Search Results (894,353)

Objective: Cerebral ischemia–reperfusion injury (IRI) is a distinct pathological phase that differs from permanent ischemia (IR) in that it triggers secondary damage despite the restoration of blood flow. The primary objective of this study is to comprehensively characterize and compare the molecular signatures—such as differential gene expression, protein activation, and metabolic alterations—between IRI and IR. By doing so, we aim to identify key pathways and biomarkers that specifically drive IRI and IR pathology, thereby providing novel therapeutic targets to mitigate reperfusion-induced damage in stroke and related neurological conditions. Methods: We employed an integrated transcriptomic and proteomic approach to compare a permanent ischemia model (IR, 24 h ischemia) with a reperfusion model (IRI, 1 h ischemia + 24 h reperfusion), using SHAM-operated animals as controls. Results: Our results demonstrate a profound decoupling between the transcriptome and proteome in IRI. While IRI induced extensive proteomic alterations (160 changed proteins in IRI vs. IR), transcriptional changes were minimal (3 genes), indicating dominant post-transcriptional regulation. Both IR and IRI activated shared inflammatory responses (e.g., Saa3, upregulated 14.33-fold in IRI/SHAM) and metabolic shifts (Gapdh, downregulated 4.03-fold). However, IRI uniquely upregulated neuroprotective genes (Arc, Npas4), activated a specific set of reperfusion-related pathways (72 proteins), and exhibited distinct extracellular matrix remodeling (Mmp3, upregulated 11.24-fold in IR/SHAM). The overall correlation between transcriptomic and proteomic dynamics was remarkably low (r = 0.014), underscoring the importance of translation and protein decay mechanisms. Conclusions: This study redefines IRI not merely as an exacerbation of ischemic damage but as a unique adaptive molecular trajectory. We identify Pisd-ps3 and Saa3 as potential therapeutic targets and show that proteomic signatures can stratify injury phases. These findings advance the prospects of precision therapeutics aimed at neuroprotection and immunomodulation in ischemic stroke. Full article

The geometric precision of ballastless tracks critically determines the performance and safety of high-speed railways. Traditional manual fine adjustment methods remain labor-intensive, iterative, and sensitive to human expertise, making it difficult to achieve sub-millimeter accuracy and global consistency. To address these challenges, this paper proposes a virtual-model–enabled pre-adjustment framework for high-speed ballastless track construction. The framework integrates a dual-frame SLAM-based and multi-sensor measurement system based on RC-SLAM principles and a local attitude compensation model, enabling accurate 3D mapping and reconstruction of long-track segments under extended-range and GNSS-denied conditions typical of linear infrastructure scenarios. A constraint-based global optimization algorithm is further developed to transform empirical fine adjustment into a computable geometric control problem, generating executable adjustment configurations with engineering feasibility. Field validation on a 1 km railway section demonstrates that the proposed method achieves sub-millimeter measurement accuracy, improves adjustment efficiency by over eight times compared with manual operations, and reduces material waste by $2800–$7000 per kilometer. This paper demonstrates a previously unexplored execution-level workflow for long-rail fine adjustment, establishing a closed-loop paradigm from measurement to predictive optimization and paving the way for SLAM-driven, simulation-based, and multi-sensor–integrated precision control in next-generation railway construction. Full article

Spermatogenesis is a tightly coordinated differentiation program that sustains male fertility while transmitting genetic and epigenetic information to the next generation. This review consolidates mechanistic evidence showing how RNA-centered regulation integrates with the epitranscriptome and three-dimensional (3D) genome architecture to orchestrate germ-cell fate transitions from spermatogonial stem cells through meiosis and spermiogenesis. Recent literature is critically surveyed and synthesized, with particular emphasis on human and primate data and on stage-resolved maps generated by single-cell and multi-omics technologies. Collectively, available studies support a layered regulatory model in which RNA-binding proteins and RNA modifications coordinate transcript processing, storage, translation, and decay; small and long noncoding RNAs shape post-transcriptional programs and transposon defense; and dynamic chromatin remodeling and 3D reconfiguration align transcriptional competence with recombination, sex-chromosome silencing, and genome packaging. Convergent nodes implicated in spermatogenic failure are highlighted, including defects in RNA metabolism, piRNA pathway integrity, epigenetic reprogramming, and nuclear architecture, and the potential of these frameworks to refine molecular phenotyping in male infertility is discussed. Finally, key gaps and priorities for causal testing in spatially informed, stage-specific experimental systems are outlined. Full article

Background: Primary Biliary Cholangitis (PBC) requires early diagnosis and specialized management to prevent progression to cirrhosis. This study evaluates the awareness levels of Turkish physicians from various specialties regarding the clinical features, diagnostic criteria, and current treatment protocols of PBC. Methods: A multi-regional cross-sectional survey was conducted with 269 physicians across Türkiye. Knowledge levels were assessed through a 28-item instrument covering epidemiology, diagnosis and therapy. Data distribution was non-normal (Skewness: −1.296, Kurtosis: 2.857), necessitating the use of the Kruskal–Wallis H test and Dunn–Bonferroni post hoc procedure for inter-group comparisons. Internal consistency was confirmed with a Cronbach’s alpha of 0.80. Results: The overall mean awareness score was 62.6%. Item-level analysis revealed a near-universal understanding of the non-mandatory role of liver biopsy in diagnosis (99.1%) yet identified a critical knowledge gap regarding second-line therapies, particularly the use of steroids (6.8%). Significant disparities were observed among specialties (p < 0.001). Gastroenterologists (Median: 91.07%) and gastroenterology fellows (Median: 85.71%) exhibited significantly higher proficiency compared to general practitioners (64.29%) and family medicine residents (67.86%). Internal medicine specialists outperformed primary care providers, while no significant differences were found among other subgroups after Bonferroni adjustment. Conclusions: Professional specialization is the primary determinant of PBC awareness. While core diagnostic knowledge is stable, significant gaps exist in pharmacological management among non-specialists. Targeted medical education for primary care physicians is essential to ensure timely referral and optimize patient outcomes. Full article

Diabetic wounds are often accompanied by severe inflammation, which is unfavorable for vascular growth and wound repair. Therefore, promoting the healing of diabetic wounds is of great significance. In this study, carboxymethyl chitosan (CMCS) was grafted with 4-formylphenylboronic acid (FPBA) and then crosslinked with oxidized sodium alginate (OAlg) to form a dual-dynamic covalent hydrogel (CPOA) based on borate ester bond and Schiff base bonds. Mesenchymal stem cells’ exosomes (Exos) were incorporated into the CPOA to construct CPOA@Exos for diabetic wound healing. Owing to the dual-dynamic covalent crosslinking network, the CPOA hydrogel showed good injectability and self-healing ability. In addition, the hydrogel displayed reactive oxygen species (ROS) responsive properties, enabling both scavenging of multiple free radicals and on-demand release of Exos in the ROS-rich wound microenvironment. A diabetic wound model was established on C57 mice, and treatment with CPOA@Exos demonstrated that it could promote the polarization of macrophages toward the M2 phenotype, enhance cellular proliferation in the wounded area, and thereby accelerate the healing of diabetic wounds. In conclusion, this study provides a new hydrogel wound dressing that can inhibit inflammation for the management of diabetic wounds. Full article

Cuba is in a unique situation in which it has a large (220,000 managed colonies) and isolated honey bee population due to a 60+ year ban on the importation of bees. Despite this, the ectoparasitic mite Varroa destructor arrived in 1996, and with it came deformed wing virus (DWV). In 2018, an island-wide survey detected varroa and DWV in 91% of colonies. In this study, we conducted a full-virome analysis on some of these samples, along with additional samples collected in 2021. For the first time, we detected two variants of Lake Sinai Virus and confirmed the absence of the normally widespread black queen cell virus in Cuba. We also detected both DWV-A and DWV-B master variants, with DWV-B being the dominant variant. Interestingly, the DWV-B/A recombinant was also detected, indicating that despite Cuba’s isolated nature, the pattern of DWV evolution mirrors that found in the USA and Europe. However, this pattern is not found in neighboring Latin America, China, or Japan, where the DWV-A master variant continues to be dominant. How and why two distinct evolutionary DWV pathways have arisen remain a mystery. Full article

Chromium-doped diamond-like carbon (DLC-Cr) nanocomposite films were successfully deposited using a high-power impulse magnetron sputtering (HiPIMS) system. The Cr content in the films was controlled by adjusting the Cr target powers. The influence of Cr content on the microstructure, mechanical properties, tribological performance, and wettability of the films was systematically investigated. The results show that the Cr content and deposition rate of the films increased with increases in the target power. The surface topography of the films evolved from smooth to rough as the Cr target increased from 10 W to 70 W. At low Cr doping rates, the film mainly exhibited an amorphous structure, whereas the nanocomposite structure was formed at proper Cr doping rates. Raman and XPS analyses revealed that Cr incorporation altered the I_D/I_G ratio and promoted the formation of Cr-C bonds, leading to a more graphitic and nanocomposite-like structure. The nanoindentation results show that an optimal Cr content enhances both hardness and elastic modulus, while higher Cr concentrations lead to a decline in mechanical strength due to more graphitization and decreasing stress. Tribological tests exhibited a significant reduction in the friction coefficient (0.21) and wear rate (0.63 × 10⁻¹⁴ m³/N·m) at a moderate Cr level. Additionally, the surface wettability evolved toward enhanced hydrophilicity with increasing Cr power, as evidenced by reduced water contact angles and increased surface energy. These findings demonstrate that controlled Cr incorporation effectively tailors the structure, stress state, and surface chemistry of DLC films, offering a tunable pathway to achieving optimal mechanical performance and tribological stability for advanced engineering applications. Full article

Background/Objectives: The arrangement and positioning of genes on chromosomes are non-random in plant genomes. Adjacent gene pairs often exhibit similar co-expression patterns and regulatory mechanisms. However, the genomic and epigenetic features influencing such co-expression, particularly in perennial crops like tea (Camellia sinensis), remain largely uncharacterized. Methods: Firstly, we identified 771 specific neighboring gene pairs (SNGs) in C. sinensis (YK10) and investigated the contributions of intergenic distance and gene length to SNGs’ co-expression. Secondly, we integrated multi-omics data including transcriptome, ATAC-seq, Hi-C and histone modification data to explore the factors influencing their co-expression. Thirdly, we employed logistic regression models to individually assess the contributions of nine factors—ATAC-seq, H3K27ac, Hi-C, GO, distance, length, promoter, enhancer, and expression level—to the co-expression of SNGs. Finally, by integrating co-expression networks with metabolic profiles, several transcription factors potentially involved in the regulation of catechin metabolic pathways were identified. Results: Intergenic distance was significantly negatively correlated with co-expression strength, while gene length showed a positive correlation. Furthermore, these two features exerted synergistic effects with threshold characteristics and functional significance. SNGs marked by either ATAC-seq or H3K27ac peaks displayed significantly higher expression levels, suggesting that epigenetic regulation promotes co-expression. In addition, correlation analysis revealed that the expression of certain SNGs was closely associated with catechin accumulation, particularly epicatechin gallate (EGC) and epigallocatechin gallate (EGCG), highlighting their potential role in modulating tissue-specific catechin levels. Conclusions: Collectively, this study reveals a multilayered regulatory framework governing SNG co-expression and provides theoretical insights and candidate regulators for understanding metabolic regulation in tea plants. Full article

Allotetraploid fish produced by distant hybridization are valuable germplasm for the mass production of sterile triploids. The allotetraploid crucian–carp hybrid (4nAT, 4n = 200) is derived from the intergeneric cross between a female red crucian carp (Carassius auratus red var., 2n = 100) and a male common carp (Cyprinus carpio L., 2n = 100). However, after 33 successive generations, this lineage faces a critical bottleneck in maintaining male fertility. The present study aimed to develop new biomarkers for testicular development and characterize the associated functional gene expression profile in 4nAT. Following whole-genome resequencing and selection signature analysis of 15 male 4nAT individuals from each of the high-development group (HDG) and low-development group (LDG), ZSWIM7 (Zinc Finger SWIM-Type Containing 7), a gene implicated in reproductive development, was selected as a candidate for further fertility association studies. Seven SNPs were screened in the coding region of ZSWIM7 of 70 4nAT males; among these, SNP3 (c.23T/C) exhibited a significant correlation between genotypes and testicular development: individuals with the CT genotype showed a higher gonadosomatic index (1.17 ± 0.68 vs. 0.65 ± 0.50) and greater counts of mature spermatozoa (2537.67 ± 283.95 vs. 341.56 ± 121.66) compared to those with the TT genotype. Further quantitative PCR and immunofluorescence assays demonstrated that ZSWIM7 was highly expressed in the testis and specifically localized to the nuclei of early meiotic primary spermatocytes. Collectively, these results establish ZSWIM7 as a promising biomarker for 4nAT testicular development, offering a potential molecular tool for maintaining male fertility in allotetraploid fish breeding. Full article

Background: Stroke and subclinical cerebral ischemia remain important neurological complications of transcatheter aortic valve replacement (TAVR). The Sentinel cerebral embolic protection (CEP) device is designed to capture embolic debris during TAVR, but its impact on clinical and imaging outcomes remains incompletely characterized. Methods: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) comparing Sentinel CEP versus no protection when TAVR was performed. Outcomes of interest included all stroke, disabling stroke, infarct volume by diffusion-weighted MRI in protected and unprotected areas, all-cause mortality, acute kidney injury, and major vascular complications. Risk ratios (RRs) and median differences with 95% confidence intervals (CIs) were calculated using random-effects models and trial sequential analysis (TSA) assessed evidence robustness. Results: Four RCTs including 10,986 patients were analyzed. Sentinel CEP did not significantly reduce clinical stroke (RR 0.88, 95% CI 0.69–1.12) or disabling stroke (RR 0.68, 95% CI 0.41–1.14). Pooled DW-MRI data showed a significant reduction in new ischemic lesion volume within Sentinel CEP-protected territories (difference in medians –75.7 mm³; 95% CI –130.4 to –21.0). Subgroup analyses in elderly, female, and high-surgical-risk patients revealed no benefit with Sentinel CEP. Additionally, TSA indicated that current data are underpowered for definitive conclusions. Conclusions: The Sentinel CEP device during TAVR did not significantly reduce clinical stroke but was associated with lower MRI-detected ischemic lesion volumes compared with no protection. Further adequately powered RCTs integrating clinical and imaging endpoints are needed to define its role in neuroprotection during TAVR. Full article

Background: Artificial intelligence (AI) and machine learning (ML) are increasingly used in the diagnosis and management of bone metastases, spanning lesion detection, segmentation, prognostic modeling, fracture risk assessment, and surgical decision support. However, the literature is heterogeneous and rapidly evolving, making it difficult for clinicians to contextualize these developments. Methods: We performed a narrative review of the literature on AI/ML applications in bone metastasis management, focusing on studies that address clinically relevant problems such as detection and segmentation of metastatic lesions, prediction of skeletal-related events and survival, and support for reconstructive decision-making. We prioritized recent, peer-reviewed work that reports model performance and highlights opportunities for clinical translation. Results: Most published studies center on imaging-based diagnosis and lesion segmentation using radiomics and deep learning, with generally high internal performance but limited external validation. Emerging work explores prognostic models and biomechanically informed fracture risk estimation, yet these remain at an early proof-of-concept stage. Very few frameworks are integrated into routine workflows, and explainability, bias mitigation, and health-economic impacts are rarely evaluated. Conclusions: AI and ML tools have substantial potential to standardize imaging assessment, refine risk stratification, and ultimately support personalized management of bone metastases. Future research should focus on externally validated, multimodal models; development of AI-augmented alternatives to the Mirels score; federated multicenter collaboration; and routine incorporation of explainability and cost-effectiveness analyses. Full article

As a vital ecological security barrier and climate regulator in northwestern China, the spatial patterns and evolving formation mechanisms of ecosystem services within the Qinghai Lake basin hold significant strategic value for ecological conservation and national park development in the region. This study selected land use data during 2000–2020, integrating the equivalent factor method, spatial correlation analysis, and the geodetector approach to systematically investigate the spatial heterogeneity characteristics of ESV in the Qinghai Lake basin and its corresponding driving mechanisms. The results indicate the following: (1) During the period 2000–2020, grassland consistently constituted the primary land cover category within the Qinghai Lake Basin, accounting for over 60% of the total area; water bodies (16.67%) and unused land (16.56%) represented the secondary land use categories. Over this twenty-year period, the total ESV exhibited a slight increasing trend, rising from USD 30.30 × 10⁸ to USD 30.75 × 10⁸, representing a growth of 0.31%. Regulating services constituted the primary component of ESV. The highest contribution to ESV originated from water bodies, with grassland ranking second. (2) ESV displayed a spatial arrangement marked by “high values in the lake center and low values in the surrounding areas” and “higher values in the southeast and lower values in the northwest.” Its spatial correlation exhibits a pronounced positive relationship. The number of units classified as high-high clusters (primarily water bodies at low elevations) and low-low clusters (mainly grasslands and unused land at high elevations) both increased over the study period, indicating a continuous intensification of ESV spatial agglomeration. (3) Results from the geographical detector reveal that both natural and anthropogenic factors collectively drive the spatial variation in ESV, with natural factors exhibiting stronger explanatory capacity. Among these, elevation and temperature are identified as the dominant drivers of ESV spatiotemporal differentiation. The combined effect of two interacting factors surpasses the influence exerted by any single factor in isolation. This research clarifies that the spatial distribution of ESV in the Qinghai Lake Basin, which features “high values in the lake center and low values in the surrounding areas” as well as “higher values in the southeast and lower values in the northwest,” is jointly shaped by the combined control of vertical zonality governed by topographic and climatic factors and the spatial differentiation of human activities. In low-altitude lakeshore zones, ESV rose as a consequence of water body expansion and the enforcement of ecological conservation measures, leading to the emergence of high-value clusters. In contrast, ESV improvement in high-elevation regions remained limited, constrained by fragile natural conditions and minimal human intervention. The insights derived from this research offer a scientific foundation for refining the “one core, four zones, one ring, multiple points” functional zoning framework of the Qinghai Lake National Park, as well as for developing tailored management approaches suited to distinct elevation-based regions. Full article

Cleaning historical silk textiles is a particularly sensitive operation that requires precise control to prevent mechanical or chemical damage. In this study, we investigate using flexible PVA–borax-based gels to remove soot from silk, i.e., polyvinyl alcohol–borax (PVA-B) gels and polyvinyl alcohol–borax–agarose double network gels (PVA-B/AG DN) loaded with different cleaning agents—namely, 30% ethanol and 1% Ecosurf EH-6—in addition to plain gels loaded with water. These gel formulations were tested on simplified model systems (SMS) and were applied using two methods: placing and tamping. The cleaning results were compared with a traditional contact-cleaning approach; micro-vacuuming followed by sponging. Visual inspection, 3D opto-digital microscopy, colorimetry, and machine-learning-assisted (ML) soot counting were exploited for the assessment of cleaning efficacy. Rheological characterization provided information about the flexibility and handling properties of the different gel formulations. Among the tested systems, the DN gel containing only water, applied by tamping, was easy to handle and demonstrated the highest soot-removal effectiveness without leaving residues, as confirmed by micro-Fourier Transform Infrared (micro-FTIR) analysis. Scanning electron microscope (SEM) micrographs proved the structural integrity of the treated silk fibers. Overall, this work allows us to conclude that PVA–borax-based gels offer an effective, adaptable, and low-risk cleaning strategy for historical silk fabrics. Full article

Objectives: To investigate the prognostic value of CEBPA (CCAAT/enhancer-binding protein α) molecular features, such as variant allele frequency (VAF), in patients with de novo acute myeloid leukemia (AML). Methods: Next-generation sequencing (NGS) was used to detect CEBPA mutations in 162 patients with newly diagnosed AML (except acute promyelocytic leukemia). Results: We established 44.2% as the optimal threshold for both maximum VAF and bZIP-domain VAF. The high-VAF group showed higher leukemia burden and inferior event-free survival (EFS). bZIP-domain VAF demonstrated superior prognostic value over maximum VAF (HR: 3.174 vs. 2.460) and was validated across subgroups, namely cytogenetically normal acute myeloid leukemia (CN-AML), chemotherapy-only, and low/intermediate-risk subgroups. Multivariate analysis confirmed high bZIP-domain VAF and DNMT3A mutation as independent risk factors. Conclusions: Our results confirm that the bZIP-domain VAF of CEBPA mutations is a more effective predictor of relapse than the maximum VAF, offering a valuable tool for the early identification of patients at high risk of relapse. Full article