Search Results (559)

Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro^® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article

The Xiong’an New Area, a newly established national-level zone in China, faces the threat of land subsidence and ground fissure due to groundwater overexploitation and geothermal extraction, threatening urban safety. This study integrates time-series InSAR and GNSS monitoring to analyze spatiotemporal deformation patterns from 2017/05 to 2025/03. The key results show: (1) Three subsidence hotspots, namely northern Xiongxian (max. cumulative subsidence: 591 mm; 70 mm/yr), Luzhuang, and Liulizhuang, strongly correlate with geothermal wells and F4/F5 fault zones; (2) GNSS baseline analysis (e.g., XA01-XA02) reveals fissure-induced differential deformation (max. horizontal/vertical rates: 40.04 mm/yr and 19.8 mm/yr); and (3) InSAR–GNSS cross-validation confirms the high consistency of the results (Pearson’s correlation coefficient = 0.86). Subsidence in Xiongxian is driven by geothermal/industrial groundwater use, without any seasonal variations, while Anxin exhibits agricultural pumping-linked seasonal fluctuations. The use of rooftop GNSS stations reduces multipath effects and improves urban monitoring accuracy. The spatiotemporal heterogeneity stems from coupled resource exploitation and tectonic activity. We propose prioritizing rooftop GNSS deployments to enhance east–west deformation monitoring. This framework balances regional and local-scale precision, offering a replicable solution for geological risk assessments in emerging cities. Full article

M-edge X-ray absorption spectroscopy (XAS), which probes 3p→3d transitions in first-row transition metals, provides detailed insights into oxidation states, spin-states, and local electronic structure with high element and orbital specificity. Operating in the extreme ultraviolet (XUV) region, this technique provides sharp multiplet-resolved features with high sensitivity to ligand field and covalency effects. Compared to K- and L-edge XAS, M-edge spectra exhibit significantly narrower full widths at half maximum (typically 0.3–0.5 eV versus >1 eV at the L-edge and >1.5–2 eV at the K-edge), owing to longer 3p core-hole lifetimes. M-edge measurements are also more surface-sensitive due to the lower photon energy range, making them particularly well-suited for probing thin films, interfaces, and surface-bound species. The advent of tabletop high-harmonic generation (HHG) sources has enabled femtosecond time-resolved M-edge measurements, allowing direct observation of ultrafast photoinduced processes such as charge transfer and spin crossover dynamics. This review presents an overview of the fundamental principles, experimental advances, and current theoretical approaches for interpreting M-edge spectra. We further discuss a range of applications in catalysis, materials science, and coordination chemistry, highlighting the technique’s growing impact and potential for future studies. Full article

The escalating demand for sustainable and eco-friendly production processes has necessitated the exploration of renewable resources for the synthesis of valuable chemicals. This study investigated the fermentative synthesis of gluconic acid (GA) and xylonic acid (XA) from hydrolyzed palm fronds by using Gluconobacter oxydans. The key variables examined included agitation speed, inoculum ratio, and composition of fermentation media. In a synthetic medium, maximum GA concentration reached 52.82 ± 12.88 g/L at 65 h using 150 rpm agitation and 15% (v/v) inoculation, while maximum XA concentration achieved 2.31 ± 1.43 g/L at 96 h using 220 rpm agitation and 9% (v/v) inoculation. In the hydrolysate medium, the maximum GA concentration was 3.24 ± 0.66 g/L at fermentation onset using 220 rpm agitation and 15% (v/v) inoculation, while the maximum XA concentration reached 0.62 ± 0.04 g/L at 24 h using 190 rpm agitation and 5% (v/v) inoculation. These findings demonstrate the feasibility of utilizing palm fronds as a renewable feedstock for the sustainable synthesis of high-value biochemicals, promoting waste valorization, and contributing to the advancement of a circular bioeconomy. Full article

Background: Direct oral anticoagulants (DOACs) are generally preferred over warfarin for preventing arterial and venous thromboembolism. However, the efficacy and safety of DOACs in patients with extremely low body weight (BW) are uncertain. This study investigates anti-factor Xa (anti-FXa) activity of apixaban and compares it between patients with normal BW (>50 kg) and underweight (≤50 kg). Methods: We enrolled 150 patients on branded generic apixaban (Apixan^TM) for atrial fibrillation (AF), venous thromboembolism, and intracardiac thrombus. Anti-FXa activity of apixaban was measured at peak concentration (C_peak) and trough concentration (C_trough) after at least one week of therapy. Results: Mean age was 64.0 ± 12.7 years, with 53.3% being male. Mean BW was 61.3 ± 15.3 kg. Of the 150 patients, 132 (88%) had AF, and 43 (28.7%) had low BW. Overall, 87.3% and 84.7% of patients had C_trough and C_peak within the expected range. Underweight patients had significantly higher mean C_trough and C_peak than normal BW patients. A higher proportion of low-BW patients exceeded the expected C_peak range compared to normal-BW patients (25.6% vs. 3.7%, p < 0.001). Low BW was the only independent predictor of exceeding C_peak specified range (adjusted OR 4.87, 95% CI 1.31–18.15, p = 0.018). Conclusions: Most patients maintained apixaban levels within expected ranges, but those with low BW were more likely to exceed the specified range of C_peak. Full article

Thrombotic diseases represent a significant global health burden, particularly for middle-aged and elderly populations. Medicinal leeches, such as Hirudinaria manillensis and Whitmania pigra, have been traditionally used for their anticoagulant properties. The genomes of these leeches each harbor three lefaxin genes, which are designated lefaxin_Hman1–3 and lefaxin_Wpig1–3, respectively. We conducted genomic and transcriptomic sequencing on wild populations of both species. Bioinformatics tools were employed to analyze intraspecific variation, molecular evolution, and protein structures. We expressed recombinant lefaxin proteins in Pichia pastoris and assessed their anticoagulant activities using in vitro coagulation assays. H. manillensis exhibited greater genetic diversity and stability, whereas W. pigra showed higher expression levels and hydrophilicity. Both species exhibited purifying selection, indicating conserved function, and their lefaxin structures are similar to the archetypal lefaxin (UniProt No. P86681.1). W. pigra lefaxins bound Factor Xa more effectively. W. pigra lefaxins exhibited more robust anticoagulant activity in vitro compared to those from H. manillensis. W. pigra, a non-hematophagous leech, shows potent anticoagulant activity through lefaxins, challenging traditional views on leech efficacy. This study underscores the potential of lefaxins as therapeutic targets for thrombotic diseases and highlights the need to reconsider the use of various leech species in medicine. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently become the leading cause of chronic liver disease and can progress to hepatocellular carcinoma (HCC) through multiple pathogenic mechanisms. Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor activated by proteases such as trypsin, tryptase or coagulation factors VII and Xa. Recent studies have shown that PAR2 expression is increased in the liver of patients with MASLD or liver fibrosis. Its activation is linked to metabolic dysfunction through several pathways, including SREBP1c activation, AMPK inhibition and Akt-induced insulin resistance. Inhibition of PAR2 has been effective in reducing MASLD progression in different animal models. Notably, PAR2 blockade has also been effective in more advanced stages of the disease by dampening chronic inflammation and fibrogenesis through the inhibition of hepatic stellate cell activation and of TGF-β and SerpinB3 production. PAR2 also plays a role in cancer development, promoting tumour proliferation, angiogenesis and expression of immune checkpoint inhibitors (like PD-L1, CD47 and CD24). Due to its multifaceted involvement in liver disease, PAR2 is emerging as a key therapeutic target in this clinical context. This review aims to summarise current knowledge on PAR2′s role in MASLD and its potential as a therapeutic target. Full article

Abandoned smelting sites in karst terrain pose a serious environmental problem due to the complex relationship between specific hydrogeological elements and heavy metal contamination. This review combines work from across the globe to consider how karst-specific features (i.e., rapid underground drainage, high permeability, and carbonate mineralogy) influence the mobility, speciation, and bioavailability of “metallic” pollutants, such as Pb, Cd, Zn, and As. In some areas, such as Guizhou (China), the Cd content in the surface soil is as high as 23.36 mg/kg, indicating a regional risk. Molecular-scale analysis, such as synchrotron-based XAS, can elucidate the speciation forms that underlie toxicity and remediation potential. Additionally, we emphasize discrepancies between karst in Asia, Europe, and North America and synthesize cross-regional contamination events. The risk evaluation is complicated, particularly when dynamic flow systems and spatial heterogeneity are permanent, and deep models like DI-NCPI are required as a matter of course. The remediation is still dependent on the site; however, some technologies, such as phytoremediation, biosorption, and bioremediation, are promising if suitable geochemical and microbial conditions are present. This review presents a framework for integrating molecular data and hydrogeological concepts to inform the management of risk and sustainable remediation of legacy metal pollution in karst. Full article

The structural, elastic, electronic, magnetic, and half-metallic properties of full-Heusler ${\mathrm{Fe}}_2$LiSi and ${\mathrm{Fe}}_2$LiGe compounds were investigated using first-principles calculations. Among the studied configurations, the cubic XA structures in the ferromagnetic state for both compounds are the most stable. They exhibit mechanical stability, elastic anisotropy, and ductility. Compared to ${\mathrm{Fe}}_2$LiGe, ${\mathrm{Fe}}_2$LiSi demonstrates higher stability, stronger anisotropy, greater brittleness, higher Debye and melting temperatures, and a smaller Grüneisen parameter. Both compounds exhibit metallic majority-spin channels and semiconducting minority-spin channels. At the equilibrium lattice constant, ${\mathrm{Fe}}_2$LiSi and ${\mathrm{Fe}}_2$LiGe exhibit half-metallic gaps of 0.141 eV and 0.179 eV, respectively. Both compounds exhibit 100% spin-polarization ratio in specific lattice constant ranges. The total magnetic moment per formula unit (3.000 ${\mu }_{\mathrm{B}}$) follows the generalized Slater–Pauling rule and depends on Fe atomic magnetic moments. These properties indicate that ${\mathrm{Fe}}_2$LiSi and ${\mathrm{Fe}}_2$LiGe hold promise for spintronic applications. Full article

We studied the adsorption thermodynamics and mechanism behind the binding of nitric oxide (NO) in the interior surfaces and structural fragments of the high metal center density microporous Metal-Organic Framework (MOF) CPO-27-Cu, by gas sorption, at a series of temperatures. For the purpose of comparison, we also measured the corresponding CO₂ adsorption isotherms, and as a result, the isosteric heats of adsorption for the two studied adsorptives were derived, being in the range of 12–15 kJ/mol for NO at loadings up to 0.5 NO molecules per formula unit (f.u.) of the bare compound (C₄O₃HCu), and 23–25 kJ/mol CO₂ in the range 0–1 CO₂ per f.u. Microscopically, the mode of NO binding near the square pyramid Cu(II) centers was directly accessed with the use of in situ NO gas adsorption X-ray Absorption Spectroscopy (XAS). Additionally, during the vacuum/temperature activation of the material and consequent NO adsorption, the electronic state of the Cu-species was monitored by observing the corresponding X-ray Near Edge Spectra (XANES). Contrary to the previously anticipated chemisorption mechanism for NO binding at Cu(II) species, we found that at slightly elevated temperatures, under ambient, but also cryogenic conditions, only relatively weak physisorption takes place, with no evidence for a particular adsorption preference to the coordinatively unsaturated Cu-centers of the material. Full article

China’s rapid urbanization has given rise to the phenomenon of “urban villages”, which are often regarded as chaotic fringe areas in traditional studies. With the rise of the concept of resilient cities, the value of urban villages as potential carriers of sustainable development has been re-examined. This study adopted research methods such as field investigations, in-depth interviews, and conceptual sampling. By analyzing the interlinked governance relationship between Xiamen City and the urban villages in the Bay Area, aspects such as rural housing improvement, environmental governance, residents’ feedback, geographical pattern, and spatial production were evaluated. A field investigation was conducted in six urban villages within the four bays of Xiamen. A total of 45 people in the urban villages were interviewed, and the spatial status of the urban villages was recorded. This research found that following: (1) Different types of urban villages have formed significantly differentiated role positionings under the framework of regional governance. Residential community types XA and WL provide long-term and stable living spaces for migrant workers in Xiamen; tourism development types DS, HX, BZ, and HT allow the undertaking of short-term stay tourists and provide tourism services. (2) These urban villages achieve the construction of their resilience through resisting risks, absorbing policy resources, catering to the expansion of urban needs, and co-construction in coordination with planning. The multi-cultural inclusiveness of urban villages and their transformation led by cultural shifts have become the driving force for their sustainable development. Through the above mechanisms, urban villages have become the source of resilience and sustainability of healthy cities and provide a model reference for high-density urban construction. Full article

As widely used peroxidase-like nanozymes, Fe-based nanozymes still suffer from an unclear reaction mechanism, which limits their further application. In this work, through alkaline treatment and then the replacement or occupation of strong acid sites by isolated Fe species, porous ZSM-5-confined atomic Fe species nanozymes with separated medium acid sites (Al-OH) and isolated Fe-O₄ sites were prepared. And the structure and the state of Fe-O₄ confined by ZSM-5 were determined by AC-HAADF-STEM, XPS, and XAS. In the oxidation of 3, 3′, 5, 5′-tetramethylbenzidine (TMB) by the hydrogen peroxide (H₂O₂) process, the heterolysis of H₂O₂ to ∙OH mainly occurs at the isolated Fe-O₄ sites, and then the generated ∙OH can spill over to the Al-OH sites to oxidize the adsorbed TMB. The synergistic effect between Fe-O₄ sites and medium acid sites can significantly benefit the catalytic performance of Fe-based nanozymes. Full article

Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major threat to global rice productivity. Although hybrid rice breeding has significantly enhanced yields, persistent genetic vulnerabilities within restorer lines continue to compromise BB resistance. This study addresses this challenge by implementing functional marker-assisted selection (FMAS) to pyramid two broad-spectrum resistance (R) genes, Xa21 and Xa23, into the elite, yet BB-susceptible, restorer line K608R. To enable precise Xa23 genotyping, we developed a novel three-primer functional marker (FM) system (IB23/CB23/IR23). This system complements the established U1/I2 markers used for Xa21. This recombination-independent FMAS platform facilitates simultaneous, high-precision tracking of both homozygous and heterozygous alleles, thereby effectively circumventing the linkage drag limitations typical of conventional markers. Through six generations of marker-assisted backcrossing followed by intercrossing, we generated K608R2123 pyramided lines harboring both R genes in homozygous states, achieving a recurrent parent genome recovery rate of 96.93%, as determined by single nucleotide polymorphism (SNP) chip analysis. The pyramided lines exhibited enhanced resistance against six virulent Xoo pathogenic races while retaining parental yield performance across key agronomic traits. Our FMAS strategy overcomes the historical trade-off between broad-spectrum resistance and the preservation of elite phenotypes, with the developed lines exhibiting resistance coverage complementary to that of both introgressed R genes. This integrated approach provides breeders with a reliable molecular tool to accelerate the development of high-yielding, disease-resistant varieties, demonstrating significant potential for practical deployment in rice improvement programs. The K608R2123 germplasm represents a dual-purpose resource suitable for both commercial hybrid seed production and marker-assisted breeding programs, and it confers synergistic resistance against diverse Xoo races, thereby providing a pivotal breeding resource for sustainable BB control in epidemic regions. Full article

Background: The gut microbiome is a key modulator of the gut–brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS). Methods: Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map™ Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites—homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)—were quantified using LC-MS/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS). Results: Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels. Conclusions: Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite–symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance. Full article

Plant-beneficial microbes are a perennial ally in an agroecosystems, providing multiple benefits to crop plants. The present study explored the potential of two microbial biocontrol agents (MBCAs), viz., Trichoderma asperellum and Pseudomonas fluorescens, against the bacterial blight pathogen of rice, Xanthomonas oryzae pv. oryzae. In vitro, MBCAs resulted in significant inhibition of X. oryzae pv. oryzae, as evidenced through the distortion of pathogen cell morphology and formation of a pathogen biofilm. Pot studies on the effect of MBCAs in rice showed increased germination, increased vigor index of seedlings, increased tiller numbers, a 10.29% reduction in percentage disease incidence (PDI), and low disease severity following individual inoculation. Activity of plant defense enzymes also increased with MBCA treatment (phenylalanine ammonia-lyase, 2.7-fold increase; peroxidase and polyphenol oxidase, 5-fold increase), establishing the priming effect of MBCAs on host defense. The quantitative polymerase chain reaction data revealed that pathogenesis-related genes (OsPR1a, OsPR1b, and OsPR10a) and X. oryzae pv. oryzae resistance genes (Xa1 and Xa26) were upregulated 4- to 14-fold in MBCA-treated rice plants over control plants. These results provide insights into the phenological, physiological, and molecular responses of rice crops treated with MBCAs in the presence of X. oryzae pv. oryzae and could be used to develop an effective field management strategy. Full article