Given the persistence of the SARS-CoV-2 virus, it is important to understand the proteome associated with breakthrough infections among COVID-19 vaccinated individuals. We conducted a nested case-control study within the frontline worker HEROES-RECOVER cohorts to specify a study population of SARS-CoV-2 infection-naïve participants who had a third dose of COVID-19 origin strain WA-1 monovalent mRNA vaccine from August 2021 to January 2022. We compared serum proteomic profiles for those who subsequently experienced Omicron breakthrough infections with those of matched controls without infections. Our study leveraged proteomics data generated from the SomaScan Platform and adopted a robust feature selection method, elastic net regularized conditional logistic regression with bootstrapping, to identify key proteins. Enrichment analyses were performed to investigate biological pathways. We identified 28 significant proteins out of over 7,000 candidate proteins. Key findings included downregulated chemokines (CXCL2, CXCL3, CCL19, CCL23) and elevated cytokine IL-7 levels in breakthrough cases, with pathway analysis revealing enrichment in chemokine signaling and cytokine-cytokine interaction pathways. Other key proteins, such as LGALS1, HAVCR2, and SELE were upregulated in breakthrough cases. These results reveal potential immune response mechanisms in breakthrough infections, characterized by viral immune evasion and compensatory T-cell regeneration. The identified biomarkers may provide valuable insights for future predictive profiles and therapeutic strategies.
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Crystalline silicon solar cells have long dominated the global photovoltaic market due to their mature manufacturing processes, excellent stability, and abundant raw material reserves, accounting for over 90% of the total PV market share. However, single-junction c-Si solar cells are approaching the Shockley-Queisser (SQ) efficiency limit of ~29.4%, creating an urgent need for next-generation PV technologies to achieve higher power conversion efficiency (PCE). Monolithic perovskite/silicon tandem solar cells (PSTSCs) stand as the most commercially promising technology to surpass the single-junction efficiency limit. Since their first demonstration in 2015, PSTSCs have experienced rapid technological advancement, with the certified PCE reaching 35.0% in 2026. This review posits that their rapid efficiency ascent is not serendipitous but driven by synergistic innovations across critical subsystems. We systematically deconstruct these efficiency drivers, encompassing top-cell materials, bottom-cell architecture, and optical management. We conclude by outlining future research frontiers essential for transforming this lab-champion technology into a mainstream energy solution.
Under the background of the rapid development of artificial intelligence (AI) technology, the postgraduate training of acupuncture professional master's degree is faced with the dual opportunities for updating educational concepts and changing practical models. This paper focuses on the deep integration of AI technology and the postgraduate cultivation of acupuncture professional master's degree, and systematically discusses the educational innovation path in the era of digital intelligence. At the level of curriculum system, taking traditional culture as the foundation and syndrome differentiation and treatment thinking as the main line, an intelligent teaching platform integrating classic research and interdisciplinary knowledge is constructed to consolidate students' foundation of traditional Chinese medicine (TCM) thinking. At the level of cross-professional clinical ability, relying on big data platform and visualization technology, students can accurately grasp the dominant diseases of acupuncture and the timing of intervention in cross-professional rotation. At the level of clinical operation, with the help of intelligent positioning and virtual training system, the accuracy and safety of operation are improved, and the closed-loop diagnosis and treatment thinking training system is constructed. Through the systematic review of the above innovative models, the aim is to provide an intelligent solution with both traditional heritage and modern vision for the postgraduate training of acupuncture professional master's degree, and to help the sustainable development of high-level acupuncture talents. 在人工智能（AI）技术快速发展的背景下，针灸专业硕士（简称专硕）研究生培养面临教育理念更新与实践模式变革的双重机遇。本文聚焦AI技术与针灸专硕培养的深度融合，系统探讨了数智化时代的教育创新路径：在课程体系层面，以传统文化为根基、以辨证论治思维为主线，构建融合经典研习与跨学科知识整合的智能化教学平台，夯实学生的中医思维根基；在跨专业临床能力层面，依托大数据平台与可视化技术，帮助学生在跨专业轮转中精准把握针灸优势病种与介入时机；在临床操作层面，借助智能定位与虚拟训练系统，提升操作精准度与安全性，构建闭环诊疗思维训练体系。通过对上述创新模式的系统梳理，旨在为针灸专硕培养提供兼具传统底蕴与现代视野的智能化解决方案，助力高层次针灸人才可持续发展。.
India faces a growing obesity epidemic within the context of persistent undernutrition, creating a dual burden with major cardiometabolic consequences. This population is particularly vulnerable to metabolic disease because of the "Asian Indian phenotype," characterized by increased visceral adiposity and higher metabolic risk at lower body mass index thresholds. To review current evidence on the relationship between sleep health, lipid dysregulation, and metabolic dysfunction in the obesity epidemic in India, with emphasis on epidemiology, biologic mechanisms, and implementation relevance. PubMed-indexed literature published from 2015 through February 2026 was reviewed, prioritizing India-specific epidemiologic studies, national reports, and policy-relevant publications. International mechanistic studies were included when relevant to biologic plausibility and translational understanding. Obesity in India shows substantial regional and urban-rural variation, while dyslipidemia remains highly prevalent and inadequately controlled, particularly in people with type 2 diabetes mellitus. Sleep disturbances, including short sleep duration, circadian misalignment, shift work, and obstructive sleep apnea, are increasingly recognized as contributors to metabolic dysfunction. Mechanistic evidence suggests that sleep disruption may impair metabolic health through clock gene dysregulation, bile acid-lipid desynchronization, microbiome-derived short-chain fatty acid signaling, inflammation, and neuroendocrine stress pathways. However, India-specific lipidomic, longitudinal, and sleep-focused interventional data remain limited. Sleep health disturbances appear to be important and potentially modifiable contributors to metabolic dysfunction in India. Improving access to obstructive sleep apnea diagnosis and continuous positive airway pressure therapy, strengthening dyslipidemia management, and integrating sleep health into broader noncommunicable disease frameworks may improve prevention and care in high-risk Indian populations.
Drug hypersensitivity is often managed by drug desensitization, yet published data remain scarce in children. This study evaluated the safety and efficacy of rapid desensitization of chemotherapeutic agents, monoclonal antibodies, and disease-modifying anti-rheumatic drugs (DMARDs). To evaluate the safety and efficacy of rapid desensitization for managing drug hypersensitivity in pediatric patients. This is a multicenter retrospective analysis of rapid drug desensitizations performed at Boston Children's Hospital, Hong Kong Children's Hospital and Queen Mary Hospital from January 2013 to December 2022. Demographic information, hypersensitivity reactions (HSRs) to drugs, premedications, desensitization protocols and modifications, and breakthrough reactions during desensitization were extracted from the medical charts. The associations between these factors and occurrences of HSRs were assessed. Twenty-three patients (median age 9.5 years, 57% male) underwent 26 rapid drug desensitizations. The underlying diagnoses included solid tumors (65%, n=15), leukemia (13%, n=3), and other medical conditions (22%, n=5). The drugs desensitized included chemotherapeutics, monoclonal antibodies, and disease-modifying anti-rheumatic drugs (DMARDs). Most desensitizations (96%, n=25) involved premedication with 1-5 drugs, such as antihistamines, steroids, leukotriene inhibitors, and non-steroidal anti-inflammatory drugs. Six desensitizations (23%) resulted in mild breakthrough reactions. One patient had clinical anaphylaxis. Most desensitizations were successful and allowed the use of the desensitized drug. A greater number of premedications was associated with the absence of breakthrough reactions (p=0.047). Rapid drug desensitization was safe and effective in managing pediatric patients with hypersensitivity to chemotherapeutic agents, monoclonal antibodies, and DMARDs. Premedication is useful in preventing breakthrough reactions.
First-in-class (FIC) oncology drugs-defined by their novel mechanisms of action or targeting of previously unaddressed molecular targets-have emerged as a leading force in cancer therapeutic innovation. In this Review, we delineate the global landscape of FIC oncology drug approvals between 2009 and 2024 and analyze the evolving characteristics of both approved FIC therapies and potential FIC (PFIC) candidates in clinical development. To clarify the underlying dynamics of this evolution, we construct an analytic framework encompassing four distinct archetypes of FIC development: new targets, new mutation subtypes, new modalities, and new multi-target strategies. This typology enables a systematic dissection of divergent translational trajectories and bottlenecks across the evolving FIC landscape. While most approved FIC drugs are driven by target novelty, PFIC candidates increasingly capitalize on technological breakthroughs, particularly in modalities such as cell and gene therapies, antibody-drug conjugates, proteolysis-targeting chimeras, cancer vaccines and bispecific antibodies. These advances not only expand the boundaries of druggability but also redefine how therapeutic interventions are conceived, delivered and translated into patient outcomes. Despite this momentum, critical bottlenecks-including the identification and validation of tractable targets, high clinical attrition rates, and persistent disparities in global access-continue to limit the real-world impact of oncology innovation. Looking forward, the convergence of artificial intelligence, next-generation modalities, and translational collaboration may serve as powerful engines for translating scientific breakthroughs into widely accessible therapies and for driving sustainable, mechanism-based innovations in oncology.
Stimuli-responsive nanostructures are a revolutionary breakthrough in the controlled delivery of drugs, allowing for their precise spatiotemporal control. These intelligent materials are designed to respond to internal stimuli (such as pH, redox gradients, enzymatic activity) or external cues (such as temperature, light, magnetic fields), thus offering greater flexibility and functionality in biomedical applications. Recent achievements have been aimed at the development of multi-stimuli-responsive systems, which utilize a combination of several stimuli to achieve sophisticated control, greater stability, and greater therapeutic accuracy in complex biological media. At the same time, the incorporation of artificial intelligence (AI) into the design and optimization of these nanostructures has brought about real, data-driven breakthroughs. Thus, supervised machine learning algorithms have been employed to predict the drug-loading efficiency and gene-delivery ability of lipid and polymeric nanoparticles based solely on their compositional characteristics, thus facilitating the rational selection of optimal formulations without the need for extensive experimental screening. Moreover, AI-based modeling tools have been shown to possess the capability to predict complete drug release profiles in response to varying pH or redox environments, thus enabling the pre-optimization of release kinetics tailored to specific pathological microenvironments. With the integration of patient-specific biological information such as genomic signatures and biomarker profiles, AI-assisted approaches also allow for the personalization of carrier composition and sensitivity to stimuli. This review offers a thorough examination of the latest developments in stimuli-responsive nanostructures and their integration with AI. This complementary combination is revolutionizing the way carriers are designed, shifting from trial-and-error methods to predictive and personalized drug delivery systems, thus propelling the development of next-generation precision nanomedicine.
Achieving selective SO2 capture at low pressures is pivotal and challenging for possible flue gas desulfurization and air pollution control. In this study, we synthesized a series of ionic covalent organic frameworks (iCOFs) with β-ketoenamine linkages and sulfonic acid groups using a solvothermal method. TpPa-SO3H and TpBD-(SO3H)2 show a higher SO2 uptake of 4.46 and 5.24 mmol g-1 than TpPa-1 (4.24 mmol g-1) at 1 bar and 298 K, respectively, due to the combination of the good SO2 affinity of the polar sulfonic acid groups, higher pore volumes, and the good stability of β-ketoenamine COFs. TpBD-(SO3H)2 captured 2.83 mmol g-1 of SO2 at 0.1 bar and 298 K, which is 1.6 times higher than TpPa-1 (1.82 mmol g-1) under the same conditions. Notably, the IAST SO2/CO2 selectivity of TpBD-(SO3H)2 and TpPa-1 are 61 and 51, respectively, reflecting the impact of the incorporated SO3H groups' higher affinity toward SO2. Notably, the multicomponent gas mixture breakthrough experiments confirm that TpBD-(SO3H)2 displays longer breakthrough time than TpPa-1 (987 vs. 311 min g-1). These β-ketoenamine iCOFs demonstrate nearly complete retention of crystallinity and porosity after exposure to dry or humid SO2. This work demonstrates that iCOFs are promising adsorbents for SO2 capture due to their high capacity, stability, and affinity for SO2 at low pressure.
Concerns regarding vaccine-associated autoimmunity and activation of cancer-related pathways persist, yet longitudinal proteome-wide evaluations of heterologous COVID-19 vaccination regimens remain limited. Here, we assessed the stability of the human 'autoantibodyome' in 30 healthy adults receiving a heterologous CoronaVac-BNT162b2 vaccination regimen (inactivated-virus priming followed by an mRNA booster). Paired serum samples collected pre-vaccination and 26 weeks post-booster were analyzed using the i-Ome™ Discovery protein microarray, which measures IgG reactivity against 1,610 native human antigens associated with autoimmune and oncogenic pathways. After quality-control filtering, 534 high-confidence autoantigens were retained for downstream analysis. Across this panel, autoantibody profiles remained highly stable over time. Linear modeling with false discovery rate correction (FDR > 0.05) and receiver operating characteristic analysis (AUC 0.59-0.67) identified no statistically significant changes in autoantibody reactivity. Principal component analysis demonstrated substantial overlap between pre-vaccination and 26-week post-booster samples, indicating that no combinatorial autoantibody signature distinguished the two timepoints. In stratified analyses, mild breakthrough SARS-CoV-2 infection did not promote aberrant autoantibody production. Within the scope of this high-resolution 1,610-antigen platform, these findings provide proteome-wide evidence that heterologous BNT162b2 boosting after CoronaVac priming is not associated with sustained induction of IgG autoantibodies linked to autoimmune or cancer-related pathways. These findings provide proteome-wide safety evidence supporting the immunological stability of the circulating autoantibody repertoire following mixed-platform COVID-19 vaccination in healthy adults.
Wound healing emerges from a tightly orchestrated bioelectric landscape shaped by ion gradients, membrane potentials, and redox dynamics physical cues that direct cell migration, immune activation, and epithelial organization long before biochemical gradients take form. Recent advances reveal that electrical signals constitute a master regulatory layer: Transient receptor potential (TRP)-channel mediated ion flux governs early wound polarity; endogenous transepithelial potential collapse triggers rapid electric fields that guide keratinocyte and fibroblast migration; and connexin-dependent gap-junction coupling coordinates tissue-level responses across multicellular sheets. Electroceutical strategies exploit these principles by recalibrating electrical and electrochemical environments rather than targeting single molecules. This shift enables simultaneous modulation of ion-channel gating, cytoskeletal dynamics, growth-factor signaling, and immunometabolic programs reshaping whole-tissue behavior in ways unattainable with classical pharmacology. Key breakthroughs demonstrate that controlled electrical stimulation can reprogram human macrophages toward reparative phenotypes, enhance keratinocyte electrotaxis even under diabetic conditions, accelerate fibroblast-driven matrix assembly, and amplify endothelial angiogenic responses. Microbial communities respond in the opposite direction. Biofilms, long considered antibiotic-impervious, depend on exquisitely tuned membrane potential, proton motive force, and redox stratification for cohesion and persistence. Low-intensity electrical cues disrupt this energetics, collapsing efflux pump function, silencing quorum systems, loosening EPS architecture, and destabilizing metabolic heterogeneity effects impossible to escape through single gene mutation. Overall, these discoveries frame electroceuticals as system-level disruptors of microbial order and restorers of host coordination. With the emergence of AI-enabled, closed-loop bioelectronic dressings capable of sensing and responding to wound physiology in real time, electricity is poised to become a foundational operating principle for next-generation regenerative and anti-infective therapy.
All-solid-state lithium batteries (ASSLBs) have garnered worldwide attention as promising next-generation energy storage technologies owing to their high energy densities and enhanced safety. However, their long cyclability remains unsatisfactory for practical application, primarily due to poor solid-solid interfacial contact. A high stack pressure is often required during operation, hampering their commercialization. This perspective presents a fundamental understanding of the roles of stack pressure in ASSLBs and analyzes the intrinsic challenges to achieve optimal battery performance under low-stack-pressure conditions. Recent advances for reducing high-stack-pressure demands are summarized from the point of views of solid electrolyte/ active electrode material design and interface engineering. Finally, the perspective layouts the key challenges and prospects for future breakthroughs to achieve low-stack-pressure ASSLBs. It is hoped that the material-centered solutions highlighted in this perspective will inspire meaningful progress in future advanced battery systems.
Cellular senescence, a complex multifactorial process, is involved in the pathophysiology of various age-related diseases, such as cardiovascular disease and neurodegenerative disorders. Traditional interventions targeting single mechanisms yield limited efficacy. As a core hallmark and driver of aging, immunosenescence provides a critical target for precision interventions. This systematic review examines the hallmarks of aging, including cellular damage, epigenetic abnormalities, and immunosenescence. It highlights immunotherapy strategies targeting senescent cells, including CAR-T/NK cell therapies, vaccines, and immune checkpoint blockade. These approaches have demonstrated significant efficacy in animal models by eliminating senescent cells and improving senescence phenotypes. Simultaneously, it analyzes current challenges such as insufficient target specificity, safety and cost concerns in cell therapies, and species differences. It also explores future directions including multi-target synergistic strategies, AI-assisted target screening, and the integration of precision medicine technologies. Immunotherapy offers a revolutionary paradigm for aging intervention, holding promise to extend healthy lifespan by regulating the immune system. However, further breakthroughs are needed for its clinical translation.
Selective extraction of uranium from seawater remains challenging due to its ultra-low concentration and the presence of competing ions. In this study, an engineered bacterial biosorbent (BDU09) was constructed by displaying the uranium-binding protein U09 on the outer membrane of Escherichia coli EcN 1917 via the Lpp-OmpA surface display system. To enhance mechanical stability and enable practical application, BDU09 cells were encapsulated within polyethylene glycol diacrylate (PEGDA), forming structurally stable microbial beads with high selectivity toward U(vi). Batch adsorption experiments demonstrated that both BDU09 and the corresponding microbial beads exhibited selective U(vi) uptake in the presence of competing ions, driven by specific coordination interactions between U(vi) and surface functional groups. The microbial beads maintained favorable selectivity and structural integrity in uranium-spiked simulated seawater as well as natural seawater. Continuous fixed-bed column experiments further confirmed effective U(vi) separation, with breakthrough behavior significantly influenced by initial concentration, bed height, and flow rate. The adsorption process was well described by the Yoon-Nelson model, and high-purity U(vi) recovery was achieved in simulated seawater. This work translates protein-level binding specificity into a mechanically robust and scalable biosorption platform, offering a promising strategy for uranium extraction from seawater.
Orthopedic infections, including osteomyelitis and prosthetic joint infection (PJI), are complicated clinical problems that urgently need to be paid attention to and solved. Clinically, antibacterial drug-loaded bone cement (ALBC) has been frequently used to treat localized orthopedic infections because of its strong local antimicrobial activity. While, ALBC faces the problem of poor therapeutic effect in clinical applications due to the development of bacterial resistance to antimicrobial drugs, as well as the limitations in the bone cement's mechanical properties and drug release properties. Numerous research efforts are currently underway to create new composite bone cement by combining the use of a wide range of antimicrobial drugs, optimizing the preparation process of bone cement, introducing new antimicrobial agents and innovative materials to overcome the shortcomings of the conventional ALBC, expanding its potential for clinical use. However, the majority of related studies are performed on the in vitro level, and additional in vivo experimental data are required to confirm their efficacy and safety. This review summarizes the development of ALBC, with a focus on the research progress and innovative breakthroughs in drug selections, drug release mechanisms, and clinical applications, which is expected to provide a reference for the in-depth investigation of multifunctional bone cement and multidisciplinary cross-collaboration, as well as to expand the potential of bone cement for clinical applications.
To determine midostaurin and posaconazole plasma concentrations and investigate adverse events (AEs) resembling drug-drug interactions (DDI) when both drugs were administered concomitantly during induction chemotherapy for acute myeloid leukemia (AML). Patients with FLT3-mutated AML who received midostaurin and posaconazole concomitantly between May 2019 and December 2022 were included and followed up to March 2023. Twice-weekly trough levels for midostaurin and posaconazole were measured with validated liquid chromatography-tandem mass spectrometry methods. Potential DDIs were independently reviewed by two physicians and attributed using the Drug Interaction Probability Scale (DIPS). Population pharmacokinetics analysis was done via nonlinear mixed-effect modeling. In 29 patients, concentrations ranged from 0.6 to 24.5 mg/L for midostaurin and from <30 to 2,572 µg/L for posaconazole. A total of 375 AEs in 66 midostaurin cycles, with 280 AEs classified as grade ≥3, were recorded. Probable DDI with a DIPS score of ≥5 was attributed in 14/375 AEs; no highly probable AEs were registered. Eight AEs led to dose modification or discontinuation of midostaurin in seven patients. Clearance for midostaurin during co-administration with posaconazole was 0.52 L/h (95% CI, 0.42-0.62 L/h). A breakthrough fungal infection was recorded in eight patients (27.5%). DDI of midostaurin and posaconazole is clinically meaningful but infrequent. High inter- and intra-individual variabilities of midostaurin and posaconazole plasma exposure were observed. Midostaurin clearance was delayed during co-administration. Midostaurin therapeutic drug monitoring may serve for decision-making when DDI with CYP3A4 inhibitors is suspected.
Photodetectors have undergone widespread, gradual application. Correlation detectors with varying properties are used in diverse fields. This review systematically summarizes the principles, properties, and applications of various photoelectric detectors reported in the past five years, compares their similarities and differences, and further discusses their respective advantages and disadvantages, applicable scenarios, and development prospects. The review covers self-powered detectors, which are very convenient and widely used in consumer electronics and portable wearable devices, and discusses the structural design and photoelectric performance of devices based on P-N junctions, perovskites, silicon-polymer hybrid composites, graphene, hybrid graphene/PbS quantum dot systems, and other novel material architectures. Compound photoelectric detectors enable multifunctional integration and intellectualization. At the same time, their high sensitivity and broad-spectrum response can expand the detection wavelength range to cover the ultraviolet, visible, and infrared bands and enhance the detection of weak optical signals. Finally, this review summarizes current challenges, including cumbersome fabrication processes, susceptibility of detection stability to environmental interference, and limited functionality, and focuses on recent advances in various photodetectors, where breakthroughs are expected.
The rice striped stem borer (Chilo suppressalis) and Colorado potato beetle (Leptinotarsa decemlineata) are notorious pests that have developed widespread resistance to conventional insecticides. RNA interference (RNAi) represents a breakthrough in pest management contingent on identifying effective target genes. This study isolated and characterized transcription factor E93 from both pests. Spatiotemporal expression profiles revealed a similar pattern: low levels in early instars, a progressive increase in later instars, and peak expression in adults, particularly within the ovaries. Functional analysis via CRISPR/Cas9 and RNAi across both species elicited analogous defects: abnormal pupation, aberrant eclosion, and impaired egg development. Furthermore, feeding on potato plants treated with dsLdE93 in pot trials significantly reduced the level of L. decemlineata pupation, emergence, and viable egg production. This study identifies E93, a transcription factor pivotal for development in both C. suppressalis and L. decemlineata, and validates it as a potential novel target for RNAi-mediated pest control.
Immunotherapy has revolutionised the clinical treatment of many types of cancer, including immune checkpoint inhibitors, adoptive cell therapies, and tumour vaccines, which are capable of providing long-term clinical benefit in some patients. Nevertheless, a high degree of tumour immune heterogeneity and an ongoing immunosuppressive the tumour microenvironment (TME) remain as limitations to therapeutic outcomes, and alternative methods to stimulate antitumor immunity are necessary. Given these limitations, recent researchers has been attracted to the fact that Toxoplasma gondii and its derivatives can be considered as unconventional parasite-derived immunomodulatory vectors in cancer immunotherapy. T. gondii infection triggers strong Th1 immunity mediated on interleukin-12 (IL-12) and interferon-γ (IFN-γ), promotes dendritic cell maturation, and activates cytotoxic T cells, thus reprogramming the TME to a more immunostimulatory condition. Attenuated or metabolic-deficient strains have shown strong antitumor efficacy in various murine tumour models by reducing tumour burden and prolonging host survival. Meanwhile, the effector proteins of the parasite, such as GRA15, GRA16, and ROP18, regulate immune cell function to induce tumour cell apoptosis, inhibit angiogenesis, and suppress metastasis. The T. gondii-infected cell-derived exosomes and T. gondii lysate antigens are also immunogenic and represent safer, non-infectious therapeutic alternatives. Here, we summarise the latest advances in the antitumor effects of T. gondii and its derivatives, focusing on immune activation, signalling regulation, direct antitumor effects, synergistic immunotherapy, potential for drug development, and challenges in future clinical translation. T. gondii and its derivatives have shown the potential to reshape TME and convert 'cold' tumours into 'hot' ones in murine cancer models. We believe that with further research in this field, the future of cancer immunotherapy will see breakthrough advancements.
Lumpy skin disease (LSD) is a transboundary animal disease that has serious implications for livestock trade and food security. This study aimed to investigate the molecular and immunological determinants of LSD in vaccinated cattle that developed clinical disease (vaccine breakthrough cases), and to identify potential biomarkers to support disease surveillance and control strategies. Blood samples were collected from 50 clinically healthy cattle (controls) and 50 vaccinated cattle with clinical signs of LSD. Each blood sample was divided into two portions: EDTA-treated blood was used for viral DNA and total RNA extraction for assessing gene expression of immune and antioxidant genes, PCR amplification, partial sequencing, and phylogenetic analysis of the ORF95 gene, whereas serum samples were used to evaluate biochemical, antioxidant, and immunological parameters. In addition, 2-3 skin nodules were surgically excised from the affected animals for pathological examination. Gene expression and sequencing analyses of TLR7, TLR8, TLR9, SOD3, CAT, and GPX were performed in both groups, and single nucleotide polymorphisms (SNPs) were detected. Clinically affected cattle exhibit pyrexia (40-41 °C) and characteristic nodular skin lesions. Partial ORF95 sequences obtained from infected cattle clustered closely with the circulating field strains, indicating active field virus circulation despite vaccination. Histopathological examination revealed typical lesions including epidermal necrosis with eosinophilic intracytoplasmic inclusions, dermal ulceration, and fibrinous exudation. Serum analyses demonstrated significant alterations in inflammatory cytokine levels, oxidative stress indices, and metabolic parameters, consistent with systemic inflammation and oxidative imbalance. Molecular analyses showed significant upregulation of toll-like receptor 7 (TLR7), toll-like recep tor 8 (TLR8), and toll-like receptor 9 (TLR9), accompanied by the downregulation of antioxidant genes; superoxide dismutase 3 (SOD3), catalase (CAT), and glutathione peroxidase (GPX) in infected cattle (p < 0.05). Five SNPs were identified in the investigated genes in the affected animals. Overall, these findings indicate a pronounced inflammatory and oxidative stress response in LSDV-infected cattle, and suggest the involvement of specific genetic variants that may contribute to disease susceptibility.