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Abstract Electrocatalysts are extensively employed to suppress the shuttling effect in lithium-sulfur (Li-S) batteries. However, it remains challenging to probe the sulfur redox reactions and mechanism at the electrocatalyst/LiPS interface after the active sites are covered by the solid discharge products Li2S/Li2S2. Here, we demonstrate the intrinsic autocatalytic activity of the Li2S (100) plane towards lithium polysulfides on single-atom nickel (SANi) electrocatalysts. Guided by theoretical models and experimental data, it is concluded that LiPS dissociates into Li2S2 and short-chain LiPS on the Li2S (100) plane. Subsequently, Li2S2 undergoes further lithiation to Li2S on the Li2S (100) surface, generating a new Li2S (100) layer, thus enabling the autocatalytic formation of a new Li2S (100) surface. Benefiting from the autocatalytic growth of Li2S, the concentration of LiPS in the electrolyte remains at a lower level, enabling Li-S batteries under high loading and low electrolyte conditions to exhibit superior electrochemical performance.

Abstract With unintentional injuries being the leading mortality cause among children, the comprehensive evaluation of the unintentional injury burden concerning heat exposure remains unknown. Here we quantified the years lived with disability (YLD) due to unintentional child injuries in Guangzhou from 2016–2020 using the injury surveillance data. A Poisson regression model was employed to explore how various magnitudes of heat exposure could increase the injury burden in different children’s subgroups. Our findings suggest a positive link between heat exposure and childhood injuries. The successive heatwave led to a 16.8–23.8% higher risk of childhood injuries. Girls and preschoolers exhibited higher vulnerability to heat. Furthermore, heat exposure increased the road injury burden for preschoolers aged 3–6 years but not for adolescents. Our study links heat exposure to childhood unintentional injuries, providing insights into the demographic features and injury causes. This evidence can be used to inform healthy childhood development.

Free-caged rearing modes, which prioritize animal welfare, are believed to enhance the quality of animal products. The impact of rearing modes on meat quality may play a key role in the superior quality of local chicken breeds. This study analyzed the cecal contents of free-range and caged black-bone chickens at different ages using metagenomic and metabolomic sequencing. We identified 32 metabolites and 367 microbial species significantly affected by the rearing mode. Linear discriminant analysis Effect Size (LefSe) highlighted five key microorganisms, Gemmiger formicilis, Bacteria unclassified, Bacteroides sp. ET225, Massilistercora timonensis, and Bacteroidales unclassified, that showed distinct abundance patterns across all age points. Among them, Bacteroides sp. ET225 and Massilistercora timonensis were positively associated with certain phospholipids and plant-derived metabolites, while negatively correlated with others like demissidine and acylcarnitine. Functional analysis revealed that rearing modes impact gut metabolites involved in gut metabolism as well as broader processes such as signal transduction, protein digestion, and autophagy. This study offers new insights into how rearing modes influence gut microbiota and metabolites, shedding light on the study of rearing mode-mediated muscle development and fat deposition.

The use of bio-enzyme as feed additives holds significant potential. This study aimed to evaluate the impact of a kind of compound bio-enzyme supplementation (the main functional components are probiotics and astragalus polysaccharides) on the production performance, serum immunity, and intestinal health of Pekin ducks. A total of 126 male Pekin ducks were randomly assigned to three groups: a control group (CG, no additive), a low-dose group (LG, 0.1 % bio-enzyme), and a high-dose group (HG, 0.2 % bio-enzyme), with 6 replicates per group. Ducks were raised until 35 days of age, with weekly measurements of growth performance. At day 35, serum immunoglobulins were measured, carcass traits were recorded, and cecal contents were analyzed using 16S rRNA sequencing and metabolomics. Results indicated a significant increase in ADG (P = 0.049) and a decrease in feed-to-gain ratio (F:G) (P = 0.020) in LG and HG compared to CG during rearing. The HG showed a notable improvement in half eviscerated yield (HEY) (P = 0.023) and full eviscerated yield (FEY) (P = 0.008). No substantial changes were observed in immunological parameters (P > 0.05). The jejunal villus height to crypt depth ratio (VH/CD) significantly increased (P < 0.001) in LG, with notable improvements in duodenal (P = 0.001) and jejunal (P < 0.001) VH/CD in HG. The Shannon index (P = 0.042) and Pielou index (P = 0.038) of cecal microbiota were markedly lower in HG. Notable changes in the relative abundance of Firmicutes and Bacteroidota were observed in LG and HG. Differential bacteria and metabolites among the treatments were identified, and their correlations were analyzed. KEGG enrichment pathways of the metabolites were also identified. In conclusion, this bio-enzyme can improve production performance, intestinal wall structure, and microbiota in Pekin ducks. A 0.1 % concentration of this bio-enzyme is optimal for Pekin duck production.

Piglets may experience a variety of stress injuries, but the molecular regulatory mechanisms underlying these injuries are not well understood. In this study, we analysed the ileum of Large White (LW) and Mashen (MS) piglets at different times of starvation using chemical staining and transcriptome analysis. The intestinal barrier of piglets was damaged after starvation stress, but the intestinal antistress ability of MS piglets was stronger than LW piglets. A total of 8021 differentially expressed genes (DEGs) were identified in two breeds. Interestingly, the immune capacity (CHUK, TLR3) of MS piglets increased significantly after short-term starvation stress, while energy metabolism (NAGS, PLA2G12B, AGCG8) was predominant in LW piglets. After long-term starvation stress, the level of energy metabolism (PLIN5, PLA2G12B) was significantly increased in MS piglets. The expression of immune (HLA-DQB1, IGHG4, COL3A1, CD28, LAT) and disease (HSPA1B, MINPPI, ADH1C, GAL3ST1) related genes were significantly increased in two breeds of piglets. These results suggest that short-term stress mainly enhances immunity and energy metabolism in piglets, while long-term starvation produces greater stress on piglets, making it difficult for them to compensate for the damage to their bodies through self-regulation. This information can help improve the stress resistance of piglets through molecular breeding.

Background Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population.Methods This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein.Results A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08–1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04–2.50). The prevalence of MGUS was significantly higher in males than in females (P

With the ongoing process of globalization and the rapid expansion of the global economy, the proliferation of coastal constructions and infrastructures has witnessed a notable surge. These structures often encounter a confluence of environmental stressors in practical engineering, including cyclic fatigue loading, chloride salt erosion, and freeze-thaw cycles. These synergistic factors accelerate concrete’s failure, resulting in accelerated deterioration and significantly reduced durability. A comprehensive understanding of the damage characteristics of concrete materials in offshore environments, under the multi-factor coupled action of freeze-thaw phenomena, along with an assessment of their residual strength, is crucial for the development of relevant structural analysis and lifetime prediction models. To address this, twenty-seven dedicated specimens were designed and fabricated for this investigation. They were employed to scrutinize the residual strength of concrete under the combined influences of fatigue, freeze-thaw, and chloride penetration. Nine distinct multi-factor coupling actions were meticulously devised and characterized by different parameters. Following the multi-factor coupling action, tests were conducted to assess the residual flexural and compressive strengths, as well as the chloride ion content near the specimen edges. The findings revealed a substantial negative correlation between the residual flexural and compressive strengths with both the number of freeze-thaw cycles and fatigue loading iterations. In contrast, chloride ion concentration and the stress level of fatigue loading (stress ratio: 0.1–0.3) exhibited a comparatively marginal influence. Despite the relatively short test duration, it was evident that both freeze-thaw cycles and fatigue loading exerted a discernible promotional effect on chloride ion ingress in the concrete of the specimens.

ABSTRACT: Fermentation of feed with probiotic and biofunctional properties has gained global attention for its potential to enhance digestive absorption and improve overall functional quality. This study investigates the antioxidant capacity and expression of antioxidant-related genes in broiler chickens fed with fermented corn gluten meal (FCGM) containing mixed microbial cultures. Seventy-two male Yellow-Feathered broiler chickens were randomly assigned to 2 groups, each consisting of 3 replicates, and were fed experimental diets containing either corn gluten meal or FCGM for 42 d. The antioxidant capacity of FCGM was assessed in vivo. Chickens fed with FCGM exhibited significant increases in serum glutathione concentration, as well as enhanced activities of total superoxide dismutase, glutathione peroxidase, and catalase (CAT) in their serum. Similar trends were observed in the liver, specifically in the activities of glutathione peroxidase and CAT. Additionally, the expression levels of key antioxidant-related genes in the liver, such as glutathione synthase, superoxide dismutase 1, superoxide dismutase 2, CAT, and glutathione peroxidase 1, were examined. The results indicated that FCGM significantly enhanced antioxidant capacity in broiler chickens. This study highlights the potential benefits of utilizing solid-state fermentation with mixed microbial cultures to improve the antioxidant properties of corn gluten meal, thereby contributing to the overall health and well-being of broiler chickens.

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.

Background: Limited attention has been paid to the health effects of long-term PM1 exposure on stroke admission. Current investigations exploring the long-term PM exposure effect are largely based on observational studies, and PM generally is not allocated randomly to participants. Using traditional regression models might confuse messaging and hinder policy recommendations for pollution control and disease prevention policies. Methods: We conducted a cohort study among 36,271 adults from one of the largest cities in China in 2015 and followed up through 2020. Hazard ratios of stroke admissions following long-term PM1 exposure were estimated via a causal inference approach, marginal structural time-varying Cox proportional hazard model, accounting for multiple confounders. Additionally, several sensitivity analyses and impact modification analyses were carried out. Results and discussion: Associations with 1 μg/m3 increase in long-term PM1 were identified for total (HR, 1.079; 95 %CI, 1.012–1.151) and ischemic stroke admissions (HR, 1.092; 95 %CI, 1.018–1.171). The harmful associations varied with exposure duration, initially increasing and then decreasing. The 2–3 years cumulative exposure was associated with a 3.3–5.4 % raised risk for total stroke. For every 1 μg/m³ increase in long-term PM1 exposure, females exhibited a higher risk of both total and ischemic stroke (13 % and 16 %) than men (4 % and 5 %). Low-exposure individuals (whose annual PM1 concentrations were under the third quartile among the annual concentrations for all the participants) exhibited greater sensitivity to PM1 effects (total stroke: 1.079 vs. 1.107; ischemic stroke: 1.092 vs. 1.116). The results underline the importance of safeguarding low-exposed people in highly polluted areas and suggest that long-term PM1 exposure may increase stroke admission risk, warranting attention to vulnerable groups.

Abstract BackgroundParticulate matter (PM), which affects respiratory health, has been well documented; however, substantial evidence from large cohorts is still limited, particularly in highly polluted countries and for PM1 ObjectiveOur objective was to examine the potential causal links between long-term exposure to PMs (PM2.5101 MethodsA total of 580,757 participants from the Guangzhou area, China, were recruited from 2009 to 2015 and followed up through 2020. The annual average concentrations of PMs at a 1-km spatial resolution around the residential addresses were estimated using validated spatiotemporal models. The marginal structural Cox model was used to estimate the associations of PM exposure with respiratory mortality, accounting for time-varying PM exposure. Results were stratified by demographics and lifestyle behaviors factors. ResultsAmong the participants, the mean age was 48.33 (SD 17.55) years, and 275,676 (47.47%) of them were men. During the follow-up period, 7260 deaths occurred due to respiratory diseases. The annual average concentrations of PM12.510312.510110 ConclusionsThis cohort study provides causal clues of the respiratory impact of long-term ambient PM exposure, indicating that PM reduction efforts may continuously benefit the population’s respiratory health.

Background: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. Aims: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. Methods: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. Results: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025–1.041), 1.032 (95% CI: 1.027–1.038), and 1.020 (95% CI: 1.016–1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009–1.035) and 1.053 (1.038–1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031–1.053), 1.041 (1.032–1.050), and 1.0473 (1.025–1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. Conclusion: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

The ribbon kirigami pattern has garnered significant attention over the past decade because of its interesting geometric and mechanical properties such as extreme elongation and high ductility, making it a viable choice for various applications such as developing medical devices and flexible electronics. Despite the promising prospects of this type of morphing structure, its deformation mechanism and sensitivity to materials properties and geometric parameters have remained largely unexplored. Here we take a computational approach to studying the deformation process and ductility of a typical ribbon kirigami metastructure. To this end, the deformation process is divided into various stages. We demonstrate the existence of a certain threshold of the process at which the deformation behavior starts to be dominated by the properties of the constituent material, after the initial geometric-design-dominated stages. This turning point, called the design–material transition (DMT) threshold, determines a key limit in the deformation capacity of such metastructures for practical applications. Based on the introduced deformation mechanism, an elongation prediction model is derived for the metastructure, followed by conducting experiments to validate the accuracy of the model. Furthermore, a genetic algorithm and an interior-point method are utilized to develop an efficient algorithm for the optimization of the geometric parameters of the kirigami pattern. We anticipate that the findings of this study open a path to engineering functional kirigami patterns for the design and fabrication of highly ductile shape-shifting structures.

Urban building energy modelling (UBEM) has consistently been a pivotal tool to evaluate and control a building stock’s energy consumption. There are two main approaches to build up UBEM: top-down and bottom-up. The latter is the most commonly used in engineering. The bottom-up approach includes three methods: the physical-based method, the data-driven method, and the grey-box method. The first two methods have previously received ample attention and research. The grey-box method is a modelling method that has emerged in recent years that combines the traditional physical method with the data-driven method while it aims to avoid their problems and merge their advantages. Nowadays, there are several approaches for modelling the grey-box model. However, the majority of existing reviews on grey-box methods concentrate on a specific technical approach and thus lack a comprehensive overview of modelling method perspectives. Accordingly, by conducting a comprehensive review of the literature on grey-box research in recent years, this paper classifies grey-box models into three categories from the perspective of modelling methods and provides a detailed summary of each, concluding with a synthesis of potential research opportunities in this area. The aim of this paper is to provide a foundational understanding of grey-box modelling methods for similar research, thereby removing potential barriers in the field of research methods.

Abstract Background Benefiting from increased life expectancy and improved perioperative management, more elderly patients with pancreatic head cancer (PHC) underwent pancreaticoduodenectomy (PD). However, individualized predictive models for the safety and efficacy of PD is still lacking. this study aimed to developed three safety‐ and efficacy‐related risk calculators for elderly (> = 65 years) PHC patients. Methods This study was designed with two research cohorts, namely, the training cohort and the validation cohort, and comprises four general steps: (1) Risk factors were analyzed for the incidence of postoperative complications, cancer‐specific survival (CSS), and overall survival (OS) in the training cohort (N = 271) using logistic and Cox‐regression analysis. (2) Nomograms were then plotted based on the above results. (3) The accuracy of the developed nomogram models was then verified with the validation cohort (N = 134) data using consistency index (C‐index) and calibration curves. (4) We then evaluated the efficacy of these nomograms using decision curve analysis (DCA) in both the training and validation cohorts, and ultimately constructed three online calculators based on these nomograms. Results We identified ASA, diabetes, smoking, and lymph node invasion as predisposing risk factors for postoperative complications, and the predictive factors that affected both OS and CSS were ASA, diabetes, BMI, CA19‐9 level, and tumor diameter. By integrating the above risk factors, we constructed three nomograms on postoperative complication, CSS, and OS. The C‐index for complication, CSS, and OS were 0.824, 0.784, and 0.801 in the training cohort and 0.746, 0.718, and 0.708 in the validation cohort. Moreover, the validation curves and DCA demonstrated good calibration and robust compliance in both training and validation cohorts. We then developed three web calculators (https://caiming.shinyapps.io/CMCD/, https://caiming.shinyapps.io/CMCSS/, and https://caiming.shinyapps.io/CMOS/) to facilitate the use of the nomograms. Conclusions The calculators demonstrated promising performance as an tool for predicting the safety and efficacy of PD in elderly PHC patients.

BackgroundResearch of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments.MethodsThe medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn.ResultsOverall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS.ConclusionIn general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1–2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment.A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders.During follow-up, a total of 717 subjects died from T2DM. For every 1 μg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019–1.053). Similarly, for every 1 μg/m3 increase in PM1 and PM1–2.5, the adjusted HRs and 95% CIs were 1.032 (1.003–1.062) and 1.085 (1.054–1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049).The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1–2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Actuator control takes a pivotal role in achieving stability and accuracy, particularly in the context of multi-axial real-time hybrid simulation (maRTHS). In maRTHS, multiple hydraulic actuators are necessitated to apply precise motions to experimental substructures thus necessitating the application of multiple-input multiple-output (MIMO)control strategies. This study evaluates the data-driven nonlinear autoregressive with external input (NARX) based compensation for the servo-hydraulic dynamics within the maRTHS benchmark model. Different from previous study, nonlinear terms are incorporated into the NARX model. Online least square and ridge regression techniques are utilized to estimate the model coefficients to achieve optimal compensation. The influence of various model order and window length is assessed for the NARX model-based compensation. The findings of this research demonstrate that NARX-based compensation has significant potential not only in facilitating precise actuator control for maRTHS but also in enabling robust control in the presence of unknown uncertainties inherent to the servo-hydraulic system.

Abstract Objective Clinical practitioners face a significant challenge in maintaining a healthy balance between overtreatment and missed diagnosis in the management of intraductal papillary mucinous neoplasm (IPMN). The current study aimed to identify significant risk factors of malignant IPMN from a series of clinical and radiological parameters that are widely available and noninvasive and develop a method to individually predict the risk of malignant IPMN to improve its management. Methods We retrospectively investigated 168 patients who were pathologically diagnosed with IPMN after individualized pancreatic resection between June, 2012 and December, 2020. Independent predictors determined using both univariate and multivariate analyses to construct a predictive model. The discriminatory power of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC). Decision curve analysis was performed to demonstrate the clinical usefulness of the nomogram. Internal cross validation was performed to assess the validity of the predictive model. Results In the multivariate analysis, five significant independent risk factors were identified: increased serum CA19‐9 level, low prognostic nutritional index (PNI), cyst size, enhancing mural nodule, and main pancreatic duct diameter. The nomogram based on the parameters mentioned above had outstanding performance in distinguishing malignancy, with an AUC of 0.907 (95% confidence interval: 0.859–0.956, p

An oscillating flow past a structure represents a complex, high-dimensional, and nonlinear flow phenomenon, which can lead to the failure of structures due to material fatigue or constraint relaxation. In order to better understand flow-induced vibration (FIV) and coupled flow fields, a numerical simulation of a two-degrees-of-freedom FIV in a cylinder was conducted. Based on the Lagrangian-based dynamic mode decomposition (L-DMD) method, the vorticity field and motion characteristics of a cylinder were decomposed, reconstructed, and predicted. A comparison was made to the traditional Eulerian-based dynamic mode decomposition (E-DMD) method. The research results show that the first-order mode in the stable phase represents the mean flow field, showcasing the slander tail vortex structure during the vortex-shedding period and the average displacement in the in-line direction. The second mode predominantly captures the crossflow displacement, with a frequency of approximately 0.43 Hz, closely matching the corresponding frequency observed in the CFD results. The higher dominant modes mainly capture outward-spreading, smaller-scale vortex structures with detail displacement characteristics. The motion of the cylinder in the in-line direction was accompanied by symmetric vortex structures, while the motion of the cylinder in the crossflow direction was associated with anti-symmetric vortex structures. Additionally, crossflow displacement will cause a symmetrical vortex structure that spreads laterally along the axis behind the cylinder. Finally, when compared with E-DMD, the L-DMD method demonstrates a notable advantage in analyzing the nonlinear characteristics of FIV.

This study introduces a novel Unmanned Aerial Vehicle-mounted (UAV-mounted) Laser Doppler Vibrometer (LDV) system for detecting debonding damage in Hidden Frame-Supported Glass Curtain Walls (HFSGCW). The established system enables UAVs to transport the LDV to high altitudes for operation. The vibration signals acquired by the UAV-LDV system are decomposed into different energy bands by wavelet packet analysis, and then the occurrence and location of the damage are identified by the Sum of Squared Differences (SSD) of the wavelet packet bands’ energy. This paper investigates the potential factors affecting the performance of the Unmanned Aerial Vehicle-Laser Doppler Vibrometer (UAV-LDV) system, including the arrangement of measuring points, measuring distance, noise level, and wind speed through the first-order natural frequency, the normalized frequency response functions, and the SSD indicator. Experimental and simulation results confirm the effectiveness of the UAV-LDV system, highlighting its advantages over traditional methods by offering remote, non-contact, and efficient debonding detection. This method not only indicates the presence of the damage, as traditional indicators do, but also pinpoints the exact location of it, ensuring safety and cost-effectiveness in high-rise inspections. The proposed method and indicator offer advantages in terms of convenience, visualization, and efficiency. The study discusses the impact of measurement point arrangement, measuring distance, noise levels, and wind speed on the system’s performance. The findings demonstrate that while the UAV-LDV system introduces new capabilities in rapid and reliable structural damage assessment, operational challenges such as wind and noise levels significantly influence its accuracy.

This paper experimentally and numerically investigates the effect of pre-tightening forces on bolted connection for double-lap FRP-steel joints, considering varied levels of pre-tightening forces. In the experimental phase of this study, six bolted double-lap pull-pull specimens with varying pre-tightening degrees (preloaded of 0, 3, 6, 7, 8, and 9 N·m, respectively) were examined. Test results indicated that all specimens exhibited bearing failure of FRP plates and the load capacity was significantly influenced by the pre-tightening forces applied through bolts. The highest loading capacity (27.1 kN) was recorded for the specimen with a preloaded of 6 N·m. In order to study the stress distribution of FRP plate for the bolted specimens, three-dimensional finite element (FE) models were conducted. Based on the FE analyzing results, the pre-tightening coefficient Pc (the coefficient of the preload increment per pre-tightening torque of bolts) of 750 m−1 was concluded and further proved by the analysis of the stress in contact zones for specimens preloaded by 0, 3, and 6 N·m.

The self-centering friction-viscous damper (SCFVD) is a novel self-centering system that utilizes preloaded ring springs to offer self-centering and friction-based energy dissipation capacity, while a viscous damper provides viscous-based energy dissipation capacity. This study is to study the seismic behavior of steel moment-resisting frames (MRFs) with SCFVDs, considering cost effectiveness. The mechanical model of the SCFVD is first presented and validated through pseudo-static tests on a full-scale specimen. Simulation models of 3-story, 9-story, and 20-story steel MRFs with SCFVDs and viscous dampers are then built, and numerical analysis under 40 earthquake records is conducted on them to compare and evaluate the structural peak dynamic response and energy dissipation from an economic perspective. The results show that the SCFVD's hysteretic response can be reliably predicted by the mechanical model. When compared to the uncontrolled steel-MRFs and the steel-MRFs with FVDs, the SCFVD can significantly mitigate structural peak and residual drift, especially under high-intensity earthquakes, but may aggravate structural peak acceleration. Besides, the SCFVD can mitigate the structural hysteretic energy dissipation and damage to the 3-story and 9-story steel MRFs. The cost/average reduction ratio of peak drift for the steel-MRFs with SCFVDs is reduced by 6.3% when compared to that for the steel-MRFs with FVDs.

ABSTRACTVaccination plays a key role in preventing morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the safety and immunogenicity of a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine SYS6006. In the two randomized, observer-blinded, placebo-controlled phase 1 trials, 40 adult participants aged 18–59 years and 40 elderly participants aged 60 years or more were randomized to receive two doses of SYS6006 or placebo (saline). Adverse events (AEs) were collected through 30 days post the second vaccination. Immunogenicity was assessed by live-virus neutralizing antibody (Nab), spike protein (S1) binding antibody (S1-IgG), and cellular immunity. The result showed that 7/15, 9/15 and 4/10 adult participants, and 9/15, 8/15 and 4/10 elderly participants reported at least one AE in the 20-µg, 30-µg and placebo groups, respectively. Most AEs were grade 1. Injection-site pain was the most common AE. Two adults and one elder reported fever. No vaccination-related serious AE was reported. SYS6006 elicited wild-type Nab response with a peak geometric mean titer of 232.1 and 130.6 (adults), and 48.7 and 66.7 (elders), in the 20-µg and 30-µg groups, respectively. SYS6006 induced moderate-to-robust Nab response against Delta, and slight Nab response against Omicron BA.2 and BA.5. Robust IgG response against wild type and BA.2 was observed. Cellular immune response was induced. In conclusion, two-dose primary vaccination with SYS6006 demonstrated good safety and immunogenicity during a follow-up period of 51 days in immunologically naive population aged 18 years or more. (Trial registry: Chictr.org.cn ChiCTR2200059103 and ChiCTR2200059104)

This paper presents experimental and numerical investigations of the seismic performance of a novel self-centering (SC) hollow-core (HC) fiber-reinforced polymer (FRP)-concrete-steel (SC-HC-FCS) bridge column. This new structure is fabricated by mounting external energy dissipators (ED) and applying unbonded post-tensioned (PT) basalt FRP (BFRP) tendon to the conventional HC-FCS column that consists of an outer FRP tube and an inner steel tube, with the space between filled with concrete. The SC-HC-FCS column combines the advantages of accelerated bridge construction and self-centering. The effects of the initial prestress force values and the configuration of the energy-dissipated aluminum bar on the column performance are studied. Based on the experimental and numerical results, it is found that the proposed SC-HC-FCS column shows adequate self-centering and energy dissipation capacities. However, it is required to properly select the configuration and material properties of the aluminum bar as energy dissipators to further refine the seismic resistance of the SC-HC-FCS column.

In recent years, motor imagery-based brain-computer interface (MI-BCI) has been applied to motor rehabilitation in patients with motor dysfunction. However, traditional MI-BCI is rarely used for foot motor intention recognition because the motor cortex regions of both feet are anatomically close to each other, and traditional event-related desynchronization (ERD) patterns for MI-BCI have insufficient spatial discrimination. This study introduced steady-state somatosensory evoked potentials (SSSEPs) by synchronous bilateral feet electrical stimulation at different frequencies, which were used as carrier signals modulated by unilateral foot motor intention. Fifteen subjects participated in MI and MI-SSSEP tasks. A Riemannian geometry classifier with a task-related component analysis (TRCA) spatial filter was proposed to demodulate the variation in SSSEP features and discriminate the left and right foot motor intentions. The feature outcomes indicated that the amplitude and phase synchronization of the SSSEPs could be well modulated by unilateral foot MI tasks under the MI-SSSEP paradigm. The classification results revealed that the modulated SSSEP features played an important role in the recognition of left-right foot discrimination. Moreover, the proposed TRCA-based method outperformed the other three methods and improved the foot average classification accuracy to 81.07± 13.29%, with the highest accuracy attained at 97.00%. Compared with the traditional MI paradigm, the foot motor intention recognition accuracy of the MI-SSSEP paradigm was significantly improved, from nearly 60% to more than 80%. This work provides a practical method for left-right foot motor intention recognition and expands the application of MI-BCI in the field of lower-extremity motor function rehabilitation.

Microspheres can break the diffraction limit and magnify nano-structure imaging, and with its advantages of low cost and label-free operation, microsphere-assisted imaging has become an irreplaceable tool in the life sciences and for precision measurements. However, the tiny size and limited imaging field of traditional solid microspheres cause difficulties when imaging large sample areas. Alternatively, droplets have similar properties to those of microspheres, with large surface curvature and refractive-index difference from the surrounding environment, and they can also serve as lenses to focus light for observation and imaging. Previous work has shown that droplets with controllable size can be generated using an optical tweezer system and can be driven by optical traps to move precisely like solid microspheres. Here, a novel microdroplet-assisted imaging technology based on optical tweezers is proposed that better integrates the generation, manipulation, and utilization of droplets.

Background: Long-term ambient particulate matter (PM) exposure has been found associated with chronic obstructive pulmonary disease (COPD) mortality in an increasing body of research. However, limited evidence was available on the potential causal links between PM1 and COPD mortality, especially in highly exposed areas. Objectives: To examine the COPD mortality risk following long-term ambient PM1 exposure in south China. Methods: The cohort included 580,757 participants recruited during 2009–2015. Satellite-based annual concentrations of PM1 were estimated at a spatial resolution of 1 km × 1 km and assigned to each participant based on their residential addresses. We analyzed the potential causal links between time-varying PM1 exposure and COPD mortality using marginal structural cox models within causal frameworks. Stratified analyses were also performed to identify the potential susceptible groups. Results: The annual average PM1 concentration continuously decreased over time. After adjusting for confounders, each 1 μg/m3 increase in PM1 concentration corresponded to an 8.1 % (95% confidence interval: 6.4–9.9 %) increment in the risk of COPD mortality. The impact of PM1 was more pronounced among the elderly and those with low exercise frequency, with a 1.9–6.9 % higher risk than their counterparts. We further observed a 0.1–9.7 % greater risk among those who lived in lower greenness settings. Additionally, we observed higher effect estimates in participants with long-term low PM1 exposure compared to the general population. Conclusions: COPD mortality risk significantly increased following long term ambient PM1 exposure, particularly among groups with certain demographics or long-term low exposure.

Abstract The catalytic performance of metal–organic frameworks (MOFs) in Li‐S batteries is significantly hindered by unsuitable pore size, low conductivity, and large steric contact hindrance between the catalytic site and lithium polysulfide (LPSs). Herein, the smallest π‐conjugated hexaaminobenzene (HAB) as linker and Ni(II) ions as skeletal node are in situ assembled into high crystallinity Ni‐HAB 2D conductive MOFs with dense Ni‐N4 units via dsp2 hybridization on the surface of carbon nanotube (CNT), fabricating Ni‐HAB@CNT as separator modified layer in Li‐S batteries. As‐obtained unique π‐d conjugated Ni‐HAB nanostructure features ordered micropores with suitable pore size (≈8 Å) induced by HAB ligands, which can cooperate with dense Ni‐N4 chemisorption sites to effectively suppress the shuttle effect. Meanwhile, the conversion kinetics of LPSs is significantly accelerated owing to the small steric contact hindrance and increased delocalized electron density endued by the planar tetracoordinate structure. Consequently, the Li‐S battery with Ni‐HAB@CNT modified separator achieves an areal capacity of 6.29 mAh cm−2 at high sulfur loading of 6.5 mg cm−2 under electrolyte/sulfur ratio of 5 µL mg−1. Moreover, Li‐S single‐electrode pouch cells with modified separators deliver a high reversible capacity of 791 mAh g−1 after 50 cycles at 0.1 C with electrolyte/sulfur ratio of 6 µL mg−1.

Submerged floating tunnels (SFTs), also known as the Archimedes Bridge, are new transportation structures designed for crossing deep waters. Compared with cross-sea bridges and subsea tunnels, SFTs offer superior environmental adaptability, reduced construction costs, and an enhanced spanning capacity, highlighting their significant development potential and research value. This paper introduces a new type of SFT scale model for hydrodynamic experiments, adhering to the criteria for geometric similarity, motion similarity, and dynamic similarity principles, including the Froude and Cauchy similarity principles. This model enables the accurate simulation of the elastic deformation of the tunnel body and complex hydrodynamic phenomena, such as fluid–structure interactions and vortex–induced vibrations. Moreover, this paper details the design methodology, fabrication process, and method for similarity evaluation, covering the mass, deflection under load, natural frequency in air, and the natural frequency of the various underwater motion freedoms of the model. The results of our experiments and numerical simulations demonstrate a close alignment, proving the reliability of the new SFT scale model. The frequency distribution observed in the white noise wave tests indicates that the SFT equipped with inclined mooring cables experiences a coupled interaction between horizontal motion, vertical motion, and rotation. Furthermore, the design methodology of this model can be applied to other types of SFTs, potentially advancing technical progress in scale modeling of SFTs and enhancing the depth of SFT research through hydrodynamic experiments.

A modified Extended State Kalman Filter (ESKF)-based Model Predictive Control (MPC) algorithm is introduced to tailor the enhanced disturbance suppression in electro-optical tracking systems. Traditional control techniques, although robust, often struggle in scenarios with concurrent internal, external disturbances, and sensor noise. The proposed algorithm effectively overcomes these limitations by precisely estimating system states and actively mitigating disturbances, thus significantly boosting noise and perturbation control resilience. The primary contributions of this study include the integration of ESKF for accurate system state and disturbance estimation in noisy environments, the embedding of an ESKF estimation-compensation loop to simulate an improved disturbance-free system, and a simplified modeling approach for the controlled device. This designed structure minimizes the reliance on extensive system identification, easing the predictive control model-based constraints. Moreover, the approach incorporates total disturbance estimation into the optimization problem, safeguarding against actuator damage and ensuring high tracking accuracy. Through rigorous simulations and experiments, the ESKF-based MPC has demonstrated enhanced model error tolerance and superior disturbance suppression capabilities. Comparative analyses under varying model parameters and external disturbances highlight its exceptional trajectory tracking performance, even in the presence of model uncertainties and external noise.

Abstract Homeobox A5 (HOXA5) is a transcription factor in mammalian and can regulate cell differentiation, proliferation, and apoptosis as well as tumorigenesis. However, little is known on whether and how HOXA5 can regulate the malignant behaviors of cholangiocarcinoma. The methylation levels of HOXA5 were evaluated by methylation microarray and bisulfite sequencing PCR. HOXA5 expression in tissue samples was examined by immunohistochemistry and Western blot. The proliferation of tumor cells was assessed by CCK-8, EdU, and nude mouse tumorigenicity assays. The invasion, apoptosis and cell cycling of tumor cells were evaluated by Wound healing assay and flow cytometry. The interaction between HOXA5 and the MXD1 promoter was examined by CUT & Tag assay, luciferase reporter assay and chromatin immunoprecipitation. Hypermethylation in the HOXA5 promoter down-regulated HOXA5 expression in extrahepatic cholangiocarcinoma (ECCA) tissues, which was correlated with worse overall survival. HOXA5 overexpression significantly inhibited the proliferation and tumor growth. HOXA5 overexpression enhanced MXD1 expression by directly binding to the MXD1 promoter in ECCA cells. MXD1 overexpression inhibited the proliferation and tumor growth while MXD1 silencing abrogated the HOXA5-mediated proliferation inhibition. HOXA5 overexpression increased p53 protein expression in an MXD1-dependent manner. HOXA5 and MXD1 acted as tumor suppressors to inhibit the mitosis of ECCA cells by enhancing the p53 signaling. Our findings may uncover molecular mechanisms by which the HOXA5/MXD1 axis regulates the progression of ECCA, suggesting that the HOXA5/MXD1 may be therapeutic targets for ECCA.

Abstract Background Nitrogen is considered the most limiting nutrient element for herbivorous insects. To alleviate nitrogen limitation, insects have evolved various symbiotically mediated strategies that enable them to colonize nitrogen-poor habitats or exploit nitrogen-poor diets. In frugivorous tephritid larvae developing in fruit pulp under nitrogen stress, it remains largely unknown how nitrogen is obtained and larval development is completed. Results In this study, we used metagenomics and metatranscriptomics sequencing technologies as well as in vitro verification tests to uncover the mechanism underlying the nitrogen exploitation in the larvae of Bactrocera dorsalis. Our results showed that nitrogenous waste recycling (NWR) could be successfully driven by symbiotic bacteria, including Enterobacterales, Lactobacillales, Orbales, Pseudomonadales, Flavobacteriales, and Bacteroidales. In this process, urea hydrolysis in the larval gut was mainly mediated by Morganella morganii and Klebsiella oxytoca. In addition, core bacteria mediated essential amino acid (arginine excluded) biosynthesis by ammonium assimilation and transamination. Conclusions Symbiotic bacteria contribute to nitrogen transformation in the larvae of B. dorsalis in fruit pulp. Our findings suggest that the pattern of NWR is more likely to be applied by B. dorsalis, and M. morganii, K. oxytoca, and other urease-positive strains play vital roles in hydrolysing nitrogenous waste and providing metabolizable nitrogen for B. dorsalis.

IntroductionFemale breast cancer has risen to be the most common malignancy worldwide, causing a huge disease burden for both patients and society. Both senescence and oxidative stress attach importance to cancer development and progression. However, the prognostic roles of senescence and oxidative stress remain obscure in breast cancer. In this present study, we attempted to establish a predictive model based on senescence-oxidative stress co-relation genes (SOSCRGs) and evaluate its clinical utility in multiple dimensions.MethodsSOSCRGs were identified via correlation analysis. Transcriptome data and clinical information of patients with breast invasive carcinoma (BRCA) were accessed from The Cancer Genome Atlas (TCGA) and GSE96058. SVM algorithm was employed to process subtype classification of patients with BRCA based on SOSCRGs. LASSO regression analysis was utilized to establish the predictive model based on SOSCRGs. Analyses of the predictive model with regards to efficacy evaluation, subgroup analysis, clinical association, immune infiltration, functional strength, mutation feature, and drug sensitivity were organized. Single-cell analysis was applied to decipher the expression pattern of key SOSCRGs in the tumor microenvironment. Additionally, qPCR was conducted to check the expression levels of key SOSCRGs in five different breast cancer cell lines.ResultsA total of 246 SOSCRGs were identified. Two breast cancer subtypes were determined based on SOSCRGs and subtype 1 showed an active immune landscape. A SOSCRGs-based predictive model was subsequently developed and the risk score was clarified as independent prognostic predictors in breast cancer. A novel nomogram was constructed and exhibited favorable predictive capability. We further ascertained that the infiltration levels of immune cells and expressions of immune checkpoints were significantly influenced by the risk score. The two risk groups were characterized by distinct functional strengths. Sugar metabolism and glycolysis were significantly upregulated in the high risk group. The low risk group was deciphered to harbor PIK3CA mutation-driven tumorigenesis, while TP53 mutation was dominant in the high risk group. The analysis further revealed a significantly positive correlation between risk score and TMB. Patients in the low risk group may also sensitively respond to several drug agents. Single-cell analysis dissected that ERRFI1, ETS1, NDRG1, and ZMAT3 were expressed in the tumor microenvironment. Moreover, the expression levels of the seven SOSCRGs in five different breast cancer cell lines were quantified and compared by qPCR respectively.ConclusionMultidimensional evaluations verified the clinical utility of the SOSCRGs-based predictive model to predict prognosis, aid clinical decision, and risk stratification for patients with breast cancer.

Owing to the high power consumption and limited control precision of traditional hydraulic drive winch systems, this study proposes hydraulic and electric-type energy recovery systems. The accumulator used in the hydraulic type has low energy density, which makes it difficult to store a large amount of energy. Meanwhile, the electric motor/generator used in the electric type cannot solve the secondary slip because of oil leakage, which leads to low controllability and high-power consumption under near-zero speed and high torque conditions. Thus, based on electric construction machinery with high-pressure, energy-dense electric energy storage units, this study proposes an electro-hydraulic composite drive winch and energy recovery system and control strategy for mobile cranes. Considering the good control characteristics of the electric motor/generator and the high-power density of the hydraulic accumulator, this hydroelectric composite drive and energy recovery system may solve the secondary sliding challenge and ensure large torque output at near-zero speed. A simulation model of the mobile crane is established to verify the feasibility of the proposed system and control strategy. The research results showed that the system is more efficient at recovering energy when the weight is lowered by a greater distance.

The J-TEXT capability is enhanced compared to two years ago with several upgrades of its diagnostics and the increase of electron cyclotron resonance heating (ECRH) power to 1 MW. With the application of electron cyclotron wave (ECW), the ECW assisted plasma startup is achieved; the tearing mode is suppressed; the toroidal injection of 300 kW ECW drives around 24 kA current; fast electrons are generated with toroidal injected ECW and the runaway current conversion efficiency increases with ECRH power. The mode coupling between 2/1 and 3/1 modes are extensively studied. The coupled 2/1 and 3/1 modes usually lead to major disruption. Their coupling can be either suppressed or avoided by external resonant magnetic perturbation fields and hence avoids the major disruption. It is also found that the 2/1 threshold of external field is significantly reduced by a pre-excited 3/1 mode, which can be either a locked island or an external kink mode. The disruption control is studied by developing prediction methods capable of cross tokamak application and by new mitigation methods, such as the biased electrode or electromagnetic pellet injector. The high-density operation and related disruptions are studied from various aspects. Approaching the density limit, the collapse of the edge shear layer is observed and such collapse can be prevented by applying edge biasing, leading to an increased density limit. The density limit is also observed to increase, if the plasma is operated in the poloidal divertor configuration or the plasma purity is increased by increasing the pre-filled gas pressure or ECRH power during the start-up phase.

The gas extraction radius is affected by coal seam gas pressure, borehole diameter, extraction time, extraction negative pressure and other factors. Under the coupling of different factors, the gas extraction radius of borehole is also different. For complex under the condition of the shortage of the radius of the gas extraction method, combining with TianAn comes up out of no. 3 coal mine coal seam gas occurrence and mining conditions, puts forward the method of pressure drop and gas flow method, combination method of determining the radius of the gas extraction, analysis of the 1∼3 m, 4 m and 5∼6 m extraction under the condition of radius of influence range, ultimately determine the radius of extraction for 3 m, It can not only meet the gas extraction rate of working face, but also ensure the safety of production and efficient utilization of gas.

The multi-leader-follower group consensus issue of a class of stochastic time-delay multi-agent systems subject to Markov switching topology is investigated. The purpose is to determine a distributed control protocol to make sure that the followers' states converge in mean square to a convex hull generated by the leaders' states. Through a model transformation, the problem is transformed into a mean-square stability issue of a new system. Then, an easy-to-check sufficient condition for the solvability of the multi-leader-follower group consensus issue is proposed by utilizing the Lyapunov stability theory, graph theory, as well as several inequality techniques. It is shown that the required feedback gain can be acquired once the condition is satisfied. Finally, an example is used to illustrate the effectiveness of the control protocol.

BackgroundHepatoblastoma has an unsatisfactory prognosis, and traditional chemotherapy has strong side effects. Dihydromyricetin is a flavonoid extracted from a woody vine of the genus Serpentine in the family Vitaceae, with effects such as preventing alcoholic liver and reducing the incidence of liver cancer. However, the effect of DHM on hepatoblastoma and its specific pathway are still unclear.PurposeThe purpose of this study was to investigate the effects of DHM on children's hepatoblastoma and its related mechanisms.MethodsCCK-8 assays were used to measure proliferation. Apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. Apoptotic cells were observed using Hoechst 33342 staining and fluorescence microscopy. Protein expression levels in HuH-6 and HepG2 cells were determined by western blotting.ResultsWe found that DHM was able to inhibit the growth and increase cellular mortality in HuH-6 and HepG2 cells. Furthermore, DHM decreased the intracellular ROS level and increased the expression of SOD1. ROS scavenger NAC promoted apoptosis, while the use of SOD1 inhibitor LCS-1 weakened the ROS scavenging effect of DHM , and to some extent reduced the killing effect of DHM on hepatoblastoma cells.ConclusionThese results suggest that regulating SOD1/ROS pathway to induce apoptosis is one of the potential mechanisms of DHM as a tumor suppressor in hepatoblastoma. Therefore, DHM may be a novel candidate for inhibiting hepatoblastoma growth and deserves further study.

Cancer cachexia (CC), a wasting syndrome of muscle and adipose tissue resulting in weight loss, is observed in 50% of patients with solid tumors. Management of CC is limited by the absence of biomarkers and knowledge of molecules that drive its phenotype. To identify such molecules, we injected 54 human non–small cell lung cancer (NSCLC) lines into immunodeficient mice, 17 of which produced an unambiguous phenotype of cachexia or non-cachexia. Whole-exome sequencing revealed that 8 of 10 cachexia lines, but none of the non-cachexia lines, possessed mutations in serine/threonine kinase 11 (STK11/LKB1), a regulator of nutrient sensor AMPK. Silencing of STK11/LKB1 in human NSCLC and murine colorectal carcinoma lines conferred a cachexia phenotype after cell transplantation into immunodeficient (human NSCLC) and immunocompetent (murine colorectal carcinoma) models. This host wasting was associated with an alteration in the immune cell repertoire of the tumor microenvironments that led to increases in local mRNA expression and serum levels of CC-associated cytokines. Mutational analysis of circulating tumor DNA from patients with NSCLC identified 89% concordance between STK11/LKB1 mutations and weight loss at cancer diagnosis. The current data provide evidence that tumor STK11/LKB1 loss of function is a driver of CC, simultaneously serving as a genetic biomarker for this wasting syndrome.

BackgroundInjuries during work are often exogenous and can be easily influenced by environmental factors, especially weather conditions. Precipitation, a crucial weather factor, has been linked to unintentional injuries, yet evidence of its effect on work-related injuries is limited. Therefore, we aimed to clarify the impact of precipitation on injuries during work as well as its variation across numerous vulnerability features.MethodsRecords on the work-related injury during 2016–2020 were obtained from four sentinel hospitals in Guangzhou, China, and were matched with the daily weather data during the same period. We applied a time-stratified case-crossover design followed by a conditional logistic regression to evaluate the association between precipitation and work-related injuries. Covariates included wind speed, sunlight, temperature, SO2, NO2, and PM2.5. Results were also stratified by multiple factors to identify the most vulnerable subgroups.ResultsDaily precipitation was a positive predictor of work-related injuries, with each 10 mm increase in precipitation being associated with an increase of 1.57% in the rate of injuries on the same day and 1.47–1.14% increase of injuries on subsequent 3 days. The results revealed that precipitation had a higher effect on work-related injuries in winter (4.92%; 95%CI: 1.77–8.17%). The elderly (2.07%; 95%CI: 0.64–3.51%), male (1.81%; 95%CI: 0.96–2.66%) workers or those with lower educational levels (2.58%; 95%CI: 1.59–3.54%) were more likely to suffer from injuries on rainy days. There was a higher risk for work-related injuries caused by falls (2.63%; 95%CI: 0.78–4.52%) or the use of glass products (1.75%; 95%CI: 0.49–3.02%) on rainy days.ConclusionsPrecipitation was a prominent risk factor for work-related injury, and its adverse effect might endure for 3 days. Certain sub-groups of workers were more vulnerable to injuries in the rain.

BackgroundHuanglian Jiedu decoction (HLJDD) is a famous traditional Chinese medicine prescription, which is widely used in the treatment of Alzheimer’s disease (AD). However, the interaction between bioactive substances in HLJDD and AD-related targets has not been well elucidated.AimA network pharmacology-based approach combined with molecular docking was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HLJDD against AD, through the regulation of microbial flora.Materials and methodsBioactives and potential targets of HLJDD, as well as AD-related targets, were retrieved from Traditional Chinese Medicine Systems Pharmacology Analysis Database (TCMSP). Key bioactive components, potential targets, and signaling pathways were obtained through bioinformatics analysis, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was performed to predict the binding of active compounds with core targets.Results102 bioactive ingredients of HLJDD and 76 HLJDD-AD-related targets were screened. Bioinformatics analysis revealed that kaempferol, wogonin, beta-sitosterol, baicalein, acacetin, isocorypalmine, (S)-canadine, (R)-canadine may be potential candidate agents. AKT1, TNF, TP53, VEGFA, FOS, PTGS2, MMP9 and CASP3 could become potential therapeutic targets. 15 important signaling pathways including the cancer pathway, VEGF signaling pathway, and NF-κB signaling pathway might play an important role in HLJDD against AD. Moreover, molecular docking analysis suggested that kaempferol, wogonin, beta-sitosterol, baicalein, acacetin, isocorypalmine, (S)-canadine, and (R)-canadine combined well with AKT1, TNF, TP53, VEGFA, FOS, PTGS2, MMP9, CASP3, respectively.ConclusionOur results comprehensively illustrated the bioactives, potential targets, and possible molecular mechanisms of HLJDD against AD. HLJDD may regulate the microbiota flora homeostasis to treat AD through multiple targets and multiple pathways. It also provided a promising strategy for the use of traditional Chinese medicine in treating human diseases.

Abstract Background We have limited information about neuroendocrine carcinoma (NEC) of the gallbladder. The purpose of this paper is to compare clinical and pathological features between different age groups and prognostic factors for gallbladder NEC and how it differs from adenocarcinoma (ADC) of the gallbladder. Patients and methods This study included 28 gallbladder NEC patients and 137 ADC patients whose clinical characteristics and pathological findings were retrospectively collected. Propensity score matching and Cox regression analysis were used for the analysis of prognostic factors. Results We divided NEC patients into two groups based on the age more than or less than 60 years. Most of the NEC patients less than 60 years old complained of abdominal pain or discomfort (p = 0.038), and more younger patients accepted adjuvant therapy (p = 0.020) than older patients did. CD56 was positive in all patients more than 60 years old, which is significantly higher than that of younger patients (p = 0.039). The mean age was similar between NEC and ADC patients. After eliminating confounding factors between NEC and ADC patients, the overall survival rates were still lower in NEC patients. Univariate analysis extracted six possible risk factors. Multivariate analysis indicated that surgery type, tumor size, and existence of gallstones were independent prognostic factors. Conclusion The overall survival of gallbladder NEC is not associated with age. In this study, surgical method and tumor size were found to be independent risk factors for NECs. In addition, NEC patients have a worse prognosis than ADC patients with similar clinical and pathological features.

Abstract Oxidation behaviors of carbon fiber reinforced SiC matrix composites (C/SiC) are one of the most noteworthy properties. For C/SiC, the oxidation behavior was controlled by matrix microcracks caused by the mismatch of coefficients of thermal expansion (CTEs) and elastic modulus between carbon fiber and SiC matrix. In order to improve the oxidation resistance, multilayer SiC-Si3N4 matrices were fabricated by chemical vapor infiltration (CVI) to alleviate the above two kinds of mismatch and change the local stress distribution. For the oxidation of C/SiC with multilayer matrices, matrix microcracks would be deflected at the transition layer between different layers of multilayer SiC-Si3N4 matrix to lengthen the oxygen diffusion channels, thereby improving the oxidation resistance of C/SiC, especially at 800 and 1000 °C. The strength retention ratio was increased from 61.9% (C/SiC-SiC/SiC) to 75.7% (C/SiC-Si3N4/SiC/SiC) and 67.8% (C/SiC-SiC/Si3N4/SiC) after oxidation at 800 °C for 10 h.

BackgroundPost-traumatic stress symptoms (PTSS) are commonly reported by psychiatric healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic and negatively affect quality of life (QOL). However, associations between PTSS and QOL at symptom level are not clear. This study examined the network structure of PTSS and its connection with QOL in psychiatric healthcare personnel during the COVID-19 pandemic.MethodsThis cross-sectional study was carried out between March 15 and March 20, 2020 based on convenience sampling. Self-report measures including the 17-item Post-Traumatic Stress Disorder Checklist – Civilian version (PCL-C) and World Health Organization Quality of Life Questionnaire - Brief Version (WHOQOL-BREF) were used to measure PTSS and global QOL, respectively. Network analysis was used to investigate the central symptoms of PTSS and pattern of connections between PTSS and QOL. An undirected network was constructed using an extended Bayesian Information Criterion (EBIC) model, while a directed network was established based on the Triangulated Maximally Filtered Graph (TMFG) method.ResultsAltogether, 10,516 psychiatric healthcare personnel completed the assessment. “Avoidance of thoughts” (PTSS-6), “Avoidance of reminders” (PTSS-7), and “emotionally numb” (PTSS-11) were the most central symptoms in the PTSS community, all of which were in the Avoidance and Numbing domain. Key bridge symptoms connecting PTSS and QOL were “Sleep disturbances” (PTSS-13), “Irritability” (PTSS-14) and “Difficulty concentrating” (PTSS-15), all of which were within the Hyperarousal domain.ConclusionIn this sample, the most prominent PTSS symptoms reflected avoidance while symptoms of hyper-arousal had the strongest links with QOL. As such, these symptom clusters are potentially useful targets for interventions to improve PTSS and QOL among healthcare personnel at work under pandemic conditions.

Background: The association between long-term particulate matter (PM) exposure and all-cause mortality has been well-documented. However, evidence is still limited from high-exposed cohorts, especially for PM1 which is smaller while more toxic than other commonly investigated particles. We aimed to examine the potential casual links of long-term PMs exposure with all-cause mortality in high-exposed areas. Methods: A total of 580,757 participants in southern China were enrolled during 2009–2015 and followed up to 2020. The annual average concentration of PM1, PM2.5, and PM10 at 1 km2 spatial resolution was assessed for each residential address through validated spatiotemporal models. We used marginal structural Cox models to estimate the PM-mortality associations which were further stratified by sociodemographic, lifestyle factors and general exposure levels. Results: 37,578 deaths were totally identified during averagely 8.0 years of follow-up. Increased exposure to all 3 PM size fractions were significantly associated with increased risk of all-cause mortality, with hazard ratios (HRs) of 1.042 (95 % confidence interval (CI): 1.037–1.046), 1.031 (95 % CI: 1.028–1.033), and 1.029 (95 % CI: 1.027–1.031) per 1 μg/m3 increase in PM1, PM2.5, and PM10 concentrations, respectively. We observed greater effect estimates among the elderly (age ≥ 65 years), unmarried participants, and those with low education attainment. Additionally, the effect of PM1, PM2.5, and PM10 tend to be higher in the low-exposure group than in the general population. Conclusions: We provided comprehensive evidence for the potential causal links between long-term PM exposure and all-cause mortality, and suggested stronger links for PM1 compared to large particles and among certain vulnerable subgroups.

Digital twins (DTs) have a great potential for bridge operation and maintenance. Geometric digital twins (gDTs) are the key component of DTs. At present, a growing number of researchers are using high-precision 3D laser point clouds to generate gDTs. However, for large bridges, such as arch, cable-stayed, and suspension bridges, comprehensive point-cloud collection stations are difficult to set up due to their large span, narrow site, and limited field of vision. Consequently, the complete point clouds of these bridges cannot be easily obtained. Thus, knowing how to process absence point clouds and generate gDTs is an urgent problem. This study proposes a semiautomatic method of extracting geometric information of a bridge’s components in the absence of point clouds. First, an algorithm based on the combination of the iterative polynomial fitting curve and sliding window is developed to extract the arch ring accurately. Second, an improved random sample consensus (RANSAC) algorithm based on distribution density is adopted to extract the cross sections of the arch bridge components, except the arch ring. For cross sections that lack point clouds, a translation strategy is used to supplement the unknown line segment. Finally, for the T-beam, a model alignment method is proposed to best match the characteristic intersections extracted by the improved RANSAC algorithm and the points corresponding to the design model. The quality of the generated models is gauged using a point cloud deviation chromatogram. In addition, the stressed component piers are compared with its design parameters to verify the accuracy of the proposed method. Results show that our method can efficiently and accurately extract geometric information and generate gDT for the bridge.

With the growing utilization of disc motors, the enhancement of their operational stability has become a critical research area. The existing studies usually focus on improving the pole structure of the rotor or the stator structure to optimize one performance of the motor and less on optimizing multiple performances. This paper simultaneously improves the rotor pole structure and stator tooth structure of the motor in order to optimize the sinusoidal waveform of the no-load back electromotive force and the cogging torque at the same time to achieve the goal of reducing the vibration and noise of the permanent-magnet synchronous dual-rotor statorless magnetically coupled disc motor and improve its operational stability. A finite element simulation model of a 20-pole, 24-slot permanent-magnet synchronous dual-rotor statorless magnetically coupled disc motor is established to analyze the influence of various factors, including the number of magnetic pole steps, the opening position, depth, and width of the stator auxiliary slot, on the motor performance. The results show that this stator–rotor combination improvement method effectively reduces the total harmonic distortion (THD) and attenuates multiple harmonics, and the peak cogging torque pulsation is significantly improved while other properties of the motor meet the technical requirements, and the motor performance is improved.

The double vertical-axis wind turbine (VAWT) system serves as a high-performance design solution. The Nautilus wind turbine investigated in this research imitated the structure of a Nautilus shell and is a vertical-axis drag-type wind turbine that exhibits relatively low efficiency. Therefore, the improvement of its wind energy efficiency is of paramount importance. This paper utilizes Computational Fluid Dynamics (CFD) software, based on the Reynolds-averaged Navier–Stokes equations and dynamic meshing techniques, to conduct numerical investigations on the aerodynamic performance of the Nautilus wind turbine array layout. The effects of wind direction, spacing ratio, and rotation direction are individually studied, and the interpretations and explanations are provided based on flow field characteristics. The results show that when the wind direction is 90°, i.e., a transverse layout, the closer the spacing between the transverse turbines, the higher the average power coefficient of the entire wind turbine system, with little effect from the three rotation directions. The maximum average power coefficient reached 28.9% and the power gain factor (TPGF) reached 11.1%. The enhancement effect primarily originates from the wake interaction among neighboring turbines. The experimental results showed a deviation of 8.1% compared to the CFD simulation results, thus validating the accuracy of the numerical CFD modeling. Ultimately, several array layouts are proposed, based on the prevalent wind direction and spacing ratio research. The enhancement of the wind turbine array’s situation could significantly increase the average efficiency of the entire wind turbine cluster. Consequently, this study provides a reference for the practical application of biomimetic vertical-axis drag-type wind turbine systems in actual engineering.

Bridge cables under traffic loads are more prone to failure during the service life due to the corrosion–fatigue coupling effect. In this study, a novel lifespan model based on the equivalent initial flaw size (EIFS) theory is established to analyze the various stages of the lifespan of steel wires. Additionally, a comprehensive corrosion-fatigue lifespan calculation method for parallel steel wire cable is established based on the series–parallel model. A case study of the Runyang Suspension Bridge is conducted to evaluate the evolution of corrosion-fatigue damage in bridge cables during the service life. The results indicate that under the action of corrosion-fatigue, steel wires are more prone to crack initiation, and their fracture toughness is further reduced. In cases where the corrosion level is relatively low, the steel wires of the bridge cables experience no corrosion-fatigue fracture. When the steel wires have initial defects and are subject to corrosion-fatigue conditions, their fracture lifespan is dependent on the severity of the corrosive medium. The reduction in the service life of the cables under the corrosion environment is much greater than that under heavy loads. This research may contribute to the understanding of corrosion-fatigue damage in bridge cables, involving assessment, maintenance, and replacement for bridge cables.