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Pilus-specific or class C sortases (SrtCs) catalyze pilus polymerization in Gram-positive bacteria and possess a critical lid near the active site that is in a closed or open conformation. The crystal structure of SrtC, which polymerizes endocarditis and biofilm-associated pili in Enterococcus faecalis, presented here at 1.9 Å resolution (PDB entry 24rr), reveals the flexible lid in both conformations. Two molecules in the asymmetric unit exhibit different lid conformations stabilized by distinct sets of contacts. The DPX motif from the lid at the active site stabilizes the closed conformation, while the TPY motif within the conserved TP(Y/L)XIN(S/T)H motif of the β7-β8 loop from the asymmetric mate pointing towards the active site stabilizes the open conformation. For the first time, proline cis-trans isomerization, likely acting as a molecular switch in SrtC, was captured, regulating the access of secondary substrate to the active-site cleft by toggling between two states at the β7-β8 loop. Lid movement regulates primary-substrate (LPXTG sorting motif) binding and harmonizes conformational changes at the β7-β8 loop for secondary-substrate (YPKN pilin motif) binding. In silico analysis and RP-HPLC-based assays helped to map residues within sorting motifs near the scissile bond, providing insights into enzyme-substrate recognition. Removing the N-terminal lid region enhances E. faecalis SrtC activity. The unprecedented structural snapshots of both open and closed lid conformations, synchronized with the proline switch in the β7-β8 loop, captured in the same crystal structure, advance the understanding of sortase-mediated virulence in enterococci and provide a framework for the development of antivirulence strategies.

Hydrogen energy emerges as a pivotal carbon-neutral alternative to fossil fuels due to its exceptional energy density and sustainability. While seawater electrolysis presents a promising avenue for scalable hydrogen generation, persistent challenges resulting from chlorine evolution reactions and chloride-induced corrosion significantly impair system durability. Here, we introduce a breakthrough strategy coupling formaldehyde oxidation (FOR) with hydrogen evolution (HER) in seawater electrolysis, which drives the overall process at an ultralow voltage while simultaneously producing value-added formate and achieving dual hydrogen generation at both electrodes. A rationally designed 3D dendritic Cu0.94Ni0.06 electrocatalyst exhibits unprecedented FOR activity, delivering a remarkable current density of 629.9 mA cm-2 at 0.2 V vs. RHE. Density functional theory (DFT) calculations elucidate that Ni doping facilitates C-H bond cleavage in *OCH2OH, accelerating *H and formate formation while lowering the H2 evolution barrier. An electrochemical system integrating HER and FOR achieves dual hydrogen output with a Faradaic efficiency of ∼200% alongside ∼100% formate selectivity. When paired with photovoltaic cells, the hybrid configuration attains a record solar-to-hydrogen efficiency of 39%. This work establishes an economically viable paradigm for marine hydrogen production, offering critical insights into the engineering of reaction mechanisms and the development of scalable clean energy infrastructure.

Plant secondary metabolites remain indispensable for pharmaceuticals, nutraceuticals, and cosmeceuticals, yet conventional plant culture systems are increasingly limited by inconsistent yields, poor scalability, and inadequate capacity for real-time process monitoring. Microfluidic technologies and organ-on-a-chip (OoC) platforms, originally developed for mammalian biology, are now emerging as powerful tools to overcome these constraints. These systems enable laminar flow, precise gradient generation, single-cell resolution, and biosensor integration, providing unprecedented control over the cellular microenvironment and supporting non-destructive, real-time metabolomic monitoring. While recent reviews have surveyed plant microfluidics broadly covering developmental biology, single-cell phenotyping, and root-microbe interactions, this review provides, to our knowledge, the first synthesis focused specifically on organ-on-a-chip approaches for plant secondary metabolite biosynthesis and real-time metabolomic monitoring. Advances in device fabrication, including PDMS, paper-based, hydrogel, and thermoplastic materials, surface engineering, gradient-based elicitation strategies, and integration of optical, electrochemical, and mass spectrometric detection systems have also been critically examined. Special emphasis is placed on root-on-a-chip, shoot meristem, protoplast, callus, and 3D organoid platforms for studying cell wall mechanics, vacuolar dynamics, cytoskeletal responses, and signalling cascades. However, challenges remain in long-term culture stability and scalability; nonetheless, these technologies offer a roadmap toward programmable 'plant biosynthetic factories' to produce high-value natural products.

This paper explores the management of mass casualty incidents in Eastern Ukraine, focusing on the application of the Eight Domains of Mass Casualty Management by the Ukrainian Medical Service. Following the Russian invasion, Ukraine's military and civilian health services have had to adapt to unprecedented casualty rates to prevent overwhelming the healthcare system. The Eight Domains-distribution, decompress, delay, delegate, deliver faster and deliver better, dynamic levels of care, and de-escalation-serve as compensatory mechanisms to manage this chronic major medical incident. The paper highlights the innovative approaches and adaptive strategies employed by the Armed Forces of Ukraine (AFU) Medical Services to maintain effective medical care despite the high demand and constrained resources. The report underscores the importance of international support and continued research to enhance the resilience and capability of the AFU Medical Services in responding to ongoing and future conflicts and proposes future direction for all military medical services to meet the challenges of large scale conflict operations and warfighting at scale.

As global ecosystems and food systems face unprecedented anthropogenic and climatic challenges, there is a demand for an integrated understanding of biological systems. Proteomics has emerged as a definitive approach offering a direct view of the molecular phenotype, yet it is traditionally separated into plant and animal disciplines. With recent advances in mass spectrometry (MS) and bioinformatics tools, this prospective review proposes that combining a One Health proteomics approach with deep-learning data analysis can revolutionize global food security, animal productivity, and ecosystem health by uncovering proteoform signatures that drive resilience across life. The potential of a unified One Health proteomic framework, highlighting major developments, including 4D proteomics, Data-Independent Acquisition (DIA), and single-cell resolution, and emphasizes their capacity to resolve the complex proteoform landscape across kingdoms. Review emphasizes the applications of proteogenomics as a cross-disciplinary tool to improve genome annotations, explain evolutionary differences, discover biomarkers in animals and resolve complex signaling networks in plants under stress. Nevertheless, contemporary proteogenomics methods still show limitations in their ability to comprehensively resolve proteoforms due to the fact that the use of peptide-based approaches makes it difficult to fully appreciate the post-translational modifications specific to each protein isoform. We show that One Health proteomics will provide a transformative roadmap for deciphering the functional proteoform signatures that underpin resilience across the tree of life.

Multifunctional carbon-based nanostructures are attracting considerable attention because of their low toxicity, excellent optical and chemical properties, and intriguing applications. Currently, the development of carbon-based nanostructures for sensing remains a challenging topic in the biosensing field. Here, we report an unprecedented example of a multi-emissive supramolecular system composed of carbon-nanodots, derived from β-cyclodextrin units by a one-pot thermal process, and Nile Red (NR) hosted in the cyclodextrin cavities (Cdots-βCD/NR). The Cdots-β-CD nanostructures were characterized by spectroscopic techniques, NMR, and atomic force microscopy. The supramolecular Cdots-βCD/NR system exhibited multi-fluorescence emissions at 410 nm and 650 nm, corresponding to the Csp2-core of the carbon nanodots and the encapsulated NR, respectively. The as-prepared Cdots-βCD/NR nanosystem showed high specificity for the detection of phenylalanine (Phe) with a limit of detection (LoD) of 0.49 µM, a limit of quantification (LoQ) of 1.25 µM over a dynamic range of 2-100 µM for the red fluorescence emission (650 nm), and a dynamic range of 20-400 µM for the blue fluorescence emission (410 nm). Good specificity for Phe over tyrosine was demonstrated and supported by molecular modelling simulations. The proposed sensing strategy exhibited good correlation with the results obtained from standard mass spectrometry when applied to human blood samples collected from PKU patients.

H9N2 low-pathogenic avian influenza viruses (LPAIV) represent an ongoing zoonotic threat due to their enzootic circulation in poultry, reassortment capacity, and increasing human transmission events. This study characterized three H9N2 isolates recovered from apparently healthy poultry in a Changchun live poultry market (September-November 2022) that exhibited unprecedented genetic and phenotypic characteristics indicating enhanced zoonotic risk. Phylogenetic analysis showed a complex mosaic genome combining segments from four distinct lineages: HA from the BJ/94-like lineage (human-associated), PB1/NP/NS from the F98-like lineage, NA from the FJ/30-C-like branch, and PB2/M genes from the G1-like lineage. Bayesian molecular clock analysis estimated the most recent common ancestor at February 2022, with HL55 and HL56 diverging by May 2022, indicating rapid local viral evolution. All isolates retained hallmark LPAIV characteristics (monobasic HA cleavage site, zero intravenous pathogenicity index in chickens). However, receptor-binding assays demonstrated a critical divergence among the isolates: while HL45 exhibited exclusive avian α2-3 receptor preference, both HL55 and HL56 retained strong avian receptor binding while additionally showing measurable affinity for human α2-6 receptors-a dual-binding phenotype associated with enhanced zoonotic potential. Most significantly, the HL55 isolate successfully infected BALB/c mice without prior adaptation, causing transient upper respiratory tract replication, moderate weight loss (~9.2%), and mild disease without mortality or systemic dissemination. These findings demonstrate that the direct mammalian infectivity of this specific mosaic H9N2 lineage adds to the growing body of evidence regarding the zoonotic potential of contemporary H9N2 variants. The presence of known mammalian-adaptation markers (PB2 A588V, NA stalk deletion, HA position 226 leucine), combined with demonstrated dual receptor-binding capacity and inherent mammalian infectivity, underscores the accelerated evolutionary trajectory of H9N2 viruses toward increased zoonotic competence. These findings warrant intensified surveillance in live poultry markets, comprehensive antigenic characterization of emerging variants, and enhanced biosecurity measures to mitigate the risk of spillover events and potential pandemic emergence.

The development of therapeutic nucleic acids has become a cornerstone of modern drug discovery. To support the clinical translation of these modalities, radiolabelled analogues are vital for absorption, distribution, metabolism and excretion (ADME) studies, particularly for quantitative whole-body autoradiography (QWBA). Access to such radio probes is limited because established methods for the preparation of 3H-labelled oligonucleotides are characterised by high costs, extensive lead times, low specific activity and the generation of substantial radioactive waste. To address these limitations, we developed a biocatalytic platform for late-stage 3H-radiolabelling of oligonucleotides using methyltransferases, reducing precursor costs and radioactive waste by orders of magnitude. We demonstrate that DNA-cytosine-5-methyltransferases can methylate oligonucleotides with high regioselectivity at a preparative scale, yielding stable- and radioisotope-labelled (2H and 3H) samples with an unprecedented molar activity up to 3 TBq mmol-1 (81 Ci mmol-1). In view of the precision and efficiency of methyltransferase-mediated radiolabelling, we anticipate that similar approaches will facilitate QWBA studies with other drug modalities.

Quantitative description of the structural dynamics of nanoparticles by kinetic data is challenging but would represent a significant knowledge leap, as this would enable the forecast of their properties, e.g., in catalysis. A striking example in catalysis is the redispersion of Pt nanoparticles into single atoms in Pt/CeO2-based catalysts. In this work, we combined environmental transmission electron microscopy (ETEM) measurements with catalytic data to monitor the individual decay of Pt nanoparticles on defined CeO2 nanocubes. Supported by density functional theory modeling, this provides unprecedented insight into their dynamic behavior, including kinetics. We observed that the rate of noble metal redispersion is strongly dependent on the local structural environment: the presence of other nearby nanoparticles and heterogeneities on the CeO2 surface reduced the redispersion rate. Independent of the initial particle size and local environment, the particle volume decreases linearly in time, indicating a constant flux of Pt atoms from the nanoparticles. These findings at the atomic scale were correlated to the observed changes in the integral catalytic performance, allowing a first prediction of the catalyst activity based on the redispersion process and demonstrating how atomic-scale kinetic insights can be correlated to macroscopic effects.

A major challenge in realizing ampere hour (Ah)-level aqueous zinc (Zn) ion pouch batteries (Ah-level AZIBs) is the requirements for high Zn utilization rate coupled with even Zn nucleation/growth. Here, we report a spiral-potato-like covalent organic framework (SP-COF) nanostructure to construct isotropic solid electrolyte interphase for Ah-level AZIBs. Compared with conventional COF nanostructures, the unique spiral-potato-like SP-COF combined with affinity sites and porosity enables isotropic interfacial regulation to achieve nearly unidirectional Zn deposition following the theoretical three-dimensional nucleation curve. As a result, symmetric cells based on SP-COF/Zn electrode display ultrastable plating/stripping over 2800 hours at 10 milliamperes per square centimeter. The successfully assembled Ah-level triple stacked layer pouch cell (SP-COF/Zn||I2, 1.2 Ah) demonstrates stable cycling over 200 cycles with an ultrahigh Zn utilization rate of 40%. The pouch cell achieves an unprecedented energy density of 156 watt-hours per kilogram. These findings highlight the strategic fine-tuning of COF-based battery architectures to be a promising route for high energy density Ah-level AZIBs.

Objective: This study seeks to synthesize the experiences, challenges, and core competency requirements of nurse managers caring for patients with emerging infectious diseases to inform targeted training and strengthen emergency response systems. Background: The frequent emergence of emerging infectious diseases has placed unprecedented strain on global public health systems, with nurse managers playing a pivotal role in coordinating and sustaining outbreak responses. Methods: A literature search was conducted across PubMed, CINAHL (EBSCO), Embase, Web of Science, Scopus, CNKI, and other databases. Qualitative studies were screened and assessed using the JBI appraisal tool. Thirteen studies were included and meta-synthesized. Thematic synthesis was used to synthesize the findings. Results: Four main themes emerged: multidimensional experiences of nurse managers, dual pressures from resource shortages and environmental constraints, core competency requirements, and the need for organizational and system support. Discussion: Outbreaks intensified physical and mental strain, increased burnout and turnover, yet also fostered professional growth. Systemic support, flexible staffing, digital training, and inclusive governance are needed to ensure well-being, care resilience, and leadership retention. Conclusion: This study outlines challenges and competencies of nurse managers during health crises, underscoring the need for comprehensive support to guide specialized training and improve public health preparedness.

Periodontitis is a chronic inflammatory disease increasingly recognized as a manifestation of complex microbial dysbiosis extending beyond the oral cavity. Recent advances in spatial metagenomics provide unprecedented resolution to investigate microbial community structure, function, and localization within periodontal niches and along the oral-gut axis. This review aims to explore how spatially resolved metagenomic approaches refine our understanding of the ecological and functional shifts in bacterial populations associated with periodontitis and their systemic implications. By integrating spatial mapping with shotgun metagenomics, we highlight distinct microenvironmental signatures within periodontal pockets, characterized by anaerobic pathobionts, metabolic reprogramming, and localized inflammatory gradients. Furthermore, we examine evidence supporting bidirectional interactions between oral and gut microbiota, suggesting that oral-derived taxa may contribute to gut dysbiosis through translocation and ecological disruption. From a basic science perspective, spatial metagenomics reveals niche-specific microbial functions and interspecies interactions that are not captured by bulk sequencing. Clinically, these insights open avenues for precision diagnostics and targeted therapeutics, including microbiome modulation strategies tailored to spatial microbial organization. Overall, this work underscores the importance of spatial context in metagenomic analyses and advances the conceptual framework linking periodontal disease to systemic microbial dysbiosis.

We disclose an unprecedented organocatalytic asymmetric decarboxylative Michael addition of β-keto acids to 2,3-dioxopyrrolidines, enabling the efficient assembly of chiral pyrrolidinone-fused [3,4-b]-4H-pyrans and [3,4-b]-pyridines. The reaction affords chiral pyrrolidinone-tethered 1,5-dicarbonyl intermediates in high yields with excellent regio- and enantioselectivities. Acid-promoted intramolecular cyclization of these adducts provides enantioenriched pyrrolidinone-fused [3,4-b]-4H-pyrans without erosion of enantiopurity, whereas cyclocondensation with hydroxylamine hydrochloride delivers diverse pyrrolidinone-fused [3,4-b]-pyridines. Notably, this protocol is compatible with a one-pot tandem process and gram-scale synthesis.

The transition from the home-based care model represents an unprecedented revolution in the healthcare industry, with the conventional clinical-based healthcare system being replaced by innovations in digital health. Yet there is no comprehensive analysis that explains how nursing practices, healthcare management, and the digital health domain work together along with the community-based care system. The data in this regard is fragmented. This review summarizes findings on integrating nursing, technology, and management to support chronic care. A literature was screened by searching in PubMed, Scopus, and Web of Science databases using keywords such as "home-based primary care," "nurse-led models," "telehealth," and "digital health equity," with a focus on studies published between 2010 and 2025. The literature was searched for high-quality, peer-reviewed publications in English. The researchers selected 115 papers to conduct their in-depth study based on titles, abstracts, and full text. These studies indicate that the shift from conventional home care methods to digital home care delivery requires nurses to develop digital skills to lead their teams while delivering personalized telehealth services. Nurses play a central role in coordinating care, facilitating patient engagement with effective technological developments that now provide better access to safer systems that enhance quality of life, while management frameworks support execution through policy development and resource allocation. The existing challenges include staff shortages, digital access problems, and obstacles created by existing regulations. Gaps still exist in the long-term cost-effectiveness of digital health, accessibility of resources equally to all areas, and effect of remote care on the relationship of nurses and patients. The field of home care requires resilient and equitable systems that need both predictive analytics and social health factor solutions and ongoing partnerships between different sectors. Home care will depend on nursing leaders with digital skills to ensure that technology helps them provide empathetic patient care.

Clinical translation of nanomedicines is greatly hindered by insufficient understanding of their in vivo process, yet a key challenge lies in quantifying the encapsulated versus free drug forms in tissues and cells. Herein, we present a facile, versatile anti-PEG single-chain variable-fragment antibody (PEG-scFv)-based method enabling quantitative measurement of both forms in various biofluids (e.g., interstitial fluid, cytoplasm). By this method, we map the in vivo process of PEGylated liposomal doxorubicin (sLip/Dox) at unprecedented resolution. In the bloodstream, doxorubicin remains largely encapsulated in liposomes (>99%). In liver as the main organ for drug elimination, less drug was distributed in the interstitium (>80% encapsulated) but more in liver cells (mainly in Kupffer cells) released in a time-dependent manner, accompanying doxorubicin transferred to hepatocytes most in free form by 12 h postinjection. After extravasation into tumors, there was a limited access of sLip/Dox to tumor cells, confining most of the drug in the interstitium mainly being encapsulated (more than 75%), and the internalized fraction underwent a gradual release process in both tumor-associated macrophages and tumor cells. These findings revealed that for sLip/Dox, which primarily underwent drug release intracellularly, cellular internalization rates could be the key factor in determining its in vivo performance. Given widespread PEGylation on developing nanomedicines and the cost-effectiveness of scFv production, PEG-scFv offers a broadly applicable tool for dissecting in vivo processes of nanomedicines to establish dose-effect relationships like small-molecule drugs, further to guide rational nanotherapeutic design.

Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, characterized by inevitable recurrence, extensive inter-and intratumoral heterogeneity, and resistance to current therapies. A defining feature of GBM is the dynamic interplay between malignant cells and a diverse tumor microenvironment (TME), which together drive disease progression, therapeutic adaptation, and relapse. Understanding these complex cellular ecosystems has therefore become a major focus of glioblastoma research. Recent advances in spatial omics technologies have transformed our ability to investigate GBM biology directly within intact tissue architectures. Over the past five years, an expanding array of spatial transcriptomic, proteomic, and multi-omic platforms has enabled high-dimensional characterization of cellular states, cell-cell interactions, and tissue niches while preserving spatial context. These approaches have generated unprecedented insights into tumor organization, cellular plasticity, immune landscapes, vascular niches, and treatment-induced ecosystem remodeling. In this review, we provide an overview of spatial omics applications in glioblastoma research so far. We summarize the technologies employed, the types and numbers of patient samples analyzed, and the major biological and clinical insights generated. We compare the strengths and limitations of different spatial platforms, discuss key considerations for study design and data interpretation, and highlight emerging trends in multimodal and longitudinal analyses. By integrating both technological and biological perspectives, this review serves as a practical resource for researchers seeking to implement spatial omics approaches in glioblastoma studies and to advance precision neuro-oncology.

Spatial transcriptomics provides unprecedented insights into gene expression in the spatial context of tissues; however, some mainstream techniques lack quantitative analysis of uncertainty. In this study, we propose a computational framework-Spatial Deconvolution via Deep Gaussian Processes (SDDGP)-that integrates deep Gaussian processes with Bayesian inference for spatially aware deconvolution of spatial transcriptomics data. The framework consists of three tightly coupled components. A multi-layer deep Gaussian process (DGP) captures nonlinear spatial dependencies in cell-type composition by propagating spatial coordinates through successive Gaussian process (GP) layers, each equipped with sparse variational inducing points and a radial basis function (RBF) kernel that can be combined with an external Matern spatial kernel. The DGP output serves as an adaptive, spatially informed prior for per-spot cell-type proportions, which are then estimated via a Negative-Binomial Markov chain Monte Carlo (MCMC) sampler with automatic proposal tuning, thinning, and split-chain convergence diagnostics. We compared our method with existing approaches on two datasets: a pancreatic ductal adenocarcinoma (PDAC) dataset with matched single-cell RNA sequencing and spatial transcriptomics, and a human thymus dataset. Across both datasets, our method estimated cell type proportions more accurately than existing methods, particularly for rare cell types, and recovered biologically meaningful spatial patterns such as the distribution of T cells and plasma cells in PDAC. The Bayesian formulation also provides a quantification of uncertainty for each estimate, which aids the interpretation of spatial heterogeneity in complex tissues.

This presidential reflection traces a developmental pathway from a culturally grounded upbringing in Gardena, California, to the unexpected role of serving as president of the American Psychological Association. Integrating a personal narrative with scholarly literature on leadership development, cultural humility, identity formation, and first-generation educational experiences, this article examines how values and lived experience shaped my professional trajectory. Themes of transformative and relational leadership and culturally responsive practice are woven throughout the narrative to illuminate the ways in which community, mentorship, and structural opportunity inform leadership emergence. It provides insights into navigating an unprecedented presidential year, where leadership required drawing upon cultural grounding, crisis expertise, and a deep commitment to collective care. The article concludes with reflections on the developmental trajectory toward the American Psychological Association presidency and the culmination of the various individual and contextual experiences leading to it. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

The dynamic glycan layer that surrounds human and microbial cells plays an essential role in the immune system's capacity to maintain immune tolerance and equilibrium, fight pathogens and cancer. Endogenous anti-glycan antibodies are an indispensable part of immune surveillance, identifying abnormal microbial glycans, viral glycoproteins, and altered tumor-associated carbohydrate antigens. These glycans serve in turn as attractive targets for passive and active immunization strategies in a range of human diseases. The enormous complexity and structural diversity of glycans has made it very difficult to unlock their full biomedical potential. Recent advances in glycan synthesis, including automated solid-phase assembly, chemoenzymatic strategies, and one-pot approaches, enabled unprecedented access to well-defined, homogenous structures. Hence, synthetic glycans of increasing structural complexity pave the way for a range of applications, from profiling endogenous antibody repertoires for biomarker discovery to therapeutic antibody development and vaccine design. Here, we summarize the strategies to utilize synthetic glycans for antibody development and their application in basic research and translational medicine. We outline how anti-glycan antibodies are utilized for diagnostic and therapeutic purposes, while emphasizing the power of synthetic glycans and highlighting their potential in personalized medicine.