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Extracellular vesicles (EVs) represent a heterogeneous group of lipid-enclosed vesicular structures. Despite their tiny bodies, EVs harbor a rich repertoire of functional molecular entities. Therein, the glycome-a diverse ensemble of glycan structures-is increasingly recognized as an essential piece of the EV biology jigsaw. This review presents a comprehensive overview of the research advances in EV glycome, recapitulating its fundamental characteristics (i.e., multiformity and heterogeneity), deciphering methodologies, biological functions, and biomedical applications. EVs are found to be enriched with diverse glycosylated components, including glycoproteins, glycolipids, proteoglycans, glycoRNAs, and free glycans. These glycome features can exhibit considerable differences across EV samples due to factors such as cellular origin, parent-cell state, EV subtype, and even isolation method. The toolkit for deciphering is undergoing substantial expansion. Besides classical glycomic methods, a series of advanced technologies has been developed to meet the specific demands of EV glycome analysis. Delving into its biological functions, EV glycome is widely involved in EV biogenesis, EV cargo sorting, EV-cell communication, immune regulation, and disease progression. It also holds immense promise across a broad range of biomedical applications, particularly in developing disease biomarkers, designing therapeutic platforms, modulating immunological activities, and advancing EV isolation methodologies. The past two decades have witnessed a progressive advancement in the understanding of EV glycome. Nevertheless, the field remains in its nascent phase. A multitude of unresolved issues and challenges persist, such as underexplored basic biology characteristics, limitations in analytical sensitivity and resolution due to inadequate deciphering techniques, poorly understood mechanisms underlying biological functions, and insufficiency for practical clinical implementation. This review outlines the current knowledge of EV glycome and underscores its significance in basic biology and translational applications, thereby serving as a robust foundational resource to support and accelerate future advancement.

Artificial intelligence (AI) is rapidly transforming surgical practice, with applications spanning preoperative planning, intraoperative guidance, postoperative management, and surgical education. Despite accelerating research activity, the structure, thematic evolution, and funding landscape of AI research in general surgery remain incompletely characterized. This study aimed to systematically evaluate scientific production on AI in general surgery in the United States over the past 5 years using a bibliometric approach. A bibliometric analysis was conducted following Preliminary Guideline for Reporting Bibliometric Reviews of the Biomedical Literature and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using Web of Science. English-language articles published between 2020 and 2025 with a U.S.-affiliated senior author and focused on AI use in general surgery were included. Publications were analyzed across five primary domains: authorship metrics, thematic endpoints, journal characteristics, country of origin, and funding patterns. Bibliometric indicators included H-index, citation counts, Article Influence Score (AIS), and Bradford's Law classification. Funding distribution across endpoints was evaluated using chi-square or Fisher's exact tests, with effect sizes estimated using Cramér's V and odds ratios. Temporal trends in endpoints and keywords were assessed using Poisson and negative binomial regression models. Fifty-nine studies met inclusion criteria, comprising 20 reviews and 39 original investigations. Scientific production increased consistently from one study in 2019 to 17 in 2023 and 16 in 2024, demonstrating sustained growth. Surgical workflow recognition (n = 19) and clinical decision support (n = 18) were the predominant research domains, representing 63% of the included literature. Temporal analysis demonstrated significant annual growth in reviews (Incidence rate ratios [IRR] 2.09, P = .002) and workflow-focused studies (IRR 1.37, P = .031). Keyword analysis revealed sustained prominence of AI and machine learning, with limited emergence of new thematic directions. Most studies reported no funding (57.6%). Although overall funding distribution did not significantly differ across application categories (P = .846), clinically actionable AI applications were significantly more likely to receive funding compared with other research areas (OR 4.0, 95% CI 1.22-13.13; P = .029). AI research in U.S. general surgery is growing but remains concentrated in workflow and decision-support domains. Funding favors clinically actionable applications, highlighting the need for broader, equity-focused AI development.

To review the literature on psychosocial care and experiences of young adults with early-onset type 2 diabetes (EOT2D), to identify what is known, current gaps and to develop recommendations to help advance psychosocial care and support for the population. We searched Medline (Ovid), Google Scholar and diabetes-specific journals for English-language articles focused on psychosocial aspects in young adults (aged 18-45 years) with EOT2D. Two people with lived experience reviewed and commented on the review findings. Growing evidence indicates that a diagnosis of EOT2D is associated with an increased risk of developing diabetes-related psychological comorbidities. Experiences of diabetes-related stigma, compounded by age-related negative preconceptions, contribute to heightening the psychosocial impact of EOT2D. Some population sub-groups appear to be more likely to experience adverse psychological effects. However, the evidence base is limited by a dearth of diverse research specifically focused on the psychosocial experiences and needs of this population (e.g., longitudinal and qualitative studies). Adults with EOT2D also experience unmet education, care and support needs relevant to optimising their psychosocial well-being and diabetes management. Overall, they require enhanced, tailored care and support that is age-appropriate, person-centred and responsive to their psychosocial needs. Digital technology and support-based strategies may help to address current gaps and improve the psychological well-being of this group, but these require further exploration. Despite the importance of psychosocial factors in young adults' diabetes management and outcomes, there remain gaps in research and practice and the need for further research, alongside changes in practice.

Cancer survivorship care emphasizes biomedical interventions, but psychological and social difficulties remain underaddressed. This study aimed to (i) quantify the association between unmet needs and quality of life (QOL), and (ii) evaluate whether these associations are consistent across two health-related QOL (HRQoL) instruments among cancer survivors. Cross-sectional survey of adults (≥ 19) in Ulsan, Korea (2021, 2022). HRQoL (EQ-5D-5 L; EORTC QLQ-C30) was related to unmet-need domains using multivariable linear regression adjusted for prespecified sociodemographic and clinical covariates (gender, age, cancer type/stage, education level, household size, household monthly income, smoking status, alcohol consumption). Statistical analyses included Student's t-tests, one-way ANOVA, and multivariable linear regression. After excluding cases with insufficient information, 372 survivors were analyzed. EQ-5D-5 L utility was negatively associated with age ≥ 60 years (B=-0.04, 95%CI[-0.07, -0.01]), advanced cancer stage (Stage IV: B=-0.11, 95%CI[-0.14, -0.07]), unmet psychological needs (B=-0.09, 95%CI[-0.13, -0.06]), and unmet financial needs (B=-0.04, 95%CI[-0.09, -0.001]). On the EORTC QLQ-C30, advanced cancer stage showed negative associations with the functional scale (Stage IV: B=-14.87, 95%CI[-18.65, -11.10]) and positive associations with the symptom scale (Stage IV: B = 9.01, 95%CI[6.44, 11.57]). Higher household income (B = 4.99, 95%CI[1.71, 8.26]) was positively associated with the functional scale, while unmet psychological needs were negatively associated with the functional scale (B=-5.96, 95%CI[-10.04, -1.89]) and positively associated with the symptom scale (B = 8.80, 95%CI[6.04, 11.57]). Unmet psychological needs showed the most consistent associations with poorer HRQoL across both generic and cancer-specific instruments. Unmet financial needs showed weaker but directionally consistent associations, and the concurrent use of both instruments provided complementary perspectives on survivorship-related quality of life.

Surgical wounds healing by secondary intention occur if a surgical wound is not closed or dehisces following primary closure. Surgical wounds healing by secondary intention are common and adversely affect patients' quality of life. Treatment is often prolonged, complex and expensive. Negative pressure wound therapy applies a controlled vacuum to the wound and is increasingly used to promote surgical wound healing by secondary intention despite limited rigorous evidence for the clinical and cost-effectiveness of negative pressure wound therapy to augment surgical wound healing by secondary intention. Assess the clinical and cost-effectiveness of negative pressure wound therapy versus usual care (no negative pressure wound therapy) in treating surgical wounds healing by secondary intention. A pragmatic, two-arm, parallel-group, randomised controlled superiority trial. Twenty-eight UK NHS Trusts randomised adult patients with a surgical wounds healing by secondary intention to receive negative pressure wound therapy or usual care (no negative pressure wound therapy). The planned sample size was 696 participants. Participants were followed up for 12 months via weekly telephone contact to collect the primary outcome (time to healing: full cover with no scab in days since randomisation) and clinical secondary outcomes: wound healing, surgical site infection, pain, hospital re-admission, current treatment and reasons for treatment change (if applicable), reoperation, amputation, antibiotic use, death. Patient-reported outcomes (pain, health-related quality of life and resource use) were collected by postal questionnaire at 3, 6 and 12 months. Validation of the Bluebelle Wound Healing Questionnaire, a patient-reported measure of surgical site infection, was also undertaken. A cost-effectiveness decision model considering all available evidence, and a within-trial cost-utility analysis, was also undertaken to evaluate the cost-effectiveness of negative pressure wound therapy against usual care. Neither participants nor the investigators were blind to treatment allocation. Between 15 May 2019 and 13 January 2023, 686 participants were recruited, randomised and included in the analysis (negative pressure wound therapy n = 349; usual care n = 337). Most participants had a single surgical wound healing by secondary intention (n = 622, 90.7%), located on the foot (n = 551, 80.3%) or leg (n = 69, 10.1%) arising following vascular surgery (n = 619, 90.2%). Most participants had comorbidities; diabetes (n = 549, 80.0%), cardiovascular disease (n = 446, 65.0%) and/or peripheral vascular disease (n = 349, 50.9%). Median time to healing was 187 days (negative pressure wound therapy) versus 195 days (usual care), with no evidence that negative pressure wound therapy reduced the time to wound healing compared to usual care (hazard ratio 1.08, 95% CI 0.88 to 1.32; p = 0.47). Odds of re-admission, reoperation, surgical site infection and antibiotic use were slightly higher, and odds of amputation or death slightly lower for negative pressure wound therapy participants. These results were not clinically or statistically significant. Bluebelle Wound Healing Questionnaire, quality of life and wound pain scores were not statistically significantly different at any time point. Serious adverse events were rare (nine negative pressure wound therapy vs. five usual-care participants). Both cost-effectiveness analyses concluded that negative pressure wound therapy generates higher costs and marginally higher quality-adjusted life-years than usual care, although findings were statistically insignificant. The probability of negative pressure wound therapy being cost-effective was under the recommended National Institute for Health and Care Excellence cost-effectiveness thresholds. The Bluebelle Wound Healing Questionnaire was acceptable to participants, had low levels of missing data and demonstrated good levels of sensitivity and specificity in the detection of surgical site infection in surgical wounds healing by secondary intention. The trial included a high proportion of diabetic participants with foot wounds, which may affect study generalisability. Negative pressure wound therapy use for 'wound management', common in certain surgical specialties, was not assessed in this study. Negative pressure wound therapy is not clinically or cost-effective in augmenting healing in patients with surgical wounds healing by secondary intention, particularly those with comorbidities. Evaluation of methods to treat or prevent infection of surgical wounds healing by secondary intention and evaluation of negative pressure wound therapy for 'wound management' are recommended. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/42/94. After an operation, most wounds are closed using stitches or staples. Some wounds cannot be closed and are left open. Some closed wounds may reopen. These ‘open’ wounds are usually left to heal slowly from the bottom up. Negative pressure wound therapy is commonly used to treat ‘open’ wounds. Negative pressure wound therapy uses a machine to apply gentle suction to a wound, which removes wound fluid, and may help keep the wound clean and perhaps aid healing. We do not know if negative pressure wound therapy is as good as, better than or worse than standard wound dressings that are also used for healing ‘open’ surgical wounds. We also do not know if negative pressure wound therapy is good value for money. There has not been enough, high quality, independent research to enable doctors and nurses to decide on the best treatment. Between May 2019 and January 2023, 686 patients with an open wound agreed to take part and were equally randomly assigned to standard dressings or negative pressure wound therapy. Most of the wounds were on patient’s feet. Most patients had diabetes, and many patients also had conditions affecting their heart and/or blood vessels. We collected wound healing data, treatment information and health outcomes for each participant for a year. We found no clear evidence that negative pressure wound therapy provided any significant benefits for patients and specifically that negative pressure wound therapy did not reduce the time it took for wounds to heal compared to standard wound care. Negative pressure wound therapy was also more expensive than standard dressings and so was not likely to be a good use of healthcare resources. Patients and doctors will be able to make more informed decisions about which dressing to use to help wounds heal. The National Health Service can save money by recommending the use of standard dressings for open wounds instead of using the more expensive negative pressure wound therapy.

Human amniotic membrane (hAM) is a widely used biomaterial with longstanding utility in ophthalmology and emerging therapeutic promise across orthopaedics, obstetrics and gynaecology, and dermatology. Clinically available biological tissue repair materials primarily encompass autologous, allogeneic, and xenogeneic tissues. However, autologous materials are limited by availability, while allogeneic and xenogeneic tissues often present challenges related to immunocompatibility. As a commonly used allogeneic biomaterial, the hAM is regarded as a highly promising tissue repair material owing to its favourable immunological profile and exceptional tissue-regenerative properties. HAM is the innermost natural barrier of the placenta and possesses unique structural and biological characteristics that facilitate tissue repair and regeneration. This review summarizes recent advances and clinical applications of hAM in orthopaedics, obstetrics and gynaecology, and dermatology, specifically focusing on its roles in promoting tendon repair, alleviating osteoarthritis, repairing endometrial injury, treating diabetic foot ulcer, and enhancing burn wound healing. With the continued development of regenerative medicine, hAM is expected to play an increasingly important role in diverse tissue repair and regenerative medicine applications.

Severe COVID-19 is marked by a dysregulated inflammatory response, known as a cytokine storm, resulting in acute respiratory distress syndrome (ARDS) and multiple organ failure. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated potential as immunomodulatory agents. This work investigates the possibility of MSC-Exos to mitigate excessive inflammation in COVID-19 by targeting the mitogen-activated protein kinase (MAPK) signalling pathway. We integrated molecular docking analysis between TGF-β and Annexin A1 as exosomal proteins and key component proteins of the MAPK pathway (p38, ERK1/2, JNK1). The in-silico results were then validated in vivo using a Syrian hamster model of SARS-CoV-2 infection. Quantitative PCR (qPCR), western blotting, and histological examination were employed to evaluate the effects of MSC-Exos therapy on MAPK pathway activation, cytokine production, and lung tissue pathology. The in-silico study revealed extensive hydrogen bonding and hydrophobic interactions at the protein-protein interfaces between exosomal proteins and MAPK components. These interactions suggest that exosomal proteins may modulate MAPK signaling pathways. In vivo, MSC-Exos administration led to marked downregulation of pivotal genes in the MAPK signaling pathway (MEKK1, MEKK2, MEKK3), diminished phosphorylation of JNK1, p38, and ERK1/2, and lowered production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Histopathological examination demonstrated ameliorated lung tissue structure, characterized by diminished alveolar wall thickness and decreased immune cell infiltration. MSC-Exos elicit immunomodulatory effects in SARS-CoV-2-Infected hamsters, partially by directly targeting and blocking the MAPK signaling pathway. These findings offer a compelling justification for the clinical assessment of MSC-Exos as a therapeutic approach to alleviate the cytokine storm and enhance outcomes in severe COVID-19 by targeting the ACE2-Independent pathway.

Published data on podocyte morphology in young domesticated pigs are scarce. The current study aimed to characterize the histological and ultrastructural characteristics of the podocyte in Sus domesticus. This study depended on kidney samples from seven healthy two-month-old domestic pigs, which were collected immediately after slaughter and processed for histological and transmission electron microscopy (TEM) examination. The renal cortical tissue consisted of nephron components, including renal corpuscles, proximal convoluted tubules, distal convoluted tubules and collecting tubules. TEM analysis showed that the cytoplasm contained few mitochondria and poorly developed endoplasmic reticulum cisternae. Some podocytes have a primary process that wraps around the basal lamina of the blood capillary and gives rise to small secondary cytoplasmic processes known as pedicels. The podocytes exhibited numerous pedicels resting on the glomerular basement membrane, closely associated with the underlying glomerular endothelium, and projecting towards the capillary lumen. The filtration barrier consisted of fenestrated endothelial cells, a trilaminar glomerular basement membrane and an intact podocyte layer. In conclusion, this study provides a detailed histological and ultrastructural description of podocytes in young Landrace pigs and establishes baseline morphological data that may support future comparative, developmental and functional renal investigations in Sus domesticus.

The COVID-19 pandemic led to unprecedented interest and participation in vaccine trials globally, and a concurrent increase in vaccine hesitancy. Whether this impacted recruitment of healthy volunteers to subsequent non-COVID vaccine trials is not well studied. We explored the impact of the COVID-19 pandemic on motivations for participating in two clinical trials of the same novel anti-plague vaccine, conducted in the United Kingdom (UK) and Uganda in 2021 and 2022. Participants enrolled in PlaVac (UK) and PlaVac Uganda, Phase I trials of ChAdOx1 Plague vaccine, were invited to complete an optional questionnaire and semi-structured interview examining motivations for participating, including questions on the impact of the COVID-19 pandemic on their decision. Questionnaires were self-administered and interviewer-administered for UK and Uganda studies, respectively. Interviews were conducted in local languages, transcribed in English, and analysed using thematic analysis. Results were compared between studies. Thirty-one of the 45 (68.9%; 25.8% female) UK trial participants and all 36 (100.0%; 27.8% female) of the Uganda trial participants completed questionnaires responses, and 19 Uganda questionnaire respondents completed interviews. Responses to questions on the impact of the COVID-19 pandemic on volunteering decisions were divergent between countries, with little effect for UK participants but a strong positive effect for Ugandan participants. Themes relating to this effect were "contributor, not cause" in the UK, and in Uganda were preparedness (wanting to contribute to vaccine development to prevent suffering and death from future epidemics), increased awareness (understanding the vaccine development process and seeing rapidly deployed COVID-19 vaccine trials gave them confidence), and personal protection (believing themselves to be protected by the novel plague vaccine). Participants in both studies expressed trust and confidence in the study vaccine which shares the same adenoviral-vectored platform technology used to elicit an immune response (ChAdOx1) with the COVID-19 vaccine ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca). For Ugandan participants, COVID-19 and mass vaccination increased knowledge about vaccines and trials and encouraged them to participate in research, but had little impact on UK volunteers. There was no evidence of a negative effect of perceptions of the related ChAdOx1 nCoV-19 vaccine on trial participants' confidence in the novel plague vaccine's safety. Current controlled trial: ISRCTN41077863, prospective registration date: 19/03/2021, and current controlled trial: ISRCTN79243381, prospective registration date 05/08/2022.

Psychological stress is a key driver of short-term blood pressure (BP) elevations and cardiovascular risk, yet its moment-to-moment impact in daily life remains difficult to predict. In this longitudinal observational study, we collected multimodal data from 20 adults with self-reported hypertension, including continuous wearable-derived heart rate and activity, ecological momentary assessment (EMA) stress ratings, and ambulatory BP measurements in free-living conditions. The dataset comprised 3694 EMA responses and 3812 BP measurements collected over approximately four weeks per participant (mean 24.1 ± 8.5 days). We evaluated whether participant-specific ("personalized") models outperform a single pooled population model. Two prediction tasks were examined: (i) prediction of near-term BP elevations from wearable signals and stress EMA responses and (ii) prediction of self-reported stress from wearable signals and BP. Across both tasks, personalized models consistently improved predictive performance. For BP prediction, personalized models achieved a mean AUROC of 0.803, exceeding the population model by 0.235, while for stress prediction they achieved a mean AUROC of 0.849, exceeding the population model by 0.208. These findings suggest that personalized wearable-based models can capture individual patterns of stress and BP dynamics, with direct implications for precision mental health assessment and just-in-time adaptive intervention design in future work.

Buruli ulcer (BU), a neglected tropical disease caused by Mycobacterium ulcerans (Mul), is treated with an 8-week regimen of rifampicin (RIF) and clarithromycin (CLA). Clinical trials are currently evaluating amoxicillin/clavulanate (AMX/CLV) co-administration to reduce treatment duration. However, conventional methods for assessing in vitro drug efficacy against Mul, like colony-forming units (CFUs), are slow and cumbersome. The ribosomal RNA synthesis ratio (RS-ratio) measures ribosome biogenesis and serves as a proxy of metabolic activity. While it is a promising predictive biomarker for treatment shortening in tuberculosis, its application in Mul remains unexplored. Here, we evaluated the RS-ratio for Mul drug activity assessment through RNA extractions from time-kill assays using RIF, CLA, and AMX/CLV, alone or in combinations. RIF + AMX/CLV-containing combinations produced a potent, rapid RS-ratio reduction, decreasing from a baseline of ≈2000 to ≈200 as early as day 3, and reaching their maximal inhibition (≈50-60) between days 7 and 10. Notably, this metabolic decline preceded the CFUs and luminescence drops observed in prior studies. Interestingly, the RS-ratio detected a metabolic recovery between days 14 and 28 (≈400), suggesting remaining bacterial viability, a phenomenon not observed by CFUs or luminescence. In summary, this is the first report using the RS-ratio to evaluate antibiotic activity against Mul. Our findings validate the RS-ratio as a molecular tool for assessing the sterilizing potential of new regimens to inform future research and clinical trial designs for the treatment of BU. Our results support the RIF + CLA + AMX/CLV regimen selection for BU treatment shortening in the BLMs4BU clinical trials (NCT05169554, PACTR202209521256638).

Hepatitis E virus (HEV) infection screening and diagnosis are critical for controlling the HEV epidemic. Serological testing for anti-HEV IgM and IgG is widely used to diagnose acute and past HEV infections, respectively. This study aims to evaluate the analytical performances of the MAGLUMI HEV IgM and IgG assays for detection of HEV antibodies and comparison with the microplate Wantai assay. We assessed the precision, cross-reactivity, and interference of the MAGLUMI HEV IgM and IgG assays, as well as their agreement rates with the Wantai HEV IgM and IgG assays. Method comparison included in total 775 samples from 405 patients with suspected HEV infection and 86 asymptomatic blood donors. Among them, the HEV infection status of 136 individuals was confirmed through HEV RNA results, including 39 cases of acute infection, 3 cases of convalescence, and 94 cases of non-infected individuals. The within-run and between-day imprecision for the MAGLUMI HEV IgM assay ranged from 1.54% to 3.71%, while for the MAGLUMI HEV IgG assay, it ranged from 0.00% to 4.35%. No cross-reactivity was observed in either assay. The positive and negative agreement rates between the MAGLUMI and Wantai IgM assay were 98.61% and 99.31%, respectively. The positive and negative agreement rates between the MAGLUMI and Wantai IgG assay were 94.95% and 97.20%, respectively. Overall, the analytical performance of the MAGLUMI HEV IgM and IgG assays is good, with reactivities comparable to those of the Wantai HEV IgM and IgG assays. However, due to the limited availability of HEV RNA detection results and lack of HEV genotype information, this study could not effectively evaluate the clinical performance of the reagent, and further studies with HEV RNA determination and genotyping are needed for a clinical validation.

Extreme environments impose conditions that are lethal to most organisms, yet a limited number of evolutionary lineages have adapted to chronic stress. However, whether distinct lineages exposed to the similar stressors rely on shared adaptive mechanisms remains poorly understood. Mangroves offer a compelling system to address this question, as they thrive in shared harsh environments. Here, we examine two mangrove species, Kandelia obovata and Avicennia marina, both inhabiting intertidal zones but deploying contrasting strategies to withstand hypoxia. Phylogenomic analyses revealed that K. obovata experienced an ancestral whole-genome duplication (WGD) prior to intertidal colonization, whereas A. marina underwent two rounds of WGD that expanded its repertoire of hypoxia-responsive genes. Comparative genomic analyses showed that K. obovata underwent contraction of hypoxia-related gene families and harbours fewer gene copies, but each copy is enriched with cis-regulatory elements. In contrast, A. marina retained significantly more hypoxia-related genes derived from recent WGD. Transcriptomic profiling under controlled hypoxia gradients further showed that K. obovata relies on rapid but stable gene expression responses, while A. marina exhibits delayed but hierarchical gene regulatory networks. Together, these results demonstrate that even under identical extreme selective pressures, plant lineages can follow distinct evolutionary routes, shaped by differences in genome evolution and regulatory architecture.

Low-level laser therapy (LLLT) is being increasingly applied in regenerative medicine due to its ability to modulate cellular metabolism and support repair processes. However, the effect of various exposure parameters on fibroblast activity still does not remain fully understood. The study aim was to evaluate the effect of selected LLLT parameters (808 nm, 100 and 200 mW, 2 and 10 J/cm², pulsed beam) on the biological activity of fibroblasts in vitro. Fibroblasts were exposed to the established exposure parameters, and then the number of adherent and metabolically active cells, their migration, adenylate kinase (AK) as well as nitric oxide (NO) levels, cytokine secretion, metalloproteinase (MMP-2, MMP-9) activity, and oxidative-antioxidant potential were assessed. The most favourable effects were achieved with 200 mW; 2 J/cm² and 100 m; 10 J/cm² exposure parameters. In these conditions, increased number of adherent and metabolically active cells, and elevated migration were observed. Moreover, in this condition decreased AK release and NO secretion were found. Furthermore, LLLT reduced in fibroblasts interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion as well as affected the activity of metalloproteinases, what corresponded with subsequent wound healing process. Additionally, a beneficial effect on maintaining the oxidative-antioxidant balance in fibroblasts was noted. In summary, the effects of LLLT on fibroblasts depend on the applied irradiation parameters, and appropriately selected LLLT treatment (200 mW; 2 J/cm² and 100 mW; 10 J/cm²,) stabilise fibroblast metabolism, limits their proinflammatory response and promotes extracellular matrix remodelling (ECM). These results confirm the potential of LLLT as an effective method supporting regenerative processes in the treatment of tissue damage.

Long-term trajectories and cumulative burden of the triglyceride-glucose-frailty index (TyGFI) exhibited nonlinear associations with hip fracture risk. Persistent metabolic-frailty imbalance markedly increased fracture susceptibility, identifying TyGFI as a potential risk factor for early detection and prevention of hip fracture. Hip fracture is a major cause of disability and mortality in older adults, yet traditional risk factors explain only part of its variability. Metabolic dysfunction and frailty may jointly contribute to skeletal fragility. The triglyceride-glucose-frailty index (TyGFI) integrates these domains, but its long-term association with hip fracture risk remains unclear. A total of 6130 adults aged&#x2009;&#x2265;&#x2009;45&#xa0;years from the China Health and Retirement Longitudinal Study were included. TyGFI was calculated as the product of the triglyceride-glucose index and frailty index. Participants were grouped into longitudinal trajectories using k-means clustering, and cumulative exposure was estimated as the area under the curve between 2012 and 2015. Cox regression and spline analyses evaluated associations with hip fracture risk. Three distinct TyGFI trajectories were identified-low-stable, moderate-increasing, and high-increasing. Compared with the low-stable group, participants in the moderate- and high-increasing groups had higher hip fracture risks (HR&#x2009;=&#x2009;1.97 and 3.79, both P&#x2009;<&#x2009;0.001). Cumulative TyGFI showed a nonlinear association with fracture risk, with a potential threshold around 4.5. Incorporating cumTyGFI significantly improved predictive performance (C-statistic&#x2009;=&#x2009;0.7340; NRI&#x2009;=&#x2009;0.4330; IDI&#x2009;=&#x2009;0.0097; all P&#x2009;<&#x2009;0.001). Results were robust across subgroups and multiple sensitivity analyses. Long-term trajectories and cumulative exposure of TyGFI were independently associated with hip fracture risk, suggesting that persistent metabolic-frailty imbalance contributes to skeletal fragility. TyGFI may serve as a practical integrative marker for early identification and prevention of high-risk individuals.

Synovial tissue (ST) biopsy has evolved from an experimental procedure into a clinically relevant tool that provides unparalleled access to the inflamed joint in rheumatoid arthritis (RA). Initially performed through blind needle and arthroscopic techniques, the adoption of minimally invasive ultrasound-guided biopsy has enabled safe, reproducible, and patient-acceptable tissue sampling across large and small joints. Histopathological evaluation, including the Krenn Synovitis Score and recognition of distinct pathotypes, has provided diagnostic and prognostic insights, while comparative analyses have highlighted shared inflammatory pathways with osteoarthritis and psoriatic arthritis. The integration of high-dimensional technologies such as bulk and single-cell transcriptomics, spatial profiling, and proteomics has uncovered novel stromal and immune cell subsets and linked tissue signatures to therapeutic outcomes. Landmark biopsy-driven trials (R4RA and STRAP) have demonstrated the feasibility of stratifying treatment on the basis of synovial biology, positioning synovial biopsy as a cornerstone in the long journey towards precision RA management.

Asthma exacerbations (AEs), especially those triggered by respiratory syncytial virus (RSV), remain clinically intractable because of limited treatment options and significant immune heterogeneity. In this study, we investigated the central cellular and molecular mechanisms driving RSV-induced AEs using a house dust mite-sensitized mouse model. Through macrophage depletion, transcriptomic profiling, and pathway inhibition, we identified monocyte-derived macrophages (Mo-M&#x3c6;s) as key orchestrators of both antiviral responses and inflammatory amplification. Mechanistically, Mo-M&#x3c6;s upregulate and secrete cathepsin C (CTSC), which in turn activates a previously unrecognized PR3/p38/RELB signaling axis. This axis established a positive feedback loop, sustaining macrophage activation and pathogenic inflammation. Pharmacological inhibition of CTSC disrupted this loop, leading to reduced lung inflammation, mucus hypersecretion, and airway hyperresponsiveness. However, this intervention was accompanied by a measurable compromise in antiviral immunity. This study reveals a previously unrecognized CTSC-driven positive feedback loop in Mo-M&#x3c6;s as a core pathogenic mechanism underlying RSV-induced AE. These findings identify CTSC as a promising mechanism-based therapeutic target, highlighting the need to carefully balance inflammation control against the preservation of antiviral immunity.

Regulatory changes and growth of hemp-derived products have increased the need for robust methods to quantify cannabinoids. To systematically evaluate a liquid chromatography photo-diode array (LC-PDA) method for 11 cannabinoids in hemp using a blinded collaborative framework, with emphasis on both fortified and endogenous analytes. A previously validated method was set up at a new&#x2011;to&#x2011;method laboratory (Veterinary Medical Diagnostic Laboratory, VMDL) and verified in-house using fortified samples. Discrepancies between certified and measured values for a hemp reference material raised questions about the method's performance for endogenous cannabinoids. To address this, an independent laboratory conducted a two-round collaborative exercise (Blinded Method Test, BMT) by preparing blind-coded samples using hemp, nettle, and hemp-nettle mixtures with various fortification levels. VMDL quantified cannabinoids by external calibration (EC) in acetonitrile (surrogate solution). Parallelism evaluation and standard-addition calibration were complementarily applied to address matrix effect and accuracy for endogenous analytes. The method showed good linearity and acceptable accuracy and precision for blinded fortified hemp, nettle, and hemp-nettle samples and quality controls using EC. Parallelism results supported the use of solvent-based EC for endogenous cannabinoids in hemp. Standard-addition estimates were directionally consistent with EC but differed by about 15-45% for some analytes. These findings underscore the need for more detailed characterization of extraction efficiency for endogenous cannabinoids to strengthen accuracy assessment for incurred cannabinoids in complex botanical matrices. The two-round BMT demonstrates how collaborative exercises can extend conventional validation by integrating multiple matrices, parallelism testing, and complementary quantification approaches. The evaluated method is suitable for routine hemp testing at VMDL, while the findings emphasize the need to evaluate extraction efficiency for incurred versus fortified analytes in complex biomatrices. A collaborative framework with parallelism and standard addition provides enhanced evaluation of method performance for complex botanical matrices.

Depression after a stroke is the most frequent and burdensome neuropsychiatric post-stroke complication. This study aimed to determine the relationship between post-stroke depression (PSD) and the levels of homocysteine (HCY) in patients with spontaneous intracerebral hemorrhage (SICH). We collected data from patients with hemorrhagic stroke (HS) admitted to the hospital and recorded their demographic and clinical characteristics. We also searched for information regarding HAM-D17 (Hamilton Depression) scores and HCY levels at 3&#xa0;m, the use of antidepressant medications and folic acid during the follow-up period in the group of patients diagnosed with PSD and hyperhomocysteinemia (HHcy) in the acute phase. A total of 1,852 patients were included. 642 (34.7%) patients with PSD and 598 (32.3%) patients with HHcy, 364 (19.7%) patients with both conditions. A link between depression and low HCY level has similarly been found in patients with HS (OR, 1.549; 95% CI, 1.358-1.768). Additionally, left-sided stroke, anterior circulatory stroke, intraventricular hemorrhage, symptoms of paralysis or dysarthria, and higher NIHSS scores occurred more often in the PSD group. Compared to the antidepressant medications (ADM) group, HAM-D17 scores decreased significantly in the ADM plus folic acid group at the end of 3&#xa0;m (P&#x2009;=&#x2009;0.036). On the basis of our data, PSD was significantly more frequent in patients with HHcy in patients with SICH at the acute phase. The location of hemorrhage and the severity of the disease are significantly correlated with the incidence of PSD. Oral doses of folic acid and ADM showed significant improvements in the HAM-D17 scores for the patients with comorbid PSD and HHcy.