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Heart failure with preserved ejection fraction (HFpEF) is a poorly understood, multisystem disease with high morbidity and mortality. To improve understanding of its pathobiology, we analyzed single-nucleus RNA sequencing in human HFpEF myocardium versus controls. Septal myocardial biopsies from 19 HFpEF and 24 nonfailing controls were analyzed using the 10× Genomics Chromium platform, with nuclei isolated from combined samples (6 patients/pool). Genotype-based demultiplexing was performed with souporcell, and gene expression was quantified with CellRanger and CellBender. After quality control, nuclei were annotated by cell types, and differential expression was performed between HFpEF versus controls using limma-voom. Functional analysis was performed using Gene Set Enrichment Analysis. Data were compared with prior single-nucleus RNA sequencing in dilated cardiomyopathy versus controls. We successfully demultiplexed pooled myocardial biopsies, assigning >70% of nuclei to individuals. After quality control, we recovered 48 886 nuclei and identified 14 cell types. Many differentially expressed genes across cell types were detected in HFpEF versus controls (fibroblasts, 5905; cardiomyocytes, 5159; endothelial cells, 2143; pericytes, 1812; and macrophages, 1405). Enriched pathways common to multiple cell types included immune activation, transcription/translation, metabolism, and protein quality control. They were particularly shared between cardiomyocytes and fibroblasts. Vascular smooth muscle cells had a more synthetic, proliferative phenotype. Immune cell analyses suggested enhanced T-cell activation and reduced macrophage clearance programs. Comparative analysis between HFpEF and dilated cardiomyopathy identified transcriptional differences primarily in cardiomyocytes. Two of 3 cardiomyocyte differential expression genes unique to HFpEF were validated to have concordant protein expression changes in HFpEF (MAP2K6 and PLPP3). Our findings reveal a distinct, cell-type-specific transcriptomic landscape in the human HFpEF myocardium. While HFpEF and dilated cardiomyopathy share significant molecular pathways across most cell types, the profound divergence within cardiomyocytes suggests a unique pathological driver for HFpEF. These signatures may provide a high-resolution roadmap for identifying precision therapeutic targets in HFpEF.

Plant leaves are widely utilised globally for the packaging and serving of traditionally prepared foods. The microbial communities associated with these wrapping leaves, particularly endophytes, are recognised to potentially influence food quality, safety, and preservation. Specifically, certain endophytes can enhance sensory attributes and nutritional value through fermentative processes, while the presence of harmful microorganisms may lead to spoilage and pose a risk of foodborne illness. This study utilised 16S rRNA, ITS metabarcoding and metagenomic functional analysis (PICRUSt2) to comprehensively investigate the composition and infer the putative functional potential of putative endophytic bacterial and fungal communities present in 53 samples of four different food wrapping leaves. The leaves examined included Thaumatococcus daniellii (n = 10), Alstonia macrophylla (n = 18), Theobroma species (n = 14), and Megaphrynium macrostachyum (n = 11). Distinct microbial community profiles were observed across the different leaf types. Highest bacterial species richness and community variability were detected in A. macrophylla samples, reflected by Principal Coordinates Analysis (PCoA) values (PCoA1 = 43.97%; PCoA2 = 10.68%). Conversely, M. macrostachyum exhibited the greatest fungal species richness and variability (PCoA1 = 20.08%; PCoA2 = 8.72%). Taxonomic analysis identified Proteobacteria as the dominant bacterial phylum and Stenotrophomonas as the dominant bacterial genus. Other notable bacterial taxa included the phyla Bacteroidota and Firmicutes, and genera such as Pseudomonas, Faecalibacterium, and Bacteroides. For fungal communities, Ascomycota was the dominant phylum. Additional fungal taxa included the phylum Basidiomycota and genera Cryptococcus, Candida, and Meyerozyma. A core microbiome analysis revealed that 42 bacterial (notably Stenotrophomonas and Chryseobacterium) and 7 fungal taxa (notably Pleosporaceae and Ascomycota) were shared across all examined wrapping leaves. The identified microbial communities (e.g., Lactobacillus and Geotrichum) encompass taxa with potential beneficial roles, such as enhancing food fermentation and potentially contributing to human gut health upon consumption of the packaged food. However, the detection of potentially pathogenic and toxigenic bacterial taxa highlights a possible public health risk associated with the use of these leaves. Further investigation into the specific functionalities of these associated bacteria and fungi is essential to maximise their beneficial applications while simultaneously mitigating potential health risks posed by harmful strains.

To examine whether different caregiving arrangements influence hospitalization risk and frequency among older adults with functional limitations. This longitudinal study used linear probability and Poisson regression models with individual and wave fixed effects, lagged predictors, and household-clustered standard errors to assess associations between different caregiving arrangements and hospitalization outcomes among community-dwelling older adults in the United States. Caregiving was categorized as no help, family help, formal help, or combined help. Outcomes included any hospitalization and the number of hospital stays over a two-year period. Data came from eight waves of the Health and Retirement Study (2004-2018). The samples included adults aged 65 and older who reported difficulty with at least one activity of daily living and participated in at least two survey waves. The final analytic sample comprised 2926 individuals contributing 5595 person-wave observations. While the overall hospitalization risk did not differ significantly by caregiving type, receiving combined support was associated with a reduced number of hospital stays among those hospitalized (IRR&#x2009;=&#x2009;0.712, p&#x2009;<&#x2009;0.01), compared to receiving no support. Cognitive functioning modified these relationships, with formal help linked to fewer hospitalizations among those with impairment but more among those without. Differences also emerged across racial and ethnic groups, where formal help was linked to lower hospitalization rates for Black individuals, and combined help was associated with increased hospitalizations among Hispanic older adults. Policies that expand access to both formal and family caregiving support may help reduce hospitalizations among older adults with functional limitations, particularly when tailored to care recipient characteristics.

Bone regeneration scaffolds represent a promising solution for bone grafting of large and severe bone defects. The ideal bone substitute material is considered to have excellent biocompatibility, osteoconductivity, osteoinductivity, and mechanical properties similar to bone. Different scaffold materials are currently available for clinical application, but despite the broad selection, no material has yet been described that has both excellent biological and mechanical properties. Bioceramics such as zirconia and alumina matrix composites could be promising alternative materials for bone grafting. Non-porous full density zirconia and alumina matrix composite implants require bioactive surface coating for osseointegration and bone formation, but porous scaffolds made of those materials may eliminate the need for bioactive porous coatings. The aim of the present study was to investigate the long-term biocompatibility and osseointegration of directly foamed porous yttria-stabilized tetragonal zirconia (Y-TZP) and zirconia-toughened alumina (ZTA) scaffolds in calvarial and femoral bone defects in an ovine model in&#xa0;vivo. Cytocompatibility of ceramic material and scaffolds was investigated in&#xa0;vitro. Porous Y-TZP and ZTA scaffolds with different porosities (60% and 70%) were implanted into calvarial and femoral bone defects in sheep in&#xa0;vivo. Osseointegration, bone formation, and host response were histopathologically analyzed 12 and 24&#x2009;weeks post implantation. The in&#xa0;vitro studies showed no negative influence on the cytocompatibility. In&#xa0;vivo, all implants were fully integrated into defect sites at both time points without any material degradation. A thick fibrous layer was present at the calvarial implant sites, which was associated with the implant's geometric misfit. After 12&#x2009;weeks, early osseointegration was observed with Y-TZP 70% and ZTA 70%, which seemed to be rather dependent on porosity than ceramic material. After 24&#x2009;weeks, bone formation and osseointegration increased and were similar for all scaffolds. A slight to moderate host response was present at both time points for all scaffolds, which was manifested by rare to mild macrophage and lymphocyte tissue infiltration and was considered an essential part of the healing process. Porous Y-TZP and ZTA scaffolds demonstrated early osseointegration, good cytocompatibility, and long-term biocompatibility in&#xa0;vivo. The porous surface of the scaffolds enables direct contact between the ceramic material and the bone, eliminating the need for additional coatings. Also, higher scaffold porosity together with pore interconnectivity facilitates intraporous bone formation, thus representing a promising alternative for bone scaffold materials for various medical applications such as orthopedics, dentistry, and cranio-maxillofacial surgery.

Psoriatic arthritis (PsA) is a complex inflammatory disease with significant musculoskeletal, dermatological, and comorbidity burden. Despite therapeutic advances, many patients remain difficult to treat (D2T). Conventional definitions often overlook distinctions between inflammatory and non-inflammatory drivers, risking inappropriate treatment escalation. Two consensus frameworks-the European Alliance of Associations for Rheumatology (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-have recently been proposed to better capture this complexity based on disease drivers. To evaluate the applicability, overlap, and clinical utility of EULAR and GRAPPA definitions for difficult/complex-to-manage (D2M/C2M) and treatment-refractory PsA (TR-PsA) in a real-world cohort. We conducted a retrospective analysis within the prospective Ottawa Rheumatology CompreHEnSive TReatment and Assessment (ORCHESTRA) cohort, including consecutive PsA patients initiating or switching advanced therapy between April 2022 and September 2025. Patients were classified according to EULAR and GRAPPA frameworks into the broader D2M-PsA (EULAR) and C2M-PsA (GRAPPA) groups, and narrower inflammation-restricted TR-PsA subsets. Prevalence, overlap, and agreement were assessed using descriptive statistics and kappa analysis. Baseline clinical, comorbidity, and ultrasound characteristics were compared across groups. Seventy-six PsA patients were included. GRAPPA identified more patients as C2M-PsA (35/76; 46%) than EULAR's D2M-PsA (16/76; 21%). All EULAR D2M-PsA patients were included in C2M-PsA, whereas 19 additional patients were uniquely identified by GRAPPA due to less stringent treatment failure thresholds. Agreement between EULAR D2M-PsA and GRAPPA C2M-PsA was moderate (&#x3ba;&#x2009;=&#x2009;0.48). TR-PsA classification showed perfect agreement (&#x3ba;&#x2009;=&#x2009;1.000), with identical patients identified by both frameworks. D2M/C2M patients had longer disease duration and greater prior therapy exposure than non-D2T patients, while objective inflammatory measures were largely comparable. EULAR and GRAPPA D2T PsA frameworks share conceptual intent but differ in real-world clinical capture. EULAR preferentially enriches for multidomain involvement and inflammatory refractoriness after multiple therapy failures, whereas GRAPPA identifies a broader population reflecting earlier disease complexity. While both frameworks identified the same patients using inflammation-restricted criteria, differences in operationalization limit assumptions of interchangeability. Understanding how different frameworks define &#x201c;difficult-to-treat&#x201d; psoriatic arthritis in real-world patients Psoriatic arthritis (PsA) is a chronic inflammatory condition that can affect joints, skin, and many other aspects of health. Although several effective treatments are available, some patients remain difficult to manage. In these patients, ongoing symptoms may be caused by active inflammation, but also by other factors such as pain sensitization, comorbid conditions, or treatment intolerance. Distinguishing between these causes is important to avoid unnecessary escalation of immune-suppressing therapy. Recently, two expert groups&#x2014;GRAPPA and EULAR&#x2014;proposed new frameworks to better define &#x201c;difficult-to-treat&#x201d; PsA by considering disease drivers rather than treatment failure alone. However, how these frameworks perform in real-world clinical practice has not been well studied. In this study, we applied both frameworks to a real-world cohort of PsA patients from the ORCHESTRA registry in Canada who were starting or changing advanced therapies. We compared how often each framework identified patients as difficult-to-manage, how much they overlapped, and whether they identified similar clinical profiles. We found that the GRAPPA framework identified more patients as having complex or difficult-to-manage PsA, capturing patients earlier in their disease course with fewer treatment failures. In contrast, the EULAR framework identified a smaller group with more advanced disease and greater treatment exposure. When focusing only on patients with true inflammatory treatment refractoriness, both frameworks identified exactly the same patients. Overall, our findings suggest that while GRAPPA and EULAR share similar goals, they identify different patient populations in practice. GRAPPA may be more useful for recognizing early disease complexity, while EULAR may better identify patients with established inflammatory refractoriness. These differences should be considered when using these frameworks in clinical care and research.

To address the bottleneck problem of slow decomposition of returned maize straw under low-temperature constraints in the cold and arid regions of northern China, this study systematically explored the microbial decomposition-promoting mechanism of microbial inoculant M44 combined with three straw returning methods: deep plowing (DPR), deep scarification and mixing (SSR), and no-tillage mulching (NTR), by integrating field tillage and in-situ micro-zone degradation experiments. The results showed that different straw returning methods combined with inoculant M44 could effectively overcome low-temperature limitations, significantly increasing the straw degradation rate by 2.33-9.81 percentage points and shortening the half-life by 20.7-62.8 d. The core mechanism was that the "tillage-inoculant" interaction regulated the soil microenvironment, directionally shaped and enriched key functional microbial taxa with degradation ability (such as Pseudoxanthomonas, Devosia, Streptomyces, Pseudomonas, etc.) and their key ASVs (such as ASV6, ASV12, ASV412, ASV1546, etc.), reshaped the soil bacterial community structure, and synergistically activated the soil extracellular enzyme system (such as &#x3b2;-glucosidase, &#x3b2;-xylosidase, etc., with the comprehensive enzyme index increased by 0.74-1.06), thereby synergistically driving the rapid degradation of returned straw. The PLS-PM model further clarified that there were differences in the pathways driven by inoculant M44 for straw degradation under different returning methods. In the DPR and SSR treatments, bacterial community composition was the most important direct driving force for degradation, and key ASVs indirectly affected the degradation process by regulating bacterial composition and enzyme activity, while in the NTR treatment, extracellular enzyme activity became the core driving force for degradation, whose activity was directly driven by bacterial composition and diversity. This study revealed the hierarchical interaction driving mechanism of "key microorganisms-bacterial community structure-extracellular enzyme activity-straw degradation" at the field scale, providing an important scientific basis for optimizing the "tillage-inoculant" synergistic technology for straw resource utilization in cold and arid regions.

Sciatic nerve injury results in motor dysfunction and muscle atrophy, with limited effective therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) may promote neuromuscular recovery, but their effects on functional and muscle recovery remain unclear. This study aimed to evaluate the effects of UC-MSC therapy on functional and muscle recovery in an animal model of sciatic nerve injury. An animal experimental study with a post-test-only control group was conducted using adult male Wistar rats. Rats were randomly allocated into three groups: sham operation, saline control with sciatic nerve injury, and UC-MSC treatment after sciatic nerve injury. UC-MSCs were administered at a dose of 1&#x2009;&#xd7;&#x2009;106 cells/kg body weight immediately after nerve injury. Functional recovery was assessed using the extensor postural thrust (EPT) test, and muscle recovery was evaluated using the gastrocnemius muscle index (GMI) post 35 days of observation. Data were analyzed using one-way ANOVA for EPT percentage recovery and Kruskal-Wallis tests for GMI values, followed by post-hoc analysis. Our data indicated there was no significant EPT percentage recovery among the study groups. In contrast, relative gastrocnemius muscle mass was significantly different across groups (p&#x2009;=&#x2009;0.012), with post-hoc analysis demonstrating a significantly higher GMI in the UC- MSC group compared to the saline control group (109.75% vs 81.68%, p&#x2009;=&#x2009;0.003), indicating improved preservation of gastrocnemius muscle mass following UC-MSC therapy. This study highlights that UC-MSC therapy significantly improved gastrocnemius muscle preservation after sciatic nerve injury but did not result in detectable functional motor recovery at the observation time point. These findings suggest that UC-MSCs might exert early structural benefits that may precede functional recovery.

Expensive platinum group metals (PGMs) are used to enhance the anodic oxygen evolution reaction (OER) kinetics, and they represent a real bottleneck in the commercialization of anion exchange membrane water electrolyzers (AEMWEs). Therefore, we present a scalable and economical homogeneous precipitation method to synthesize NixFe1-xO nanoparticles with different Ni/Fe ratios, while reducing the dependence on expensive PGM-based electrocatalysts. The effects of Ni/Fe ratios in the synthesized NixFe1-xO, along with morphological and surface chemical characteristics, on electrocatalytic performance were thoroughly investigated with half-cell measurements. Furthermore, critical electrode design factors, that is, ink composition and electrocatalyst loading, were scientifically investigated and optimized. Among the explored compositions, amorphous Ni0.28Fe0.72O and crystalline Ni0.66Fe0.34O exhibited superior OER activity, achieving mean overpotentials of 359&#x2009;mV and 359.1&#x2009;mV at 10 mA cm-2, respectively. This superior activity was attributed to a higher concentration of Ni3+ (NiOOH), a highly active compound for OER. These high-performing samples were integrated as anodes in a lab-scale AEMWE for device-level evaluation. Ni0.28Fe0.72O achieved the highest performance at 80 &#xb0;C, by delivering the current density of 7.81&#x2009;A cm-2 against a cell voltage of 2.2&#x2009;V. Whereas, Ni0.66Fe0.34O achieved a current density of 6.49&#x2009;A cm-2 at 2.2&#x2009;V. Both samples exhibited excellent stability during short-term durability tests (ca. 90&#x2009;h) at 1&#x2009;A cm-2 and 80&#xb0;C.

Non-O157 Shiga toxin-producing Escherichia coli (STEC), particularly the O118 serogroup, are emerging pathogens linked to severe foodborne illnesses, which are characterized by the production of a potent phage-borne cytotoxin. This study explores the genomic landscape, virulence factors, and resistance traits of O118 STEC. We analyzed 357 publicly available O118 genomes, all but three available only in draft stage spanning ten different H-antigen types. To enhance the availability of high-quality reference genomes, we additionally included two O118:H16 STEC strains from our collection that were sequenced to closure. Multilocus sequence typing based on the 4,160 shared genes revealed phylogenetic clustering by H-type and delineated distinct STEC-phylogroups, alongside relationships to non-STEC pathovars such as uropathogenic E. coli (UPEC), enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Identified STEC-phylogroups encompass H6, H12, H16, and H2 strains with diverse Shiga toxin profiles (stx1a, stx2a, stx2b, stx2c, stx2f). A subset of H2-STEC lacked stx, suggesting potential secondary phage loss. Most STEC groups carried the locus of enterocyte effacement (LEE). Further, a strong correlation was observed between H-antigens and eae subtypes, with specific pairings such as H6/eae-&#x3b9;, H16/eae-&#x3b2;, and H2/eae-&#x3b5;. Horizontally acquired pathogenicity islands, including O-island 122 in H16 strains and a novel pathogenicity-associated island carrying antibiotic resistance, along with other loci related to colonization and interbacterial competition, further enhance their virulence potential. Our findings underscore the genetic diversity and virulence potential of O118 STEC. Understanding such phylogroup-linked virulence and resistance traits is crucial for effective surveillance and public health interventions.

Mycophenolic acid (MPA) is a potent antiproliferative immunosuppressive agent used to prevent organ transplant rejection and to treat various immune-mediated diseases. MPA is the active metabolite formed from the biotransformation of the prodrugs mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). MPA exerts its therapeutic effects by inhibiting guanosine nucleotide synthesis in lymphocytes. Through this inhibition, cell and humoral immunity is suppressed, resulting in a reduction of cytotoxicity and inflammation. Systemic exposure to MPA is influenced by a complex pharmacokinetic pathway, which involves various drug-metabolizing enzymes (DMEs) and transporters. Substantial interindividual variability exists in MPA exposure, efficacy, and adverse effects. Genetic polymorphisms in the genes encoding DMEs and transporters have been reported to influence this observed variability; however, evidence remains inconsistent and is largely derived from non-African populations. African populations exhibit high levels of genetic diversity, and their underrepresentation in pharmacogenetic studies may hinder the identification of important variants influencing MPA disposition and clinical outcomes. This review evaluates the genes that have been reported to affect MPA exposure as well as highlights conflicting results on the role of these pharmacogenetic variants in different populations. The review highlights the lack of data on African populations and provides justification for their inclusion in the study of MPA pharmacogenetics.

Drought is a major constraint on rice production, yet the coordinated responses of rhizosphere microbial communities and metabolites across rice genotypes with contrasting drought tolerance remain insufficiently understood. In this study, we combined metagenomic and metabolomic analyses to investigate drought-induced changes in the rhizosphere of three rice genotypes with distinct ecological backgrounds: the drought-sensitive cultivar Bhutan, the upland rice genotype TGR78, and Oryza rufipogon K111. Field experiments were conducted under well-watered and drought conditions, and rhizosphere soil samples were collected for multi-omics profiling. Drought stress reduced plant height and panicle number in all three genotypes, but the magnitude of these effects differed among genotypes. Bhutan showed the greatest reduction in plant height (42.1%) and the largest number of differential metabolites (146), indicating a stronger drought response at both phenotypic and metabolic levels. In contrast, TGR78 and K111 displayed relatively greater phenotypic stability under drought stress. Metagenomic analysis revealed pronounced genotype-dependent shifts in rhizosphere bacterial community composition, whereas metabolomic profiling showed distinct changes in metabolite accumulation patterns among genotypes. Correlation analysis further demonstrated that drought substantially reshaped rhizosphere microbe-metabolite associations, shifting the interaction network from broadly positive and highly connected under well-watered conditions to more selective associations under drought stress. Collectively, these results indicate that rice drought adaptation is associated with genotype-dependent reorganization of the rhizosphere microbiome and metabolic profile. This study provides new insight into rhizosphere-mediated drought responses in rice and offers a basis for developing microbiome-informed strategies for drought-resilient crop improvement.

We report here the design of orthogonal, enzyme-driven DNA transcriptional timers that enable precise programming of time delays in cell-free in vitro transcription. These timers utilize blocker strands that transiently bind to the promoter domain, preventing transcription onset. Selective enzymatic cleavage of the blocker strands triggers their removal, allowing input DNA strands to bind and initiate transcription. By tuning the kinetics of enzymatic blocker degradation&#x2500;through varying enzyme or blocker strand concentrations&#x2500;we achieve fine temporal control over transcription half-life (t1/2) from 0.48 &#xb1; 0.02 h up to 8.4 &#xb1; 0.1 h. Using three different blocker-degrading enzymes (RNase H, uracil-DNA glycosylase (UDG), and formamidopyrimidine DNA glycosylase (Fpg)), we also demonstrate orthogonal temporal control of multiple transcription templates in a single solution. Finally, we show the programmed termination control and downstream regulation of Cas12a enzymatic collateral cleavage activity through such transcription timers. Together, these orthogonal DNA transcriptional timers establish a generalizable and straightforward framework for programming time-resolved transcription and gene expression in cell-free synthetic biology.

Garlic-flavored light soy sauce is a representative composite seasoning whose taste formation depends not only on fermentation-derived components in light soy sauce but also on the time-dependent transfer of garlic-derived taste substances. However, evidence regarding the dynamic migration of non-volatile taste-active compounds-particularly free amino acids (FAAs)-and their roles in taste formation during soaking remains limited. This study aimed to elucidate the time-dependent migration of garlic-derived FAAs during soaking and their contribution to taste formation, and to assess a practical soaking endpoint. Samples at different soaking times were evaluated using electronic tongue analysis and targeted FAA quantification. The soaking procedure was used to establish a controlled experimental model rather than to represent an industrial standard protocol. Taste activity values (TAVs) and orthogonal partial least squares-discriminant analysis (OPLS-DA) with variable importance in projection (VIP) values were used to identify key taste-active and discriminating amino acids and to assess a practical soaking endpoint. Electronic tongue analysis showed that sourness and bitterness gradually decreased, whereas sweetness and umami exhibited an overall increasing trend with soaking time; the 30- and 40-day samples exhibited highly similar global taste profiles, indicating stabilization of the taste profile. A total of 16 FAAs were detected: total FAAs reached a maximum at day 20, whereas glutamic acid accumulated continuously and reached its highest level at day 30. TAV analysis indicated multiple taste-active amino acids, with glutamic acid making the greatest contribution, and OPLS-DA (VIP values) likewise highlighted glutamic acid among the discriminating variables. These taste shifts were consistent with the time-dependent migration and accumulation of garlic-derived taste-active FAAs, particularly glutamic acid. Under the tested conditions, glutamic acid is the key driver of umami enhancement and taste stabilization in the garlic-light soy sauce soaking system. A soaking period of approximately 30&#x202f;days can be considered a practical soaking endpoint to achieve a relatively stable and reproducible taste profile, supporting process optimization and standardization of garlic-flavored light soy sauce.

Transport is a major contributor to urban air pollution and premature mortality worldwide. This systematic review evaluates the air-quality and public health co-benefits of national and regional transport policies aimed at reducing population exposure to air pollution. Following PRISMA 2020 guidelines, this review synthesized evidence published between 2011 and 2024 on the health and environmental impacts of national or regional transport policies. Ten eligible studies were reviewed, covering diesel vehicle phase-outs, inspection and maintenance programs, electric vehicle incentives, fuel taxation, and promotion of public or active transport. Across multiple settings, these policies were associated with reductions in PM2.5 concentrations and with avoided premature mortality, respiratory and cardiovascular hospitalizations, and healthcare costs. The largest and most consistent health benefits were observed for integrated policy packages, particularly those combining regulatory and technological measures such as fuel quality improvements, vehicle electrification and diesel phase-out, complemented by behavioral or fiscal instruments. Most available evidence originates from high-income countries, while studies from low- and middle-income regions remain scarce. The limited number of eligible studies and their concentration in specific regions and modeling approaches constrain generalizability, especially to settings with different transport systems, resource availability, and air-quality profiles. Embedding health-impact assessment within transport planning and expanding long-term evaluations in low- and middle-income countries are essential to ensure equitable and sustained air-quality and health improvements. Future policy frameworks should prioritize source-oriented regulatory and technological measures such as vehicle electrification, fuel-quality regulation, and diesel phase-out implemented within integrated policy packages to maximize public-health co-benefits.

Saline soils, characterized by elevated salinity, depleted soil organic carbon (SOC), and degraded structure, constrain global agricultural productivity. While straw incorporation is known to promote SOC turnover, its efficacy in saline soils is limited by salt-impaired microbial decomposition. We evaluated how straw form regulates microbial-driven SOC turnover across salinity gradients (light-S1, moderate-S2, severe-S3) and temperatures (10&#x202f;&#xb0;C-T1, 20&#x202f;&#xb0;C-T2, 30&#x202f;&#xb0;C-T3) through a 360-day incubation. Treatments included conventional chopped wheat straw (CW), granular wheat straw (GW), wheat straw biochar (BW), and no-straw control (CK). Straw form significantly altered fungal &#x3b1;-diversity (p&#x202f;<&#x202f;0.05) but not bacterial. Fungal diversity was enhanced by BW and T3, while S2 exhibited maximal fungal richness. Ascomycota dominated fungal communities (65.0-97.7%), with GW increasing their relative abundance. Higher temperatures reduced Ascomycota dominance (T1&#x202f;>&#x202f;T2&#x202f;>&#x202f;T3, p&#x202f;<&#x202f;0.05). Multivariate analyses confirmed that straw form, temperature, and salinity collectively drove distinct clustering of microbial communities. Under the same environmental temperature and soil salinity, the soil fungal communities of each treatment were significantly separated according to the different forms of straw application. Among them, the distribution of soil fungal communities in the GW treatment differed significantly from other treatments. Co-occurrence networks revealed GW enhanced microbial network complexity and stability. The Mantel test analysis showed that straw form to SOC turnover via microbial restructuring, demonstrating stronger fungal-physicochemical correlations than bacterial. Critically, GW altered microbial community structure, as evidenced by the distinct separation of fungal communities and increased complexity of co-occurrence networks, and promoted SOC turnover. These findings establish granular straw as an effective practice to overcome the decomposition barriers inherent to conventional straw in saline soils, thereby promoting nutrient cycling and supporting sustainable land management.

Hepatocellular carcinoma (HCC) presents a global health burden due to its asymptomatic early course and aggressive progression. Conventional ultrasound often detects HCC at intermediate or advanced stages, beyond optimal intervention windows. This diagnostic limitation highlights the critical need for highly sensitive early detection methods. Although microfluidic platforms offer advantages in throughput and integration, their current focus on single biomarkers restricts diagnostic accuracy and clinical applicability. This study introduces the "Pro-Exo" chip, an innovative liquid-biopsy platform where antibody-conjugated microbeads disrupt laminar flow to improve binding efficiency, while multichannel parallel detection enables simultaneous analysis of multiple HCC biomarkers. This platform enables concurrent analysis of plasma proteins (DCP, GP73, AFP) and exosomal surface markers (CD9+CD81, EpCAM, GPC3) from minimal plasma volumes. By integrating different biomarker categories, it overcomes the limitations of single-analyte detection technologies. Validation studies demonstrated that the assay requires only 50 &#x3bc;L plasma per chamber and can be completed within 60 min, with low detection limits for all target biomarkers. Receiver operating characteristic analysis confirmed that single-marker detection provides insufficient diagnostic power, whereas combined plasma protein and exosomal marker detection significantly improved the accuracy of HCC identification. The Pro-Exo Chip establishes a robust platform for rapid, sensitive multibiomarker liquid biopsy, effectively addressing critical needs in early HCC detection. This integrated methodology not only advances cancer diagnostic strategies but also highlights the substantial clinical value of exosomal biomarkers, offering significant implications for both translational research and clinical practice.

Studies have explored the relationship between eosinophilic esophagitis (EoE) and various factors such as race, gender, and geographic elements, including urbanization, population density, and climate zones. However, the relationship between socioeconomic advantage or disadvantage and key pathology findings-particularly the esophageal peak eosinophil count at diagnosis, as well as access to biologic therapy-has not been extensively studied in pediatric EoE. This study aimed to examine these relationships to uncover potential influences. This retrospective cohort study involved children aged 0 to 18 years evaluated in EoE clinic, including 16 patients who were refractory to other conventional therapies and ultimately treated with dupilumab. Details regarding eosinophil count per high power field (HPF) in the proximal and distal esophagus at the time of diagnosis were obtained from electronic medical records. Patients' socioeconomic status was stratified using the Area Deprivation Index (ADI), which ranks neighborhoods based on socioeconomic disadvantage, calculated from the patients' residential addresses. Data were analyzed using two-tailed t-test and multivariate regression analysis. A total of 145 pediatric patients were included in the study. The patient population was spread relatively evenly across the different levels of the ADI. Our analysis showed no significant correlation between ADI and eosinophil count in the distal and proximal esophagus. One hundred twenty-nine patients demonstrated significant histological response to conventional non-dupilumab therapies. In a subset of 16 patients receiving dupilumab, the analysis revealed no significant difference of ADI, and baseline eosinophil count at the diagnosis in the proximal and distal eosinophil count compared with the overall cohort. However, dupilumab treatment was associated with a significant reduction in eosinophil counts, suggesting improved histologic outcomes compared with non-dupilumab therapies. This study examined the potential impact of socioeconomic disparities on pediatric patients with EoE, including those who were refractory to other previous therapies and ultimately treated with dupilumab. Our results suggest that socioeconomic deprivation, as measured by the ADI, is not associated with baseline histologic severity in pediatric EoE. Dupilumab demonstrated significant therapeutic benefit in patients who were refractory to other therapies, and access to dupilumab was not influenced by ADI.

American protective gun ownership privatizes collective behavior, transmuting the role of the state to keep citizens safe into individual actions to protect one's family and one's immediate community. In doing so, owners may sharpen the ingroup/outgroup divide into those who need protection and those who need to be protected against. Using nationally representative individual-level data from the General Social Survey, we find that American gun owners have friendship structures that are more ingroup-focused than nonowners: more cohesive (more of owners' friends are friends with each other) and less diverse (fewer of owners' friends are of different races or religions). Using county-aggregated data from over 70 million Facebook users (over 21 billion friendship ties), we similarly find that US counties with higher rates of gun ownership have friendship structures that are more cohesive and less diverse. This is mirrored in our findings that states and counties with higher rates of firearm ownership have lower rates of social infrastructural sites that bring communities together and lower rates of civic trust. Finally, we show evidence that the presence of guns is a quasi-causal factor in declining social capital-using modern time-series analyses, we show that a state-level increase in gun sales predicts a significant decrease in the next year's rates of social capital.