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Maternal transfer of nonylphenol drives oxidative, immune, and epigenetic dysregulation in zebrafish offspring.

Nonylphenol (NP), a widespread surfactant and endocrine-disrupting pollutant, poses significant ecological and public health risks globally; however, its transgenerational effects remain poorly understood. Using zebrafish (Danio rerio), we compared chronic maternal NP exposure (50 and 100 µg/L, 28 days) with acute embryonic exposure (0.22 µmol/L) during 0-3 days post-fertilization (dpf) to delineate mechanistic differences in toxicity. Maternal NP exposure produced severe developmental defects in offspring, including edema, axial curvature, impaired swim bladder inflation, reduced growth, cardiac dysfunction, and decreased viability. These phenotypes were accompanied by systemic molecular disruptions including oxidative stress, altered estrogen receptor (ER) expression, dysregulated mitogen-activated protein kinase (MAPK) signaling, and suppressed innate immune response characterized by attenuated neutrophil/macrophage density, reduced CD68 and complement protein C3 expression, diminished nitrite load, and downregulation of pro-inflammatory mediators at both transcript and protein levels. Maternal exposure further induced apoptosis and persistent epigenetic reprogramming (alterations in DNA methylation and histone-modifying enzymes), hallmarks of transgenerational toxicity. In contrast, direct embryonic NP exposure elicited morphological abnormalities without significant lethality, accompanied by induction of pro-inflammatory cytokines, nitric oxide (NO) synthesis, and MAPK activation, reflecting an augmented inflammatory response. These mechanistic contrasts reveal that maternal NP exposure is a potent driver of systemic, heritable molecular reprogramming, whereas embryonic exposure triggers acute inflammatory pathways. Together, our findings underscore the global relevance of NP as a transgenerational toxicant, advocating for its urgent inclusion in ecotoxicological risk assessments and regulatory frameworks.

Animals

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique ε and κ OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals

The R2R3-MYB transcription factor ScMYB20 negatively regulates drought and salt tolerance through a dual-repression of ScCHALCONE SYNTHASE-1 (ScCHS1)-mediated flavonoid biosynthesis in the desert moss Syntrichia caninervis.

The desert moss Syntrichia caninervis is one of the most desiccation-tolerant land plants known and provides a powerful system for dissecting the molecular foundations of extreme stress adaptation in early-diverging land lineages. The MYB transcription factor superfamily orchestrates secondary metabolism and stress signaling across plants, yet its lineage-specific evolution and mechanistic deployment in bryophytes remain poorly understood. Here, we identified 65 ScMYB genes in the S. caninervis genome and showed that the family expanded predominantly through dispersed duplication, with no detectable synteny to vascular-plant MYBs, indicating bryophyte-specific neo-functionalization. Integrating phylogenetic clustering, cis-element architecture and stress-responsive expression profiling, we pinpointed ScMYB20, a nuclear-localized, S13-subgroup R2R3-MYB that is rapidly and strongly induced by dehydration and salinity. Heterologous overexpression in Arabidopsis, together with overexpression and RNAi in S. caninervis, demonstrated that ScMYB20 negatively regulates drought and salt tolerance by suppressing antioxidant capacity, osmotic adjustment and photosynthetic performance, while concomitantly elevating ROS and MDA accumulation. Mechanistically, ScMYB20 directly binds a TAACCA motif in the ScCHS1 promoter to repress its transcription, and simultaneously sequesters the WD40 protein ScTTG1, a positive transcriptional activator of ScCHS1, thereby antagonising ScTTG1-mediated activation. Transient ScCHS1 overexpression restored flavonoid accumulation, antioxidant capacity and stress tolerance. Together, our findings define a dual-repression module (ScMYB20-ScTTG1-ScCHS1) that fine-tunes flavonoid flux under abiotic stress, and provide evolutionary and mechanistic insights into how R2R3-MYB repressors evolved to balance metabolic investment and stress survival in land plants.

Syntrichia caninervis

Towards microplastic bioremediation: Fungal degradation of pristine and pretreated high-density polyethylene and polystyrene.

Microplastic (MP) contamination has become a significant ecological issue because of its enduring existence in the ecosystem and its possible negative impacts. Therefore, using degrading strategies to eliminate these stubborn polymers has been a subject of scientific research. However, the currently used degradation methods are relatively inefficient. Given the pervasiveness of High-Density Polyethylene (HDPE) and Polystyrene (PS) and their resistance to biodegradability, disposal strategies are critical and must be addressed. This manuscript examines the biodegradation of pristine and UV-treated HDPE and PS MPs by Aspergillus flavus species in minimal growth media over 70 days. The maximum weight loss observed at 70 days for pristine HDPE and PS in sole carbon source (SCS) media was (29.33 ± 0.28) % and (17.67 ± 0.35) %, respectively. Whereas, for UV-treated HDPE and PS MPs, the % weight reduction was (33 ± 0.21) % and (25 ± 0.19) %, respectively. UV-treated MPs exhibited greater weight reduction, as UV induced oxygenated functional groups enhance polymer susceptibility to enzymes, thereby promoting biodegradation. HDPE MPs typically show a higher proportion of particles in the lower size range compared to PS MPs. This assertion was based on the weight loss, particle size distribution, and SEM analysis. Furthermore, chemical changes were evaluated using Fourier transform Infrared Spectroscopy (FTIR) analysis, which also displayed chemical oxidation occurring during biodegradation. Liquid Chromatography-Mass Spectrometry (LC-MS) results indicate that UV pretreatment enhances biodegradability by promoting chain scission. These findings further suggest that this fungus's natural and ubiquitous occurrence in terrestrial and marine environments may actively contribute to MP biodegradation while requiring few nutrients.

Microplastics

Testing How Mindfulness Skills Change for Novice Meditators Using Headspace: Examining Trait Mindfulness and Perceived Stress as Moderators.

Mindfulness-based interventions are found to effectively reduce stress and improve mental health outcomes. Yet, it is not always clear how the mindfulness skills of attention and acceptance develop throughout the intervention. This knowledge gap is especially pertinent for novice meditators learning these skills for the first time, including whether some individuals are more prone to learning them. Using a randomized waitlist-controlled trial, we tested the effect of the app Headspace on changes in attention and acceptance over 8 weeks among participants new to mindfulness meditation. Further, we tested the moderating effects of trait mindfulness and perceived stress. Non-faculty university employees were randomized to a Headspace or waitlist control condition. Trait mindfulness and perceived stress were measured at baseline. Ecological momentary assessment survey data for attention and acceptance were collected five times a day in 4-day bursts at baseline and 2, 5, and 8 weeks post-randomisation. Attention and acceptance were significantly higher at Week 8 compared to baseline for the Headspace group, but not the control group. For the Headspace group, both skills showed significant change by Week 2. Trait mindfulness moderated this effect with those who were lower in trait mindfulness displaying greater increases in attention, but not acceptance. Perceived stress also moderated this effect with those who were lower in perceived stress displaying greater increases in attention and acceptance. Our discussion draws attention to implications for matching intervention content to individual needs to ensure participants reporting different levels of characteristics benefit from mindfulness training.

Humans

The effects of cold temperature on the development, microbiome, and transcriptome of the sea anemone Nematostella vectensis.

Thermal conditions impact essentially all aspects of the physiology for ectotherms. While the effects of high temperatures have been widely studied, cold temperature effects on aquatic invertebrates and their microbial communities have been poorly characterized. To determine the diverse effects of exposure to cold temperatures, we assessed acute and long-term impacts of ecologically relevant low temperatures on the development, microbiome, and gene expression of the sea anemone Nematostella vectensis. Two hours post fertilization, embryos were exposed to temperatures from 4°C to 35°C and development rate to the juvenile stage was quantified. We found temperature impacts the development rate of embryos, where lower temperatures extended development time and resulted in mortality below 10°C. For both microbiome and host transcriptomic responses, anemones were held at 20°C, 10°C, and 0°C and compared at 24 hours and 7 days. Extended exposures to colder temperatures caused restructuring of the host-associated microbiome, with the loss of common taxonomic groups from the class Bacteroidia and Bacilli. Lastly, cold stress induced significant changes in gene expression, which were more pronounced at the 10°C than 0°C but showed little change over time in each temperature. Interestingly, expression of genes associated with innate immunity were among the most differentially expressed genes including heat shock proteins and innate immune genes providing a potential host-imposed mechanism to explain the shift in the microbiome. Overall, cold temperatures have broad effects on many facets of this sea anemone and its microbial community and indicate the importance of cold temperature events when characterizing how ectotherms acclimate to thermal variation.

Animals

Integrated electronic nose, GC-MS, and metagenomic analyses reveal volatile flavor and microbial community differences in heap-fermented grains of Jiangxiangxing Baijiu across different fermentation degrees.

The fermentation degree of heap-fermented grains in Jiangxiangxing Baijiu production is a critical factor influencing base Baijiu quality. However, conventional assessment methods largely rely on empirical experience and therefore suffer from limited objectivity and accuracy. In this study, integrated volatile profiling and metagenomic approaches were employed to investigate volatile characteristics and microbial functional potential differentiation in fermented grains with different fermentation degrees (under-fermented, normally fermented, and over-fermented). Significant differences in physicochemical properties were observed among fermentation degrees, particularly in acidity and reducing sugar content. Electronic nose analysis revealed distinct sensor response patterns among different fermentation degrees, indicating differences in overall volatile odor fingerprint patterns. A total of 81 volatile compounds were identified by HS-SPME-GC-MS, with aldehydes, ketones, and pyrazines showing pronounced variations among fermentation degrees, and acetaldehyde exhibiting strong discriminatory potential. LEfSe analysis identified 18 microbial taxa as potential biomarkers associated with different fermentation degrees, including Pichia kudriavzevii, Lentibacillus daiqui, and Acetobacter pasteurianus. Correlation analysis revealed significant positive associations between acetaldehyde levels and Acetobacter abundance. Furthermore, KEGG, CAZy, and eggNOG analyses revealed differentiated functional potentials among fermentation degrees, providing insights into the potential metabolic basis associated with flavor differentiation. Overall, these findings highlight that fermentation degree differentiation is closely associated with coordinated changes in physicochemical conditions, microbial communities, and functional potentials, providing ecological insights into flavor differentiation and theoretical support for objective fermentation degree evaluation and quality control of Jiangxiangxing Baijiu production.

Fermentation

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans

Gloeotrichia echinulata genomes from the United States are nontoxigenic and likely geosmin producers.

Six Gloeotrichia echinulata genomes derived from planktonic harmful algal blooms (HABs) with similar colonial morphology have been sequenced from lakes in the west and northeast regions of USA, four of them to completion. The c. 7 Mbp genomes exhibit a high level of conservation, with 98-99% pairwise genome-wide average nucleotide identity and high levels of synteny, representing a single species cluster. We observed strong conservation of gene clusters responsible for the synthesis of the secondary metabolites and bioactive peptides that are characteristic of HAB-forming cyanobacteria. All six G. echinulata genomes lack genes for the synthesis of classic cyanotoxins, including microcystin, but possess genes responsible for the synthesis of the taste and odor compound geosmin. Interestingly, the geoA geosmin synthase gene in three genomes is homologous to other cyanobacterial geoA genes, while the other three geoA genes are related to actinomyces geoA. Phylogenomic analysis places the G. echinulata genomes within a clade of benthic Nostocales, reflecting an ecological niche featuring extensive growth on the sediment surface before colonies disperse into the epilimnion for planktonic growth. We identify genes conserved in all six genomes that could represent physiological adaptations supporting active growth on sediments and pelagic recruitment independent of wind-driven mixing: phycoerythrin light harvesting complexes for optimal photosynthesis at depth; gliding motility to access patchy nutrient distributions; and gas vesicles with relatively small GvpC proteins that predict resistance to higher hydrostatic pressure. The strong genomic similarity across geographically distant populations suggests that G. echinulata in the United States is a tightly related non-toxigenic species group with predictable properties relevant to public health and drinking water management.

Cyanobacteria

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans

Meta-analysis of growth and inactivation kinetics of Legionella.

Quantitative risk assessments intended to inform evidence-based water management plans and public health targets for Legionella in engineered water systems are constrained by fragmented and heterogeneous growth and inactivation kinetics. We conducted a meta-analysis of 25 growth and 39 thermal- and chemical-inactivation studies, fitting microbial persistence models to harmonize parameters. Nonlinear models outperformed first-order formulations, indicating that lag phases and resistant or protected subpopulations are central to Legionella persistence. Random forest analysis identified environmental and methodological drivers of variability based on 226 growth rates and reduction times for thermal (209) and chemical (135) inactivation. Growth was primarily governed by temperature, nutrient availability, and compatible Legionella-host pairings; thermal inactivation by quantification method, temperature, and turbidity; and chemical inactivation by inoculum size, disinfectant type, concentration, and host-associations. Accordingly, temperature-dependent growth parameters and exposure metrics for heat, free-chlorine, and monochloramine, expressed as TT (Temperature×time) and CT (Concentration×time), were derived as condition-specific inputs for predictive models. Growth optima around 37-40 °C, together with lag-time estimates, indicate that hot-water temperature setbacks and energy-saving practices may favor Legionella proliferation under repeated or prolonged lukewarm exposure. Culture- and viability-based TT differences highlight the need to consider viable‑but-non-culturable persistence in monitoring programs. CT comparisons suggest monochloramine may be advantageous because of its lower apparent sensitivity to host-associated protection. Although limited by restricted experimental conditions, the findings show that predictive models should account for microbial ecology, water matrix effects, and quantification endpoints. Future kinetic studies should prioritize realistic multi-host systems, strain pre-adaptation, complementary viability measurements, and standardized protocols and reporting to ensure reproducibility and enable robust system-level predictive modeling.

Legionella

From commensal to pathobiont: The emergence of virulence-enhanced Escherichia coli in China's food-animal systems - insights with future implications.

A fundamental shift in Escherichia coli epidemiology is being driven by convergence of virulence determinants and antimicrobial resistance within linked human-animal-environment systems. In China, the rapid growth of food-animal production, extensive antimicrobial use, and complex food networks are accelerating the emergence and dissemination of virulence-enhanced E. coli pathobionts. This review synthesizes recent epidemiological, genomics, and outbreak data to characterize China's evolving landscape of food-animal-associated E. coli. We highlight a significant shift from classical pathotypes to hybrid lineages that simultaneously carry virulence factors and last-resort antibiotic resistance determinants, including mcr-1, tet(X4), and blaNDM. These traits disseminate rapidly via plasmid-mediated horizontal gene transfer, facilitating rapid adaptation and enabling cross-sectoral One Health transmission. National surveillance, foodborne outbreak investigations, and whole-genome sequencing data show that food-animal reservoirs are active evolutionary niches that drive pathogen diversity and fitness, rather than serving merely as contamination sources. Whole-genome sequencing also pinpoints high-risk clones (e.g., ST394) and plasmid-mediated co-selection of virulence and AMR. The emergence of hybrid pathotypes (e.g., STEC/ETEC) and AMR-virulence co-selection challenges traditional classification and limits the effectiveness of conventional surveillance approaches. The 2017 colistin ban reduced mcr-1, yet ongoing resistance and emerging tet(X4) demand integrated surveillance. Collectively, these findings call for reconceptualizing E. coli as a dynamic genomic entity embedded within a unified ecological network. Addressing this threat requires an integrated One Health strategy including genomic surveillance, agricultural antimicrobial stewardship, and coordinated food-environment-clinical monitoring to prevent high-risk clone emergence and global spread.

Animals

Comparative efficacy of percutaneous vertebroplasty combined with minimally invasive pedicle screw fixation versus percutaneous vertebroplasty alone in the treatment of elderly osteoporotic vertebral compression fractures.

The study aimed to assess the comparative efficacy of percutaneous vertebroplasty (PVP) combined with minimally invasive pedicle screw fixation versus PVP alone in elderly patients with osteoporotic vertebral compression fractures (OVCF). Ninety-four elderly patients with OVCF were randomly classified into the control (47 patients) and combined (47 patients) groups. The control group received PVP, while the combined group received PVP combined with minimally invasive pedicle screw fixation. Perioperative indicators such as intraoperative blood lose, operative time, and hospitalization time were recorded. Pain was assessed using the VAS before and at baseline and 1, 3, and 7 days postoperatively. At 1 and 3 days postoperatively, Serum CRP levels, WBC, and neutrophil counts were measured postoperatively. Radiographic outcomes (vertebral height ratio and Cobb angle), ADL scores, JOA scores, and ODI were evaluated preoperatively and at 3 months post-operation. Postoperative complications were documented. Baseline characteristics were comparable. The combined group showed superior pain relief, vertebral height restoration, Cobb angle correction, functional recovery, and reduced inflammatory markers (CRP, WBC, neutrophils) postoperatively (all P&#x2009;<&#x2009;0.05). Blood loss and hospital stay were shorter in the combined group, though operative time was longer (P&#x2009;<&#x2009;0.05). Complication rates did not differ significantly (P&#x2009;>&#x2009;0.05). PVP combined with minimally invasive pedicle screw fixation yields better outcomes in elderly OVCF patients by enhancing pain control, vertebral height, and functional recovery without increasing perioperative risk.

Humans

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/&#x3b2;-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8&#x2009;weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-&#x3b2;-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-&#x3b2;-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

Humans

Relational care in community mental health: Evaluating staff experiences in Intensive Community Care Services (ICCS) vs treatment as usual.

BACKGROUND: The quality of healthcare delivery relies heavily on building strong relationships between healthcare providers (HCPs) and clients. This study presents the results of a process evaluation for a Randomised Controlled Trial (RCT) examining the effectiveness of Intensive Community Care Service (ICCS) vs Treatment as Usual (TAU; inpatient or core community CAMHS). METHODS: Thirty-four semi-structured interviews were conducted with staff across various services, including 20 from ICCS and 14 other TAU services. A thematic decomposition analysis was conducted on the data, and specific themes relevant to staff experiences of young people's engagement with services and overall recovery. RESULTS: Three main themes were observed in the HCP data (1. Relational Ecologies: barriers and enablers to engagement, 2. flexibility of approach amidst systemic pressures and 3. the web of trust in the relationship-building process). HCPs highlighted the necessity of developing trust and rapport through non-clinical engagement strategies, such as informal visits and personalised interactions. HCPs emphasised that without trust, treatment effectiveness diminishes, necessitating a tailored approach rather than a one-size-fits-all model. The flexibility in duration of treatment and methods of engagement was noted as crucial in accommodating individual client needs and fostering an open, trusting environment necessary for long-term recovery. CONCLUSION: The findings highlight the vital importance of relational care models, especially ICCS, in addressing the complex needs of Children and Young People (CYP). Flexible, family-centred approaches improve trust, engagement, and long-term recovery outcomes. Recommendations include tackling systemic barriers and expanding relational care models within CAMHS to meet increasing mental health demands effectively. Further research should investigate scalable strategies for integrating these insights into wider mental health service frameworks.

Humans

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans

Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity.

Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14&#xa0;weeks (W14). From W12 onward, mice received glutamine in drinking water (2&#xa0;g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.

Animals