Search Results (4,604)

Public transport companies are aware that the success of their operations largely depends on the proper sizing and optimization of their processes. Among the key activities are the maintenance and repair of the vehicle fleet. This paper presents the application of mathematical optimization methods from the field of operations research to improve the efficiency of service workshops for bus maintenance and repair. Based on an analysis of collected data using queueing theory, the authors assessed the current system performance and found that the queueing system still has spare capacity and could be downsized, which aligns with the company’s management goals. Specifically, the company plans to reduce the number of bus repair service stations (servers in a queueing system). The main question is whether the system will continue to function effectively after this reduction. Three specific downsizing solutions were proposed and evaluated using queueing theory methods: extending the daily operating hours of the workshops, reducing the number of arriving buses, and increasing the productivity of a service station (server). The results show that, under high system load, only those solutions that increase the productivity of individual service stations (servers) in the queueing system provide optimal outcomes. Other solutions merely result in longer queues and associated losses due to buses waiting for service, preventing them from performing their intended function and causing financial loss to the company. Full article

Most existing assembly accuracy analysis methods focus on rigid assemblies or assume assemblies to be rigid bodies, neglecting the influence of assembly deformation in weak rigid components (WRCs) such as thin-walled structures, cantilever structures, etc. As a result, the assembly accuracy analysis becomes inaccurate, and the accuracy of key components cannot be effectively controlled. This may lead to serious issues such as forced assembly, repair, and rework. To address these problems, this study proposes a rigid–flexible coupling-based assembly accuracy analysis method for WRCs. The stiffness matrix and assembly deformation of WRCs are calculated, and by coupling assembly deformation with other assembly deviations, a rigid–flexible coupling assembly accuracy data model is established. This model incorporates multiple deviation sources, including assembly process variations, design tolerances, and assembly deformations. Assembly deviation transfer modeling and accumulation calculation methods for WRCs are investigated, enabling assembly accuracy simulation and statistical analysis. A case study on WRC assembly accuracy analysis is conducted, and the results demonstrate that the proposed method improves the accuracy of assembly analysis for WRCs, verifying its reliability. Full article

Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions. Full article

Carbon flow tracking and spatial pattern optimization at the scale of urban functional zones are key scientific challenges in achieving carbon neutrality. However, due to the complexity of carbon metabolism processes within urban functional zones, related studies remain limited. To address these scientific challenges, this study, based on the “source–sink–flow” ecosystem services framework, develops an integrated analytical approach at the scale of urban functional zones. The carbon balance is quantified using the CASA model in combination with multi-source data. A network model is employed to trace carbon flow pathways, identify critical nodes and interruption points, and optimize the urban spatial pattern through a low-carbon land use structure model. The research results indicate that the overall carbon balance in Hangzhou exhibits a spatial pattern of “deficit in the center and surplus in the periphery.” The main urban area shows a significant carbon deficit and relatively poor connectivity in the carbon flow network. Carbon sequestration services primarily flow from peripheral areas (such as Fuyang and Yuhang) with green spaces and agricultural functional zones toward high-emission residential–commercial and commercial–public functional zones in the central area. However, due to the interruption of multiple carbon flow paths, the overall carbon flow transmission capacity is significantly constrained. Through spatial optimization, some carbon deficit nodes were successfully converted into carbon surplus nodes, and disrupted carbon flow edges were repaired, particularly in the main urban area, where 369 carbon flow edges were restored, resulting in a significant improvement in the overall transmission efficiency of the carbon flow network. The carbon flow visualization and spatial optimization methods proposed in this paper provide a new perspective for urban carbon metabolism analysis and offer theoretical support for low-carbon city planning practices. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Background: Peripheral nerve injuries, especially involving the facial nerve, present unique reconstructive challenges due to their complex functional demands and limited regenerative potential. While autografts remain the gold standard, their drawbacks—such as donor-site morbidity and limited availability—have driven interest in processed nerve allografts. Acellular grafts, in particular, offer promising off-the-shelf alternatives without the need for immunosuppression. Methods: We conducted a narrative review of the literature (1990–2023), identifying 55 peer-reviewed studies via PubMed, Embase, and Cochrane Library. The studies included clinical and preclinical work on motor nerve regeneration using processed nerve allografts, with particular attention to outcomes in facial nerve repair. Two independent reviewers conducted abstract screening, full-text review, and data extraction. Results: Processed nerve allografts show encouraging motor recovery in gaps under 50 mm, with recovery rates of up to 85% reported. Outcomes decrease significantly in longer gaps (>50–60 mm) and in complex cases, including facial nerve repairs, where evidence remains sparse and largely extrapolated from broader motor nerve data. Registry data (e.g., RANGER) support their use but are limited by heterogeneity and lack of randomization. Conclusions: Processed nerve allografts represent a viable alternative to autografts in selected cases—especially short to mid-length motor nerve defects. However, their role in facial nerve reconstruction remains insufficiently studied. Further trials are needed to address specific anatomical and functional challenges in this subgroup and to clarify long-gap efficacy. Full article

Microglia, the brain’s resident innate immune cells, play a fundamental role in maintaining neural homeostasis and mediating responses to injury or infection. Upon activation, microglia undergo morphological and functional changes, including phenotypic switching between pro- and anti-inflammatory types and the release of different inflammatory mediators. These processes contribute to neuroprotection and the pathogenesis of various central nervous system (CNS) disorders. Mast cells, although sparsely located in the brain, exert a significant influence on neuroinflammation through their interactions with microglia. Through degranulation and secretion of different mediators, mast cells disrupt the blood–brain barrier and modulate microglial responses, including alteration of microglial phenotypes. Notably, mast cell-derived factors, such as histamine, interleukins, and tryptase, activate microglia through various pathways including protease-activated receptor 2 and purinergic receptors. These interactions amplify inflammatory cascades via various signaling pathways. Previous studies have revealed an exceedingly complex crosstalk between mast cells and microglia suggesting a bidirectional regulation of CNS immunity, implicating their cooperation in both neurodegenerative progression and repair mechanisms. Here, we review some of the diverse communication pathways involved in this complex interplay. Understanding this crosstalk may offer novel insights into the cellular dynamics of neuroinflammation and highlight potential therapeutic targets for a variety of CNS disorders. Full article

The combination of scaffold materials and bioactive factors is a promising strategy for promoting bone defect repair in tissue engineering. Previous studies have shown that osteoglycin (OGN) is highly expressed in the bone repair process using deer antler as an animal model of bone defects. It suggests that OGN may be a key active component involved in the bone repair process. The aim of this study was to investigate whether deer OGN (dOGN) could effectively promote bone regeneration. We successfully expressed dOGN using the E. coli pET30a system and evaluated its biological activity through cell proliferation and migration assays. At a concentration of 5 μg/mL, dOGN significantly promoted cell proliferation and migration. We then incorporated dOGN onto decellularized antler cancellous bone (DACB) scaffolds and assessed their osteogenic potential both in vitro and in vivo. The results indicated that dOGN loading enhanced cell proliferation, adhesion, and osteogenic activity. In vivo experiments confirmed that the dOGN-DACB scaffold significantly improved bone regeneration compared to DACB alone. This study demonstrates that dOGN-loaded DACB scaffolds hold great potential for clinical applications in treating critical-sized bone defects by mimicking the rapid regenerative properties of deer antlers. Full article

Given the intricate operating environment of steel truss bridges, data anomalies are frequently initiated by faults in the sensor monitoring system itself during the monitoring process. This paper utilizes a steel truss bridge as a case study in engineering, with a primary focus on the deflection of the main girder. The paper establishes an Attention Mechanism-based Bidirectional Long Short-Term Memory Neural Network (ATT-BiLSTM) model, with the objective of accurately repairing abnormal monitoring data. Firstly, correlation heat maps and Gray correlation are employed to detect anomalies in key measurement point data. Subsequently, the ATT-BiLSTM and Support Vector Machine (SVR) models are established to repair the anomalous monitoring data. Finally, various evaluation indexes, including Pearson’s correlation coefficient, mean squared error, and coefficient of determination, are utilized to validate the repairing accuracy of the ATT-BiLSTM model. The findings indicate that the repair efficacy of ATT-BiLSTM on anomalous data surpasses that of SVR. The repaired data exhibited a tendency to decrease in amplitude at the anomalous position, while maintaining the prominence of the data at abrupt deflection change points, thereby preserving the characteristics of the data. The repair rate of anomalous data attained 93.88%, and the mean square error of the actual complete data was only 0.0226, leading to substantial enhancement in the integrity and reliability of the data. Full article

With the acceleration of the pace of life, increased stress levels, and changes in lifestyle factors such as diet and exercise, the incidence of diseases such as cancer and immunodeficiency has been on the rise, which is closely associated with the impaired antioxidant capacity of the body. Polypeptides and polysaccharides derived from edible fungi demonstrate significant strong antioxidant activity and immunomodulatory effects. Auricularia auricula, the second most cultivated mushroom in China, is not only nutritionally rich but also offers considerable health benefits. In particular, its polysaccharides have been widely recognized for their immunomodulatory activities, while its abundant protein content holds great promise as a raw material for developing immunomodulatory peptides. To meet the demand for high-value utilization of Auricularia auricula resources, this study developed a key technology for the stepwise extraction of polypeptides (AAPP1) and polysaccharides (AAPS3) using a composite enzymatic hydrolysis process. Their antioxidant and immunomodulatory effects were assessed using cyclophosphamide (CTX)-induced immune-suppressed mice. The results showed that both AAPP1 and AAPS3 significantly reversed CTX-induced decreases in thymus and spleen indices (p < 0.05); upregulated serum levels of cytokines (e.g., IL-4, TNF-α) and immunoglobulins (e.g., IgA, IgG); enhanced the activities of hepatic antioxidant enzymes SOD and CAT (p < 0.05); and reduced the content of MDA, a marker of oxidative damage. Intestinal microbiota analysis revealed that these compounds restored CTX-induced reductions in microbial α-diversity, increased the abundance of beneficial bacteria (Paramuribaculum, Prevotella; p < 0.05), decreased the proportion of pro-inflammatory Duncaniella, and reshaped the balance of the Bacteroidota/Firmicutes phyla. This study represents the first instance of synergistic extraction of polypeptides and polysaccharides from Auricularia auricula using a single process. It demonstrates their immune-enhancing effects through multiple mechanisms, including “antioxidation-immune organ repair-intestinal microbiota regulation.” The findings offer a theoretical and technical foundation for the deep processing of Auricularia auricula and the development of functional foods. Full article

Human colorectal cancer (CRC) encompasses tumors affecting a segment of the large intestine (colon) and rectum. It is the third most commonly diagnosed malignancy and the second leading cause of cancer deaths worldwide. It is a multifactorial disease, whose carcinogenesis process involves genetic and epigenetic alterations in oncogenes and tumor suppressor genes, including genes related to DNA repair. The pathogenic mechanisms are described based on the pathways of chromosomal instability, microsatellite instability, and CpG island methylator phenotype. When detected early, CRC is potentially curable, and its treatment is based on the pathological characteristics of the tumor and factors related to the patient, as well as on drug efficacy and toxicity studies. Therefore, the aim of this study was to review the pathogenesis and molecular subtypes of CRC and to describe the main targets of disease-directed therapy used in patients refractory to current treatments. Full article

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article

DNA connects the domains of genetic regulation and environmental interactions and plays a crucial role in neural development and cognitive function. The complex roles of genetic and epigenetic processes in brain development, synaptic plasticity, and higher-order cognitive abilities were reviewed in this study. Neural progenitors are formed and differentiated according to genetic instructions, whereas epigenetic changes, such as DNA methylation, dynamically control gene expression in response to external stimuli. These processes shape behavior and cognitive resilience by influencing neural identity, synaptic efficiency, and adaptation. This review also examines how DNA damage and repair mechanisms affect the integrity of neurons, which are essential for memory and learning. It also emphasizes how genetic predispositions and environmental factors interact to determine a person’s susceptibility to neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. Developments in gene-editing technologies, such as CRISPR, and non-viral delivery techniques provide encouraging treatment avenues for neurodegenerative disorders. This review highlights the fundamental role of DNA in coordinating the intricate interactions between molecular and environmental factors that underlie brain function and diseases. Full article

The incorporation of nucleoside analogs into DNA by polymerases, followed by their removal through base excision repair (BER), represents a promising strategy for cancer chemotherapy. In this study, we investigated the incorporation and cytotoxic effects of several nucleoside analogs—some of which are epigenetic reprogramming intermediates—in the U87 glioblastoma cell line. We found that two analogs, 5-hydroxymethyl-2′-deoxyuridine (5HmdU) and trifluorothymidine (TFT), are both cytotoxic and are efficiently incorporated into genomic DNA. In contrast, the 5-carboxy analogs—5-carboxy-2′-deoxyuridine (5CadU) and 5-carboxycytidine (5CadC)—showed no cytotoxicity and were not incorporated into DNA. Interestingly, 5-hydroxymethyl-2′-deoxycytidine (5HmdC) was cytotoxic but was not directly incorporated into DNA. Instead, it was deaminated into 5HmdU, which was then incorporated and likely responsible for the observed toxicity. 5HmdU is actively removed from DNA through the BER pathways. In contrast, TFT remains stably incorporated and is neither excised by BER nor does it hydrolyze into 5CadU—a known substrate for the DNA glycosylase SMUG1. We also found that N⁶-benzyladenosine (BzAdo), an inhibitor of the enzyme 2′-deoxynucleoside 5′-phosphate N-hydrolase (DNPH1), enhances the cytotoxicity of 5HmdU. However, the thymidine phosphorylase inhibitor tipiracil hydrochloride (TPI) does not increase the cytotoxic effect of TFT in U87 cells. Together, these findings highlight 5HmdU and TFT as promising chemotherapeutic agents for glioblastoma, each with distinct mechanisms of action and cellular processing. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article