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Brief Report: Beyond Testing: Exploring the Psychosocial Impact of HIV Self-Testing Among Ugandan Gender-Diverse Sex Workers.

BACKGROUND: The psychosocial effect of HIV self-testing (HIVST) on sex workers' self-esteem, depression, alcohol misuse, perceived sex work stigma, and empowerment remains poorly characterized. We hypothesized that HIVST would reduce sex work stigma and improve these psychosocial outcomes by enabling private, autonomous testing and reducing exposure to stigmatizing healthcare encounters. SETTING: Kampala, Uganda. METHODS: We conducted a secondary analysis of the Empower study (NCT03426670), an open-label randomized trial in which 117 cisgender female, transgender female, and cisgender male sex workers were assigned 1:1 to monthly HIVST plus quarterly clinic-based testing, or to quarterly clinic-based testing alone, and followed for 12 months. Self-esteem (Rosenberg Self-Esteem Scale), depressive symptoms (PHQ-2), alcohol misuse (RAPS4), perceived sex work stigma (adapted Female Sex Worker Stigma Scale), and empowerment were assessed quarterly. Mixed-effects regression models, adjusted for baseline values, evaluated intervention effects. RESULTS: Data from 117 participants were analyzed, including 7 early disenrollments. Over 12 months, HIVST participants reported significantly lower perceived sex work stigma than standard of care participants (β = -0.38, P = 0.04; monthly reduction P = 0.003), although the rate of decline did not differ significantly between arms (interaction P = 0.08). Self-esteem and depressive symptoms improved in both arms, with no between-arm differences (interaction P = 0.41 and 0.32). Alcohol misuse and empowerment showed no significant arm differences. CONCLUSION: HIVST may reduce sex work stigma without adverse psychosocial effects, supporting its integration into combination HIV prevention for gender-diverse sex workers in sub-Saharan Africa.

Humans

Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 ± 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation

In vitro EVALUATION OF Beauveria bassiana ISOLATES AGAINST GASTROINTESTINAL NEMATODES FROM GOATS.

Biological control has emerged as a promising alternative for the control of gastrointestinal nematodes in small ruminants. However, additional information is still needed on the nematicidal portencial of Beauveria bassiana and on the early interaction between fungal conidia and infective larvae. In this study, six B. bassiana isolates (LCMS19-LCMS24) were evaluated in vitro using a coproculture assay with fecal samples from naturally infected goats. Larval recovery was compared with that of an untreated control to estimate the percentage reduction in third-stage larvae (L3). The most effective isolate was subsequently examined by scanning electron microscopy (SEM) to characterize its interaction with L3. All isolates reduced L3 recovery compared with the control, although their efficacy differed. LCMS21 showed the greatest reduction in L3 recovery and differed significantly from the other treatments. SEM revealed extensive adhesion of LCMS21 conidia to the L3 cuticle, in the anterior and median regions. However, no clear evidence of conidial germination, germ tube formation, cuticle penetration, or hyphal development was observed after 48 or 72 h. These results indicate that B. bassiana isolates differ in their in vitro activity against gastrointestinal nematodes and identify LCMS21 as the most promising isolate among those tested. The ultrastructural observations support an early fungus-larva interaction, but they do not allow the nematicidal effect to be attributed to adhesion. Further studies are needed to clarify the mechanisms involved and to evaluate the potencial application of this isolate in integrated parasite control programs.

Beauveria bassiana

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145 particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI = 10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals

Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.

Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI&#x2009;<&#x2009;95%; dDDH&#x2009;<&#x2009;70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from -&#x2009;8.8 to -&#x2009;9.0&#xa0;kcal/mol. Daidzein exhibited the highest thermodynamic stability (-&#x2009;9.0&#xa0;kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.

Bradyrhizobium

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the &#x3b2;-carotene hydroxylase (BCH) increases &#x3b2;-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831&#x202f;&#xb5;g/mL FW to 4.236&#x202f;&#xb5;g/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344&#x202f;&#xb5;g/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11&#x202f;mg/mL FW to 0.36&#x202f;mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09&#x202f;mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum

Neighborhood Hostility is Associated With the Relationship Between Park Proximity and Physical Activity Among Youth: National Evidence From Chile.

PURPOSE: Physical inactivity among youth is highly prevalent worldwide. Although proximity to parks and recreational facilities is generally associated with higher physical activity (PA), unsafe or hostile neighborhood environments may limit their use. This study examined whether neighborhood hostility moderates the association between access to recreational facilities and adherence to World Health Organization PA guidelines among Chilean youth. METHODS: This cross-sectional study analyzed data from the 2024 National Physical Activity and Sport Survey of Chile, including 3,477 urban participants stratified into childhood (5-10 years), early adolescence (11-13 years), and late adolescence (14-17 years). Built environment exposures included perceived access to recreational facilities, a cumulative neighborhood hostility score (0-5). Logistic regression models were stratified by age group and adjusted for covariates. Interaction terms assessed moderation by neighborhood hostility, and causal mediation analyses were performed. RESULTS: Adherence to World Health Organization guidelines was low (41.9% in childhood, 43.8% in early adolescence, and 43.9% in late adolescence). Greater distance to recreational facilities was associated with lower odds of meeting activity guidelines. Higher neighborhood hostility was independently associated with lower PA levels. Among adolescents, neighborhood hostility substantially attenuated the association between proximity and activity. Mediation analyses indicated partial mediation, with effective park utilization emerging as the strongest mechanism, accounting for 21.8% of the association (p < .001), followed by psychological motivation (11.9%). DISCUSSION: Proximity to recreational infrastructure alone is insufficient to promote PA in hostile neighborhoods. Policy approaches should integrate infrastructure provision with strategies addressing neighborhood safety and promoting active engagement.

Humans

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60&#xa0;days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals

Getting to the Core of the Matter-Assessing the Role of Replication in Metabarcoding-Based sedaDNA.

Replication is central to most experimental and sampling designs, increasing inferential power and capturing fine-scale data heterogeneity. However, its importance remains poorly evaluated in some ecological and evolutionary settings. This is the case of metabarcoding studies using DNA recovered from sedimentary archives, in which biological signals integrate ecological information through depositional and burial processes, yet are commonly inferred from a single sediment core per site. Here, we evaluated the effect of different types of replication using sedimentary DNA metabarcoding data from two genetic markers (mitochondrial COI and nuclear 18S) using a nested sampling design. The design included three intertidal sites, three spatially separated sediment cores per site (biological replicates), two sediment horizons per core, and eight PCR (technical) replicates per sediment sample. Variance partitioning showed that site identity and sediment age group together explained >&#x2009;70% of the variation in beta diversity, indicating that among-site spatial and stratigraphic differences were the dominant drivers of community composition. PERMANOVA likewise identified non-significant effects of biological replication. Among PCR replicates from the same sediment sample, richness varied substantially, whereas Shannon diversity was more consistent. Despite this variability, differences in community composition among technical replicates remained smaller than those associated with biological replication or site identity, indicating a limited influence on broader ecological patterns. Community composition was highly similar among replicate cores within sites, consistent with stratigraphic coherence. These results indicate limited within-site heterogeneity and suggest that, under stratigraphically coherent conditions, increasing biological replication may provide little additional information, whereas enhancing technical replication and stratigraphic resolution can improve ecological inference from sedimentary DNA metabarcoding datasets.

DNA Barcoding, Taxonomic

Long-term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women. SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024. SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms. AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.

Humans

Genomic characterization of a hypervirulent Aeromonas veronii NN0115 from Nile tilapia and head kidney transcriptome of infected fish reveals B-cell-dominated immune response with specific immunoglobulin downregulation.

Aeromonas veronii is a pathogen of multiple fish species, yet systematic understanding of its infection in Nile tilapia (Oreochromis niloticus) remains limited. A dominant strain, NN0115, was isolated from a natural outbreak and identified as A. veronii by 16S rRNA and whole-genome average nucleotide identity (ANI, 96.33%). Experimental infection revealed high virulence (LD50&#x202f;=&#x202f;3.41&#x202f;&#xd7;&#x202f;106&#x202f;CFU/mL, equivalent to 8.53&#x202f;&#xd7;&#x202f;104&#x202f;CFU/fish). The genome is 4.58&#x202f;Mb (58.57% GC) and encodes 4216 proteins. Virulence factor analysis identified 1253 genes, dominated by motility-related (264) and immune modulation (208) factors. Genomic island GI2 harbors 7 virulence genes and two dual-function resistance-virulence genes. The strain is resistant to 9 of 25 agents tested but carries three RND efflux pump genes whose predicted resistance was not phenotypically observed. The head kidney transcriptome of tilapia at 24&#x202f;h post-bacterial infection identified 773 differentially expressed genes; among them, 57 were immunoglobulin (Ig) genes, and 56 were down-regulated. Integration of published single-cell transcriptomic data showed that non-Ig B-cell marker genes were down-regulated by 32%, whereas Ig genes were reduced by 63%, indicating selective transcriptional suppression of Ig genes rather than a general decrease in B-cell transcriptional activity. Together, this study provides a comprehensive characterization of a highly virulent A. veronii from Nile tilapia and reveals that selective downregulation of B-cell Ig genes is the dominant transcriptional feature of the host head kidney response.

Animals

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n&#x202f;=&#x202f;8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n&#x202f;=&#x202f;4) and 181 in low motile (n&#x202f;=&#x202f;4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7&#x202f;&#xd7; 10&#x207b;2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9&#x202f;&#xd7; 10&#x207b;2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0&#x202f;&#xd7; 10&#x207b;2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3&#x202f;&#xd7; 10&#x207b;1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3&#x202f;&#xd7; 10&#x207b;2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines

Exposure to size-specific particulate matter accelerates DNA methylation aging in people with HIV.

BACKGROUND: People with HIV (PWH) face accelerated aging and increased health risks, with DNA methylation age (DNAmAge) as a critical senescence biomarker. Particulate matter is linked to DNAmAge acceleration (DNAmAA) in general population, but its impact in PWH remains unstudied. METHODS: Thirty-two PWH from Wuhan, China, were enrolled in a prospective panel study with follow-up, and each participant underwent at least two repeated measurements during the study period. Portable air quality monitor measured PM 1 , PM 2.5 , and PM 10 exposures 72&#x200a;h preblood sampling. We analyzed genome-wide DNA methylation in peripheral blood and calculated six AA metrics. Linear mixed-effects and weighted quantile sum regression models evaluated associations between particulate matter exposure and DNAmAA. RESULTS: Significant associations between particulate matter exposure and DNAmAA were observed at various lag windows. For every 10&#x200a;&#x3bc;g/m 3 increase in 24-h average PM 2.5 , Hannum DNAmAA, Pheno DNAmAA, Grim DNAmAA, SkinBlood DNAmAA, and Elastic DNAmAA increased by 0.266&#x200a;years [95% confidence interval (CI): 0.035-0.480], 0.421&#x200a;years (95% CI: 0.032-0.701), 0.336&#x200a;years (95% CI: 0.073-0.546), 0.295&#x200a;years (95% CI: 0.021-0.495), and 0.254&#x200a;years (95% CI: 0.034-0.445), respectively. PM 10 contributed most substantially to the cumulative PM effect on epigenetic AA in the lag0-24&#x200a;h window. CONCLUSION: Short-term particulate matter exposure, particularly PM 10 , significantly accelerates epigenetic aging in PWH, highlighting the need to integrate air quality management into healthy aging strategies for this vulnerable population.

China

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals

Molecular characterization and biological characteristics of a highly pathogenic recombinant ALV-J strain (HUE2023) with cross-clade gp85 recombination.

Avian leukosis virus subgroup J (ALV-J) has undergone extensive diversification into phylogenetically distinct clades, yet whether recombination between these clades within the gp85 envelope glycoprotein generates variants with altered pathogenicity has received little direct investigation. A field strain (HUE2023) was recovered from breeding roosters displaying vascular tumors. The viral genome was sequenced and subjected to phylogenetic and recombination analyses. The three-dimensional structure of gp85 was predicted with AlphaFold3; electrostatic surface potentials and surface hydrophobicity were computed using the Adaptive Poisson-Boltzmann Solver and the Eisenberg hydrophobicity scale, respectively. Pathogenicity and immunosuppressive effects were assessed in Hy-Line Brown chickens. Recombination analysis revealed that HUE2023 is an inter-clade recombinant derived from Clade 1.1 (major parent: JS14NT01) and Clade 1.2 (minor parent: JS09GY3). A single-residue deletion at position 61 within receptor-binding domain 1 (RBD-1), unique to the recombinant, induced a localized conformational rearrangement that generated a concentrated electronegative surface patch and a contiguous hydrophobic pocket not observed in either parental gp85. Animal challenge showed that HUE2023 is highly pathogenic: female chickens in the high-dose group reached only 61% survival and displayed significant growth retardation (P&#x202f;<&#x202f;0.05) together with marked immunosuppression. The recombination in the RBD-1 led to local conformational rearrangement, resulting in a concentrated and negatively charged surface area as well as a continuous hydrophobic pocket, which were never present in any of the parental gp85 sequences. These results indicate that gp85 recombination across clades can yield variants with fundamentally altered receptor-binding surfaces and argue for integrating structural surveillance into ALV-J monitoring programmes.

Animals

Efficacy of prescription-eligible digital health applications for depression and generalized anxiety disorder in Germany: a systematic review and meta-analysis.

In Germany, prescription-eligible digital mental health applications (DiGA) were introduced in 2020 as promising interventions to address, among others, depression and anxiety disorders, two of the most prevalent mental health conditions worldwide. Despite growing interest in DiGAs, their overall efficacy remains uncertain. This study aimed to systematically evaluate and quantify the efficacy of prescription-eligible digital interventions for depression and generalized anxiety disorder by synthesizing evidence from randomized controlled trials (19 trials; total N&#x2009;=&#x2009;4,078; pooled mean age&#x2009;=&#x2009;38.7 years, SD&#x2009;=&#x2009;12.1). Here we show that prescription-eligible digital applications for depression and generalized anxiety disorder reduce symptom severity compared with control conditions. For depression, effects were observed both immediately after the intervention (number of apps&#x2009;=&#x2009;5; k&#x2009;=&#x2009;17; SMD = -&#x2009;0.49; 95% CI -&#x2009;0.65 to -&#x2009;0.32) and at follow-up (number of apps&#x2009;=&#x2009;1; k&#x2009;=&#x2009;4; SMD = -&#x2009;0.35; 95% CI -&#x2009;0.46 to -&#x2009;0.29), while evidence for generalized anxiety disorder was limited due to a small number of available studies (number of studies&#x2009;=&#x2009;2). These findings support the integration of evidence-based digital tools into mental health treatment strategies in Germany. However, the available evidence is currently dominated by a small number of applications, particularly Deprexis, and should therefore not be interpreted as equally representative of all DiGAs currently listed for depression in Germany. The findings also highlight methodological limitations of current research and underscore the need for real-world evaluations, which address not only efficacy but also the effectiveness, content, quality and implementation.

Generalized Anxiety Disorder