Tree seedling regeneration after wildfire will determine the long-term trajectory of forests under climate change, yet increasing drought and heat extremes can suppress regeneration and result in forest type conversion. We combined field observations and a controlled drought-heat growth chamber experiment to investigate how these stressors independently and jointly affect drought- and heat-tolerance physiology in seedlings of montane conifer species from drought- and wildfire-prone regions in the southern Sierra Nevada. In both the field and growth chamber experiment, we found that exposure to elevated leaf temperatures in post fire-like environments dwarfed the effect of physiological adjustments in heat tolerance (temperatures causing initial impairment (Tcrit) or 50% loss (T50) of photosystem II capacity) and drought tolerance (turgor loss point). In the field, this resulted in narrower thermal safety margins across five conifer species in burn scars with no remaining canopy, while in the growth chamber experiment three species showed narrower or even negative thermal and hydraulic safety margins. In the growth chamber experiment, leaf temperatures were also frequently decoupled from air temperature, highlighting that biophysical feedbacks between leaf temperature and transpiration may amplify seedling water loss even under stomatal closure. For both the field and growth chamber experiment, we found no evidence of a trade-off between drought and heat tolerance within or among species. Among species, seedlings of the range-restricted Sequioadendron giganteum (giant sequoia) were observed to be the most vulnerable to combined drought and heat stress in the growth chamber experiment. Our results highlight that direct thermal stress may strongly constrain post-fire conifer regeneration and underscore the need to integrate seedling energy balance and microclimate into predictions of post-fire recovery and management strategies, especially for vulnerable species such as giant sequoia.

Hypertrophic scar (HS) is characterised by excessive fibroblast proliferation and abnormal differentiation; however, the underlying molecular mechanisms remain incompletely understood. Here, we identify the collagen receptor discoidin domain receptor 1 (DDR1) as a key regulator of fibroblast activation during HS formation. We observed markedly increased expression and phosphorylation of DDR1 in human HS tissues compared with adjacent normal skin. To investigate the functional role of DDR1, primary fibroblasts derived from human HS tissues were stimulated with collagen III to induce DDR1 activation in vitro. DDR1 activation significantly enhanced fibroblast proliferation and promoted myofibroblast differentiation, as evidenced by increased collagen III and α-smooth muscle actin (α-SMA) expression. Concomitantly, DDR1 activation suppressed the expression of the tumour suppressor phosphatase and tensin homologue (PTEN) and promoted nuclear translocation of NF-κB p65, a known inhibitor of PTEN transcription. Consistent with these findings, HS tissues exhibited elevated DDR1 expression and reduced PTEN levels relative to adjacent normal skin. The pathological role of DDR1 in HS was further validated in a rabbit ear model, in which local administration of a selective DDR1 inhibitor significantly attenuated scar formation. Together, these findings delineated a collagen III-DDR1-PTEN signalling axis that drives fibroblast proliferation and activation in hypertrophic scarring, highlighting DDR1 as a promising therapeutic target for the prevention and treatment of HS.

Foam dressings are vital for exuding wounds, yet antibacterial modification remains challenging and relies heavily on cytotoxic silver compounds. To address these challenges, in this study we developed a process for the antibacterial modification of polyurethane foam dressings using hyperbranched polylysine. The modification process consisted of a simple five-step procedure (soaking-drying-reacting-washing-drying) that did not compromise the foam's intrinsic properties, including hydrophilicity, pore structure and mechanical performance. The optimized modified foam achieved above 99.9% killing of both methicillin-resistant Staphylococcus aureus and Escherichia coli under experimental conditions, competitive with the commercial silver-containing dressing. The HBPL-modified foam dressings also exhibited Grade 1 cytotoxicity and a hemolysis ratio below 1%, showing good biosafety far better than that of silver dressings. In an infected burn wound model in vivo, the modified foam dressings achieved complete wound closure within 21 d, similar to that of silver dressing. More importantly, the healing quality was significantly improved, including enhanced inflammation resolution, angiogenesis and collagen remodeling. Given the convenience of operation and the success of modification, the method to prepare antibacterial foam dressings proposed here has great potential for applications in real world.

Peripheral blood smear review is a fundamental skill that aids in the timely diagnosis of morbid conditions in hematology. There is a lack of existing, evidence-based assessment tools to evaluate learners and guide curricular development both in peripheral blood smear review and analogous visuospatial skills across medical specialties. We collected validity evidence for a novel assessment tool for use in hematology education. We recruited attending hematologists, hematology fellows, and internal medicine residents to participate in the development of this assessment tool. The attending cohort participated in iterative revision of a digital microscopy-based assessment tool encompassing classical and malignant hematology. The validated tool then compared performance across attending, clinical fellow, and resident cohorts. Attending accuracy was poor with peripheral blood smear images alone and improved significantly with the addition of clinical context. Performance increased across training levels with attending and fellow performance significantly outpacing resident performance. Characteristics of morphologic descriptions varied significantly across cohorts. Digital microscopy image quality was considered to be equivalent to light microscopy with minor limitations. This tool offers hematology and pathology educators a validated method to assess learners and evaluate microscopy-based curricular developments. Further investment is required to broaden applications within hematology and pathology education.

Face transplantation carries a critical risk of vascular occlusion. Traditional monitoring relies on subjective clinical signs, which may detect compromise after irreversible ischemia. We report the first application of continuous near-infrared spectroscopy (NIRS) for postoperative monitoring in a partial face transplant recipient. Over ten days, NIRS identified 51 subclinical perfusion events (hemodynamic, positional, or mixed), enabling prompt non-surgical rescue. Regional oxygen saturation (rSO₂) drops preceded clinical signs, guiding fluid resuscitation and patient repositioning. No graft loss occurred. Continuous NIRS oximetry provides objective, real-time data that complements clinical examination and may improve allograft survival.

The first-generation Spike-based COVID-19 vaccines reduced the risk of hospitalization, serious illness, and death from SARS-CoV-2 infections. However, waning immunity failed to prevent immune escape, resulting in multiple variants of concern (VOCs) and prolonging the pandemic. We hypothesize that next-generation CoV vaccines incorporating highly conserved SARS-CoV-2 T cell antigens would confer potent, broad, long-lasting cross-protective immunity against multiple VOCs. In this study, we identified 10 non-Spike antigens common and highly conserved across 8.7 million SARS-CoV-2 strains, prior VOCs, SARS-CoV-1, MERS-CoV, seasonal human cold CoVs, and animal CoVs. Seven antigens were preferentially recognized by CD8+ and CD4+ T cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC. Three conserved antigens (NSP2, NSP14, Nucleoprotein) administered to golden Syrian hamsters: (i) induced high frequencies of lung-resident polyfunctional CXCR5+CD4+ TFH cells, GzmB+CD4+/CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+/CD8+ effector T cells; (ii) reduced morbidity, viral load, lung pathology, and COVID-19-like symptoms from various VOCs, including the pathogenic B.1.617.2 Delta and the recent KP.3 Omicron variants; (iii) improved protection conferred by spike-alone mRNA; and (iv) conferred protection that lasted for more than 1 year. This multi-antigen CoV vaccine could provide potent, broad-spectrum, and durable cross-protective immunity against current and future variants of concern in the clinic.

The sternalis muscle is an uncommon anatomical variant of the anterior thoracic wall. Although regarded as functionally insignificant, its presence may influence diagnostic interpretation, surgical dissection and reconstructive planning in breast surgery. We report bilateral sternalis muscles discovered during bilateral skin-sparing mastectomy and immediate autologous reconstruction in a woman in her late 40s. The sternalis muscles were identified intraoperatively, following which retrospective review of preoperative imaging confirmed their presence. Recognition of this variant aided orientation and safe exposure of the internal mammary vessels during reconstruction. Awareness of the sternalis muscle can prevent imaging misinterpretation, avoid intraoperative confusion and optimise reconstructive outcomes.

Burn injuries are often accompanied by severe vascular damage, local tissue hypoxia, and subsequent scar formation. Although nitric oxide (NO) has been widely recognized for its ability to promote angiogenesis and tissue regeneration, achieving sustained NO delivery remains a major challenge. Herein, we developed a formylfuroxan-conjugated NO-releasing micelle (NORM) for burn wound repair. Compared with conventional small-molecule NO donors, the micellar architecture effectively mitigates burst NO release and enables prolonged, sustained NO delivery. In vitro studies demonstrated that NORM exhibits excellent hemocompatibility, minimal cytotoxicity, and a pronounced pro-angiogenic effect. Furthermore, therapeutic evaluation in a murine burn wound model revealed that NORM significantly accelerated wound closure. Collectively, these results demonstrate that sustained NO delivery through NORM effectively promotes vascularized tissue regeneration and highlight its potential as a promising therapeutic strategy for burn wound management.

To review the safety, efficacy, and clinical considerations of vaginal estrogen therapy for the treatment of genitourinary syndrome of menopause (GSM) in patients with a history of breast or gynecologic cancer. This is a narrative review of the current literature and clinical guidelines which evaluate vaginal estrogen use in cancer survivors, with a focus on the key outcomes of cancer recurrence and mortality as well as dosing considerations. Vaginal estrogen therapy is consistently associated with significant improvement in GSM symptoms and quality of life. There is minimal systemic absorption with low-dose formulations, with serum estradiol levels remaining within postmenopausal ranges. Large observational studies and meta-analyses show no increased risk of breast cancer recurrence or mortality among users, including those with estrogen receptor-positive disease and those on tamoxifen. Data on patients receiving aromatase inhibitors (AIs) are more limited. Current evidence supports the safety and efficacy of low-dose vaginal estrogen for GSM in most cancer survivors, with no clear increase in recurrence or mortality. Although nonhormonal therapies should be considered first-line, low-dose vaginal estrogen is an appropriate and effective option for patients with refractory symptoms along with shared decision making and multidisciplinary care. Further prospective studies are needed, especially in patients receiving AIs.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from infection globally yet the contribution of non-classical T-cell pathways to human immunity remains poorly defined. CD1c-autoreactive T-cells, which recognise self-lipids presented by the antigen-presenting molecule CD1c, are frequent in human blood but their role during infection remains unclear. Here, we investigate how CD1c-expressing antigen-presenting cells (APCs) and Mtb infection shape CD1c-autoreactive T-cell responses using engineered human APC systems, complemented by single-cell transcriptomic profiling to define the ex vivo phenotypic landscape of these T-cells. CD1c is present within human TB granulomas, whereas Mtb down-modulates CD1c expression on infected APCs, consistent with an immune evasion strategy. CD1c-autoreactive T-cells respond more strongly to Mtb-infected CD1c+ APCs than to uninfected cells, exhibiting enhanced activation, cytotoxicity, and diverse cytokine secretion via CD1c-dependent recognition. Under in vitro conditions, these T-cells reduce relative Mtb burden in infected phagocytes. Single-cell RNA sequencing reveals cytotoxic effector-memory programmes and expression of antimicrobial molecules, providing a mechanistic basis for these responses. Together, these findings define a human CD1c-restricted T-cell response to Mtb-infected APCs and identify autoreactive CD1c-restricted T-cells as a candidate cellular axis for lipid-directed immunity in TB.