Healing after split-skin grafting remains difficult to anticipate in small-area burns, particularly when wounds show no clinically diagnosed infection. We tested whether the burn wound microbiome before grafting captures early wound states linked to subsequent healing. Twenty-six adults with mid-dermal to full-thickness burns involving < 10% total body surface area underwent longitudinal sampling at surgery, graft check and clinic review. At surgery, swabs were collected from the burn wound before grafting, the split-skin donor site and anatomically matched uninjured control skin. Across 170 infection-free samples, microbiome profiling showed that pre-grafting burn wounds already had reduced microbial diversity and distinct community structure compared with matched control skin. This baseline dysbiosis included depletion of commensal-associated anaerobes, including Finegoldia and Anaerococcus and enrichment of opportunistic burn-associated taxa, including Pseudomonas and Acinetobacter. Donor sites acquired a related wound-like microbiome and remodelled in parallel with burn wounds during healing, but post-grafting burn microbiota were not preferentially similar to matched donor sites, arguing against a donor-to-burn microbial transfer. The clearest clinical signal was present before grafting: lower burn wound diversity at surgery was associated with delayed healing, and baseline community structure differed in wounds that later required regrafting. These findings suggest that the pre-grafting burn wound microbiome may provide an early, infection-independent marker of healing trajectory and should be tested as a predictive biomarker in larger prospective cohorts.

Exosomes derived from lung cancer cells play a critical role in modulating the tumour microenvironment, particularly through their effects on macrophage polarization. We investigated how exosomes from A549 lung adenocarcinoma cells, both unstimulated and stimulated with a toll-like receptor 4 (TLR4) agonist, influence the phenotype and function of THP-1 derived macrophages. We used differential centrifugation and immunobead assay to isolate exosomes. Exosomes from unstimulated A549 cells promoted a mixed M1/M2 macrophage phenotype with a bias towards M2 polarization, while exosomes from TLR4-stimulated A549 cells reduced M2 marker expression without affecting M1 polarization. Both types of exosomes increased macrophage phagocytic capacity compared to PMA-differentiated controls, but TLR4-agonists did not increase it further. These findings provide new insights into how TLR agonist-stimulated lung cancer-derived exosomes shape macrophage phenotypes and functions, with implications for understanding tumour-immune interactions and developing novel therapeutic strategies targeting the tumour microenvironment.

Time perception is a fundamental aspect of human cognition, influencing motor coordination, decision-making, and planning. Unlike sensory modalities such as vision or hearing, which rely on dedicated sensory organs, the perception of time lacks a specific neural substrate, making it highly dependent on internal physiological and psychological states. Research suggests that physiological arousal plays a crucial role in temporal distortions, with pacemaker-accumulator models proposing that heightened arousal accelerates the internal clock, leading to an overestimation of time. We provide a systematic review of the available literature on the complex relationship between physiological indices of arousal and time distortion. Overall while a relatively consistent association emerged between baseline cardiac autonomic activity and temporal accuracy. When physiological arousal was experimentally manipulated, its relationship with temporal distortion was substantially less consistent. These differences were observed across pain, stress, emotional, and physical-activity paradigms and appeared to vary according to the characteristics of the eliciting stimulus. This pattern highlights the need to distinguish physiological arousal from the other cognitive processes involved and provides a basis for future research investigating also the other potential explanatory factors in the relationship between arousal and time perception.

Diverticulitis is a common emergency general surgical condition that affects patients worldwide. Research remains heterogeneous, meaning the provision of high-quality, evidence-based care for these patients remains a challenge. We aimed therefore to complete a core outcome and core descriptor set for acute left-sided diverticulitis.

Cholesterol and oxysterols are key molecules that regulate physiological processes and participate in the occurrence and progression of various major diseases. Accurate and efficient analytical detection of these substances in complex biological matrices is critical for disease mechanism research and biomarker discovery. However, challenges including complex biological matrices, large differences in analyte abundance, susceptibility to auto‑oxidation, low ionization efficiency, and difficulty in isomer separation pose severe obstacles to reliable analysis, making sample preparation the core step for accurate quantification and valid identification. Continuous innovations have been achieved in sample preparation techniques, such as liquid-liquid extraction, solid‑phase extraction, deep eutectic solvent extraction, molecularly imprinted extraction, derivatization, as well as integrated and automated workflows. These advances improve extraction efficiency, selectivity, antioxidant protection, and throughput, while effectively reducing matrix interference and artificial oxidation. This paper systematically reviews the research progress in sample preparation for cholesterol and oxysterol analysis in complex biological matrices from 2015 to 2026, highlights the technical advantages, application scenarios, and current limitations of various pretreatment strategies, and prospects the development trends toward greening, intelligence, and high throughput.

Over the past two decades, coronaviruses have caused three major public health crises, including the epidemics of SARS-CoV, MERS-CoV, and SARS-CoV-2. Following the outbreak of SARS-CoV-2, several antiviral drugs have been approved for the treatment of COVID-19. However, the high mutation rate of SARS-CoV-2 has led to the emergence of multiple variants, some of which can escape vaccine-induced immunity and develop resistance to virus-targeted drugs. Viruses rely on host cell mechanisms to complete replication and transmission. Host-directed therapy is an emerging strategy that inhibits infection by targeting host cell factors essential for pathogen replication. Interventions targeting host factors have been proven effective in limiting viral infections and have the potential to reduce the risk of drug resistance. Our previous study found that the sigma-1 receptor (σ1R) is involved in the autophagic process mediated by the SARS-CoV-2 non-structural protein NSP6, suggesting that σ1R may serve as a therapeutic target against SARS-CoV-2. In this study, we found that the σ1R antagonists BD-1047 and σ1RA1 inhibited SARS-CoV-2 and its variants in vitro and showed antiviral activity in vivo. At the cellular level, these compounds also inhibited porcine epidemic diarrhea virus (PEDV) and infectious bronchitis virus (IBV), indicating cross-model antiviral activity. BD-1047 further showed antiviral activity against HCoV-OC43 in both in vitro and in vivo models. In addition, Ocaperidone, identified through computer-aided screening, exhibited protective effects against SARS-CoV-2 and HCoV-OC43 in both cell-based and mouse models. Collectively, these findings support σ1R as a host-associated antiviral target candidate and provide several compounds for further optimization and mechanistic investigation.

The global ageing of the population has significantly increased the demand for long-term informal care, particularly in the context of Alzheimer's disease (AD). Although research on caregiver burden and coping strategies is extensive, limited attention has been paid to the temporal evolution of caregiving roles and their intersections with caregivers' life trajectories. This systematic review, conducted across literature published between 2004 and 2024, examines how the life course perspective has been applied in sociological research on family caregiving for people with AD, aiming to analyse the interplay between caregiving timing, biographical transitions, and socio-institutional contexts. The selected studies reveal that caregiving is not a static or homogeneous role but evolves across the life span, shaped by transitions, linked lives and structural conditions. Adopting a life course perspective enhances the understanding of caregiving as a dynamic and socially embedded process. This approach underscores the need for policies that are temporally sensitive, culturally reflexive and capable of supporting caregivers across different life stages.

Sequence-selective control of gene expression by synthetic DNA-binding molecules is attractive for developing chemical biology tools and potential therapeutic applications. Here we report a cyclic pyrrole/lysine polyamide (cPKP) that preferentially binds AT-rich DNA, with selective recognition of ATAT and ATGT motifs. In a HeLa nuclear extract-based transcription system, cPKP repressed transcription in a promoter-dependent manner, showing stronger inhibition of a cytomegalovirus (CMV) core promoter than of the human c-MYC promoter. RNA sequencing showed that cPKP was associated with downregulation of genes whose proximal promoters were enriched for ATAT and ATGT motifs, while causing limited perturbation of global cellular homeostasis in HeLa cells. Together, these results establish cPKP as a motif-selective DNA-binding scaffold that can modulate transcription in a promoter-dependent manner with limited global transcriptomic perturbation in human cells.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in a variety of consumer and industrial applications for their water- and oil-resistant properties. Firefighters can be exposed to PFAS as part of their job through gear, aqueous film-forming foams (AFFFs) used to extinguish aircraft and liquid fuel fires, along with exposure through other combustible materials during fire suppression activities. PFAS exposure has been linked to a variety of health conditions including cancer, obesity, reproductive issues, and immunosuppression. Epigenetic modifications may be one mechanism underlying PFAS toxicity. In this study, we used epigenetic indicators to assess association of PFAS serum concentrations with (1) epigenetic aging and (2) DNA methylation at loci within genes related to immune function. Blood leukocyte DNA methylation was quantified via the Infinium EPIC array from 184 participants in the Fire Fighter Cancer Cohort Study involved in aircraft rescue and firefighting, and serum PFAS was measured via on-line solid phase extraction liquid chromatography isotope dilution tandem mass spectrometry. We observed inverse associations between PFAS concentrations and epigenetic clocks including between serum linear perfluorooctanoic acid (n-PFOA) with four epigenetic clocks (p < 0.05); however, most did not remain significant in sensitivity analyses. Associations (q < 0.1) were observed between perfluorodecanoic acid, n-PFOA, sum of branched perfluorooctane sulfonic acid isomers and differential methylation of specific loci within 34 immune-related genes. Further research can help to better understand the functional impacts of the observed differential methylation on immune health.