Reproductive injury is a core pathological process leading to gamete dysfunction, gonadal structural damage, and impaired reproductive capacity. Basic research has revealed that its pathogenesis involves a complex regulatory network of oxidative stress, inflammatory response, germ cell apoptosis, hypothalamic-pituitary-gonadal (HPG) axis disorder, mitochondrial dysfunction, and epigenetic dysregulation. Panax ginseng C. A. Meyer, a classic medicinal and edible herb, and its bioactive constituents have shown reproductive protective effects in numerous in vitro and in vivo basic studies. This review systematically summarizes the core pathological mechanisms of reproductive injury revealed by basic research, sorts out the main bioactive constituents of ginseng and their remarkable functional characteristics in reproductive protection, focuses on the potent molecular mechanisms and basic research progress of ginseng and its active ingredients against reproductive injury, and identifies the limitations of current basic research and future research directions. This review aims to provide a systematic theoretical basis for further basic research of ginseng in the field of reproductive protection, and to support the in-depth exploration of its intervention mechanism and active ingredient development.

Basic Life Support (BLS) is a crucial life-saving skill, and the effectiveness of different training methods for acquiring and transferring BLS knowledge and skills remains an important area of investigation. Traditional methods, such as lectures, may be less engaging and lack the practical application necessary for optimal skill transfer. New training modalities, including serious games on tablets and in virtual reality (VR) environments, offer interactive experiences, enable personalized feedback, and repetitive practice, potentially enhancing the learning process. However, the effectiveness of these newer training delivery methods on skill acquisition, transfer, and the underlying neurophysiological mechanisms needs further investigation. Hence, this study explores the effectiveness of various BLS training modalities, including traditional lecture-based instruction, tablet-based serious gaming, and VR-based serious gaming. A wearable functional near-infrared spectroscopy (fNIRS) sensory system is used to monitor prefrontal cortex (PFC) activity during training and subsequent hands-on testing. A total of 51 participants, who were randomly assigned to one of three training groups (lecture, tablet, VR), were analyzed. These participants underwent fNIRS monitoring during the training sessions and a final hands-on exam. Our findings revealed that while all three training modalities led to comparable hands-on exam performance, there were notable differences in neural activation patterns. VR-based training appeared to elicit neural responses indicative of more efficient use of cognitive resources during the hands-on test, suggesting its potential effectiveness as a practice mode for skill acquisition and transfer. These findings highlight the importance of considering both behavioral and neurophysiological metrics when assessing the efficacy of educational interventions.

Heat stroke causes life-threatening systemic inflammation and multiorgan injury, but the intracellular mechanisms that sustain inflammatory amplification after heat exposure remain unclear. Here, using heat stroke mouse models, genetic NLRP3 deletion, pharmacological inhibition, myeloid-specific NLRP3 deficiency, macrophage depletion, and heat-stressed macrophage systems, we show that tissue macrophage NLRP3 inflammasome activation is a central driver of interleukin-1β/interleukin-18 release, organ injury, and mortality. Mechanistically, heat stroke enhances phospholipase C delta 4 signaling, promotes diacylglycerol accumulation at trans-Golgi network/Golgi-associated membranes, recruits protein kinase D1, and increases phosphatidylinositol 4-kinase β-dependent phosphatidylinositol 4-phosphate production. This lipid remodeling supports NLRP3 recruitment, ASC speck formation, caspase-1 activation, and inflammatory cytokine release. Phospholipase C delta 4 knockdown preferentially suppresses NLRP3 activation induced by heat stroke, but not by canonical stimuli. These findings link heat stroke to membrane lipid remodeling and spatial inflammasome assembly, identifying a potential organ-protective pathway in heat stroke.

Obstructive sleep apnea (OSA) is a highly prevalent yet substantially underdiagnosed sleep-related breathing disorder increasingly recognized as a heterogeneous systemic disease rather than a purely mechanical consequence of recurrent upper-airway collapse. This review provides an updated and integrated overview of OSA, spanning epidemiology, multifactorial pathophysiology, heterogeneous clinical presentation, major cardiometabolic and end-organ consequences, diagnostic principles, and evolving personalized management, while also emphasizing the limitations of conventional severity classification, which is predominantly based on the apnea-hypopnea index. We highlight how intermittent hypoxia-reoxygenation, sleep fragmentation, sympathetic activation, intrathoracic pressure stress, endothelial dysfunction, inflammation, oxidative stress, and metabolic dysregulation interact to drive systemic injury, and why physiologically enriched metrics such as hypoxic burden, T90, event duration, sleep-stage dependency, and endotypic heterogeneity may better capture biological risk than event frequency alone. Within this broader framework, fibrosis-linked structural remodeling emerges as an important yet under-supported dimension of OSA pathobiology. Experimental and clinical evidence suggests that OSA may contribute to remodeling of the lungs, liver, kidneys, and heart, although the strength of the evidence and the degree of causal inference vary across organs. By integrating established knowledge with this emerging fibrosis-oriented perspective, this review defines key mechanistic, diagnostic, and translational priorities for future research and phenotype-aware clinical stratification.

Translating academic discoveries into clinical investigation remains a major barrier in translational science, particularly when investigators lack the regulatory infrastructure required to sponsor clinical trials. These challenges are especially pronounced for natural product therapeutics, which often lack commercial sponsorship despite promising preclinical evidence. The Penn State Cancer Institute established an Investigator-Initiated Trial Sponsor Support Unit (SSU) to facilitate investigator-initiated trials and support progression toward National Cancer Institute designation. We describe a translational science case study of a Sponsor-Proxy operational model in which a centralized institutional unit performs sponsor-level regulatory and trial infrastructure functions while investigators retain scientific and clinical leadership. Two National Institutes of Health-funded trials evaluating Angelica gigas Nakai extract (INM176) illustrate this framework. The SSU authored regulatory documentation including Investigator's Brochures, coordinated Investigational New Drug submissions, and supported trial infrastructure while clinical teams maintained participant oversight. Both trials achieved activation timelines of 112 and 105 days, shorter than previously reported activation times and within National Cancer Institute operational benchmarks. Sponsor-level oversight continued throughout trial conduct, including regulatory reporting, safety monitoring, and protocol amendment support. This case study demonstrates how centralized institutional expertise can overcome sponsor-level barriers and enable translation of basic science discoveries into investigator-initiated early-phase clinical trials.

BackgroundNeonatal encephalopathy is a leading cause of death and disability in neonates. Most cases are due to hypoxic-ischemic encephalopathy (HIE) which is treated with therapeutic hypothermia (TH). Treatment is only effective if initiated within 6 h of birth, leaving a narrow window for diagnosis. Early recognition is challenging because clinicians must rely on nonspecific clinical signs and basic laboratory indicators. Although multiple biomarkers, including metabolites and electroencephalography, show potential, none have demonstrated adequate diagnostic accuracy or practicality for universal bedside use. As a result, many infants at risk remain unidentified in time for treatment. Therefore, we developed a predictive model using early clinical data to identify neonates at risk for HIE requiring TH.MethodsA secondary analysis was conducted on 362 neonates from the Midwest Neonatal Encephalopathy Registry. Eligible neonates had HIE receiving TH or controls requiring positive pressure ventilation in the delivery room but no HIE/TH. Logistic regression was used to predict HIE.ResultsHIE was associated with higher ALT, AST, creatinine, lactate, nucleated red blood cells, and lower pH compared to those receiving resuscitation in the delivery room but without a diagnosis of HIE receiving TH. The regression model incorporating base excess, signs of possible fetal hypoxia, and 5-min Apgar scores provided the best discrimination with an AUC of 0.831 in 259 infants.ConclusionThis simple model demonstrates robust accuracy as a screening tool for HIE using data available within the first hours of life but requires validation in larger cohorts.

In eukaryotes, the three RNA polymerases (RNAPs) share a flexible acidic N-terminal tail (NTT) derived from the common subunit RPB6. In human, NTT interacts with the PH domain (PH-D) of the p62 subunit in the general transcription/repair factor TFIIH. Although the respective binding sites are highly conserved in vertebrates, they are poorly conserved in fungi. Here, using NMR spectroscopy, we reveal that in the fission yeast Schizosaccharomyces pombe, NTT interacts with PH-D via a distinct binding mode. In human, NTT adopts a defined structure on the basic surface of PH-D, sequentially forming an acidic string, inserting phenylalanine into a pocket, contributing an acidic β-strand to a β-sheet with PH-D, and inserting valine into another pocket. In S. pombe, by contrast, NTT adopts the acidic string and inserts phenylalanine but neither contributes a β-strand nor inserts valine, suggesting that the former features constitute the core binding elements, whereas the latter provide additional interaction modules. Docking models of S. pombe RNAPs and TFIIH support NTT as a suitable binding platform for TFIIH and suggest that it has a role in transcription elongation and DNA repair. Moreover, substitutions of acidic residues within the NTT affect the stability of Rpb6 in S. pombe cells, and mutant cells expressing Rpb6 varinats with selected substitutions exhibit increased sensitivity to methyl methanesulfonate (MMS), which induces DNA-damage repaired by nucleotide excision. Collectively, our findings provide structural insight into the conserved function of RPB6 NTT in RNAP-mediated processes.

The increase in chronic diseases, situations of dependency, population aging, and life expectancy has led to a rise in the demand for long-term care, making caregiving a central factor in social and healthcare systems. The purpose of this review was to identify, analyze, and group validated scales that assess caregiving tasks in formal and informal caregivers of dependent individuals. The study was conducted following the guidelines established by the PRISMA statement, with prior registration in PRÓSPERO, using searches in Scopus, Web of Science, PubMed, ScienceDirect, and Dialnet. The 36 studies included were evaluated using the COSMIN tool to measure the methodological quality and psychometric characteristics of the selected instruments. The findings show a high degree of conceptual and methodological heterogeneity, with scales identified based on three main areas: caregiving tasks, organization of care, and emotional and relational competencies. Although most instruments show adequate content validity and internal consistency, significant fragmentation is observed in cross-cultural validity, measurement error, and responsiveness. Furthermore, the creation of instruments in specific cultural and institutional settings predominates, which limits their generalizability. In conclusion, the evaluation of caregiving tasks remains partial and requires more integrative tools that are sensitive to the social, cultural, and organizational context, which will improve the quality of care, guide professional practice, and support the design of sustainable public policies in the field of dependency.

Vibrio cholerae is a highly motile, comma-shaped, Gram-negative bacterium, which can cause severe diarrhea, dehydration, and even human death. Accumulating evidence suggests that gut microbiota and their culture supernatants affect the fitness and colonization of V. cholerae in the host intestine. However, the effects of the most abundant gut bacterial strains on the physiological activities of V. cholerae have not been systematically investigated at the strain level. Here, our systematic screening revealed that gut bacterial culture supernatants exert profound and diverse effects on the physiology of V. cholerae. Specifically, the culture supernatants from Clostridium butyricum L65, Ruminococcus bromii CNGBCC 1800554, and Bacteroides clarus CNGBCC 1801343 strongly inhibited the growth of V. cholerae. In contrast, the culture supernatants of Akkermansia muciniphila L86 and Roseburia inulinivorans DSM 108,070 enhanced the biofilm formation of V. cholerae. Additionally, ROS resistance in Eubacterium rectale CNGBCC 1801156 and R. inulinivorans 108,070 was linked to their KatE activity, while the culture supernatants of Bifidobacterium animalis L73 and R. inulinivorans DSM 108070 significantly suppressed motility. Furthermore, gut microbial culture supernatants modulated the expression of major regulatory genes in V. cholerae. Integration of our data with human cholera cohort data validated Ruminococcus bromii CNGBCC 1800554 as a promising probiotic candidate. This work provides a theoretical foundation and valuable strain resources for further elucidating the interactions between the gut microbiota and V. cholerae at the strain level, and supports the development of next-generation probiotics for cholera prevention and treatment.

Self-amplifying mRNA (samRNA) vaccines can induce potent immune responses at lower doses than conventional non-replicating mRNA vaccines; however, large RNA size and manufacturing considerations associated with 5' capping remain important challenges. Here, we developed a capless samRNA (CLsamRNA) vaccine platform derived from a Coxsackievirus B5 replicon that uses IRES-mediated cap-independent translation. Systematic optimization of key genetic elements enhanced antigen expression from the CLsamRNA backbone. Using reporter RNAs, LNP-formulated CLsamRNA showed rapid early expression and RNA amplification, with expression kinetics distinct from VEEV-based saRNA and nucleoside-modified mRNA comparators. When encoding the hemagglutinin antigen of highly pathogenic avian influenza clade 2.3.4.4 H5 viruses, CLsamRNA induced potent immune responses after LNP formulation. In mouse models, CLsamRNA induced potent neutralizing antibody responses, cross-reactive activity against clade 2.3.4.4b H5N1 virus, Th1-skewed humoral immunity, and strong antigen-specific cellular immune responses. CLsamRNA also elicited platform-specific early inflammatory and lymph-node immune gene signatures associated with antigen presentation, costimulation, and cellular immune priming. Notably, a minimal 0.01 μg dose of CLsamRNA conferred complete protection against lethal H5N8 influenza virus challenge in BALB/c mice. These findings support CLsamRNA as a distinct cap-independent RNA vaccine platform with dose-sparing protective efficacy against HPAI H5 viruses.

Photosynthesis sustains life on Earth by converting light to chemical energy through the coordinated action of photosystem I (PSI) and photosystem II (PSII) within thylakoid membranes[1-4]. Although structures of isolated photosystems are available, their native organization in chloroplasts remains unknown. Here, using in situ cryo-electron microscopy, we directly imaged Oryza sativa (rice) chloroplasts and determined structures of photosystem supercomplexes in their native membrane environment. We resolved a C2S2M2L4-type PSII-light harvesting complex II (LHCII) supercomplex, including four LHCII antenna trimers that were not retained in purified preparations. Excitation energy transfer calculations based on this architecture closely reproduce in vivo measurements, indicating its physiological relevance. We also resolved asymmetric PSII-LHCII dimers, including side-by-side, trans-lumenal and trans-stromal architectures, and higher-order assemblies of trimers and tetramers. On the basis of these observations, we propose that PSII forms a trans-lumenal and trans-stromal 'skeleton' that shapes thylakoid morphology and supports grana stacking. In addition, we obtained high-resolution structures of PSI-LHCI-LHCII and PSI-LHCI supercomplexes. Together, these structures reveal extensive networks of lipids, pigments and cofactors, providing the first molecular framework for understanding how the native architecture of plant photosystem supports the exceptional photon-to-electron efficiency of photosynthesis.

Plastic drinking straws are a visible single-use plastic product, yet selecting suitable substitutes remains challenging because literature-derived climate evidence and reported user experience are rarely evaluated together. This study develops and demonstrates an interpretable AI-enabled decision-support workflow that integrates literature-derived per-use greenhouse gas (GHG) indicators with review-derived user evidence extracted from online customer reviews using natural language processing (NLP). Drinking-straw alternatives were used as an information-rich case study. The integrated assessment combined a GHG-derived score, a user-experience feature score, and rating-based consumer approval within a transparent multi-criteria decision analysis (MCDA) under four predefined decision-priority scenarios. Among the five shortlisted materials and within the evaluated dataset, the selected per-use GHG assumptions, review-derived user evidence, normalization procedure, and scenario-specific weights resulted in Silicone achieving the highest integrated MCDA score across all four scenarios, whereas Paper ranked lowest. Silicone combined a low per-use GHG indicator with the highest user-experience feature score and high consumer approval. Paper had the highest per-use GHG indicator and a moderate user-experience feature score, while lexical analysis identified recurring functionality-related expressions in its reviews. A shallow decision tree identified a 0.081 kg CO₂e/use threshold separating Paper from the lower-per-use-GHG reusable alternatives within the evaluated decision matrix. The study is not a new process-based life-cycle assessment or comprehensive sustainability assessment. Instead, it demonstrates decision support limited to per-use GHG indicators and review-derived user evidence; broader sustainability dimensions were outside the scope. Future studies may adapt and evaluate the workflow for other product categories using product-appropriate environmental criteria and relevant user-derived evidence.