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Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT cells recognize microbial small molecules presented by the major histocompatibility complex class Ib molecule MR1. MAIT cells are absent in germ-free mice, and the mechanisms by which microbiota control MAIT cell development are unknown (see the Perspective by Oh and Unutmaz). Legoux et al. show that, in mice, development of MAIT cells within the thymus is governed by the bacterial product 5-(2-oxopropylideneamino)-6- d -ribitylaminouracil, which rapidly traffics from the mucosa to the thymus, where it is captured by MR1 and presented to developing MAIT cells. Constantinides et al. report that MAIT cell induction only occurs during a limited, early-life window and requires exposure to defined microbes that produce riboflavin derivatives. Continual interactions between MAIT cells and commensals in the skin modulates tissue repair functions. Together, these papers highlight how the microbiota can direct immune cell development and subsequent function at mucosal sites by secreting compounds that act like self-antigens. Science , this issue p. 494 , p. eaax6624 ; see also p. 419 In neonatal mice, microbial small molecules presented in the thymus drive the expansion of mucosal-associated invariant T cells. How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)–producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1–, IL-18–, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.

The transcriptome represents an attractive but underused set of targets for small-molecule ligands. Here, we devise a technology that leverages fragment-based screening and SHAPE-MaP RNA structure probing to discover small-molecule fragments that bind an RNA structure of interest. We identified fragments and cooperatively binding fragment pairs that bind to the thiamine pyrophosphate (TPP) riboswitch with millimolar to micromolar affinities. We then used structure-activity relationship information to efficiently design a linked-fragment ligand, with no resemblance to the native ligand, with high ligand efficiency and druglikeness, that binds to the TPP thiM riboswitch with high nanomolar affinity and that modulates RNA conformation during cotranscriptional folding. Principles from this work are broadly applicable, leveraging cooperativity and multisite binding, for developing high-quality ligands for diverse RNA targets.

High-riding vertebral artery (HRVA) increases vertebral artery injury risk during C2 instrumentation. We conducted a cross-sectional study of cervical computed tomography angiography (CTA) in southern Chinese adults (18–60 years; four centers, 2019–2025) to validate a modified HRVA classification. Measurements included C2 isthmus height (C2IsH) and C2 internal height (C2InH) on sagittal reconstructions 3 mm lateral to the spinal canal border, and C2 pedicle width (C2PW) and C2 lamina width (C2LW) in axial images. The modified classification includes two previously unrecognized variants: Type 4 (isthmio-absent; C2IsH = 0 mm) and Type 5 (internal-absent; C2InH = 0 mm). Among 1,804 participants, yielding 3,608 potential screw insertion sites (PSIS), HRVA prevalence was 29.60%. Mean C2IsH and C2InH were 7.00 and 6.02 mm, significantly lower than those for Caucasians (7.73 and 7.06 mm; P  < 0.01), and HRVA prevalence also differed ( P  < 0.05). Types 4 and 5 comprised 0.14% and 0.08% of PSIS. Narrow pedicles and laminae were more frequent in HRVA than non-HRVA (both P  < 0.01). Intraobserver and interobserver agreements were satisfactory. The modified classification demonstrates high reliability and clinical utility, supporting individualized preoperative assessments and tailored C2 screw placement strategies to reduce vertebral artery injury risk. Research registration : This study has been registered with the Chinese Clinical Trial Registry (ChiCTR2500096630, https://www.chictr.org.cn/ ).

The suborder Massarineae, within the order Pleosporales (class Dothideomycetes), includes many fungi that act as dominant endophytes in Poaceae plants. However, despite recent advancements, the phylogeny and taxonomy of endophytic Massarineae remain insufficiently resolved. In this study, comprehensive phylogenetic and morphological analyses were conducted for two key families within Massarineae - Didymosphaeriaceae and Periconiaceae - by incorporating collections of novel endophytic strains from Poaceae hosts. Multilocus phylogenetic analyses revealed distinct clades in both families, leading to the proposal of 10 new taxa within Massarineae. Within Didymosphaeriaceae, two new genera (Proxiconiothyrium gen. nov. and Chlamydosphaeromyces gen. nov.) and three new species (Proxiconiothyrium yunnanense sp. nov., Neptunomyces yunnanensis sp. nov., and Chlamydosphaeromyces glomeratus sp. nov.) are described; for Periconiaceae, three new species (Periconia catenata sp. nov., P. neomacrospinosa sp. nov., P. longibrachiatum sp. nov.), one new combination (P. fueloephazae comb. nov.), and one new sensu stricto taxon (P. macrospinosa s.s.) are introduced. Detailed morphological descriptions are provided for each newly established taxon. The results significantly improve the taxonomic and phylogenetic framework for Massarineae endophytes and provide a valuable reference for exploring the diversity and evolutionary differentiation within other taxonomic groups of Pleosporales.

Deletion of the maternal UBE3A allele causes Angelman syndrome (AS) ; because paternal UBE3A is epigenetically silenced by a long non-coding antisense ( UBE3A-ATS ) in neurons, this nearly eliminates UBE3A protein in the brain. Reactivating paternal UBE3A holds promise for treating AS. We previously showed topoisomerase inhibitors can reactivate paternal UBE3A , but their therapeutic challenges prompted our search for small molecule unsilencers with a different mechanism of action. Here, we found that ( S )-PHA533533 acts through a novel mechanism to significantly increase paternal Ube3a mRNA and UBE3A protein levels while downregulating Ube3a-ATS in primary neurons derived from AS model mice. Furthermore, peripheral delivery of ( S )-PHA533533 in AS model mice induces widespread neuronal UBE3A expression. Finally, we show that ( S )-PHA533533 unsilences paternal UBE3A in AS patient-derived neurons, highlighting its translational potential. Our findings provide a lead for developing a small molecule treatment for AS that could be safe, non-invasively delivered, and capable of brain-wide unsilencing of paternal UBE3A . Angelman syndrome is a neurodevelopmental disorder caused by the deletion of a single gene. Here, researchers discovered a small molecule that could be delivered peripherally to activate a dormant copy of the gene throughout the brain, providing a potential treatment opportunity.

ObjectivesThis study aims to describe the knowledge, attitude and practice (KAP) regarding surgical scars among patients who had postorthopaedic surgery, and to explore correlations between these factors.DesignA multicentre, cross-sectional, observational study.SettingConducted across multiple secondary/tertiary care hospitals between July and September 2024.ParticipantsOf 816 enrolled participants undergoing orthopaedic surgery, 54.5% were male, 43.6% were aged 31–45 years, 73.9% were urban dwellers, 31.2% had a bachelor’s degree and 65.4% were married.InterventionsNone (questionnaire-based assessment).Outcome measuresPrimary outcomes were KAP scores (knowledge: 0–22; attitude: 9–45 and practice: 7–35), analysed via correlation and regression.ResultsMean scores: knowledge (12.5±6.9), attitude (27.6±3.3) and practice (28.2±6.5). Knowledge was negatively correlated with attitude (r=−0.24, p<0.001) but positively with practice (r=0.73, p<0.001). Attitude negatively influenced practice (r=−0.19, p<0.001). Multivariable analysis showed that knowledge was negatively associated with attitude (OR=0.93, 95% CI: 0.90 to 0.96) but positively with practice (OR=1.24, 95% CI: 1.19 to 1.30), while attitude was negatively associated with practice (OR=0.93, 95% CI: 0.87 to 0.999). Structural equation modelling confirmed that knowledge directly positively influenced attitude (β=21.6) and practice (β=43.3), with attitude positively impacting practice (β=7.9) (p<0.001 for all).ConclusionsPatients who had postorthopaedic surgery demonstrated poor scar-related knowledge and negative attitudes but proactive practices. Greater knowledge correlated with better practice, suggesting targeted education could optimise scar management. Further research should explore causal relationships and the efficacy of interventions.

We present the method of online self-tuning PD controller for the problem of contouring control of robot manipulators. Previously, the dynamics of the robot is transformed into dynamic errors problem by considering the equivalent errors method. It becomes the control problem of stabilization such that it is suitable for advanced control to improve control performance regarding contouring control, i.e., contour accuracy with high speed. Conventional PD tuned by the fuzzy controller with robust extended Kalman filter where it was acting as the robust adaptive controller is utilized to stabilize that control problem. It could determine the stationary point of different processes without knowing prior. In practice, the proposed controller is easily dealt with the problem of stabilization. The experiment results reveal that the proposed technique yields excellent performance under a large disturbance.

In this paper, we investigate the global exponential stability and periodicity of nonautonomous cellular neural networks with reaction-diffusion, impulses, and time-varying delays. By establishing a new differential inequality for nonautonomous systems, using the properties of M-matrix and inequality techniques, some new sufficient conditions for the global exponential stability of the system are obtained. Moreover, sufficient conditions for the periodic solutions of the system are obtained by using the Poincare mapping and the fixed point theory. The validity and superiority of the main results are verified by numerical examples and simulations.

Background High-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition. Results Newly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens ( P  < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue ( P  < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium , Escherichia , and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD. Conclusions The results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota–bile acid profile pathways. Graphical Abstract

To identify and synthesize randomized controlled trials (RCTs) of oral traditional Chinese medicine (TCM) for postherpetic neuralgia (PHN), map the volume, methodological quality, and evidence distribution, identify evidence gaps, and inform future research. We systematically searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database, the Chinese Clinical Trial Registry (ChiCTR), and China Biomedical Literature Database (CBM). RCTs published from database inception to 1 August 2025 were included. The evidence was summarized using evidence maps and narrative synthesis. Risk of bias in the included RCTs was assessed using the Cochrane Risk of Bias tool (RoB 1.0). A total of 357 RCTs were included, most were small studies with sample sizes ranging from 50 to 100 participants. Most studies reported diagnostic criteria and inclusion/exclusion criteria, however, limited attention was paid to TCM syndrome differentiation and its standardization. The main outcomes were pain degree, clinical effective rate, adverse reactions, sleep quality, negative emotions, and quality of life, however, outcomes such as recurrence and TCM syndrome scores were infrequently reported. Overall methodological quality was low, as assessed using the RoB 1.0. Although many included studies reported favourable findings, the formulas and preparations differed substantially in composition, and high-quality evidence remains limited. Future trials should better incorporate key features of TCM (e.g., syndrome differentiation), use standardized and clinically meaningful outcome measures, and strengthen trial design and reporting to reduce risk of bias and improve the credibility of evidence. URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251110786, identifier CRD420251110786.