Search Results (8,354)

Objective: This study aimed to experimentally validate the hepatoprotective efficacy of Sheshang Jiedu Decoction (SSJDD) against Deinagkistrodon acutus (D. acutus) venom-induced acute liver injury (ALI) and systematically elucidate its multicomponent, multitarget mechanisms using an integrated multi−omics strategy. Methods: SSJDD constituents and serum-absorbed metabolites were profiled using UPLC-Q-Exactive HFX MS, and potential targets were predicted via network pharmacology. An in vivo model was established by intraperitoneally injecting Kunming mice with D. acutus venom, followed by a 7-day oral SSJDD intervention. The therapeutic efficacy was assessed by histopathological examination, serological analysis, and detection of oxidative stress markers in liver tissues. Label-free quantitative proteomics was performed on murine livers to map dynamic protein alterations and signaling cascades. Results: Integrated metabolomic and network analyses identified 15 primary active serum metabolites converging on core regulatory targets, including TP53, AKT1, and CASP3. In vivo, SSJDD dose-dependently ameliorated venom-induced lobular necrosis, suppressed elevated transaminases, and restored redox homeostasis without intrinsic hepatotoxicity. Quantitative proteomics revealed that venom triggered profound acute oxidative stress and coagulopathies, progressing to chronic metabolic disruption. SSJDD intervention substantially attenuated these proteomic alterations—reducing differentially expressed proteins by 84%—steering the hepatic microenvironment toward baseline homeostasis. Enrichment analyses demonstrated that these effects were primarily driven by modulating the coagulation-inflammation axis and the PI3K−Akt signaling pathway. Conclusions: SSJDD provides robust protection against D. acutus venom-induced ALI. Its active metabolites synergistically orchestrate hepatic repair and restore microenvironmental stability, primarily by targeting the PI3K−Akt pathway and regulating the coagulation-inflammation axis. Full article

Aging and deterioration of urban underground drainage pipelines frequently trigger road collapses, urban waterlogging and groundwater contamination, posing critical challenges to the operation, maintenance and disaster prevention of urban underground infrastructure. Conventional rehabilitation solutions, including cement-based linings and traditional polymer liners, suffer from inherent limitations such as reduced effective flow cross-sections caused by excessive lining thickness, unsatisfactory corrosion resistance and durability, and high construction disturbance. In this study, a modified polyurea (MPU) material was applied to the trenchless rehabilitation of drainage pipelines via spray-applied pipe lining technology. The mechanical properties and interfacial bonding performance of MPU were systematically characterized at the material scale; full-scale external pressure tests were conducted to investigate the effects of 3–8 mm thick MPU linings on the bearing capacity and failure characteristics of structurally damaged concrete pipes; and the anti-seepage repair performance for local perforation defects was evaluated through void-crossing testing. The results demonstrate that MPU lining can meet the engineering performance requirements for pipeline rehabilitation when applied with matched interfacial primer following standard construction procedures. Even the baseline bond strength tested without primer remains sufficient to ensure stable cooperative load bearing between the lining and the host concrete pipe. The 3–8 mm thick linings increase the cracking load of damaged pipes by 61.7–145.7% and the ultimate load by up to 162.2%, while transforming the failure mode from brittle fracture to ductile failure. For local perforation repair, the 3 mm thick MPU lining achieves a critical hydrostatic failure pressure of 1.23 MPa, maintaining favorable structural integrity and interfacial bonding stability under the test conditions. With a well-balanced combination of thin lining thickness, rapid curing and high structural strengthening efficiency, as well as favorable inherent corrosion resistance, the MPU lining provides novel material alternatives and fundamental experimental evidence for the green trenchless rehabilitation of aged underground pipelines and offers technical support for the safe operation and maintenance of urban underground infrastructure. Full article

Osteopontin (OPN), encoded by the SPP1/Spp1 gene, is increasingly recognized as an extracellular matrix-associated immunoregulatory molecule in the central nervous system (CNS). In CNS-related contexts, OPN does not act as a uniformly protective or detrimental factor. Instead, its effects depend on the producing cell type, molecular form, receptor axis, disease stage, and lesion compartment. Accumulating evidence indicates that OPN may participate in reparative processes, including tissue preservation, debris clearance, vascular remodeling, and support of myelin-related repair, while sustained or ectopic OPN activity may contribute to synaptic injury, persistent glial reactivity, remyelination failure, and immunosuppressive tumor progression. In this review, we summarize the molecular basis of SPP1/Spp1 expression and OPN protein signaling, with emphasis on isoforms, proteolytic processing, receptor usage, and secreted versus intracellular OPN. We then discuss its roles in CNS development, chronic neurological diseases, acute CNS injury, and neuro-oncology, and highlight the need to distinguish biomarker associations, omics-based candidate pathways, and functionally validated mechanisms when considering OPN-related diagnostic or therapeutic strategies. Full article

Carbon nanotube (CNT) films prepared via floating catalyst chemical vapor deposition generally suffer from residual iron impurities, structural defects, and weak inter-tube interfaces, which severely limit their mechanical performance. Here, we propose a post-treatment approach, which is dominated by Joule heating, to substantially improve the mechanical properties of CNT films. Acid washing after Joule heating effectively removes iron catalyst and amorphous carbon, increasing the specific strength from 0.64 N/tex to 2.96 N/tex. Pre-stretching induces alignment of the CNTs along the stretching direction, further raising the specific strength to 5.57 N/tex. Subsequent Joule heating not only raises graphitization degree and repairs lattice defects but also transforms the weak van der Waals contacts between tubes into continuous carbon networks, leading to network densification and locking of the aligned structure. The final specific strength reaches 7.04 N/tex and true tensile strength 8.05 GPa, surpassing previous representative carbon materials. The purification mechanism of Joule heating depends on the initial iron content of the film: for high-iron films, iron melts, migrates and forms Fe/Fe₃C@C core–shell particles, which can be converted into hollow carbon shells via acid etching; for low-iron films, iron is removed via atomic diffusion and evaporation. This work provides a fast, controllable and synergistic technical route for the preparation of high-performance CNT macrostructures. Full article

Background: The Codubix^® ŻEBRA and Codubix^® S ŻEBRA prostheses (by Tricomed SA), made of a biocompatible polypropylene–polyester braid, were developed as tools for the treatment of bone defects resulting from cancer surgery or mechanical injuries. Methods: The retrospective analysis investigation presents the efficacy and safety of rib bone prostheses made of knitted polyester–polypropylene fabric used to fill defects in the ribs and sternum. Data were collected from 113 patients (68 males, 45 females) undergoing surgery at three clinical centres. Prosthesis implantation was performed to bridge bone defects in the ribs and/or sternum. The analysis included preoperative and intraoperative data, two follow-up visits and a final interview with the patients. All prostheses were implanted using two techniques for filling defects in the chest wall: the ‘hammock’ (suspension) fixation method in 87 patients, and the ‘rigid’ fixation method in 26 patients. Results: The main cause of defects was cancer surgery (95.6%) performed in cases of sarcomas, squamous cell carcinomas, and desmoid tumours. Other causes (e.g., congenital defects and mechanical trauma) were less common. The ‘rigid’ fixation method extended the surgery time by approximately 16 min compared to the suspension method. Differences were also noted in the recovery period—an average of 56 days for the ‘hammock’ method and 30 days for the ‘rigid’ method. During the second follow-up visit, the treatment outcome using these prostheses was rated as good in 90.3% of cases. The average duration of hospitalisation was 21 days, regardless of the implantation method. No prosthesis-related adverse events were reported. Complications were observed in 21 cases in the first days after surgery. The most common ones were sensory disturbances (5.3%), infections (3.5%), haematomas and blood effusions (2.7%). Conclusions: A retrospective study demonstrates that knitted prostheses are safe and effective solution for repairing extensive defects resulting from tumours, trauma or congenital malformations. The implants ensure high patient comfort and maintain normal physical functioning without interference. Full article

Docker simplifies application deployment, yet improperly written Dockerfiles often lead to suboptimal images with security and efficiency issues, termed “Docker smell”. Existing approaches for the identification and repair of Docker smells predominantly rely on expert-defined static rules, which exhibit notable limitations when addressing structurally complex or infrequent smells. This paper proposes a novel Detect–Guide–Repair (DGR) framework, which integrates rule-based smell detection with a context-aware repair mechanism driven by large language models (LLMs), enabling a more flexible and intelligent automated repair process. We systematically evaluated DGR on 417 real Dockerfiles from prominent GitHub projects. Experimental results show that DGR reduces the number of smells to 44.68% of the original while maintaining a build success rate of 89.20%, demonstrating significant improvements in both repair effectiveness and usability. Furthermore, we present three practical enhancement pathways: (1) a hybrid strategy combining rules and DGR to improve repair effectiveness further; (2) an automated error-correction mechanism to restore buildability; and (3) task-specific model fine-tuning to enable efficient deployment of smaller models. Collectively, these approaches provide a promising empirical foundation for automated Docker smell repair. Full article

Acellular bone matrix, with its natural extracellular matrix components, has been considered a potential alternative platform for bone grafting. Our study focused on fabricating acellular bovine bone matrix (ABBM) and evaluating its in vitro characteristics and in vivo effect on bone repair. The bovine cancellous bone was subjected to ABBM preparation, which included partial demineralization and decellularization processing. The effects of the ABBM on human bone marrow-derived stem cells (hBMSCs) were evaluated, including viability, migration, attachment, and proliferation. A rabbit bone defect model was implanted with ABBM and histologically assessed for bone healing. The acellular properties were determined by the absence of nuclear material and the accepted minimum residual DNA content. An in vitro study indicated the ABBM’s positive effect on the migration of hBMSCs. ABBM was also demonstrated to support hBMSC attachment and proliferation. In vivo testing was performed in rabbits with a cranial bone defect, which showed complete bone healing after 8 weeks of grafting with ABBM. Overall, the fabricated ABBM demonstrated in vitro and in vivo biocompatibility and effective support for bone healing in vivo, and therefore represents a potential xenogeneic biomaterial for bone tissue repair. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune disease in which persistent synovitis drives interconnected cartilage degradation, bone erosion, and functional decline. Conventional synthetic, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) remain the foundation of RA management. Hydrogel-based local therapy should therefore be positioned as an adjunct for selected joints rather than as a substitute for systemic disease control. Hydrogels provide a versatile local materials platform because their injectability, tunable crosslinking, tissue retention, stimulus-responsive release, interfacial adhesion, lubrication, and extracellular matrix-mimetic properties can be tailored to the inflamed joint microenvironment. This narrative, evidence-graded review evaluates local hydrogel therapies using two complementary frameworks: the synovium–cartilage–bone pathological axis and a materials-science chain linking composition and crosslinking to structure and properties, release and degradation, and tissue-level outcomes. Evidence is classified as direct RA evidence, transferable evidence from related disease or tissue-engineering models, or conceptual evidence from mechanistic and materials-science studies. Therapeutic outcomes are separately graded as local immunomodulation, structural protection, tissue repair, or functionally validated structural disease modification. Current preclinical evidence supports the use of hydrogels for sustained local delivery and synovial immunomodulation, while selected systems demonstrate cartilage-protective or anti-erosive effects. However, durable multitissue restoration accompanied by functional recovery remains insufficiently demonstrated. Future studies should prioritize RA-relevant long-term models, in vivo intra-articular pharmacokinetics and biodistribution, standardized structural and functional endpoints, repeat-dose safety, and evaluation as add-on therapy to systemic DMARDs. Full article

This article discusses the relevant problem of ensuring transport connectivity under the conditions of temporal restrictions of the road network, which arise during repair, communal and emergency operations. It is established that the existing organizational and intellectual methods of traffic management do not eliminate physical decrease in road capacity, while construction of stationary structures with different levels is limited by high costs and long terms of implementation. The above substantiates the need for the development of mobile overpasses as adaptive engineering solutions ensuring continuity of the traffic flows. The purpose of the research is to develop a scientifically substantiated theoretical and experimental methodology for designing a mobile overpass as an integrated system “structure-moving load”, taking into account its dynamic behavior. The paper proposes an integrated approach based on the use of physical similarity theory and dimensionless analysis. A differential equation of dynamic bending of a beam on an elastic foundation is formulated taking into account inertia, damping, base reaction and the effect of a moving mass, and then its nondimensionalization is performed to obtain a similarity criteria system. The scientific novelty of the research consists in developing a system of dimensionless criteria to describe the relationship between the structural, dynamic and operational parameters of a mobile overpass, as well as in the formation of a criterion base for large-scale modeling and transfer of the results to full-scale structures. The proposed methodology describes the mobile overpass as an integrated transport-engineering system accounting for the coupled interaction between the deformable structure, moving traffic load, elastic foundation, and damping effects. Experimental verification was performed on a specially designed stand in the scale 1:4. The results obtained showed the quasi-static nature of the structure performance with moderate damping and rigid base. It is established that the distribution of engineering stresses along the span length has a regular character and retains its shape when the load level changes, which confirms fulfillment of similarity conditions. Regression analysis revealed a close to linear dependence of stresses on the load mass with a high degree of confidence $(R^2\approx 0.995)$. The practical significance of the research consists in creating an engineering method for express design of mobile overpasses, which allows for assessing their stress–strain state, stability and serviceability without expensive full-scale tests. The proposed approach can be used in designing temporary transportation structures under the conditions of urban area, and in operation in areas of road operations and emergency situations. Full article

(-)-Epigallocatechin gallate (EGCG) possesses potent bioactivities but its applications in functional cosmetics is severely limited by its poor water solubility and chemical instability. To overcome these challenges, this study engineered a recombinant levansucrase from Vibrio natriegens to catalyze the transfructosylation of EGCG. The conversion rate of EGCG to fructoside reached 65.59%. The purified product was unequivocally identified as EGCG-1F, with a fructosyl group linked to the 3′-hydroxyl group. Compared to pristine EGCG, EGCG-1F exhibited remarkably enhanced water solubility (96.6-fold that of EGCG) and aqueous stability under acidic and thermal conditions. Biological evaluation revealed that EGCG-1F significantly enhanced HaCaT cell migration, upregulated the expression of basement membrane-associated collagens in ultraviolet B-damaged HaCaT cells, and modulated ultraviolet A-induced senescence in human dermal fibroblasts by type I collagen, type III collagen and matrix metalloproteinase-1 balance. This study demonstrates that enzymatic fructosylation is an effective approach to generate a stable and safe EGCG derivative with potential applications in skin barrier repair and anti-aging functional cosmetics. Full article

Lipopolysaccharide (LPS) impairs the function of ovine follicular granulosa cells (GCs), representing a primary cause of follicular atresia. Selenium (Se), an essential trace element, possesses anti-inflammatory and cytoprotective properties; however, its effects on GC ultrastructure remain largely unknown. In this study, primary ovine GCs were exposed to LPS (10 µg/mL) and treated with sodium selenite (25 nM). Transmission electron microscopy (TEM), JC-1 staining, enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) detection, flow cytometry, and quantitative real-time PCR (qRT-PCR) were employed to evaluate cellular ultrastructure, mitochondrial membrane potential (ΔΨm), and downstream physiological processes. LPS induced severe mitochondrial pyknosis, cristae loss, and reduced ΔΨm, accompanied by inflammation, oxidative stress, apoptosis, and impaired steroidogenesis. Se intervention markedly ameliorated these ultrastructural injuries, preserving mitochondrial morphology and ΔΨm. Functionally, Se suppressed the release of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β); enhanced the activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) while attenuating ROS accumulation; inhibited apoptosis by upregulating BCL-2 and downregulating BAX and CASPASE-3; and restored E₂ and P₄ secretion via upregulation of STAR and NR5A1. This study provides direct morphological evidence that Se protects ovine GCs from LPS-induced damage by repairing mitochondrial ultrastructure. This structural restoration is central to its integrated anti-inflammatory, antioxidant, anti-apoptotic, and steroidogenic effects. These in vitro findings suggest that Se may serve as a promising nutritional strategy for mitigating inflammation-driven follicular atresia, pending further in vivo validation. Full article

Background: Thoracic endovascular aortic repair (TEVAR) is an established minimally invasive approach for selected aortic arch pathologies; however, it is associated with risks including stroke and spinal cord ischemia. Revascularization techniques, such as in situ fenestration (ISF), play a critical role in preserving supra-aortic branch perfusion and reducing neurological complications. Methods: This prospective, single-center observational cohort study enrolled 74 consecutive patients undergoing TEVAR with ISF between October 2017 and September 2023. Data collected included demographics, lesion morphology, procedural details, and clinical outcomes. The primary endpoint was procedural technical success; secondary endpoints included 30-day complications, reintervention rate, and all-cause mortality. Results: Technical success was achieved in 100% of cases (74/74; 95% CI: 95.2–100.0%), defined as successful fenestration creation, patent bridging stent graft without kinking or embolization, absence of Type I or III endoleak on completion angiography, and restored antegrade branch flow. Physician-modified fenestration was combined with ISF-thoracic endovascular aortic repair (TEVAR) in 28.4% (21/74) of cases. At 30-day follow-up, 30-day clinical success (freedom from mortality, reintervention, and procedure-related complications) was achieved in 87.8% (65/74) of patients. No mortality was recorded at 30 days. Treatment-related complications included subclavian branch thrombosis (n = 1, 1.4%), transient ischemic attack (n = 1, 1.4%), and endoleaks (n = 7, 9.5%; including Type Ia, Type II, and Type III), with reintervention required in 6 patients (8.1%) during the follow-up period. Beyond 30 days, three late deaths were documented: one aorta-related death (aneurysm rupture at 9 months), one neurological death (ischemic stroke at 13 months), and one cardiovascular death (myocardial infarction at 60 days post-procedure), yielding a late all-cause mortality rate of 4.1% (3/74). Conclusions: ISF-TEVAR demonstrated a high procedural technical success rate and a low 30-day complication and mortality profile in this single-center prospective series of selected patients treated at an experienced center. These early and mid-term results are encouraging; however, given the single-center, non-comparative design and limited standardized follow-up, broader conclusions regarding durability and comparative effectiveness remain premature. Larger multicenter prospective studies with standardized long-term imaging follow-up are warranted. Full article

The performance of haul trucks in open-pit mining is strongly affected by haul-road geometry, surface condition, rolling resistance, and operational traffic regimes. However, existing studies often consider road-surface mapping, vehicle dynamic response, and onboard telemetry as separate information streams, which limits the reproducible assessment of how road-related factors are associated with VIMS-derived fuel-use proxy burden, mechanical dynamic response, and transport-cycle instability. This study proposes a field-based, segment-level multisensor framework that integrates unmanned aerial vehicle/light detection and ranging (UAV/LiDAR) road-surface reconstruction, global positioning system/inertial measurement unit (GPS/IMU) trajectory and vibration data, and Caterpillar Vial Information Management System (VIMS) telemetry into a unified spatiotemporal analytical dataset. The methodological contribution consists in the synchronization of heterogeneous data sources at the road-segment level, the calculation of interpretable road-condition and vehicle-response indicators, and the statistical assessment of road-related effects while explicitly accounting for confounding factors such as longitudinal grade, payload state, speed regime, truck class, and operational variability. Unlike studies that use LiDAR mapping, vibration monitoring, or onboard telemetry as separate diagnostic channels, the proposed approach introduces a segment-level analytical framework in which road morphology, truck response, and operational penalties are aligned within the same spatial unit, interpreted under confounder-aware conditions, and verified through repeat-pass reproducibility and robustness checks. The framework was tested on haul roads around the Ekibastuz open-pit coal mine. The field analysis identifies road segments where degraded surface morphology, increased waviness, unfavorable longitudinal profile, and higher rolling resistance coincide with increased mechanical dynamic response, VIMS-derived fuel-use proxy burden, braking instability, and travel-time variability. The results are interpreted as controlled field-supported associations rather than as isolated causal effects. The proposed maintenance ranking should therefore be regarded as a decision-support output, while the operational effectiveness of specific repair interventions requires future before–after validation. Full article

A biphasic osteochondral construct has been developed to repair focal chondral and osteochondral lesions. This study aimed to evaluate the safety and preliminary clinical feasibility of using the biphasic osteochondral construct in treating patients having mild-to-moderate-stage knee osteoarthritis. This single-center, prospective, open-label, single-arm feasibility trial compared 2-year knee functional outcome (KOOS and IKDC scores), pain VAS score, and radiological assessment of repaired cartilage (MOCART score) after treatment versus the corresponding preoperative scores. All enrolled patients had a clinical history of primary knee osteoarthritis (OA), Kellgren Lawrence grade 13 without valgus or varus deformity greater than 5 degrees. Five men and three women completed the two-year follow-up, with a mean age of 53.9 ± 9.3 years (range 34–63 years). The average lesion size was 4.5 ± 2.9 cm² (range 2–9 cm²). The patients received one to three biphasic osteochondral constructs. No major adverse effects or complications were reported postoperatively. The mean KOOS subscale values, VAS scores, and IKDC scores were all improved significantly at six months post operation and were maintained for two years. The changes in MOCART scores of the regenerated cartilage were parallel to the changes observed in KOOS values. Our findings provide preliminary evidence of the safety and clinical feasibility of using biphasic osteochondral constructs to treat focal chondral and osteochondral lesions in patients with mild- or moderate-stage osteoarthritis, and support the rationale for larger controlled trials. Full article

Mitochondria-targeting metal complexes (MTMCs) are a mechanistically distinct class of metallopharmaceuticals. Unlike first-generation platinum drugs that form nuclear DNA adducts, MTMCs exploit organelle-specific vulnerabilities such as hyperpolarised mitochondrial membrane potential (ΔΨm), elevated reactive oxygen species (ROS), limited mitochondrial DNA (mtDNA) repair capacity, and redox-dependent enzymes such as thioredoxin reductase (TrxR). We systematically searched PubMed, Web of Science, Scopus, and Google Scholar databases for studies published between 2016 and 2026, applying predefined inclusion criteria that included subcellular localization evidence and functional bioenergetic endpoints. The search identified 147 studies covering Pt(II/IV), Ru(II/III), Au(I/III), Ir(III), Os(II), Re(I), and V(IV/V) complexes and metal–organic framework nanoplatforms. Mechanistic evidence converges on four intramitochondrial target categories: inhibition of ETC (Electron Transport Chain) Complexes I/III with consequent ATP depletion; ROS overproduction, coupled with glutathione and TrxR depletion; outer mitochondrial membrane permeabilization and intrinsic apoptotic cascade activation; and mtDNA damage within a compartment limited to base excision repair. Multi-modal cell death—the co-occurrence of apoptosis, ferroptosis, necroptosis, and autophagic cell death—was a recurrent finding across the reviewed studies. This review thoroughly surveys the latest trends in MTMC drug design (metals, ligand structures, and mechanisms of action) and summarises analytical techniques for speciation, pharmacokinetics, safe monitoring, and resistance, while critically analysing translational barriers and clinical failures. To address the field’s inconsistent terminology, we introduce an explicit localization evidence hierarchy that distinguishes mitochondria-targeting complexes (through quantitative ICP-MS fractionation or co-localization with defined Pearson/Manders coefficients) from simply mitochondria-localising or mitochondria-perturbing agents, and we apply it throughout. We also point out that the idea of selectivity being purely driven by membrane voltage (ΔΨm) and thermodynamics is constrained by membrane and protein binding, as well as the transmembrane pH gradient, kinetic limitations, and demonstrated heterogeneity of cancer-cell membrane potential, and, as such, the functional mitochondrial effects must not be equated with mitochondrial accumulation. Since elemental quantification cannot distinguish intact complex from protein adducts and decomposition products, speciation-aware pharmacokinetics emerges as a prerequisite for a credible exposure–response interpretation. The translational progress will depend less on new chemotypes than on this analytical and pharmacokinetic rigour, together with organelle-level safety monitoring and biomarker-guided patient selection. Full article