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To evaluate the budget impact on the China's basic medical insurance fund (BMIF) following the inclusion of aztreonam-avibactam (ATM-AVI) for metallo-β-lactamase carbapenem-resistant enterobacterales (MBL-CRE) infections in the National Reimbursement Drug List (NRDL). A budget impact model was developed with a 2-year time horizon (2026-2027) from the perspective of China's basic medical insurance. The analysis included drug acquisition costs and other direct medical costs. Relevant data were collected from published literature, and supplemented through expert consultation. The study compared costs under two scenarios with and without ATM-AVI reimbursement to estimate its impact on BMIF. One way sensitivity analyses were conducted to identify key parameters influencing the results. After the inclusion of ATM-AVI in the NRDL, the BMIF was projected to save 152,156,598 Chinese yuan (21,310,448 United States dollar) and 210,914,875 Chinese yuan (29,539,898 United States dollar) in 2026 and 2027, respectively. Following reimbursement, ATM-AVI was expected to yield 291 and 342 additional cured patients, 804 and 888 fewer deaths, 11,256 and 13,031 fewer intensive care unit days, and 11,336 and 13,071 fewer total hospitalization days in 2026 and 2027, respectively. Across all parameter variations, ATM-AVI remained cost-saving to BMIF. In China, timely reimbursement of innovative antibiotics can simultaneously improve patient outcomes and reduce medical insurance fund expenditure, underscoring the value of value-based reimbursement policies in promoting access to effective therapies while supporting the sustainability of the health insurance system.

Evidence regarding sexual health among patients with breast cancer undergoing endocrine therapy remains under-addressed in clinical practice. This review synthesised articles both in English and Chinese to explore the sexual health status and related factors in these patients. An integrative review was conducted. Articles published from database inception to March 2025 were retrieved from CINAHL, Cochrane Library, China National Knowledge Infrastructure, PubMed, OVID, ScienceDirect, Web of Science, and Wiley Online Journals. Whittemore and Knafl's five steps were followed, and the methodological quality was assessed using a mixed methods appraisal tool. Data were synthesised and compared to identify similarities and differences among articles. A total of 43 articles were selected from 3590 records for analysis: 39 quantitative, three qualitative, and one mixed methods study. Eleven articles reported sexual dysfunction prevalence between 51 and 93%, whereas only one article indicated a rate of 29%. Thirteen articles reported various symptoms of genitourinary syndrome of menopause while vaginal dryness and dyspareunia were consistently the main complaints. Age, financial burden, partnerships, physical and psychological status, and treatment factors were associated with women's sexual health. A "silence gap" in sexual health care was identified, with many healthcare professionals failing to address it. Patients undergoing endocrine therapy experience a high prevalence of sexual dysfunction and symptoms of genitourinary syndrome of menopause. Several factors affect women's sexual health, including sociodemographic, physical, psychological, and treatment factors. A comprehensive assessment and targeted support should be offered to enhance sexual health outcomes in this population.

This study aimed to elucidate the mechanism of San Jie Tong Mai Formula (SJTMF) against atherosclerosis (AS), a leading cause of cardiovascular morbidity. Using ApoE-/- mouse models, we demonstrated that SJTMF significantly inhibits AS plaque progression. Through an integrated network pharmacology and proteomics strategy, five core bioactive components were identified: beta-sitosterol, naringenin, luteolin, isorhamnetin, and 3beta-hydroxy-24-methylene-8-lanostene-21-oic acid. Concurrently, proteomics revealed 129 AS-related proteins that were differentially expressed. Molecular docking confirmed high-affinity binding interactions between these components and the key target Hsd11b1, with their binding energies all below -5 kcal/mol. Mechanistic investigations further revealed that SJTMF may regulate Hsd11b1-mediated glucocorticoid metabolism. This regulation contributes to significant amelioration of both dyslipidemia and vascular inflammation, thereby suppressing AS development. Collectively, this work demonstrates, for the first time, the innovative mechanism by which a traditional Chinese medicine formula exerts anti-AS effects through multi-component synergistic regulation of the Hsd11b1 target, offering new insights for therapeutic intervention.

DNA repair plays a critical role in the development of smoking-related cancers. We hypothesized that DNA repair capacity (DRC) and nucleotide excision repair (NER) mRNA expression are associated with increased head and neck squamous cell carcinoma (HNSCC) risk in the Chinese population. We conducted a case-control study including 349 patients with HNSCC and 316 cancer-free controls. DRC and NER mRNA expression levels were measured in lymphoblastoid cells exposed to benzo[a]pyrene diol epoxide (BPDE). Correlations between DRC and NER mRNA expression were analyzed, and their associations with HNSCC risk were evaluated. The mean DRC was significantly lower in patients with HNSCC (9.72%&#x2009;&#xb1;&#x2009;2.25%) than in healthy controls (10.81%&#x2009;&#xb1;&#x2009;2.63%, P&#x2009;<&#x2009;0.001). Compared with individuals with higher DRCs, those with lower DRCs had a significantly greater risk of HNSCC (odds ratio [OR]&#x2009;=&#x2009;2.23, 95% confidence interval [CI]&#x2009;=&#x2009;1.60-3.10, P&#x2009;<&#x2009;0.001; Ptrend&#x2009;<&#x2009;0.001). Correlation analyses demonstrated significant associations between DRC and the expression of XPA and XPB. Moreover, predictive models combining DRC with XPA and/or XPB mRNA expression significantly improved risk prediction, as evidenced by increased area under the curve (AUC) values (P&#x2009;<&#x2009;0.05). Suboptimal DRC and reduced expression of key NER genes, particularly XPA and XPB, are associated with increased HNSCC risk. Integrating these two NER biomarkers may provide a novel and improved model for HNSCC risk assessment.

Millet agriculture was foundational to the emergence of complex societies in Neolithic East Asia, yet the environmental mechanisms shaping its spatiotemporal development remain unresolved. Here, we present a high-resolution reconstruction of Holocene growing-season soil temperature from biomarker proxies in a precisely dated loess sequence from the central Chinese Loess Plateau. Our data reveal a pronounced ~3 &#xb0;C soil cooling between ~7.5 to 6.0 thousand years B.P. (kyr B.P.), followed by rapid warming and millennia-long relatively stable conditions. By integrating archaeological datasets with transient climate simulations, we show that this mid-Holocene soil cooling which reflects coupled climatic forcing and vegetation-related land surface changes likely compressed the thermally suitable niche for frost-sensitive millets, contributing to a southward displacement of cultivation and delaying large-scale agricultural expansion until the subsequent soil temperature recovery after ~6.0 kyr B.P. These findings suggest that large-amplitude soil temperature fluctuations acted as a modulating climatic constraint on the geographic distribution and development trajectory of millet agriculture in East Asia, providing refined insights into climate-society interactions during the Neolithic.

Ultrafine particles (UFP, <100 nm) may pose more significant health risks compared to larger particulate matter due to higher specific surface area and potential for deposition throughout the respiratory system. However, their spatial distribution remains poorly characterized, particularly in Asian megacities such as Beijing with high population density and diverse emission sources. We developed a high-resolution land use regression (LUR) model to predict UFP spatial distribution in Beijing during August 2022-July 2023, using stop-and-go mobile monitoring data from 164 sites. Time adjustments were validated and applied to adjust short-term observations to 1-year average concentrations. Four modeling approaches were compared to address high-dimensional covariates, with linear regularization showing the best performance (R2 = 0.73 and 0.65; RMSE = 971 and 1050 pt/cm3 in the full model and 10-fold cross-validation). Key predictors included population density, impervious surfaces, bus stop proximity, and Chinese restaurant density, indicating significant contributions from human activity and vehicular emissions. Predicted concentrations ranged from 1.5 to 22.5 &#xd7; 103 pt/cm3, with hotspots concentrated in the urban core and along major roadways. This first quantitative assessment of UFP spatial variability in Beijing underscores the value of dense mobile monitoring and robust statistical modeling for UFP exposure assessment in densely populated urban areas.

Advances in digital orthodontics and artificial intelligence (AI) planning have the potential to enhance treatment precision, but randomized evidence based on the Peer Assessment Rating (PAR) index remains limited. In this single-center, parallel-group randomized controlled trial registered retrospectively in the Chinese Clinical Trial Registry (ChiCTR2500108499), 140 patients aged 12-35 years with Angle Class I malocclusion were randomized to receive an AI-assisted digital workflow (Digital and AI group) or conventional fixed appliances (Conventional group). PAR scores were assessed at baseline (T0), 6-month intervals (T1), and immediately after treatment completion (T2) by calibrated, blinded examiners following British Standards Institute criteria. Analyses followed the intention-to-treat principle, applying independent t-tests, &#x3c7;&#xb2;/Fisher's exact tests, repeated-measures mixed-effects models, and multivariable linear regression. Effect sizes were expressed as mean difference (MD) or relative risk (RR) with 95% confidence intervals (CI). Baseline PAR scores did not differ significantly between groups (MD&#x2009;=&#x2009;0.63, 95% CI: -0.13 to 1.40; p&#x2009;=&#x2009;0.105). At T2, the Digital and AI group had lower mean PAR scores (4.88&#x2009;&#xb1;&#x2009;0.45) than the Conventional group (7.81&#x2009;&#xb1;&#x2009;0.70; MD&#x2009;=&#x2009;2.93, 95% CI: 2.73-3.13; p&#x2009;<&#x2009;0.001). A higher proportion of patients in the Digital and AI group achieved &#x2265;70% PAR reduction (82.9% vs 50.0%; RR&#x2009;=&#x2009;1.66, 95% CI: 1.27-2.17; p&#x2009;<&#x2009;0.001). Repeated-measures mixed-effects analysis showed significant effects of intervention, time, and their interaction (all p&#x2009;<&#x2009;0.001), indicating different improvement trajectories between groups. Multivariable regression identified allocation to the Digital and AI group, higher baseline PAR, and younger age as independent predictors of greater PAR reduction. No severe adverse events occurred, and no participants were lost to follow-up between T0 and T2. Under controlled trial conditions, the AI-assisted digital workflow produced greater short-term improvements in PAR-based occlusal outcomes than conventional fixed appliances. These findings suggest a potential benefit of integrating an AI-assisted digital system into orthodontic practice; however, conclusions are limited to short-term occlusal changes, and further multicenter studies with longer follow-up, patient-reported outcomes, and economic evaluation are warranted.

ObjectiveGenome-wide association studies have identified over 80 loci associated with nonsyndromic orofacial cleft (NSOC), yet substantial heritability remains unexplained. Insights from syndromic orofacial cleft (SOC) implicated genes could help bridge this gap.DesignA case-control association study in a Han Chinese cohort was conducted to evaluate the association between SOC-implicated genes and NSOC subtypes using association, linkage disequilibrium (LD), and haplotype analyses.SettingTertiary medical center.Patients, ParticipantsThe study included 1626 cases of non-syndromic cleft lip with or without cleft palate, 930 cases of non-syndromic cleft palate only, and 2255 controls.InterventionsPeripheral blood (cases) and umbilical cord blood (controls) were collected for DNA extraction.Main Outcome MeasuresAllelic (Pearson' s &#x3c7;2, 1 df) and genotypic (Pearson' s &#x3c7;2, 2 df) associations between SNPs and NSOC subtypes were evaluated, with odds ratios (ORs) and 95% confidence intervals (CIs). LD and sliding-window haplotype association analyses were performed in Haploview. SNPs with minor allele frequency (MAF) >0.05 and in Hardy-Weinberg equilibrium in controls were analyzed. The significance threshold was P&#x2009;<&#x2009;1.27&#x2009;&#xd7;&#x2009;10-5 after Bonferroni correction.ResultsAllelic analysis identified 23 SNPs that were significantly associated with NSOC subtypes (lowest P&#x2009;=&#x2009;2.02&#x2009;&#xd7;&#x2009;10-22). Genotypic analysis identified 39 significant SNPs (lowest P&#x2009;=&#x2009;1.09&#x2009;&#xd7;&#x2009;10-36). Signals mapped to 7 genes. Haplotype analyses revealed a shared causal variant block at MYMK and TWIST2, and allelic heterogeneity at NEDD4L.ConclusionsWe identified MYMK, TWIST2, and NEDD4L as NSOC-associated genes. Using SOC genes as prior knowledge reveals loci missed by standard GWAS, offering key insights into NSOC pathogenesis.

Patients with mucopolysaccharidosis (MPS) appear to have an increased risk of developing dental disease. This study aimed to evaluate the status of dental caries and dental anomalies among Chinese patients with different types of MPS. This retrospective study analyzed a consecutive cohort of 102 pediatric patients with MPS who visited the Department of Stomatology at the Capital Center for Children's Health between August 2010 and August 2025. Eligible patients were defined as those with a confirmed diagnosis of MPS who were aged &#x2264;14 years at the time of their dental visit and had complete dental examination records available. Dental caries and anomalies were assessed through clinical records and radiographic data. Dental caries were observed in 55.9% (57/102) of patients, and no statistically significant difference was observed across the MPS subtypes (P=.72). Deep dentinal caries (d4-6mft) were observed in 40.2% (41/102) of the participants and contributed most to the total decayed, missing, and filled teeth index score. The overall prevalence of dental anomalies was 32.4% (33/102), with a statistically significant difference among MPS subtypes (P=.005). Patients with MPS type IV had a significantly higher risk of dental anomalies compared to those with MPS type II (odds ratio 6.32, 95% CI 1.55-28.28; P=.01), after adjusting for age and gender. The prevalence of dental anomalies differed significantly across MPS subtypes, while that of dental caries did not. These findings emphasize the need for early, targeted preventive care and tailored dental interventions to improve oral health outcomes in this population.

Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39) is a purinergic immune checkpoint protein and a potential biomarker in tumor immunotherapy. The enzyme can hydrolyze extracellular adenosine tri- and diphosphate (ATP, ADP) to generate adenosine monophosphate (AMP), which is subsequently hydrolyzed by ecto-5'-nucleotidase (CD73) to generate immunosuppressive adenosine (ADO). CD39 inhibition increases the extracellular concentration of immunostimulatory ATP, concomitantly reducing ADO production. In the tumor microenvironment, ATP can recruit a variety of antitumor immune cells, including T cells, dendritic cells, M1 macrophages, B cells, natural killer cells, and N1 neutrophils, to the tumor site, thereby suppressing various tumor activities. Here, we present non-nucleotidic and nucleotide-derived CD39 inhibitors, structural insights, current clinical studies, and strategies for combination therapy. We highlight the potential advantages of targeting CD39 in tumor immunotherapy and provide valuable insights to guide future drug development and therapeutic applications.

This study elucidates a novel intercellular communication mechanism underlying radiotherapy resistance in cervical cancer, focusing on the functional role of cancer-associated fibroblast-derived exosomes (CAF-Exo) in modulating redox homeostasis and cell death pathways. We demonstrate that CAF-Exo serve as critical vehicles for transferring radioresistant phenotypes to tumor cells through coordinated regulation of antioxidant defense systems and copper-dependent cell death processes. Our findings reveal that CAF-Exo activate the Nrf2-HO-1 signaling axis while simultaneously suppressing key cuproptosis regulators, establishing a dual-pathway mechanism for treatment resistance. Bone morphogenetic protein 4 (BMP4) was identified as the essential molecular cargo within these exosomes, functioning as a master regulator of this protective cellular response. The pathological significance of this pathway was confirmed through comprehensive functional assays showing that BMP4 knockdown effectively restored radiosensitivity in&#xa0;vitro and significantly enhanced radiotherapy efficacy in&#xa0;vivo. These results uncover a previously unrecognized biological axis wherein tumor-stroma interactions mediated by exosomal BMP4 orchestrate a sophisticated defense mechanism against radiotherapy-induced stress. This study elucidates key molecular mechanisms underlying treatment resistance and highlights potential therapeutic targets for cervical cancer, offering a basis for future intervention strategies.

ConspectusTraditional metal nanoparticles have been widely utilized as heterogeneous catalysts in both fundamental scientific research and industrial applications. Their catalytic performances are commonly statistical and represent averaged results from all of the nanoparticles due to their inherent size polydispersity and structure heterogeneity. Recently, metal clusters (1-2 nm) with precise compositions and well-defined structures have provided opportunities to precisely correlate the catalytic properties with the structure and composition of the clusters at the atomic level. Specifically, the distinct metal core, interface, and surface structures of these clusters render them ideal for exploring the contributions of the surface/interface/core of cluster-based catalysts to catalytic properties.In this Account, we introduce the correlation of the catalytic properties of clusters with their ligand, interface, and metal kernel, ultimately mapping out the key factors that dictate the catalytic activity and selectivity. We first preview atomically precise clusters and the structural characteristics of the surface, interface, and kernel. Then, we emphasize the modulation of catalytic properties of cluster catalysts through the ligand, interface, and core. (i) Surface ligand: An efficient surface modification via ligand exchange is able to not only remarkably enhance the catalytic activity but also effectively modulate the product selectivity. (ii) Metal-ligand interface and cluster-cluster interface: The metal-ligand interface can enable the catalytic sites to directly control the whole catalytic process through the synergy between the metal atom and the ligand. Additionally, the interfaces between the clusters and their surrounding environment can cooperatively tailor the catalytic activity and selectivity. (iii) Metal core: The one-atom variation in the cluster kernel composition can effectively tune the overall electronic structures of clusters, thereby indirectly improving their catalytic activities. Furthermore, the central atom within an open core can also act as the active site to directly participate in and facilitate the catalytic reaction. Ultimately, looking to the future of catalysis science, there are still many challenges, but atomically precise metal clusters deserve more future efforts to unravel fundamental catalysis. Therefore, we offer several perspectives on the future research of precise catalysis using atomically precise cluster catalysts. We anticipate that this Account can provide fundamental insight into the unique contributions of the surface/interface/core of heterogeneous catalysts to their overall catalytic performances. By learning these fundamental principles, we will ultimately be able to design high-performance catalysts for a variety of catalytic processes.

Fuping goat milk powder is a kind of geographical indication protected food in China. To realize a rapid and accurate identification of Fuping goat milk, in this paper, an identification method was proposed based on nuclear magnetic resonance and machine learning to accurately distinguish Fuping goat milk on small scale geographical authenticity. Deuterated chloroform was selected as extraction solvent, partial least squares discriminant analysis (PLSDA), random forest (RF) and support vector machine (SVM) models were constructed using seven different geographical origin goat milk samples in Shaanxi Province. The identification based on PLS-DA model was unsatisfactory, the RF model performed better, and the SVM model showed best performance with accuracy rate reached 100% based on selected 17 features, and the 5-fold cross-validation accuracy was 94.7%&#xa0;&#xb1;&#xa0;7.2%. It is disclosed that different geographic samples have different chemical compositions, particularly unsaturated fatty acids, such as conjugated linoleic acid.

Healthy aging has emerged as a global priority. However, older adults' participation in health promotion programs remains low, and traditional health promotion models have achieved limited success in fostering sustained engagement among this population. Mobile health (mHealth)-based gamification interventions offer a promising way to address these challenges. However, no published reviews support or oppose the use of mHealth-based gamification interventions as health promotion strategies in older adults. The study aimed to identify mHealth interventions using gamification to promote health among older adults. Our scoping review was conducted following the Joanna Briggs Institute recommendations for scoping reviews and Arksey and O'Malley's framework. The process followed PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Literature Search Extension) checklist. A comprehensive literature search was conducted across 8 databases: PubMed, Scopus, Web of Science, Embase, Cochrane Library, CINAHL, PsycARTICLES, and IEEE Xplore Digital Library, from their inception to December 10, 2025. Two reviewers independently screened titles, abstracts, and full texts via Rayyan, with disagreements resolved by a third reviewer. This scoping review identified 11 studies. Only 1 article was published before 2022. The interventions were found to improve enjoyment and motivation (n=5), cognitive function (n=3), physical activity (n=2), and digital literacy (n=2). Individual studies also reported improvements in mental health (n=1) and adherence (n=1), a reduction in suicidal ideation (n=1), improvements in physical function (n=1), the promotion of social engagement (n=1), and the identification of mild cognitive impairment (n=1). Game elements used were ranked by frequency as progress, challenges, goals, levels, reward, sensation, storytelling or narration, leaderboard, surprise, and avatar. No research was found to use the game element of "social sharing." mHealth types included augmented and virtual reality-based training systems, wearable devices, mobile phones, tablets, and Windows platforms and devices. Notably, only 4 studies applied theoretical frameworks, and 3 omitted the concrete approach to gamification. As the first scoping review to identify and map mHealth-based gamification interventions for older adults, this study highlights their potential as an innovative approach to health promotion. By systematically synthesizing evidence regarding intervention designs, gamification strategies, and preliminary health outcomes, it establishes a foundation for future inquiry. However, this review is limited by the small number of included studies, precluding broad generalizations. Future research should assess long-term impacts, integrate theoretical frameworks, establish reporting guidelines, design personalized social-interactive interventions, and expand to broader health domains. Ultimately, these insights provide targeted guidance for developing age-appropriate digital health solutions, contributing to the realization of active aging.

Acute pancreatitis (AP) is an under-recognized but clinically relevant complication of dengue fever (DF), associated with rapid clinical deterioration and increased risk of mortality. However, the true incidence of this condition remains uncertain. Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) up to May 2025 for observational studies reporting AP among DF hospitalized patients. Eligible studies were identified according to predefined inclusion and exclusion criteria based on the Population, Intervention, Comparison, Outcome, and Study design (PICOS) framework. Two reviewers independently screened the literature and assessed study quality using the Newcastle-Ottawa Scale (NOS). Pooled incidence rates were estimated using random or common effect models depending on heterogeneity. Eight observational studies from five countries, comprising 1,078 hospitalized patients with DF, were included. Among them, 135 were diagnosed with AP. The pooled incidence of AP complicating DF was 12.4% (95% CI: 10.5-14.4%). Subgroup analysis suggested a higher incidence in studies with &#x2265;100 participants compared to smaller cohorts (13.5% vs. 8.3%, P&#x2009;=&#x2009;0.03). No evidence of significant publication bias was detected. DF-associated AP represents a clinically important complication, given the global burden of dengue and the potential severity of AP. Our findings underscore the importance of considering pancreatic enzyme testing, supplemented by imaging when clinically warranted, in dengue patients with persistent or severe abdominal symptoms and/or features of severe dengue. Large-scale, multicenter prospective studies are warranted to establish the true incidence and case-fatality risk, thereby informing evidence-based prevention and management strategies.

Laccase is an environmentally friendly catalyst characterized by a wide substrate spectrum and clean reaction processes. It demonstrates the ability to efficiently oxidize various pollutants, with water being the sole by-product. Consequently, laccase holds significant potential for applications in diverse fields such as papermaking, environmental protection, food processing, and bioenergy production. In this study, crude laccase produced by Schizophyllum commune was immobilized within a composite material through chemical cross-linking to enhance the enzyme's activity and stability. Free laccase was immobilized using a gelatin/chitosan (GEL/CS) hydrogel, and the conditions for this process were optimized. Enzymatic properties of immobilized laccase (GEL/CS-laccase) were investigated to assess its potential applications. Results indicated that the maximum laccase activity by Schizophyllum commune reached 343.9 U&#xb7;mL-&#x2009;1 on day 6. Following optimization, GEL/CS-laccase achieved an activity recovery of 33.9% and an activity of 113.8 U&#xb7;g-&#x2009;1. Compared with free laccase, GEL/CS-laccase shows better adaptability to pH and temperature. Furthermore, GEL/CS-laccase demonstrates moderate reusability and excellent long-term storage stability: its activity remains above 34.7% after 5 cycles and exceeds 52.9% following 180 days of storage at -80&#xa0;&#xb0;C and vacuum. This study has developed an efficient enzyme immobilization method, enhancing its stability and operability, and laying a solid foundation for the practical application of laccase.

Ebolaviruses, including EBOV, SUDV, and BDBV, cause severe hemorrhagic fever, yet currently licensed monoclonal antibody (mAb) therapies against EBOV lack cross-species efficacy. While mAbs offer high specificity, favorable safety profiles, and durable serum persistence, their susceptibility to viral escape highlights the need for broader, more resilient antibody strategies. Bispecific antibodies (bsAbs), which concurrently target non-overlapping epitopes, have the potential to enhance neutralization potency, expand strain coverage, and mitigate mutation-driven resistance. In this study, we engineered three bsAb formats-CrossMab&#xae;, DVD-IgG, and IgG-ScFv-directed against distinct ebolavirus epitopes and systematically characterized their antiviral activities. All bsAbs exhibited potent neutralizing activity and conferred substantial protection in mouse challenge models. Notably, the IgG-ScFv format demonstrated the greatest improvements in neutralization potency and in vivo efficacy. These findings provide a framework for rational bsAb design and underscore their promise as next-generation immunotherapeutics capable of broad and durable protection against diverse ebolaviruses.