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Background and purpose To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P -value < 0.05 during univariate analysis were included in multivariate analysis. Results Compared with the good outcome group, the poor outcome group had higher SIRI, IPI, and SII. Spearman correlation analysis showed that the SIRI, IPI, and SII levels significantly correlated with the admission NIHSS score ( r  = 0.338, 0.356, 0.427, respectively; P s  < 0.001). Univariate analysis and Multivariate logistic regression analysis revealed high SIRI, SII, and IPI values as independent risk factors for poor 90-day prognosis (OR = 1.09, 1.003 and 7.109, respectively). Conclusions High SIRI, IPI, and SII values are correlated with poor 90d outcomes in AIS patients undergoing intravenous thrombolysis.

Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution. The osteoimmunology microenvironment in the occurrence and development of periodontitis remains poorly understood at the single-cell level. In this study, we used single-cell transcriptomics to comprehensively reveal the complexities of the molecular components and differences with counterparts residing in periodontal tissues. We performed scRNA-seq to identify 51248 single cells from healthy controls (n=4), patients with severe chronic periodontitis (n=5), and patients with severe chronic periodontitis after initial periodontal therapy within 1 month (n=3). Uniform manifold approximation and projection (UMAP) were further conducted to explore the cellular composition of periodontal tissues. Pseudotime cell trajectory and RNA velocity analysis, combined with gene enrichment analysis were used to reveal the molecular pathways underlying cell fate decisions. CellPhoneDB were performed to identify ligand-receptor pairs among the major cell types in the osteoimmunology microenvironment of periodontal tissues. A cell atlas of the osteoimmunology microenvironment in periodontal tissues was characterized and included ten major cell types, such as fibroblasts, monocytic cells, endothelial cells, and T and B cells. The enrichment of fibroblasts with high expression of , and was detected in patients with periodontitis compared to healthy individuals. The fractions of mesenchymal stem cells (MSCs), pre-osteoblasts (pre-OBs), and osteoblasts decreased significantly in response to initial periodontal therapy. In addition, MSC-like pericytes could convert their identity into a pre-OB state during inflammatory responses even after initial periodontal therapy confirmed by single-cell trajectory. Moreover, we portrayed the distinct subtypes of monocytic cells and abundant endothelial cells significantly involved in the immune response. The heterogeneity of T and B cells in periodontal tissues was characterized. Finally, we mapped osteoblast/osteoclast differentiation mediators to their source cell populations by identifying ligand-receptor pairs and highlighted the effects of Ephrin-Eph signaling on bone regeneration after initial periodontal therapy. Our analyses uncovered striking spatiotemporal dynamics in gene expression, population composition, and cell-cell interactions during periodontitis progression. These findings provide insights into the cellular and molecular underpinning of periodontal bone regeneration.

Objectives NLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied. Materials and methods We used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3KO) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/RosanTnG mouse to trace the changes of Lysm‐Cre+ osteoclast precursors in ligature‐induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro. Results Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3KO mice compared with WT littermates, by using ligature‐induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm‐Cre/RosanTnG mice to demonstrate that MCC950 decreases the number of Lysm‐Cre+ osteoclast precursors in ligature‐induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL‐1β activation and osteoclast differentiation in ligature‐induced periodontitis. Conclusion Our findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation. NLRP3 Regulates Alveolar Bone Loss in Ligature‐induced Periodontitis by Promoting Osteoclastic Differentiation. Bacterial infection in periodontal tissues leads to the activation of NLRP3 inflammasome in osteoclast precursor cells, which promotes osteoclast differentiation and alveolar bone resorption. Thus, NLRP3 inflammasome contribute significantly to the pathologic bone loss in periodontitis. MCC950, a specific inhibitor of the NLRP3 inflammasome, inhibits osteoclast differentiation, thereby reduces alveolar bone loss in periodontitis.

The frequency-modulated continuous-wave (FMCW) technology combined with optical phased array (OPA) is promising for the all-solid-state light detection and ranging (LiDAR). We propose and experimentally demonstrate a silicon integrated OPA combined with an optical frequency microcomb for parallel LiDAR system. For realizing the parallel wavelengths emission consistent with Rayleigh criterion, the wide waveguide beyond single mode region combined with the bound state in the continuum (BIC) effect is harnessed to obtain an ultra-long optical grating antenna array. The single soliton comb, generating about multiple distinct wavelength channels and combined with the high performance integrated OPA, is also demonstrated for coherent three-dimensional (3D) imaging by utilizing FMCW method. The modulation bandwidth of parallel modulation of the microcomb is beyond the modulation region of single soliton microcomb. The result paves the way for developing all-solid-state and ultrahigh-frame-rate coherent LiDAR systems. The massive data stream and fast processing capability is essential for light detection and ranging (LiDAR). Here the authors demonstrate a silicon integrated optical phased array combined with optical frequency microcomb for parallel LiDAR system.

To develop a postoperative recurrence/metastasis risk prediction model for cervical cancer based on circulating tumor cells (CTCs) and tumor fibrosis distance (TFD), and to validate its biological mechanisms through animal experiments. This model aims to guide preoperative risk stratification and personalized treatment strategies. A total of 148 patients with stage IB–IIA cervical cancer who underwent radical surgery between 2020 and 2022 were retrospectively enrolled. Preoperative CTC counts, TFD measurements, and clinicopathological data were collected. Independent prognostic factors were identified using Cox regression analysis. The model’s performance was assessed using receiver operating characteristic (ROC) curves, and risk stratification was evaluated with Kaplan–Meier survival analysis. Additionally, an orthotopic tumor model was established in 60 Sprague-Dawley rats divided into six groups (Control, Model, HTFD, LTFD, HCTCs, and LH). Tumor burden, CD4+/CD8 + ratios, IL-6, TNF-α, MDA, and SOD levels were measured to explore the model’s underlying metabolic and immune mechanisms. Patients with poor outcomes had significantly higher CTC counts (30.50 vs. 23.74/5 mL, P  < 0.001) and lower TFD values (5.47 vs. 5.98 mm, P  < 0.001). CTCs ≥ 28/5 mL (OR = 6.63) and TFD ≤ 5.7 mm (OR = 3.37) were identified as independent predictors of poor prognosis. The combined model yielded an AUC of 0.91, with a sensitivity of 90.6%, specificity of 84.5%, and a negative predictive value (NPV) of 94.7%. Patients were stratified into low-, intermediate-, and high-risk groups, with corresponding clinical management recommendations. In high-risk rat groups, elevated CTC release, reduced CD4+/CD8 + ratios, increased IL-6 and TNF-α levels, and significant oxidative damage were observed, supporting the biological plausibility of the clinical model. Unlike conventional models that mainly rely on clinicopathological features, our model incorporates both CTCs and TFD, providing superior discrimination for recurrence risk and offering a novel integrative approach for postoperative surveillance. This dual validation underscores the translational potential of the model, which may be incorporated into individualized postoperative monitoring strategies and multidisciplinary decision-making.

Background Cardiovascular-kidney-metabolic (CKM) syndrome integrates metabolic, renal, and cardiovascular disease risk. While increasing evidence suggests that triglyceride-glucose (TyG)-related indices are associated with the future risk of cardiometabolic multimorbidity (CMM), their link to CMM in CKM syndrome has not been established. Methods This study analyzed participants with CKM syndrome stage 0–3 from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020. We used Cox regression analysis, restricted cubic spline (RCS) curves, and Kaplan–Meier (K–M) survival curves to evaluate the relationship between TyG-related indices and CMM risk in patients with CKM stage 0–3 syndrome. Receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses were used to assess the predictive performance of the TyG-related indices for CMM. Results During a median follow-up of 9 years, 652 participants (9.5%) developed CMM. The fully adjusted model revealed an elevated CMM risk across the highest quartiles of all indices, with hazard increases ranging from 72 to over 200%. A linear dose-response relationship was observed for most indices, except for triglyceride glucose-a body shape index (TyG-ABSI) and C-reactive protein-triglyceride-glucose index (CTI). The triglyceride glucose-Chinese visceral adiposity index (TyG-CVAI) achieved the highest area under the curve (AUC) for CMM prediction (0.679), and compared with the fully adjusted model (Model 4), all indices provided significant incremental predictive values. Conclusion Nine TyG-related indices, particularly TyG-CVAI, are strong independent predictors of future CMM in patients with CKM syndrome stage 0–3. These findings underscore the utility of TyG-related indices, particularly TyG-CVAI, in identifying high-risk individuals, thereby informing strategies for the early detection and prevention of CKM syndrome. Graphical abstract

The inhibition of the PD-1/PD-L1 axis has exhibited significant advancements in cancer immunotherapy, improving patient outcomes in various cancers. However, the clinical efficacy of these monotherapies remains limited in many cases. Integrin αvβ3 has been identified as a positive regulator of PD-L1 expression and a critical contributor to cancer immune evasion. To address this, we developed a dual function antibody, B1451, that recognizes both PD-L1 and αvβ3 and evaluated its antitumor efficacy in pre-clinical models and . We first analyzed the correlation between PD-L1 and αvβ3 expression, as well as the role of αvβ3 in modulating sensitivity to immunotherapy, using the TISIDB database. Subsequently, we designed and constructed a dual function PD-L1×αvβ3 antibody (B1451) by conjugating an integrin αvβ3-binding peptide to the C-terminal of the heavy chain of the anti-PD-L1 monoclonal antibody, Atezolizumab, using a (G4S)×3 linker. The antitumor efficacy of B1451 was then evaluated in preclinical models and . Our findings demonstrated a significant positive correlation between the gene expression of PD-L1 and αvβ3 across various human solid tumors. Additionally, high αvβ3 expression appears to influence the sensitivity to immunotherapy. The dual function antibody B1451 was capable of recognizing human PD-L1 and αvβ3 antigens, effectively blocking both the PD-1/PD-L1 and vitronectin/αvβ3 pathways. B1451 inhibited tumor cell migration, adhesion, and angiogenesis , and exhibited superior anti-tumor activity than monotherapy. The dual function antibody targeting both αvβ3 and PD-L1 holds the potential to reverse immune evasion and exhibit synergistic anti-tumor effects, offering a promising therapeutic strategy for the treatment of solid tumor.

An optical phased array (OPA) with 2-D circular sparse array aperture has been proposed and demonstrated in the silicon integrated photonic platform. The sparse distribution of the antenna array can realize no grating lobes in 2-D full field of view (FOV). To achieve fast and accurate phase calibration for OPA, an improved rotating element electric field vector algorithm based on golden section search method (GSS-REV) has also been proposed and verified. The 32-element antenna sparse distribution of the proposed OPA is designed and fabricated. A far-field beam steering measurement across 20° × 20° range features the side lobe suppression ratio (SLSR) of larger than 4.81 dB and a full width at half-maximum (FWHM) of approximately 0.63° × 0.59°. The resolvable points are derived to be ∼1076. The OPA chip has also been demonstrated on range measurement with frequency-modulated continuous-wave (FMCW) system.

As a critical task in intelligent navigation systems, high-accuracy prediction of ship motions proves essential for maritime safety and energy efficiency optimisation. Recent studies have demonstrated the effectiveness of metaheuristic optimisation algorithms (e.g. Particle Swarm Optimization, PSO) in multivariate dynamic response prediction. This study proposes a hybrid Simulated Annealing Particle Swarm Optimization (SAPSO) algorithm that achieves superior wave-induced ship motion prediction through innovative simplification of memory terms in radiation potential integral equations into fitness functions. A novel visualisation methodology is introduced to enhance the interpretability of particle exploration processes in both SAPSO and PSO frameworks. Comparative analysis reveals that SAPSO achieves significant performance enhancements over standard PSO, with mean reductions of 70.8% in Mean Squared Error (MSE) and 40.1% in Root Mean Squared Error (RMSE), indicating substantially improved convergence stability. Temporal domain analysis demonstrates SAPSO's superior time-domain stability, maintaining consistent R² values (mean 91.7% ± 7.1%) throughout the 1.1-second observation window. This performance eliminates the initial fitting degradation and operational fluctuations observed in PSO implementations (64.2% ± 20.8%). Validation through temporal response analysis and multi-hull computational results confirms the algorithm's robust optimisation process, establishing SAPSO as an efficient and accurate technical solution for hydrodynamic forecasting of marine structures. The proposed methodology shows substantial engineering applicability in naval architecture and ocean engineering applications.

Background The association of neutrophil-to-lymphocyte ratio (NLR) and depressive symptoms with stroke risk, mortality, and major adverse cardiovascular events (MACE) is currently unknown. This study aimed to investigate the effects of neutrophil-to-lymphocyte ratio (NLR) and depressive symptoms on stroke risk, mortality, and MACE in NHANES 2005–2018. Methods The National Health and Nutrition Examination Survey (NHANES) was conducted by the National Center for Health Statistics between 2005 and 2018, recruiting a nationally representative sample of participants aged 20 years and older. The NLR reflects inflammatory status and the Patient Health Questionnaire 9 (PHQ-9) indicates depressive symptoms. Independent and joint associations between NLR, depressive symptoms, and stroke and mortality were then examined, and relative risk was calculated using weight-based Cox regression analyses. Finally, mediation analysis was used to explore the indirect impact of the PHQ-9 score on stroke and mortality mediated through NLR. Results NLR and depressive symptoms were positively associated with stroke risk ( p  < 0.05). Participants with higher NLR levels had an increased risk of all-cause mortality and MACE (HR, 1.406; 95% CI 1.261–1.567; HR, 1.927; 95% CI 1.518–2.447), while those with higher PHQ-9 score were associated with an elevated risk of all-cause mortality and MACE (HR, 1.762; 95% CI 1.516–2.047; HR, 1.755; 95% CI 1.396–2.206). In addition, joint analyses indicated that participants with PHQ-9 score ≥ 10 and high NLR levels had the highest risk of all-cause mortality and MACE (HR, 2.079; 95% CI 1.673–2.585; HR, 2.858, 95% CI 2.007–4.069). Specifically, participants with elevated NLR levels and moderate-severe depressive symptoms faced the greatest risk of mortality. Mediation analyses revealed that NLR partially mediated the association between PHQ-9 score and stroke risk, all-cause mortality, and MACE by0.6%, 5.9%, and 4.8%, respectively. Conclusion Our research indicates that elevated NLR levels and more severe depressive symptoms were associated with increased risk of stroke, all-cause mortality and MACE. In addition, NLR plays a mediation role in linking depressive symptoms to stroke, MACE, and all-cause mortality.