprised 10 sessions over 2 weeks. Active stimulation was delivered at 2 mA for 20 min (anode F3, cathode F4); sham used the same montage with brief ramping only. No washout interval was used. No washout interval was used. The primary outcome was HAMD-17; secondary outcomes were DSST and CGI ratings. RESULTS: Of 38 randomized participants, 32 completed both periods and were analyzed per protocol. HAMD-17 scores were lower during active than sham stimulation (mean difference -3.63, 95% CI -5.86 to -1.40; p = 0.002), but the condition-by-sequence interaction was significant (p = 0.026). No condition effect was observed for DSST (p = 0.261) or CGI-Severity (p = 1.000); CGI-Improvement was strongly sequence-dependent (p < 0.001). In an exploratory first-period analysis, adjusted T1 HAMD-17 scores were lower in the active-first group (adjusted difference -4.90, 95% CI -7.92 to -1.87; p = 0.003). Adverse effects were mild and transient. CONCLUSIONS: Active tDCS was associated with lower HAMD-17 scores, but the pooled contrast was order-dependent and cannot be interpreted as a definitive treatment effect. No DSST benefit was observed.

Humans↗

PubMed2026

Genome-wide identification and characterization of ABC transporters and their expression in response to saline-alkaline stress and WSSV infection in Fenneropenaeus chinensis.

ATP-binding cassette (ABC) transporters play crucial roles in stress responses across organisms, yet their functions in Fenneropenaeus chinensis remain largely unknown. In this study, we identified 42 FcABC genes (FcABCs) in the F. chinensis genome and analyzed their phylogenetic relationships, gene structures, and chromosomal distributions. Phylogenetic analysis grouped the FcABCs into eight subfamilies (ABCA-ABCH), with conserved motif and domain compositions within each subfamily. Expression analysis showed that several FcABC genes, including FcABCG5, FcABCA1, and FcABCC3, were significantly induced under saline-alkaline stress in gill and hepatopancreas tissues. In contrast, most FcABCs were downregulated after WSSV challenge, though a subset (e.g., FcABCB1, FcABCC1) exhibited early upregulation. Functional validation via RNA interference demonstrated that knockdown of FcABCG5 increased shrimp mortality under saline-alkaline stress. Cis-regulatory element analysis revealed an enrichment of stress- and immune-related elements in FcABC promoters. Protein-protein interaction network predictions indicated potential roles for FcABCs in cholesterol metabolism and organic anion transport. Our findings provide insights into the roles of FcABC genes in stress adaptation and immune defense, offering candidate genes for the breeding of stress-resistant shrimp varieties.

Animals↗

PubMed2026

Sleep stage-dependent distribution of interictal epileptiform discharges in epilepsy: A systematic review.

BACKGROUND: Sleep and epilepsy interact through complex bidirectional mechanisms. Although NREM sleep facilitates interictal epileptiform discharges (IED), the diagnostic contribution of individual sleep stages remains uncertain. In particular, it is unclear whether deeper sleep stages such as N3 provide an advantage over N2 for spike detection or localization in clinical (electroencephalography) EEG practice. METHODS: This systematic review followed PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies reporting quantitative IED measures across sleep stages in patients with epilepsy. Eligible studies included scalp EEG, video-EEG, polysomnography, or intracranial recordings. Mean IED rates per minute were derived when possible. Comparisons between NREM and REM sleep and between N2 and N3 stages were performed using study level non-parametric tests. Risk of bias was assessed with the ROBINS-I tool. RESULTS: Ten observational studies including 266 patients (mean age 30.1 years) were analyzed. IED rates were significantly higher during NREM than REM sleep (Wilcoxon signed-rank test, W = 0, p = 0.0019, r = 0.87). No significant difference was observed between N2 and N3 sleep, although median spike rates were slightly higher during N3 than N2 (0.99 vs 0.86 IED/min). REM showed the lowest activity. CONCLUSIONS: NREM sleep consistently exhibited higher IED rates than REM sleep, reinforcing the neurophysiological association between sleep stage and epileptiform activity without establishing diagnostic superiority.

Humans↗

PubMed2026

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer↗

PubMed2026

The effect of drysuit diving in warm water on body temperature and post immersion orthostatic hypotension.

INTRODUCTION: Warm-water diving can limit heat dissipation, particularly when performed in fully encapsulating protective gear, leading to substantial thermal and cardiovascular strain that may impair diver safety. Following immersion, removal of hydrostatic support combined with heat-induced vasodilation may reduce central blood volume and increase susceptibility to orthostatic intolerance during egress and recovery. The extent to which this thermal strain impairs post-immersion orthostatic tolerance remains unknown. METHODS: Four randomised, crossover immersion trials were conducted at 28°C, 33°C, 38°C without precooling (38°C), and 38°C with precooling (38°C + Cool), with subjects wearing fully encapsulating dive gear. Subjects walked for up to 60 minutes at approximately 50% of O2max heart rate (HR) or until core temperature (Tc) reached 38.5°C, or they voluntarily stopped. Tc, HR, and perceptual measures were recorded every 10 minutes. Orthostatic tolerance was assessed after immersion via a 70° head-up tilt test. RESULTS: Eight healthy adults completed all aspects of the study. Tc and HR were higher during both 38°C conditions compared with 28°C and 33°C (all P < 0.01) with no differences between 38°C and 38°C + Cool. Sweat loss exceeded 1.2 (SD 0.67) L⋅h-1 in both 38°C conditions compared with ≤ 0.3 (0.32) L⋅h-1 at 28°C and 33°C (P < 0.01). Survival analysis showed orthostatic tolerance decreased with increasing thermal stress (log-rank P = 0.027; trend P = 0.003). Precooling did not reduce peak Tc or HR, nor did it improve tolerance time in 38°C water. CONCLUSIONS: Encapsulated warm-water diving causes heat stress and cardiovascular strain that persists after immersion, impairing orthostatic tolerance. Precooling does not significantly reduce these outcomes.

Humans↗

PubMed2026

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans↗

PubMed2026

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (ΔCAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p = 0.049), particularly for those with higher non-planning impulsivity (p = 0.012). In participants randomized to CPT improvement in PTSD symptom severity (ΔCAPS) was negatively related to baseline total impulsivity (p = 0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans↗

PubMed2026

Evolution of maize recombination landscape during domestication.

Despite the plethora of knowledge about the benefits of meiotic recombination and numerous theoretical studies examining how recombination rates evolve, there is a general lack of empirical support and consensus across species. To fill this knowledge gap, we characterized the evolution of recombination landscape in maize during its domestication from teosinte and related the observed changes to established theoretical frameworks. Through examining recombination in experimental populations of maize and teosinte and the population genomics approach of identifying historical recombination events using ancestral recombination graph inference to generate saturated maize and teosinte recombination maps, we found that during domestication, maize experienced a 12% increase in its genome-wide recombination rate. Furthermore, maize evolved higher recombination rates on the long arms of chromosomes in regions closer to centromeres, where recombination is generally very low. The repatterning of crossover events came from changes in global crossover positioning rather than alterations in cis-acting chromatin factors. Consequently, we found evidence of selection acting on trans-acting recombination modifiers affecting crossover interference and controlling the interference-dependent class I crossover pathway. We show that CO repatterning was likely beneficial for maize fitness, as significant recombination rate increases were predominantly in gene-rich regions, which harbor domestication-related variation. This work suggests genomic and mechanistic processes leading to the evolution of meiotic recombination landscape in response to directional selection pressure and provides evidence for the evolutionary advantage of recombination.

Zea mays↗

PubMed2026

Rhinoplasty Difficulty Scale: Development and Psychometric Analysis of a Surgeon's Assessment of Rhinoplasty Technique and Nasal Deformity Correction.

BACKGROUND: Rhinoplasty surgeons lack a universal scale of the relative difficulty of rhinoplasty techniques and rhinoplasty deformities. OBJECTIVE: To compare the expert opinion of the difficulty of rhinoplasty techniques and rhinoplasty deformities among international rhinoplasty surgeons, as measured by a scale of difficulty. METHODS: A cross-sectional survey of rhinoplasty surgeons collected training levels, experience, case volume, and perceived expertise. Rhinoplasty techniques/deformities (n = 64) were rated from 1-10, representing the least to most technically demanding. Rasch analysis was used to examine the fit of the observed data to Rasch model requirements, assess rating scale functioning, and provide estimates of internal consistency. RESULTS: Respondents (n = 63) were in practice (<5 years, 14%; 5-10, 20%; 10-20, 20%; 20-30, 26%; >30, 20%), and rhinoplasty volume ranged from <25 (14%) to >100 cases/year (32%). Self-reported expertise was comfortably novice (32%), intermediate (10%), advanced (28%), and expert (30%). Otolaryngology (42%), facial plastic surgery (30%), and plastic surgery (28%) were represented. Rasch estimates of internal consistency reliability were excellent (0.96 for surgeons and 0.99 for items); the item difficulties were more heterogeneous (mean: 0, SD: 1.23) than the distribution of surgeons (mean: -0.09, SD: 0.58). Survey items were ordered by difficulty, ranging from least difficult (inferior turbinate reduction = 1.01) to most difficult (contracted nose repair post-infection = 8.24). CONCLUSION: The newly developed Rhinoplasty Difficulty Scale provides ratings of common rhinoplasty techniques and deformities with a high correlation among experts using this rating scale.

Humans↗

PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P < 0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-κB-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-κB-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗

PubMed2026

Light regulates capsaicinoid biosynthesis via the CaHY5-CaBBX2-CaACS8 module in pepper.

Capsaicinoids are a class of unique alkaloids that confer the pungent taste to pepper fruits. However, it remains largely unknown how light regulates the biosynthesis of capsaicinoids. We conducted a metabolic analysis on light- and dark-adapted pepper fruits. The results showed that dark-adapted pepper fruits had lower capsaicinoid contents and correspondingly downregulated transcription of capsaicinoid biosynthetic genes (CBGs), indicating that light plays a crucial role in capsaicinoid biosynthesis. Furthermore, silencing of CaHY5, a pivotal transcription factor gene in the light signaling pathway, decreased the content of capsaicinoid and suppressed the expression of CBGs, whereas transient overexpression of CaHY5 generated exactly opposite results. CaHY5 can bind to the G-box motif in the promoters of CaBBX2 and CaACS8, thereby enhancing their transcriptional levels. The activated CaBBX2 then binds to the T/G-box in the CaACS8 promoter to stimulate its expression. CaBBX2 or CaACS8 silencing led to decreased levels of capsaicinoids, while their transient overexpression produced increased capsaicinoid contents. Collectively, our results indicated that the light-activated CaHY5-CaBBX2-CaACS8 regulatory module plays a pivotal role in capsaicinoid biosynthesis. These findings provide new insights into the influence of light on capsaicinoid biosynthesis and potential targets for activation of this biosynthetic pathway in pepper.

Capsicum↗

PubMed2026

Genome-wide scans reveal candidate genes associated with wing morph differentiation in Tetrix japonica.

Wing dimorphism is an important dispersal-related trait in insects, but its genomic basis remains poorly understood in pygmy grasshoppers. Here, we integrated genome-wide single-nucleotide polymorphism (SNP) analyses, population structure inference, selection scans, and functional annotation to investigate genomic differentiation between long- and short-winged Tetrix japonica. Principal component analysis (PCA), ADMIXTURE, and phylogenetic analyses revealed weak genome-wide separation between morphs, indicating differentiation on a largely shared genetic background. Genome-wide scans based on the fixation index (FST), nucleotide diversity ratios, and Tajima's D, using 50-kb non-overlapping windows and empirical top-5% outlier thresholds, identified multiple candidate regions across seven chromosomes. The broader long- and short-winged candidate sets spanned 9.35 Mb and 9.37 Mb and directly overlapped 82 and 77 genes, respectively. Candidate genes were associated with signaling/hormone regulation, membrane transport, metabolism, cytoskeletal organization, extracellular matrix structure, and development. Short-winged candidate genes were significantly enriched for ABC-type transporter activity and ATP hydrolysis activity. Because all individuals originated from a single laboratory-maintained population with weak genome-wide structure, these regions should be regarded as candidate loci from a screening-stage analysis that require validation in independent populations and by functional assays, rather than as confirmed targets of selection.

Animals↗