Search Results (17,665)

The unique ecological gradients of Xinjiang have fostered a rich reservoir of genetic resources in local sheep populations. However, the population genetic structure, adaptive mechanisms to extreme environments, and the genetic basis underlying key economic traits of these breeds remain poorly understood. To address this gap, we performed whole-genome resequencing of 140 individuals from seven indigenous sheep populations—Altay, Bayinbuluke, Kazakh, Kirgiz, Bashibai, Turpan Black, and Yemule White—identifying 18,700,507 high-quality SNPs. Genetic diversity analyses revealed that all populations exhibited comparable levels of genetic diversity, with modest variation across breeds, with Turpan Black sheep exhibiting the highest observed heterozygosity (Ho = 0.3110) and proportion of polymorphic sites, whereas Kirgiz sheep showed comparatively lower values. Population structure analyses consistently indicated that geographic isolation is the primary driver of genetic differentiation, with Kirgiz sheep from the Pamir Plateau in southern Xinjiang displaying the greatest genetic distance relative to northern Xinjiang populations. By integrating multiple selection signature detection methods—including F_ST, π ratio, and XP-CLR—we found that genes under selection in Kirgiz sheep were significantly enriched in biological pathways related to stem cell pluripotency regulation (e.g., BMPR1B), DNA repair (e.g., DDB2), and neural development, thereby elucidating their unique genetic adaptations to high-altitude environments. In contrast, Turpan Black sheep appear to cope with heat stress through mechanisms involving basal transcriptional regulation (e.g., GTF2I), maintenance of protein homeostasis (e.g., DNAJB14), and melanin biosynthesis (e.g., MC1R). Furthermore, comparative analysis of body size identified a suite of candidate genes associated with growth and development (e.g., CUX1, KIT), which are primarily involved in transcriptional regulation, protein kinase activity, and the ubiquitin-mediated proteolytic system, thereby revealing a multi-layered genetic regulatory network governing body conformation. Collectively, this study provides a comprehensive genomic framework for understanding the genetic structure, adaptive evolution, and molecular basis of economically important traits in indigenous sheep breeds from Xinjiang, offering valuable candidate targets for future functional validation and precision breeding programs. Full article

Toscana virus (TOSV) is an arthropod-borne virus, transmitted by sandflies, which represents a major cause of aseptic meningitis in Mediterranean countries during summer months. Despite its epidemiological importance, recent genomic data on circulating Italian strains remain limited. We performed comprehensive phylogenetic and genotypic characterization of 34 TOSV isolates (32 obtained from human biological samples and 2 from sandfly homogenates) collected between 2022 and 2025 from Northern/Central Italy. All the sequenced isolates clustered within Lineage A, with strains circulating in Tuscany showing significantly lower intra group genetic divergence (p < 0.05), indicative of compartmentalized local circulation. Both S and M segments exhibited negative selection and identified non-synonymous mutations deserving functional investigation. This study documents stable Lineage A predominance across Italian regions, with Tuscany showing distinct phylogeographic structuring. mNGS proves effective for TOSV genomic surveillance, supporting refined public health strategies, including targeted sandfly control in endemic foci. Full article

Limosilactobacillus fermentum KUB-D18 is a probiotic strain with significant potential in food fermentation and health promotion, yet the systems-level mechanisms underlying its physiological robustness remain elusive. To elucidate the metabolic remodeling strategies operating across growth phases, we developed an integrated framework combining genome-scale metabolic modeling (GSMM) with transcriptomics. A high-quality metabolic model for L. fermentum KUB-D18, designated iYH640 and comprising 640 genes, 1530 metabolites, and 1922 reactions, was constructed and validated against experimental growth data. Specifically, in vitro assays measuring biomass and glucose concentrations showed a maximum specific growth rate of 0.2696 h⁻¹ and a glucose uptake rate of 11.75 mmol gDCW⁻¹ h⁻¹, providing physiological constraints for the model. Using transcriptome-regulated flux balance analysis (TR-FBA), gene expression profiles from the logarithmic phase (L-phase) and stationary phase (S-phase) were integrated to quantify growth phase-specific metabolic flux distributions. These simulations revealed a distinct transcription-driven metabolic shift, in which the organism moves from a proliferation-oriented metabolic state with active central carbon metabolism and macromolecule synthesis to a maintenance-oriented state. This S-phase is characterized by reduced flux through anabolic pathways together with the selective preservation of redox balance and nucleotide homeostasis. Collectively, these results provide a quantitative explanation of how L. fermentum KUB-D18 balances growth and maintenance, offering a mechanistic basis for improving its stability and functional performance in industrial probiotic applications. Full article

Anther-derived somatic embryogenesis is a valuable approach in rubber tree (Hevea brasiliensis) breeding; however, its effectiveness is highly influenced by the developmental stage of the microspores. The present investigation focused on male flower buds of the cultivar Reyan 73397 at successive developmental stages to examine the relationship between visible bud characteristics and internal microspore development, assess how microspore developmental stage affects callus induction and somatic embryo formation, and identify the stage with the greatest embryogenic potential. Cytological observations distinguished six well-defined phases of microspore development, spanning from microspore mother cells to fully mature pollen grains, each reliably linked to particular bud diameters, coloration, and anther morphology. Anthers corresponding to each developmental phase were cultured in vitro, and their ability to initiate callus and produce somatic embryos was systematically evaluated. Anthers containing uninucleate microspores exhibited the highest rates of both callus formation and somatic embryogenesis, with the early-uninucleate stage showing the strongest response. This stage consistently matched flower buds measuring 1.42–1.57 mm in transverse diameter and displaying a green to yellowish-green appearance. In contrast, anthers collected at the microspore mother cell and tetrad stages did not produce embryogenic responses. Histological evidence has indicated that both callus and somatic embryos originate from diploid somatic tissues of the anther wall, particularly connective parenchyma cells, rather than from microspores themselves. Based on these findings, a rapid, non-destructive selection method integrating bud diameter, bud color, and sieve-based size separation was developed to identify responsive explants efficiently. Overall, this study defines the optimal developmental window for anther culture in rubber trees, verifies the somatic origin of embryogenic tissues, and provides a practical morphological and cytological basis for improving anther culture efficiency in rubber tree breeding programs. Full article

This study investigates how asphalt mixture type influences the degradation of pavement-marking retroreflectivity and luminance contrast under real operational conditions on Israeli intercity roads. Field measurements were collected along 65.1 km of roadway constructed with three asphalt mixtures: basalt dense-graded concrete (Basalt DCG), basalt stone mastic asphalt (Basalt SMA), and basalt–dolomite dense-graded concrete (Zebra DCG). Linear degradation models provided the best representation of retroreflectivity decay (R² = 0.63). Results show that asphalt mixture type significantly affects initial retroreflectivity, contrast, and effective service life of left-side white paint markings. Markings applied on Basalt DCG exhibited initial retroreflectivity values up to 1.6–1.9 times higher and maintained acceptable visibility for approximately 7–8 months, compared with about 3 months on Zebra DCG under comparable conditions. Traffic volume was not a statistically significant predictor, indicating that degradation is dominated by time-dependent material and optical aging processes. Pavement background reflectivity and its evolution play a critical role in contrast degradation. The results demonstrate that asphalt mixture selection can reduce repainting frequency by approximately 10–15%, highlighting asphalt mixture choice as a practical and previously underrecognized lever for improving pavement-marking durability and long-term visibility. Full article

Wheel–rail coupled excitation introduces strong low-frequency modulation, random impact interference, and broadband background noise into the vibration system of locomotive gearboxes, causing early weak bearing fault features to become submerged and making traditional deconvolution methods insufficient for effective enhancement. To address this challenge, this study proposes an adaptive parameter optimization method for MCKD based on the weighted envelope spectrum factor (WESF). WESF integrates the Hoyer index, kurtosis, and envelope spectrum energy to jointly characterize sparsity, impulsiveness, and periodicity of signal components. By using WESF as the fitness function, the sparrow search algorithm (SSA) is employed to simultaneously optimize the key MCKD parameters L, T, and M, enabling optimal enhancement of weak periodic impacts. To further mitigate modal aliasing caused by wheel–rail excitation, the original signal is first adaptively decomposed using successive variational mode decomposition (SVMD), and modes with WESF values above the average are selected for signal reconstruction. The reconstructed signal is subsequently enhanced via SSA–MCKD, and fault characteristic frequencies are extracted using envelope spectrum analysis. Experimental validation using gearbox bearing data collected under 40, 50, and 60 Hz operating conditions shows that the proposed method achieves fault feature coefficient (FFC) values of 12.8%, 7.5%, and 7.2%, respectively—representing an average improvement of approximately 156% compared with traditional methods (average FFC of 3.6%). These results demonstrate that the proposed SVMD–WESF–SSA–MCKD approach can significantly enhance weak periodic impact features under strong background noise and wheel–rail excitation, exhibiting strong practical applicability for engineering implementation. Full article

Dihydroquercetin (DHQ) is a promising object for the development of a treatment for patients with obesity and prediabetes requiring a moderate therapeutic effect. This paper reports a clinical case of DHQ application in a 30-year-old Caucasian male and proposes a molecular mechanism of its anti-obesity effect. DHQ was administrated as a dietary supplement at a dose of 100–200 mg/day during 3 months with treatment interruption for 1 month. The data collected one month before the treatment were used as a control. The molecular aspects were studied via molecular docking with β₃-adrenoceptor (ADRB3, PDB ID: 9IJE) and peroxisome proliferator-activated receptor γ (PPARG, PDB ID: 2ZNO) and molecular dynamic simulation under conditions mimicking a human cellular environment. A pronounced weight decrease up to 0.73 kg/week was observed during DHQ administration. The highest affinity to ADRB3 was observed for the non-ionized H2aH3e-conformation of 2S,3R-DHQ (–8.846 kcal/mol). Molecules with 2S-configuration demonstrate 0.332 kcal/mol higher affinity to PPARG compared to 2R-stereoisomers. The intermolecular complex with cis-DHQ demonstrated higher stability in molecular dynamics simulation. The insights gained from this study may contribute to our understanding of flavonoids not merely as antioxidants but also as active ingredients that selectively interact with receptors. If future investigations confirm these results, they may serve as a foundation for developing a new class of anti-obesity remedies that act via ADRB3. Full article

Soybean (Glycine max L. Merr.) is a globally significant oilseed crop. The number of four-seeded pods in the lower part (FSPL) serves as a critical yield component under high-density planting. To date, numerous crop-specific traits have been investigated in multiple breeding studies of soybean; however, little attention has been paid to studies on FSPL. Hence, in this study, we investigated the genetic basis of FSPL using a recombinant inbred line population (RIL3613) across four environments. The segregated genetic mapping population was cultivated during the field experiments, and the collected phenotypic dataset of FSPL exhibited quantitative genetics and high broad-sense heritability (0.724), indicating stable genetic control. Further, we performed quantitative trait locus (QTL) mapping using raw means in each environment and identified 10 QTL, explaining phenotypic variations (PVE) ranging from 0.10% to 2.94%. Among the identified environmentally stable QTL, qFSPL-15-1 was consistently detected across all environments. Two candidate genes [Glyma.15G034100 (encoding lysophosphatidic acid acyltransferase 2) and Glyma.15G034200 (encoding an RNA-binding protein)] were predicted within the flanking genomic interval. The allele frequencies of haplotype combinations of Hap1: Pro2 + CDS1 for Glyma.15G034100 and Hap3: Pro3 + CDS1 for Glyma.15G034200 in wild soybeans (26.6–30.0%) were larger than improved cultivars (52.6–53.4%). We believe that our current findings elucidate the molecular mechanisms regulating lower-pod formation and provide precise genetic targets for marker-assisted selection in high-yield soybean breeding. Full article

Traffic accidents are among the leading causes of injury worldwide, highlighting the urgent need to better understand the factors that contribute to accident occurrence and severity in order to improve road safety and reduce injuries and fatalities. This study analyzes the U.S. Accidents dataset, comprising data collected from 2016 to 2023, to identify the key determinants of accident severity and to evaluate feature-selection techniques for predictive modeling. To this end, several feature-selection methods are examined, including L1-regularized logistic regression, minimum redundancy maximum relevance (mRMR), conditional mutual information maximization (CMIM), ReliefF, and tree-based importance measures; these are compared with the Weighted Conditional Mutual Information (WCFR). The selected feature subsets are then evaluated using three machine learning models: logistic regression, random forest, and XGBoost. Experimental results show that WCFR consistently outperforms the competing methods, achieving higher validation accuracy (up to approximately 0.84) and Macro-F1 scores (up to approximately 0.55), while using fewer features and maintaining model interpretability. These results indicate that WCFR is particularly effective for accident severity modeling and highlight its potential as a robust feature selection strategy for large-scale transportation safety analytics and future severity prediction studies. Full article

Surgical resection remains a cornerstone in the multidisciplinary management of central nervous system (CNS) tumors, particularly diffuse gliomas. Traditionally, the role of surgery has been evaluated primarily through quantitative metrics such as extent of resection and its association with survival outcomes. However, despite maximal and radiologically complete resections, recurrence remains nearly universal in malignant CNS tumors, suggesting that surgical cytoreduction alone does not fully account for post-surgical disease dynamics. Emerging biological and molecular evidence indicates that surgery represents not merely a technical intervention, but a biologically active event that profoundly reshapes tumor evolution and treatment response. In this review, we propose a conceptual framework that redefines surgery as a key biological driver in CNS tumor progression. We synthesize evidence demonstrating that surgical trauma induces inflammation, hypoxia, vascular remodeling, immune modulation, and extracellular matrix reorganization, collectively reprogramming the residual tumor microenvironment. These changes create selective pressures that favor the survival and expansion of adaptive tumor cell subpopulations, including invasive and stem-like phenotypes. From an evolutionary perspective, surgical resection functions as an acute selective bottleneck acting on heterogeneous tumor ecosystems, contributing to clonal selection and molecular divergence at recurrence. We further examine the dissociation between surgical (anatomical) margins and molecular (biological) margins, highlighting how biologically active tumor cells infiltrate beyond radiologically defined boundaries. This discrepancy provides a biological explanation for marginal and distant recurrences and challenges anatomy-based paradigms of surgical completeness. Importantly, we discuss how surgery-induced biological changes influence postoperative radiotherapy and systemic therapies, affecting radiosensitivity, target delineation, and therapeutic vulnerability. Finally, we outline future directions toward surgery-integrated precision neuro-oncology, emphasizing the potential of spatial profiling, liquid biopsy, advanced imaging, and artificial intelligence to capture perioperative tumor evolution. By reframing surgery as a biological inflection point rather than a neutral prelude to adjuvant treatment, this review advocates for a dynamic, biology-driven continuum of care aimed at anticipating tumor adaptation and improving long-term disease control in CNS tumors. Full article

Targeted drug delivery (TDD), specifically through targeting ligand–drug conjugates, has reshaped oncology by enabling selective delivery of cytotoxic payloads to cancer cells while minimizing uptake by normal tissues. A key approach relies on exploiting overexpressed cell surface receptors (CSRs) to enable selective uptake of drug conjugates via receptor-mediated endocytosis. This review delineates four clinically validated CSRs (HER2, Trop-2, Nectin-4, and SSTR2) with several FDA-approved drug conjugates. Furthermore, emerging CSRs (EGFR, DLL3, and keratin 1) that may support next-generation TDD platforms for cancer treatment are also highlighted. We discuss how CSR type, density on cancer cells, and its mechanism of endocytosis, as well as the conjugate design for cellular uptake, tissue distribution, ligand size, and linker stability, collectively determine tumor drug accumulation and therapeutic efficacy. From representative examples, we elucidate the rationale for judicious refinement of these parameters, guiding the development of more potent ligands and drug conjugates to enhance the therapeutic efficacy of cytotoxic agents. Full article

The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic–epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA–mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic–epigenetic–transcriptional convergence as a potential avenue for therapeutic intervention. Full article

Large-scale Virtual Power Plants (VPPs) are increasingly essential as Distributed Energy Resources (DERs) assume ancillary service duties once supplied by conventional generation, yet scaling a VPP exposes a persistent trilemma among economic efficiency, data privacy, and operational security. Centralized coordination can approach optimal revenue but requires collecting fine-grained DER operational data and creates a single point of compromise. Federated Learning (FL) mitigates raw data centralization by keeping measurements and experience local, but it introduces a fragile trust assumption that the aggregator will correctly and fairly combine model updates. This trust gap is acute in reinforcement learning-based VPP control because aggregation deviations, including selectively dropping updates, manipulating weights, replaying stale models, or injecting a replacement model, can silently bias the learned policy and degrade both profit and compliance. We propose a zero-knowledge federated reinforcement learning framework for trustless VPP coordination in which each DER trains a local deep reinforcement learning agent to solve a multi-objective dispatch problem that balances ancillary service revenue against battery degradation under operational and grid constraints, while the global aggregation step is made externally verifiable. In each round, participants bind membership via signed receipts and commit to their updates, and the aggregator produces a zk-SNARK, proving that the published global parameters equal the agreed aggregation rule applied to the receipt-bound set of committed updates under a fixed-point encoding with range constraints. Verification is lightweight and can be performed independently by each DER, removing the need to trust the aggregator for aggregation integrity without centralizing raw DER operational data or trajectories. The proposed design does not aim to hide model updates from the aggregator. Instead, it provides external verifiability of the aggregation computation while keeping raw measurements and local experience. We formalize the threat model and verifiable security properties for aggregation correctness and update inclusion, present a circuit construction with proof complexity characterized by model dimension and fleet size, and evaluate the approach in power and cyber co-simulation on the IEEE 33 bus feeder with ancillary service signals. Results show near-centralized economic performance under benign conditions and improved robustness to aggregator side deviations compared to standard federated reinforcement learning. Full article

Water towers are historically significant hydraulic infrastructures that evolved from simple masonry structures to technologically advanced and architecturally expressive forms. This study presents a typological and material analysis of water towers, focusing on their construction techniques, durability, and potential for adaptive reuse. The research combines visual inspection, archival and bibliographic research, and photographic documentation, of selected European and Italian examples for comparative insights on design and materials choices. Data were collected and organized according to parameters such as construction materials, structural type, tank and roof form, access system, and current function. Assessments were conducted following the UNI EN 16096, providing a structured framework to evaluate heritage value, material conditions, and adaptive reuse potential. Main results demonstrate that water towers, beyond their original hydraulic function, retain significant technical, architectural, and cultural value, offering opportunities for adaptive reuse as cultural, educational, residential, or community spaces. Key findings identify material vulnerabilities, structural challenges (including wind, seismic, and thermo-hygrometric effects), and possibilities for sustainable interventions that respect historical authenticity. The study highlights how systematic typological assessment and documentation can guide evidence-based conservation and support innovative reuse strategies, integrating heritage preservation with urban regeneration and community engagement. Water towers exemplify the intersection of engineering, architecture, and cultural heritage, and their conservation requires a multidisciplinary approach between technical performance, material preservation, and socio-cultural significance. Finally, the implemented procedure is proposed as a methodological framework replicable and scalable for assessing similar infrastructures in other contexts. Full article

Background/Objectives: Bone-anchored prostheses provide an alternative to socket prostheses, directly connecting the prosthesis to the residual limb via osseointegration. However, limited evidence exists on how spatiotemporal gait parameters and gait symmetry change over time following osseointegration in individuals with unilateral transfemoral amputation. This study aimed to examine changes in spatiotemporal and gait symmetry parameters before osseointegration and at 6 and 12 months post-surgery. Methods: Common spatiotemporal parameters were collected from six individuals with unilateral transfemoral amputation at baseline (with socket prosthesis) and at 6 and 12 months post-osseointegration using a motion analysis system. Group-level differences were assessed using repeated measures ANOVA. Gait symmetry was evaluated using selected spatiotemporal parameters. Results: Following osseointegration, individuals with unilateral transfemoral amputation experienced significant spatiotemporal changes over time. At the group level, walking velocity and stride length decreased at 6 months, with stride length increasing at 12 months. Step width and prosthetic-side step length increased at 12 months relative to 6 months, while intact-side step length decreased. Prosthetic-side toe-off timing was shorter at 12 months. Gait symmetry responses varied individually: some with poor baseline symmetry improved, while those with better baseline symmetry became more asymmetric, indicating heterogeneous outcomes. Conclusions: This study highlights longitudinal changes in gait biomechanics following osseointegration in individuals with unilateral transfemoral amputation. Gait adaptations were highly variable across individuals and time points. Future research should involve larger, more homogeneous samples and incorporate kinetic, muscle activity, and functional outcome measures to better understand the impact of bone-anchored prostheses on gait and mobility. Full article