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Abstract Unleashing the land sector’s potential for climate mitigation requires purpose-driven changes in land management. However, contributions of past management changes to the current global and regional carbon cycles remain unclear. Here, we use vegetation modelling to reveal how a portfolio of ecological restoration policies has impacted China’s terrestrial carbon balance through developing counterfactual ‘no-policy’ scenarios. Pursuing conventional policies and assuming no changes in climate or atmospheric carbon dioxide (CO2) since 1980 would have led China’s land sector to be a carbon source of 0.11 Pg C yr−1 for 2001–2020, in stark contrast to a sink of 175.9 Tg C yr−1 in reality. About 72.7% of this difference can be attributed to land management changes, including afforestation and reforestation (49.0%), reduced wood extraction (21.8%), fire prevention and suppression (1.6%) and grassland grazing exclusion (0.3%). The remaining 27.3% come from changes in atmospheric CO2 (42.2%) and climate (−14.9%). Our results underscore the potential of active land management in achieving ‘carbon-neutrality’ in China.

Stress relaxation with synchronous aging (SRSA) could not only reduce springback but as well improve the performance of titanium alloy components. To reveal the relaxation mechanisms during SRSA, solution treatments of Ti-6.5Al–2Zr–1Mo–1V alloy under different temperatures were carried out to obtain diverse initial microstructures. The evolutions of microstructure including phase transformation, dislocation movement and stress-induced twinning were meticulously characterized. The progress of activation energy was analyzed quantitatively by the Kohlrausch-Williams-Watts equation. Results show that SRSA under all different conditions exhibits a rapid stress decline initially followed by a quasi-static stage, due to a shift in the driving force from stress-driven to thermally activated driven. The activation energy changes from a quasi-static state to a rapid rise with relaxation time. After two-phase solution treatment, the primary α (αp) dominant mechanism is the dislocation movement, including dislocation tangles and then recovery. The relaxation mechanism of the supersaturated metastable β phase is phase transformation (precipitation and growth of secondary α (αs)) and stress-induced twinning, and the αs realizes stress release through the globularization in the later stage. The full martensite microstructure was obtained by solution treatment in a single-phase region, and the main relaxation mechanism involves stacking faults, stress-induced twinning and then globularization. The enhancement in strength following SRSA is primarily attributed to the formation of αs, dislocation strengthening, and stress-induced twinning.

Abstract Purpose This study aims to investigate the risk factors for lymph node metastasis (LNM) in synchronous multiple primary lung cancer (sMPLC) using clinical and CT features, and to offer guidance for preoperative LNM prediction and lymph node (LN) resection strategy. Materials and methods A retrospective analysis was conducted on the clinical data and CT features of patients diagnosed with sMPLC at the Third Affiliated Hospital of Kunming Medical University from January 1, 2018 to December 31, 2022. Patients were classified into two groups: the LNM group and the non-LNM (n-LNM) group. The study utilized univariate analysis to examine the disparities in clinical data and CT features between the two groups. Additionally, multivariate analysis was employed to discover the independent risk variables for LNM. The diagnostic efficacy of various parameters was evaluated using the receiver operating characteristic (ROC) curve. Results Among the 688 patients included in this study, 59 exhibited LNM. Univariate analysis revealed significant differences between the LNM and n-LNM groups in terms of gender, smoking history, CYFRA21-1 level, CEA level, NSE level, lesion type, total lesion diameter, main lesion diameter, spiculation sign, lobulation sign, cavity sign, and pleural traction sign. Logistic regression identified CEA level (OR = 1.042, 95%CI: 1.009-1.075), lesion type (OR = 9.683, 95%CI: 3.485-26.902), and main lesion diameter (OR = 1.677, 95%CI: 1.347-2.089) as independent predictors of LNM. The regression equation for the joint prediction was as follows: logit(p)= -7.569+0.041*CEA level +2.270* lesion type +0.517* main lesion diameter.ROC curve analysis showed that the AUC for CEA level was 0.765 (95% CI, 0.694–0.836), for lesion type was 0.794 (95% CI, 0.751–0.838), for main lesion diameter was 0.830 (95% CI, 0.784–0.875), and for the combine predict model was 0.895 (95% CI, 0.863–0.928). Conclusion The combination of clinical and imaging features can better predict the status of LNM of sMPLC, and the prediction efficiency is significantly higher than that of each factor alone, and can provide a basis for lymph node management decision.

Abstract This study aimed to investigate the clinical outcomes of local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures. This retrospective case series study included patients with Gustilo IIIB open tibiofibular fractures treated by local muscle or myocutaneous flap transfer in Weifang People’s Hospital between May 2016 and April 2021. Fifteenpatients (11 males aged 19–72 years) were included. The follow-up ranged from 8 to 24 months. The ranges of bone healing time and wound healing time were 6–17 months and 1–3 weeks, respectively. The length of hospital stay was 26 days (11–50 days). All patients reported acceptable functional recovery and satisfactory leg appearance, with Johner-Wruhs scores of excellent, good, and fair in 10, four, and one patients, respectively. The excellent-good rate was 93.3%. The complications included one case of infection and one case of nonunion. In conclusion, local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures may be useful in providing adequate soft tissue coverage and fracture healing with low complication and infection rates.

Abstract Infrared images of sensitive targets are difficult to obtain and cannot meet the design and training needs of target detection and tracking algorithms for mobile platforms such as aircraft. This paper proposes an image translation algorithm TransImg, which can achieve visible light image translation to the infrared domain to enrich the dataset. First, the algorithm designed a generator structure consisting of a deep residual connected encoder and a region perception feature fusion module to enhance feature learning, thereby avoiding issues such as generating infrared images with insufficient details in the transfer task. Afterward, a multi-scale discriminator and a composite loss function were designed to further improve the transfer effect. Finally, an automatic mixed-precision training strategy was designed for the overall migration algorithm architecture to accelerate the training and generation of infrared images. Experiments have shown that the image translation algorithm TransImg has good algorithm accuracy, and the infrared image generated by visible light image translation has richer texture details, faster generation speed, and lower video memory consumption, and the performance exceeds the mainstream traditional algorithm, and the generated images can meet the requirements of target detection and tracking algorithms design and training for mobile platforms such as aircraft.

Abstract Ovarian cancer is the fifth most prevalent cancer in women. Chemotherapy is a major treatment option for patients with advanced ovarian cancer (OC). Quinoline-2-thione and its derivatives are potential candidates for tumor therapy. In this study, we investigated the anticancer activity of the quinoline-2-thione derivative KA3D against ovarian cancer. The effect of KA3D on the viability of ovarian cancer cells was evaluated using MTT assay, and its effects on apoptosis and the cell cycle were detected using flow cytometry. Western blotting was performed to identify apoptosis-and cell cycle-related proteins altered by KA3D treatment. A xenograft model was used to verify the inhibitory effect of KA3D in vivo. H&E staining, biochemical indicator detection, and blood cell counts were used to observe the toxicity and side effects of KA3D. KA3D treatment impeded cell viability, induced apoptosis, and impeded the G2 phase of the cell cycle in ovarian cancer cells. Mechanistically, we found that KA3D enhanced the expression of proapoptotic molecules such as BAX and Caspase 3, while antiapoptotic proteins such as BCL2 were inhibited. The G0/G1 phase-related protein cyclin D1 was reduced and the G2 phase-related protein cyclin B1 was upregulated. In vivo, KA3D displayed potent anticancer activity, with no apparent toxicity in BABLC/c nude mice bearing SKOV3 cells. KA3D demonstrated remarkable chemotherapeutic drug efficacy in terms of significant cancer suppression in vitro and in vivo with low toxicity.

Abstract Background Percutaneous vertebroplasty or kyphoplasty is the preferred procedure for stage I and II Kümmell’s diseases (KDs), but there exist controversies on the operative option of stage III KD. This study aimed at exploring the safety and efficacy of ultrasonography-guided canal decompression (UG-CD) combined with vertebroplasty and cement-augmented pedicle screw fixation (CA-PSF) for treating stage III KD with neurological deficit (ND). Methods Between September 2017 and December 2023, all patients who received the UG-CD combined with vertebroplasty and CA-PSF for managing stage III KD with NDs were reviewed retrospectively with their demographic and operation data, and complications recorded. Besides, the scores of Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI), together with imaging data including the kyphotic Cobb angle (KCA), wedge angle (WA), spinal canal area (SCA) at the narrowest level as well as anterior (AHR) and middle (MHR) height ratios were measured and compared between pre- and post-operation. Results A total of eleven patients with a mean age of 70.09 ± 2.98 years old were included in our study with their surgical time, hospitalization length, blood loss, and follow-up time being 150.91 ± 17.94 min, 202.09 ± 39.95 ml, 8.18 ± 1.17 days, and 16.91 ± 4.09 months, respectively. During the final follow-up, the KCA, WA, VAS scores, ODI scores, AHR, MHR, and SCA were significantly improved (P

Abstract Background Current evidence underlines the active role of neural infiltration and axonogenesis within the tumor microenvironment (TME), with implications for tumor progression. Infiltrating nerves stimulate tumor growth and dissemination by secreting neurotransmitters, whereas tumor cells influence nerve growth and differentiation through complex interactions, promoting tumor progression. However, the role of neural infiltration in the progression of non-small cell lung cancer (NSCLC) remains unclear. Methods This study employs the techniques of immunohistochemistry, immunofluorescence, RNA sequencing, molecular biology experiments, and a murine orthotopic lung cancer model to deeply analyze the specific mechanisms behind the differential efficacy of NSCLC immunotherapy from the perspectives of neuro-tumor signal transduction, tumor metabolism, and tumor immunity. Results This study demonstrates that nerve growth factor (NGF) drives neural infiltration in NSCLC, and 5-hydroxytryptamine (5-HT), which is secreted by nerves, is significantly elevated in tumors with extensive neural infiltration. Transcriptome sequencing revealed that 5-HT enhanced glycolysis in NSCLC cells. Pathway analysis indicated that 5-HT activated the PI3K/Akt/mTOR pathway, promoting tumor metabolic reprogramming. This reprogramming exacerbated immunosuppression in the TME. Neutralizing 5-HT-mediated metabolic reprogramming in tumor immunity enhanced the efficacy of PD-1 monoclonal antibody treatment in mice. Conclusions The findings of this study provide a novel perspective on the crosstalk between nerves and lung cancer cells and provide insights into further investigations into the role of nerve infiltration in NSCLC progression.

Abstract Background We aimed to characterize the associations between physical activity levels and the risk of developing age-related diseases in the Coronary Artery Risk Development in Young Adults (CARDIA) study and used Mendelian randomization (MR) to assess whether there are causal relationships between physical activity levels and the risk of developing 8 age-related diseases (coronary atherosclerosis, ischemic heart disease, angina, Alzheimer’s disease, hypertension, type 2 diabetes, hyperlipidemia, and venous thromboembolism). Methods Based on the data available in the CARDIA, we obtained data related to five disease states: coronary heart disease, hypertension, diabetes, hyperlipidemia, and venous thromboembolism. Binary logistic regression analysis estimated the multivariable-adjusted associations between different physical activity statuses and diseases. For the MR study, we used summary-level data from a recently published genome-wide association study on physical activity (including vigorous physical activity and accelerometer-based physical activity) conducted with participants from the UK Biobank study. We selected the above 8 age-related diseases as our outcomes. Results In the CARDIA-based analysis, the risk of developing coronary heart disease [OR (95% CI): 0.562 (0.397–0.795)], hypertension [OR (95% CI): 0.703 (0.601–0.821)], diabetes [OR (95% CI): 0.783 (0.620–0.988)], and hyperlipidemia [OR (95% CI): 0.792 (0.662–0.949)] was negatively related to physical activity status when participants achieved the physical activity target. Our MR results support a negative causal association between genetically determined vigorous physical activity levels and the risk of developing 3 age-related diseases, namely, angina, hypertension and type 2 diabetes. Moreover, our results also support a negative causal association between genetically determined accelerometer-based physical activity levels and the risk of developing angina. Conclusions Promotion of physical activity is likely to prevent specific age-related diseases.

Abstract The microscopic reaction pathway plays a crucial role in determining the electrochemical performance. However, artificially manipulating the reaction pathway still faces considerable challenges. In this study, we focus on the classical acidic water oxidation based on RuO2 catalysts, which currently face the issues of low activity and poor stability. As a proof-of-concept, we propose a strategy to create local structural symmetry but oxidation-state asymmetric Mn4-δ-O-Ru4+δ active sites by introducing Mn atoms into RuO2 host, thereby switching the reaction pathway from traditional adsorbate evolution mechanism to oxide path mechanism. Through advanced operando synchrotron spectroscopies and density functional theory calculations, we demonstrate the synergistic effect of dual-active metal sites in asymmetric Mn4-δ-O-Ru4+δ microstructure in optimizing the adsorption energy and rate-determining step barrier via an oxide path mechanism. This study highlights the importance of engineering reaction pathways and provides an alternative strategy for promoting acidic water oxidation.

Abstract Background Ischemic stroke belongs to “apoplexy” and its pathogenesis is characterized by qi deficiency and blood stasis combining with phlegm-damp clouding orifices. Buqi-Huoxue-Tongnao decoction (BHTD) is a traditional Chinese medicine formula for qi deficiency, blood stasis and phlegm obstruction syndrome. However, its efficacy and potential mechanism on ischemic stroke are still unclear. This study aims to investigate the protective effect and potential mechanism of BHTD against ischemic stroke. Materials and methods Middle cerebral artery occlusion (MCAO) surgery was carried out to establish an ischemic stroke model in rats. Subsequently, the rats were gavaged with different doses of BHTD (2.59, 5.175, 10.35 g/kg) for 14 days. The protective effects of BHTD on the brain and gut were evaluated by neurological function scores, cerebral infarction area, levels of brain injury markers (S-100B, NGB), indicators of gut permeability (FD-4) and bacterial translocation (DAO, LPS, D-lactate), and tight junction proteins (Occludin, Claudin-1, ZO-1) in brain and colon. 16S rRNA gene sequencing and metabolomic analysis were utilized to analyze the effects on gut microecology and screen for marker metabolites to explore potential mechanisms of BHTD protection against ischemic stroke. Results BHTD could effectively mitigate brain impairment, including reducing neurological damage, decreasing cerebral infarction and repairing the blood–brain barrier, and BHTD showed the best effect at the dose of 10.35 g/kg. Moreover, BHTD reversed gut injury induced by ischemic stroke, as evidenced by decreased intestinal permeability, reduced intestinal bacterial translocation, and enhanced intestinal barrier integrity. In addition, BHTD rescued gut microbiota dysbiosis by increasing the abundance of beneficial bacteria, including Turicibacter and Faecalibaculum. Transplantation of the gut microbiota remodeled by BHTD into ischemic stroke rats recapitulated the protective effects of BHTD. Especially, BHTD upregulated tryptophan metabolism, which promoted gut microbiota to produce more indole lactic acid (ILA). Notably, supplementation with ILA by gavage could alleviate stroke injury, which suggested that driving the production of ILA in the gut might be a novel treatment for ischemic stroke. Conclusion BHTD could increase gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis. Our current finding provides evidence that traditional Chinese medicine can ameliorate central diseases through regulating the gut microbiology.

Abstract Collagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders.

Abstract Background Cystathionine accumulates selectively in 1p/19q-codeleted gliomas, and can serve as a possible noninvasive biomarker. This study aims to optimize the echo time (TE) of point-resolved spectroscopy (PRESS) for cystathionine detection in gliomas, and evaluate the diagnostic accuracy of PRESS for 1p/19q-codeletion identification. Methods The TE of PRESS was optimized with numerical and phantom analysis to better resolve cystathionine from the overlapping aspartate multiplets. The optimized and 97 ms TE PRESS were then applied to 84 prospectively enrolled patients suspected of glioma or glioma recurrence to examine the influence of aspartate on cystathionine quantification by fitting the spectra with and without aspartate. The diagnostic performance of PRESS for 1p/19q-codeleted gliomas were assessed. Results The TE of PRESS was optimized as (TE1, TE2) = (17 ms, 28 ms). The spectral pattern of cystathionine and aspartate were consistent between calculation and phantom. The mean concentrations of cystathionine in vivo fitting without aspartate were significantly higher than those fitting with full basis-set for 97 ms TE PRESS (1.97 ± 2.01 mM vs. 1.55 ± 1.95 mM, p

The complex deformation behavior would result in surface roughening such as orange peel defect during the hydroforming process of aluminum alloy tubular parts. In order to control the surface quality of hydroformed tubular parts, the effect of strain state on the surface roughening for 2219 aluminum alloy tube was analyzed based on a cross-scale model. The model combined the crystal plasticity model and macroscopic finite element model. During the uniaxial tension, the surface morphology reveals an equiaxed pattern characteristic of orange peel due to the strain incompatibilities between grains, and the peak and valley are stretched along the tensile direction. The surface roughness under tension-compression plane strain state is the lowest due to the low through-thickness strain. In the biaxial tension region, the change rate of surface roughness gradually increases with the decrease of the second principal strain especially in the late deformation stage, and the surface features evolve from an orange peel pattern to a ridging pattern. The forming limit diagram under different strain states based on surface roughness was established to guide the optimization of hydroforming process. Compared with the one-step hydroforming, the surface roughness of the bulging peak of 2219 aluminum alloy tube using multi-step hydroforming with the axial self-feeding decreases obviously from 16.3 to 10.8 μm due to the significant reduction of the equivalent strain.

AbstractContext Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs.Objective This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC.Methods The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data.Results Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96–3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia.Conclusions Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.

Abstract The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P

Abstract The high uncertainty of wind power output greatly affects the rapid reactive power optimization of power systems. This paper proposes a neural network‐based comprehensive reactive power optimization method for large‐scale wind power grids, effectively addressing the challenges of rapid reactive power optimization in power systems. Firstly, by constructing typical wind‐power‐load scenarios, the generalization ability of the neural network is improved. Then, focusing on the comprehensive reactive power optimization problem after integrating typical wind‐power‐load scenarios into the system, the improved Harris hawks optimization algorithm (HHO) is compared with the particle swarm optimization algorithm and traditional HHO algorithm, highlighting its advantages. Finally, HHO is utilized for solving, thereby constructing a comprehensive reactive power optimization strategy tag set. Furthermore, through deep fitting of the neural network between the power grid operating state and the comprehensive reactive power optimization strategy, the computational complexity and decision‐making time of reactive power optimization are reduced.

ObjectiveTo analyze the predictive effect of miRNA-let-7 combined with serum markers on the chemotherapy effect and prognosis of glioma (GBM) patients. MethodsWe collected the data of 25 patients with GBM. Twenty healthy volunteers were included as the control group. Fasting serum samples were collected. The levels of let-7b, let-7d, and let-7e in serum samples were analyzed by quantitative real-time PCR. ResultsCompared with the control group, the levels of let-7b (192.5±18.71 vs. 98.13±11.68, t=6.42, P

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat, and seriously threatens safe production of the crop worldwide. In China, new races historically appeared and rapidly developed to be predominant races and have resulted in ineffectiveness and replacement of wheat resistance cultivars as well as massive reduction in yield. In the present study, the relative parasitic fitness of the two newly-emerged Yr5-virulent races (TSA-6 and TSA-9) were compared with those of four currently predominant Chinese races (CYR31, CYR32, CYR33, and CYR34) based on evaluation on 10 Chinese wheat cultivars. As a result, there were significant differences in the relative parasitic fitness parameters among overall tested races based on multiple comparison (LSD) analysis (PTSA-9 (0.95)>TSA-6 (0.92)>CYR34 (0.29)>CYR31 (–1.54)>CYR33 (–1.77). The results indicated that two Yr5-virulent races TSA-9 and TSA-6 possessed relative parasitic fitness higher than races CYR34, CYR31, and CYR33, but lower than race CYR32, and have potential risks in developing to be predominant races. Therefore, continual monitoring of both Yr5-virulent races, and their variants is needed. The use of wheat cultivars (lines) with Yr5 resistance gene singly in wheat breeding is essential for being avoided, and is suggested to combine with other effective stripe rust resistance genes.

Abstract Background Insulin resistance and diabetes are associated with an increased risk of frailty, and frailty is associated with cardiovascular disease and premature mortality. We aim to investigate the impact of long‐term insulin resistance trajectories on future frailty and cardiovascular risk among young adults. Methods In total, 3168 participants with a 30‐year follow‐up period. The baseline period covered the first 15 years as the exposure period. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA‐IR), and three trajectories (low, moderate, and high) were constructed. The subsequent 15 years constituted the event accrual period. Frailty was assessed using a deficit accumulation mode, and cardiovascular outcomes were obtained from the 15‐year event accrual period. Results The mean age of all 3168 participants was 41.0 (37.0–43.0) years, with 1750 (55.2%) being women. Participants in the high level of insulin resistance trajectory had an increased prevalence of frailty (OR: 1.55, 95% CI: 1.05–2.30, P = 0.028). Although no statistically significant associations were observed after full adjustment, single‐factor analysis indicated association between the moderate and high trajectories and frailty progression. Additionally, participants with high level of insulin resistance trajectory were associated with an increased risk of cardiovascular disease, coronary heart disease, and stroke. A notable correlation between HOMA‐IR trajectory and cardiovascular diseases was still discernible within the subgroup where the frailty index ≥0.12 (HR: 2.12, 95% CI: 1.17–3.83, P = 0.013) (P for interaction >0.05). Conclusions Long‐term high level of insulin resistance is associated with high prevalence of frailty, and an increased risk of cardiovascular events. Emphasizing the importance of early prevention and intervention for abnormal glucose metabolism in young adults to prevent frailty and cardiovascular disease.

Abstract Although circular RNAs (circRNA) have been demonstrated to modulate tumor initiation and progression, their roles in the proliferation of hepatocellular carcinoma (HCC) are still poorly understood. Based on the analysis of GEO data (GSE12174), hsa-circRNA-0015004 (circ-0015004) was screened and validated in 80 sets of HCC specimens. Subcellular fractionation analysis was designed to determine the cellular location of circ-0015004. Colony formation and cell counting kit-8 were performed to investigate the role of circ-0015004 in HCC. Dual-luciferase reporter gene assays, RNA immunoprecipitation and chromatin immunoprecipitation were employed to verify the interaction among circ-0015004, miR-330-3p and regulator of chromatin condensation 2 (RCC2). The expression level of circ-0015004 was significantly upregulated in HCC cell lines and HCC tissues. HCC patients with higher circ-0015004 levels displayed shorter overall survival, and higher tumor size and TNM stage. Moreover, knockdown of circ-0015004 significantly reduced HCC cell proliferation in vitro and inhibited the growth of HCC in nude mice. Mechanistic studies revealed that circ-0015004 could upregulate the expression of RCC2 by sponging miR-330-3p, thereby promoting HCC cell proliferation. Furthermore, we identified that Ying Yang 1 (YY1) could function as an important regulator of circ-0015004 transcription. This study systematically demonstrated the novel regulatory signaling of circ-0015004/miR-330-3p/RCC2 axis in promoting HCC progression, providing insight into HCC diagnosis and treatment from bench to clinic.

Abstract The traceability of groundwater nitrate pollution is crucial for controlling and managing polluted groundwater. This study integrates hydrochemistry, nitrate isotope (δ15N-NO3 − and δ18O-NO3 −), and self-organizing map (SOM) and end-member mixing (EMMTE) models to identify the sources and quantify the contributions of nitrate pollution to groundwater in an intensive agricultural region in the Sha River Basin in southwestern Henan Province. The results indicate that the NO3 −-N concentration in 74% (n = 39) of the groundwater samples exceeded the WHO standard of 10 mg/L. According to the results of EMMTE modeling, soil nitrogen (68.4%) was the main source of nitrate in Cluster-1, followed by manure and sewage (16.5%), chemical fertilizer (11.9%) and atmospheric deposition (3.3%). In Cluster-2, soil nitrogen (60.1%) was the main source of nitrate, with a significant increase in the contribution of manure and sewage (35.5%). The considerable contributions of soil nitrogen may be attributed to the high nitrogen fertilizer usage that accumulated in the soil in this traditional agricultural area. Moreover, it is apparent that most Cluster-2 sampling sites with high contributions of manure and sewage are located around residential land. Therefore, the arbitrary discharge and leaching of domestic sewage may be responsible for these results. Therefore, this study provides useful assistance for the continuous management and pollution control of groundwater in the Sha River Basin.

Abstract Objectives Ants are ecologically dominant insects in most terrestrial ecosystems, with more than 14,000 extant species in about 340 genera recorded to date. However, genomic resources are still scarce for most species, especially for species endemic in East or Southeast Asia, limiting the study of phylogeny, speciation and adaptation of this evolutionarily successful animal lineage. Here, we assemble and annotate the genomes of Odontoponera transversa and Camponotus friedae, two ant species with a natural distribution in China, to facilitate future study of ant evolution. Data description We obtained a total of 16 Gb and 51 Gb PacBio HiFi data for O. transversa and C. friedae, respectively, which were assembled into the draft genomes of 339 Mb for O. transversa and 233 Mb for C. friedae. Genome assessments by multiple metrics showed good completeness and high accuracy of the two assemblies. Gene annotations assisted by RNA-seq data yielded a comparable number of protein-coding genes in the two genomes (10,892 for O. transversa and 11,296 for C. friedae), while repeat annotations revealed a remarkable difference of repeat content between these two ant species (149.4 Mb for O. transversa versus 49.7 Mb for C. friedae). Besides, complete mitochondrial genomes for the two species were assembled and annotated.

Abstract Background The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research. Methods This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings. Results Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22–1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3–2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications. Conclusions The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients. Graphical abstract

Abstract Background Telemedicine is beneficial for improving treatment efficiency and reducing medical expenses of cancer patients. This study focuses on cancer patients participating in teleconsultations through a regional telemedicine platform in China, analyzes the consultation process, and provides references for the clinical application of telemedicine. Methods We collected information on teleconsultations of cancer patients conducted from 2015 to 2022 through the regional telemedicine platform. Utilizing SPSS 23.0 software, we conducted descriptive analysis to summarize the distribution of patient gender, age, region, and disease types. The ordinal logistic regression analysis was adopted to analyze the factors influencing the waiting time and consultation duration for teleconsultations. Results From 2015 to 2022, a total of 23,060 teleconsultations were conducted for cancer patients via regional telemedicine platform, with an average growth rate of 11.09%. The main types of consultations were for lung cancer, liver cancer, and breast cancer, accounting for 18.14%, 10.49%, and 9.46% respectively. 57.05% of teleconsultations had a waiting time of less than 24 h, while patient age, consultation expert level, and disease type were the main factors influencing the waiting time. 50.06% of teleconsultations had a duration of more than 20 min, and the inviting hospital level and the title of invited consultant were the main factors influencing the consultation duration. Conclusions In China, telemedicine has been widely employed in the clinical diagnosis and treatment of cancers, covering various types of oncological diseases. However, the waiting time for teleconsultations was generally more than 12 h, indicating the need to enhance consultation scheduling and allocate more expert resources to further optimize the efficiency of teleconsultations. Additionally, further exploration is required for remote health management of outpatients with cancers outside the hospital.

Abstract Background Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. Methods Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. Results A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. Conclusions This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China. Graphical Abstract

Abstract Background Hepatocellular carcinoma (HCC) ranks as the second leading cause of global cancer-related deaths and is characterized by a poor prognosis. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) have been proved to play important roles in various human cancers, whereas the deubiquitination of EEF1A1 was poorly understood. Methods The binding and regulatory relationship between Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) and EEF1A1 was validated using clinical tissue samples, reverse transcription quantitative real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, co-immunoprecipitation, and immunofluorescence, as well as ubiquitin detection and cyclohexamide tracking experiments. Finally, the impact of the UCHL3/EEF1A1 axis on HCC malignant behavior was analyzed through functional experiments and nude mouse models. Results UCHL3 was found to have a high expression level in HCC tissues. Tissue samples from 60 HCC patients were used to evaluate the correlation between UCHL3 and EEF1A1. UCHL3 binds to EEF1A1 through the lysine site, which reduces the ubiquitination level of EEF1A1. Functional experiments and nude mouse models have demonstrated that the UCHL3/EEF1A1 axis promotes the migration, stemness, and drug resistance of HCC cells. Reducing the expression of EEF1A1 can reverse the effect of UCHL3 on the malignant behavior of HCC cells. Conclusion Our findings revealed that UCHL3 binds and stabilizes EEF1A1 through deubiquitination. UCHL3 and EEF1A1 formed a functional axis in facilitating the malignant progression of HCC, proving new insights for the anti-tumor targeted therapy for HCC.

To ensure the operational safety of nuclear power plants, we present a Quadruped Inspection Robot that can be used for many types of steam generators. Since the Inspection Robot relies on the Holding Modules to grip the tube-sheet, it can be regarded as a hybrid robot with variable configurations, switching between 4-RRR-RR, 3-RRR-RR, and two types of 2-RRR-RR, and the variable configurations bring a great challenge to dimensional synthesis. In this paper, the kinematic model of the Inspection Robot in multiple configurations is established, and the analytical solution is given. The workspace mapping is analyzed by the solution-space, and the workspace of multiple configurations is decomposed into the workspace of 2-RRR to reduce the analysis complexity, and the workspace calculation is simplified by using the envelope rings. The optimization problem of the manipulator is transformed into the calculation of the shortest contraction length of the swing leg. The switching performance of the Inspection Robot is evaluated by stride-length, turning-angle, and workspace overlap-ratio. The performance indexes are classified and transformed based on the proportions and variation trends of dimensional parameters to reduce the number of optimization objective functions, and Pareto optimal solutions are obtained using an intelligent optimization algorithm.

Abstract Introduction Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies. Methods A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay. Results Pharmacokinetic analysis of the drug concentration–time data showed that the mean maximum observed serum QX002N concentration (C max) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration–time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration–time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%. Conclusions Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects. Trial Registration www.chinadrugtirals.org.cn , CTR20220430.

Abstract Background Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. Methods A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. Results Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). Conclusions There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.

Abstract Continuous cultivation of tobacco could cause serious soil health problems, which could cause bacterial soil to change to fungal soil. In order to study the diversity and richness of fungal community in tobacco-growing soil under different crop rotation, three treatments were set up in this study: CK (tobacco continuous cropping); B (barley-tobacco rotation cropping) and R (oilseed rape-tobacco rotation cropping). The results of this study showed that rotation with other crops significantly decreased the soil fungal OTUs, and also decreased the community richness, evenness, diversity and coverage of fungal communities. Among them, B decreased the most. In the analysis of the composition and structure of the fungal community, it was found that the proportion of plant pathogens Nectriaceae decreased from 19.67% in CK to 5.63% in B, which greatly reduced the possibility of soil-borne diseases. In the analysis of the correlation between soil environmental factors and fungal communities, it was found that Filobasidiaceae had a strong correlation with TP and AP, and Erysiphaceae had a strong correlation with TK and AK. NO3 −-N and NH4 +-N were the two environmental factors with the strongest correlation with fungal communities. The results of this study showed that rotation with other crops slowed down the process of soil fungi in tobacco-growing soil and changed the dominant species of soil fungi community. At the same time, crop rotation changed the diversity and richness of soil fungal community by changing the physical and chemical properties of soil.

Abstract Background Assessing the aggressiveness of pure ground glass nodules early on significantly aids in making informed clinical decisions. Objective Developing a predictive model to assess the aggressiveness of pure ground glass nodules in lung adenocarcinoma is the study’s goal. Methods A comprehensive search for studies on the relationship between computed tomography(CT) characteristics and the aggressiveness of pure ground glass nodules was conducted using databases such as PubMed, Embase, Web of Science, Cochrane Library, Scopus, Wanfang, CNKI, VIP, and CBM, up to December 20, 2023. Two independent researchers were responsible for screening literature, extracting data, and assessing the quality of the studies. Meta-analysis was performed using Stata 16.0, with the training data derived from this analysis. To identify publication bias, Funnel plots and Egger tests and Begg test were employed. This meta-analysis facilitated the creation of a risk prediction model for invasive adenocarcinoma in pure ground glass nodules. Data on clinical presentation and CT imaging features of patients treated surgically for these nodules at the Third Affiliated Hospital of Kunming Medical University, from September 2020 to September 2023, were compiled and scrutinized using specific inclusion and exclusion criteria. The model’s effectiveness for predicting invasive adenocarcinoma risk in pure ground glass nodules was validated using ROC curves, calibration curves, and decision analysis curves. Results In this analysis, 17 studies were incorporated. Key variables included in the model were the largest diameter of the lesion, average CT value, presence of pleural traction, and spiculation. The derived formula from the meta-analysis was: 1.16×the largest lesion diameter + 0.01 × the average CT value + 0.66 × pleural traction + 0.44 × spiculation. This model underwent validation using an external set of 512 pure ground glass nodules, demonstrating good diagnostic performance with an ROC curve area of 0.880 (95% CI: 0.852–0.909). The calibration curve indicated accurate predictions, and the decision analysis curve suggested high clinical applicability of the model. Conclusion We established a predictive model for determining the invasiveness of pure ground-glass nodules, incorporating four key radiological indicators. This model is both straightforward and effective for identifying patients with a high likelihood of invasive adenocarcinoma.

Abstract The improvement in transportation efficiency, security, safety, and environmental effects may be possible due to the impending advent of autonomous ships. Automatic situational awareness, risk detection, and intelligent decision-making are the key features of the intelligent ship network, differentiating it from conventional ships. There is an immediate need to implement a system for marine information management and network security due to the growing importance of this field, which poses a risk to national and societal stability due to factors, such as the diversity and complexity of marine information types, the challenges associated with data collection, and other similar factors. By recognizing different vulnerabilities and through research cases of the ship systems and Artificial Intelligence (AI) technologies, this paper presents Adaptive Fuzzy Logic-assisted Vulnerability Analysis of Intelligent Ship Networks (AFL-VA-ISN) in various cyberattack scenarios for autonomous ship intrusion detection and information management. Fuzzy logic has been combined with AI, providing a framework for handling uncertainty and imprecision in intelligent ship networks and effective decision-making. This work presents a method for detecting anomalies in risk data based on the collaborative control structure of the Ship Information System. Maintaining the network security of intelligent ships is the primary focus of this research, which mainly employed multi-sensor nodes to evaluate data containing information about malicious attacks and placed self-execution protection organize generating nodes into place to intercept and protect against attacks. The experimental outcomes demonstrate that the suggested AFL-VA-ISN model increases the data transmission rate by 99.2%, attack detection rate by 98.5%, risk assessment rate by 97.5%, and access control rate of 96.3%, and reduces the network latency rate of 11.4% compared to other existing models.

Abstract Background Whether patients with cT1 − 2N1M0 breast cancer can benefit from postoperative radiotherapy (RT) after receiving neoadjuvant chemotherapy (NAC) has been controversial. Therefore, the purpose of this study was to explore whether postoperative RT can benefit this group of patients in terms of survival. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to conduct a retrospective review of women with cT1 − 2N1M0 breast cancer diagnosed between 20 and 80 years of age who received NAC between 2010 and 2015. Our study compared the impact of postoperative RT on overall survival (OS) and cancer-specific survival (CSS) in breast cancer patients using propensity score matching (PSM) and performed subgroup analysis. Results This study finally included 1092 cT1 − 2N1M0 breast cancer patients. Regardless of the patient’s PSM status, postoperative RT was significantly associated with OS of cT1- 2N1M0 breast cancer patients who received NAC. Specifically, the 10-year OS rate was 78.7% before PSM matching, compared with 71.1% in patients who did not receive postoperative RT, and the difference was more significant after PSM matching, which was 83.1% and 71.1% respectively. However, postoperative RT did not significantly benefit CSS in patients with cT1 − 2N1M0 breast cancer who received NAC. The 10-year CSS rate was 81.4% VS 76.2% (P = 0.085) before PSM matching and 85.8% VS 76.2%(P = 0.076) after matching. Due to the intersection of OS and CSS curves, this restricted mean survival time (RMST) method was chosen as a supplement. After 60 months, the OS difference in RMST between the postoperative RT group and the non-radiotherapy (noRT) group was 7.37 months (95%CI: 0.54–14.21; P = 0.034), and the CSS difference was 5.18 months (95%CI: -1.31-11.68; P = 0.118). Subgroup analysis found that in patients with right-sided breast cancer, postoperative RT improved the patient’s OS (HR = 0.45, 95%CI: 0.21–0.95, P = 0.037) and CSS (HR = 0.42, 95%CI: 0.18–0.98, P = 0.045). Conclusions Our results showed that additional postoperative RT improved the OS of cT1 − 2N1M0 breast cancer patients who received NAC, but failed to improve their CSS. It is worth noting that in the subgroup analysis of patients with right-sided breast cancer, we observed significant improvements in OS and CSS. And further prospective studies are still needed to verify the effect of postoperative RT in different subgroups.

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H2S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivo results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.

ObjectivesTo investigate the causal relationship between type 2 diabetes mellitus (T2DM, exposure) and isolated REM sleep behavior disorder (iRBD, outcome).MethodsGenome-wide association study (GWAS) data for iRBD comprised 9,447 samples, including 1,061 iRBD cases from the International RBD Study Group. Initially, we performed linkage disequilibrium score regression (LDSC) to explore the genetic correlation between T2DM and iRBD. Then the two-sample univariate MR (UVMR) analysis was conducted to examine the effects of T2DM and blood sugar metabolism-related factors on iRBD. Subsequently, we applied multivariable MR (MVMR) methods to further adjust for confounders. Lastly, we executed a network MR analysis, with cytokines and immune cell characteristics as potential mediators, aiming to investigate indirect effect of T2DM on iRBD.ResultsResults from LDSC suggest a genetic correlation between T2DM and iRBD (rg=0.306, P=0.029). UVMR analysis indicates that both T2DM (Odds Ratio [95% Confidence Interval] = 1.19 [1.03, 1.37], P = 0.017) and high blood glucose levels (1.55 [1.04, 2.30], P = 0.032) are risk factors for iRBD. Even after adjusting for confounders in MVMR, the association between T2DM and iRBD remains robust. Finally, results from network MR analysis suggest that T2DM may indirectly promote the development of iRBD by reducing levels of Stromal Cell-Derived Factor 2 in circulation and by increasing BAFF-receptor expression in IgD- CD38- B cells.ConclusionsT2DM may promote the onset of iRBD by influencing immune-inflammatory responses. Our findings provide valuable insights and directions for understanding the pathogenesis of iRBD, identifying high-risk groups, and discovering new therapeutic targets.

ObjectiveThis study aims to report the application of 18F-AlF-NOTA-Octreotide PET/CT and 3D printing technology in the diagnosis and treatment of phosphaturic mesenchymal tumors (PMT) in patients with tumor-induced osteomalacia (TIO).Case presentationA 68-year-old male patient (Case 1) was admitted to the Weifang People’s Hospital in August 2022 with complaints of “persistent pain in the bilateral flank and lumbosacral region”. 18F-AlF-NOTA-Octreotide PET/CT showed high octreotide expression in the left femoral region. A 48-year-old male patient (Case 2) was admitted to the Weifang People’s Hospital in November 2022, complaining of “pain in the lumbar region and ribs”. 18F-AlF-NOTA-Octreotide PET/CT showed high octreotide expression in the pancreatic uncinate process and the left acetabulum. They were diagnosed with hypophosphatemic osteomalacia, with a strong consideration of an underlying neuroendocrine tumor. Preoperative design of 3D virtual surgery, CAD/CAM, and 3D printing technology were used to customize the digital surgical guide plates, and the surgery was carried out. They were both finally confirmed as phosphateuric mesenchymal tumors (PMT) based on postoperative pathology and immunohistochemistry results. Both patients experienced substantial relief from their clinical manifestations after surgery.Conclusion18F-AlF-NOTA-Octreotide PET/CT may be a precise diagnostic method for TIO, while 3D printing technology may serve as an effective and dependable adjunct for the treatment of PMT in patients with TIO.

IntroductionLow back pain (LBP) was commonly induced by intervertebral disc degeneration (IVDD), which is accompanied by the loss of disc height and osteophyte generation. Cell-based therapy is a promising treatment for preventing the degeneration of interverbral disc. In our study, allogeneic fibroblasts are shown to ameliorate intervertebral disc degeneration by reducing osteophytes in rabbits.MethodsWe established a rabbits-derived fibroblast (Rab-Fib) which could be expanded in vitro and constructed puncture-induced intervertebral disc degeneration rabbit model. Histologic and imaging examinations and analyses were performed after 2 weeks, 3 months, and 12 months.ResultsOur data indicate that stable and reliably-extracted allogeneic fibroblasts can effectively ameliorate intervertebral disc degeneration by reducing osteophytes.ConclusionOur study provides a basis for advancing the further translation of fibroblasts in intervertebral disc therapy.

The activation of complement receptor 3 (CR3) in microglia contributes to neurodegeneration in neurological disorders, including Parkinson's disease (PD). However, it remains unclear for mechanistic knowledge on how CR3 mediates neuronal damage. In this study, the expression of CR3 and its ligands iC3b and ICAM-1 was found to be up-regulated in the midbrain of rotenone PD mice, which was associated with elevation of iron content and disruption of balance of iron metabolism proteins. Interestingly, genetic deletion of CR3 blunted iron accumulation and recovered the expression of iron metabolism markers in response to rotenone. Furthermore, reduced lipid peroxidation, ferroptosis of dopaminergic neurons and neuroinflammation were detected in rotenone-lesioned CR3−/− mice compared with WT mice. The regulatory effect of CR3 on ferroptotic death of dopaminergic neurons was also mirrored in vitro. Mechanistic study revealed that iron accumulation in neuron but not the physiological contact between microglia and neurons was essential for microglial CR3-regulated neuronal ferroptosis. In a cell-culture system, microglial CR3 silence significantly dampened iron deposition in neuron in response to rotenone, which was accompanied by mitigated lipid peroxidation and neurodegeneration. Furthermore, ROS released from activated microglia via NOX2 was identified to couple microglial CR3-mediated iron accumulation and subsequent neuronal ferroptosis. Finally, supplementation with exogenous iron was found to recover the sensitivity of CR3−/− mice to rotenone-induced neuronal ferroptosis. Altogether, our findings suggested that microglial CR3 regulates neuron ferroptosis through NOX2 -mediated iron accumulation in experimental Parkinsonism, providing novel points of the immunopathogenesis of neurological disorders.

Abstract Solid‐state sodium batteries (SSSBs) are poised to replace lithium‐ion batteries as viable alternatives for energy storage systems owing to their high safety and reliability, abundance of raw material, and low costs. However, as the core constituent of SSSBs, solid‐state electrolytes (SSEs) with low ionic conductivities at room temperature (RT) and unstable interfaces with electrodes hinder the development of SSSBs. Recently, composite SSEs (CSSEs), which inherit the desirable properties of two phases, high RT ionic conductivity, and high interfacial stability, have emerged as viable alternatives; however, their governing mechanism remains unclear. In this review, we summarize the recent research progress of CSSEs, classified into inorganic–inorganic, polymer–polymer, and inorganic–polymer types, and discuss their structure–property relationship in detail. Moreover, the CSSE–electrode interface issues and effective strategies to promote intimate and stable interfaces are summarized. Finally, the trends in the design of CSSEs and CSSE–electrode interfaces are presented, along with the future development prospects of high‐performance SSSBs.

BackgroundMechanical failure following total spondylectomy is a surgical challenge. The cervicothoracic junction region is a special anatomical site with complex biomechanics, and few studies have reported a detailed surgical management strategy for cases where the mesh cage subsides and compresses the spinal cord in the cervicothoracic junction region after total spondylectomy.Case presentationA 56-year-old male patient experienced screw and rod fracture and mesh cage retropulsion into the spinal canal 5 years after total spondylectomy for osteochondroma in the first to third thoracic vertebrae. The patient complained of numbness and discomfort in both lower extremities, accompanied by unstable walking for 8 months prior to admission at our hospital. We concluded that uncorrected local kyphosis in the cervicothoracic junction after the first surgery resulted in current mesh cage subsidence and rod/screw fracture. Considering the difficulty and risks of removing the mesh cage from the anterior approach, we initially freed the superior end of the mesh cage without removing the mesh from the anterior approach by resecting the C6/7 intervertebral disc and the destroyed C7 vertebral body. We then removed the original screws and rods and performed long segment fixation from C4 to T6 via a posterior approach after recovering sagittal alignment by skull traction. Finally, the iliac bone was harvested and transplanted between the superior end of the mesh cage and the inferior end plate of C6 to fill the defect caused by kyphosis correction and C7 vertebral resection. After surgery, the patient experienced sagittal alignment reconstruction and symptom relief, and he was asked to wear a cast for at least 6 months until bone fusion was achieved. At the 3-year follow-up, there was fusion between the mesh cage and the C6 vertebra with successful instrument reconstruction and no mesh cage subsidence were observed.ConclusionsWhen a subsided and migrated titanium mesh cage is difficult to remove after mechanical failure following total spondylectomy, recovering sagittal alignment to achieve indirect decompression based on unique anterior and middle column reconstruction, solid instrument construction, and bone fusion is an alternative solution.

Retinal surgery requires enclosed spatial constraints to improve the safety and success of the surgery. Herein, a shared control method is proposed for master–slave robot systems, utilizing tubular guidance constraints based on a novel potential field function to optimize the commands of the surgeon. Within the tube, attractive constraints intensify with increasing task error and approach infinity at the boundary of the tube. This ensures that the surgery is confined within a closed tubular space. Haptic feedback provides force cues to inform the surgeon about the feasibility of the input commands. Theoretical derivations demonstrate that the entire closed‐loop system is passive. Two simulation experiments are conducted on the ophthalmic surgery robot platform to evaluate the functionality of the proposed method. The experimental results indicate that translational errors are kept less than certain predefined values. Furthermore, the proposed method outperforms the comparison method in terms of task accuracy and efficiency.

IntroductionSoil contamination with copper (Cu) threatens ecological security and human health. Rapeseed demonstrates potential in remediating copper-contaminated soil, and biochar-assisted phytoremediation is increasingly being employed to improve remediation efficiency. However, the combined application of them has not been thoroughly studied in terms of the synergistic effects and the mechanisms of their interaction.MethodsIn this regard, this study conducted a pot experiment to evaluate biochar-assisted remediation under Cu-contaminated soil with varying biochar application rates; Furthermore, the plant physiological mechanism and soil physicochemical properties involved in the biocharrapeseed system was explored.ResultsOur results showed that the exchangeable pool of copper in soil decreased by 10.0% and 12.3% with adding 5% biochar (BC1) and 10% biochar (BC2) relative to control (BC0), respectively, prior to rapeseed cultivation. The rapeseed cultivation for one season further reclaimed 4.9%, 9.0%, and 13.6% of the available copper in this soil by root extraction under the BC0, BC1, and BC2 treatments, respectively. The overall copper concentration in plants decreased by 23.7% under BC2 and 13.3% under BC1 compared to BC0. However, the plant’s dry biomass at BC1 and BC2 treatments increased by 1.7-fold and 2.7-fold relative to BC0, which offset the negative impact of the decreased copper concentration on phytoremediation. Physiological analysis showed adding 10% biochar decreased the MDA content by 36% in the leaf and 49% in the root, compared to BC0. The transmission electron microscopy for cell wall ultrastructure in root tips showed that biochar addition in Cu-contaminated soil increased the mechanical strength of the celL wall, explicitly increasing the thickness of the secondary cell wall. Further cell wall components analysis revealed a remarkable increment of the pectin content in BC2 relative to BC0, increased by 56% in the leaf and 99% in the root, respectively. Additionally, 10% biochar application led to a roughly 2-fold increase in seed yield via ameliorating the soil physicochemical properties and increasing the rapeseed growth.DiscussionThese findings offer insights into synergistic rapeseed-biochar use for Cu-contaminated soil remediation.

ObjectiveThe aim of this study was to investigate whether a potential moral cognitive impairment (failure in understanding moral rules) exists in patients with schizophrenia (SCZ) and to explore the effect of childhood trauma (CT) on moral cognition in a group of patients with SCZ.MethodsA total of 99 patients with SCZ and 102 healthy controls (HCs) were included in this study. The Childhood Trauma Questionnaire-Short Form (CTQ) was administered to assess childhood trauma experiences in both groups, while the Moral Identity Measure (MIM) and the Moral Foundations Questionnaire (MFQ) were applied for a comparative evaluation of moral cognition across the two groups. The Positive and Negative Syndrome Scale (PANSS) was administered to assess the psychopathology.ResultsPatients with schizophrenia had significantly greater CTQ scores than HCs (42.77 ± 13.50 vs. 29.11 ± 4.25, t=9.697, p

A new configuration of a 9-degree-of-freedom (DOF) robot has been designed to address the prevalence of balance disorders in patients and the increasing demand for exercise rehabilitation training. This lower-limb end rehabilitation robot can assist patients with repetitive movements to stimulate and rebuild their nervous system and improve their pelvic and muscle motion control abilities. Starting from functional requirements, multiple robot configuration design schemes are proposed, and various performance indicators are comprehensively considered to ultimately select and optimize a 9-DOF redundant series-parallel hybrid robot and complete its kinematic analysis and derivation. This robot consists of a 6-DOF vestibular parallel device and a 3-DOF proprioceptive parallel device in series, which are modular in structure and function while retaining the advantages of the strong load-bearing capacity of series robots and the large workspace of parallel robots. A new structural form is proposed for investigating lower-limb rehabilitation robots.

Abstract Background Leukemia is the tenth most common cause of cancer death worldwide and one of the most important causes of disability. To understand the current status and changing trends of the disease burden of leukemia at the global, regional, and national levels, and to provide a scientific basis for the development of leukemia prevention and treatment strategies. Methods Based on open data from the Global Burden of Disease Study 2019 (GBD 2019), R software was used to calculate estimated annual percentage changes to estimate trends in the age‐standardized incidence (ASIR) and the age‐standardized disability‐adjusted life years (DALY) rate due to leukemia and its major subtypes from 1990 to 2019. Results In 2019, globally, the number of incidences and DALYs of leukemia were 643.6 × 103 (587.0 × 103, 699.7 × 103) and 11,657.5 × 103 (10529.1 × 103, 12700.7 × 103), respectively. The ASIR (estimated annual percentage change (EAPC) = −0.37, 95%UI −0.46 to −0.28) and the age‐standardized DALY rate (EAPC = −1.72, 95%UI −1.80 to −1.65) of leukemia showed a decreasing trend from 1990 to 2019. The APC model analysis showed that the age effect of leukemia risk was a “U”‐shaped distribution of relative risk (RR) with increasing age from 1990 to 2019, globally. The time effect was an increase in incidence rate with increasing years but a decrease in DALY rate with increasing years. The cohort effects of both incidence and DALY rates tended to increase and then decrease with the development of the birth cohort. In 1990 and 2019, smoking, high body‐mass index, occupational exposure to benzene, and occupational exposure to formaldehyde were risk factors for DALY in leukemia, especially in areas with high SDI. Conclusions From 1990 to 2019, the disease burden of leukemia showed a decreasing trend, but it is worth noting that its overall severity is still very high. The disease burden of leukemia varies greatly from region to region, and exclusive strategies for the prevention and treatment of leukemia should be developed according to the economic and cultural development of each region.

BackgroundArtificial intelligence (AI) has increasingly been applied to computed tomography angiography (CTA) images to aid in the assessment of atherosclerotic plaque. Our aim was to explore the diagnostic accuracy of AI-assisted CTA for plaque diagnosis and classification through a systematic review and meta-analysis.MethodsA systematic literature review was performed by searching PubMed, EMBASE, and the Cochrane Library according to PRISMA guidelines. Original studies evaluating the diagnostic accuracy of radiomics, machine-learning, or deep-learning techniques applied to CTA images for detecting stenosis, calcification, or plaque vulnerability were included. The quality and risk of bias of the included studies were evaluated using the QUADAS-2 tool. The meta-analysis was conducted using STATA software (version 17.0) to pool sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) to determine the overall diagnostic performance.ResultsA total of 11 studies comprising 1,484 patients were included. There was low risk of bias and substantial heterogeneity. The overall pooled AUROC for atherosclerotic plaque assessment was 0.96 [95% confidence interval (CI) 0.94–0.97] across 21 trials. Of these, for ≥50% stenosis detection, the AUROC was 0.95 (95% CI 0.93–0.96) in five studies. For identifying ≥70% stenosis, the AUROC was 0.96 (95% CI 0.94–0.97) in six studies. For calcium detection, the AUROC was 0.92 (95% CI 0.90–0.94) in six studies.ConclusionOur meta-analysis demonstrates that AI-assisted CTA has high diagnostic accuracy for detecting stenosis and characterizing plaque composition, with optimal performance in detecting ≥70% stenosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO, identifier (CRD42023431410).

BackgroundThe chronic respiratory condition known as chronic obstructive pulmonary disease (COPD) was one of the main causes of death and disability worldwide. This study aimed to explore and elucidate new targets and molecular mechanisms of COPD by constructing competitive endogenous RNA (ceRNA) networks.MethodsGSE38974 and GSE106986 were used to select DEGs in COPD samples and normal samples. Cytoscape software was used to construct and present protein-protein interaction (PPI) network, mRNA-miRNA co-expression network and ceRNA network. The CIBERSORT algorithm and the Lasso model were used to screen the immune infiltrating cells and hub genes associated with COPD, and the correlation between them was analyzed. COPD cell models were constructed in vitro and the expression level of ceRNA network factors mediated by hub gene was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsIn this study, 852 differentially expressed genes were screened in the GSE38974 dataset, including 439 upregulated genes and 413 downregulated genes. Gene clustering analysis of PPI network results was performed using the Minimum Common Tumor Data Element (MCODE) in Cytoscape, and seven hub genes were screened using five algorithms in cytoHubba. CCL20 was verified as an important hub gene based on mRNA-miRNA co-expression network, GSE106986 database validation and the analysis of ROC curve results. Finally, we successfully constructed the circDTL-hsa-miR-330-3p-CCL20 network by Cytoscape. Immune infiltration analysis suggested that CCL20 can co-regulate immune cell migration and infiltration through chemokines CCL7 and CXCL3. In vitro experiments, the expression of circDTL and CCL20 was increased, while the expression of hsa-miR-330-3p was decreased in the COPD cell model.ConclusionBy constructing the circDTL-hsa-miR-330-3p-CCL20 network, this study contributes to a better understanding of the molecular mechanism of COPD development, which also provides important clues for the development of new therapeutic strategies and drug targets.

Summary: Background: Internet exclusion and depressive symptoms are prevalent phenomena among older adults; however, the association between internet exclusion and depressive symptoms remains limited. This study aims to investigate the association between internet exclusion and depressive symptoms among older adults from high-income countries (HICs) and low- and middle-income countries (LMICs). Methods: We conducted a comprehensive longitudinal, cross-cultural analysis, and the participants were adults aged 60 years and older from 32 countries participating in five nationally representative longitudinal cohort studies: the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), the China Health and Retirement Longitudinal Study (CHARLS), and the Mexican Health and Ageing Study (MHAS). Internet exclusion was defined as the self-reported absence from internet use. Depressive symptoms were evaluated using the Centre for Epidemiologic Studies of Depression scale (CES-D) or the Euro-Depression scale (Euro-D). These five cohorts, being heterogeneous, were respectively conducted with panel data analysis. Logistic regression, implemented within the generalized estimating equations framework, was used to examine the association between internet exclusion and the likelihood of experiencing depressive symptoms, adjusting for the causal-directed-acyclic-graph (DAG) minimal sufficient adjustment set (MSAS), including gender, age, education, labour force status, household wealth level, marital status, co-residence with children, residence status, cognitive impairment, and functional ability. Findings: Our study included a total of 129,847 older adults during the period from 2010 to 2020, with a median follow-up of 5 (2, 7) years. The pooled proportion of internet exclusion was 46.0% in HRS, 32.6% in ELSA, 54.8% in SHARE, 92.3% in CHARLS, and 65.3% in MHAS. Internet exclusion was significantly associated with depressive symptoms across all cohort studies: HRS (OR = 1.13, 95% CI 1.07–1.20), ELSA (OR = 1.22, 95% CI 1.11–1.34), SHARE (OR = 1.55, 95% CI 1.47–1.62), CHARLS (OR = 1.49, 95% CI 1.26–1.77), and MHAS (OR = 1.48, 95% CI 1.39–1.58). Moreover, internet exclusion was found to be associated with all dimensions of depression in the SHARE, MHAS, and ELSA cohorts (except for sleep and felt sad) cohorts. Interpretation: A considerable proportion of older adults experienced internet exclusion, particularly those in LMICs. Internet exclusion among older adults, irrespective of their geographic location in HICs or LMICs, was associated with a higher likelihood of experiencing depressive symptoms, which demonstrated the importance of addressing barriers to internet access and promoting active participation in the internet society among older adults. Funding: National Key R&D Program of China (grant number 2022ZD0160704), the Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University (grant number ZYCXTD2023005), the Collaborative Innovation Major Project of Zhengzhou (grant number 20XTZX08017), the Joint Project of Medical Science and Technology of Henan Province (grant number LHGJ20220428), and National Natural Science Foundation of China (grant number 82373341).

Abstract The photoinduced non-thermalized hot electrons at an interface play a pivotal role in determining plasmonic driven chemical events. However, understanding non-thermalized electron dynamics, which precedes electron thermalization (~125 fs), remains a grand challenge. Herein, we simultaneously captured the dynamics of both molecules and non-thermalized electrons in the MXene/molecule complexes by femtosecond time-resolved spectroscopy. The real-time observation allows for distinguishing non-thermalized and thermalized electron responses. Differing from the thermalized electron/heat transfer, our results reveal two non-thermalized electron dynamical pathways: (i) the non-thermalized electrons directly transfer to attached molecules at an interface within 50 fs; (ii) the non-thermalized electrons scatter at the interface within 125 fs, inducing adsorbed molecules heating. These two distinctive pathways are dependent on the irradiating wavelength and the energy difference between MXene and adsorbed molecules. This research sheds light on the fundamental mechanism and opens opportunities in photocatalysis and interfacial heat transfer theory.