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The advancements in innovative cancer prevention and treatment strategies have achieved remarkable results in the prevention and treatment of various malignant tumors. However, the increasing trend of incidence and mortality of pancreatic cancer (PC) has not shown a significant turnaround. The clarification of the material basis of traditional Chinese medicine (TCM) syndromes can contribute to the multidisciplinary integrated diagnosis and treatment of PC. Damp-heat syndrome is the core syndrome of patients with PC. It has a crucial material basis of inflammatory microenvironment. Formulas with heat-clearing and dampness-removing efficacies can inhibit malignant phenotypes by remodeling the tumor microenvironment. Conventional therapy plus heat-clearing and dampness-removing formulas can enhance the quality of life of patients with PC and significantly prolong their survival time. The systemic inflammatory response index (SIRI) is closely correlated with cytokine changes underlying damp-heat syndrome, and it can be used to direct PC prognosis assessment. In the future, PC diagnosis and treatment based on SIRI classification could distinguish patient subgroups that are responsive to heat-clearing and dampness-removing therapy. Taking damp-heat syndrome as the core point to explore the whole period of syndrome evolution throughout the course of PC could contribute to syndrome-based TCM precision treatment of PC.

Abstract The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.

Abstract Background Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients. Methods This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression. Results Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study. Conclusions PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.

Abstract Despite the importance of radiation therapy as a nonsurgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern because of poor patient response and outcomes. Therefore, it is crucial to identify novel targets to increase the effectiveness of radiotherapy and investigate the mechanisms underlying radioresistance. Previously, we demonstrated that Spindlin 1 (SPIN1) was related to tumour initiation and progression. In this study, we found that SPIN1 expression was higher in NSCLC tissues and cell lines than in the corresponding controls. SPIN1 overexpression in NSCLC patients was closely correlated with disease progression and poor prognosis. Functionally, SPIN1 depletion inhibited cell proliferation, decreased the percentage of cells in the G2/M phase and suppressed cell migration and invasion. Moreover, SPIN1 knockdown decreased the clonogenic capacity, impaired double-strand break (DSB) repair and increased NSCLC radiosensitivity. Mechanistically, forkhead box M1 (FOXM1) was identified as a key downstream effector of SPIN1 in NSCLC cells. Furthermore, SPIN1 was found to facilitate MDM2-mediated FOXO3a ubiquitination and degradation, leading to FOXM1 upregulation. Moreover, restoration of FOXM1 expression markedly abolished the inhibitory effects and increased radiosensitivity induced by SPIN1 depletion. These results indicate that the SPIN1-MDM2-FOXO3a/FOXM1 signalling axis is essential for NSCLC progression and radioresistance and could serve as a therapeutic target for increasing radiotherapy efficacy.

Along the hollow stay lane roadside filling body is divided into letting pressure layer and compression layer, letting pressure layer material should have the characteristics of large deformation, slow down the violent activities of the basic roof rock beam. The compressive layer material should be characterised by high strength and rigidity, and effective control of the overlying rock beams should be achieved after flexible letting pressure. Therefore, this paper analyzes the mechanical properties of different ratios of yield layer and compressive layer materials, and analyzes the microstructure of the control group and optimization group of yield layer and compressive layer by scanning electron microscope ( SEM ). Finally, the optimal ratio of yield layer and compressive layer is tested. The results of the study showed that the optimum ratio of the material for letting the compaction layer was 1.5:1 for the water-cement ratio, 0.06% for the blowing agent dosage and 0.2% for the fibre dosage. The compressive strength of the optimised group reached 8.84 MPa at 28 d. Strain at different ages was 1.8 to 2.6 times higher in the optimised group than in the control group. The compressive layer material ratio of 40% fine gangue rate, slurry mass concentration of 78%, cement dosage of 20% is optimal, the average compressive strength of 13.21 MPa, tensile strength of 0.97 MPa, modulus of elasticity of 0.75 GPa, the angle of internal friction of 26°, cohesion of 2.85 MPa. The filler at this ratio showed a gradual increase in strength with the increase in cement dosage in the later stages. When the yield layer accounts for 10%−20% of the composite specimen, it has good yield capacity and certain key bearing capacity. The research results provide a reference for the material ratio of roadside filling body in gob-side entry retaining.

Abstract The ultra‐low frequency oscillation (ULFO) imposes an emerging stability challenge to the high proportion of hydropower grids. To suppress ULFO without reducing the primary frequency regulation of the hydro governor, a novel idea to exploit the voltage regulation effect of load is implemented. First, the additional damping controller is designed and configured in static var compensator (SVC), and the frequency analysis model considering the configuration of SVC as well as damping controller is established. Based on the model, the specific influence of SVC and controller on ULFO is analysed through eigenvalue calculation. In addition, the influence of various load models and SVC location on the damping level are further studied. Consequently, a parameter optimization design method for SVC additional damping control is proposed, it is modelled as the optimization problem of damping ratio in ULFO mode under multi‐operation conditions, which is solved by a particle swarm optimization algorithm. Finally, the effectiveness of the designed SVC additional damping controller is verified in the improved four‐machine two‐area power system and the actual power grid in China.

Abstract Background A comprehensive assessment of combined modifiable risk factors in relation to infectious diseases among individuals with hypertension is lacking, and the potential mechanisms of these associations remain unclear. To investigate the prospective associations of a combination of lifestyle behaviors and cardiometabolic factors with the risk of infectious diseases among individuals with hypertension and to estimate whether and to what extent blood biomarkers mediate these associations. Methods This cohort study included 147,188 participants with hypertension and complete data on modifiable risk factors from the UK Biobank. Health score was constructed from eight modifiable risk factors, including four lifestyle behaviors (diet, physical activity, smoking, and sleep duration) and four cardiometabolic factors (body mass index, blood lipids, blood glucose, and blood pressure). Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the health score and infectious diseases. The mediation analysis was performed to assess the potential intermediation effects of blood biomarkers. Results Over a median follow-up of 12.5 years, 27,398 participants with infectious diseases were documented, with 960 respiratory infectious diseases and 7940 digestive infectious diseases. After adjusting for potential confounders, the HR (95% CI) for the highest versus the lowest quartile of health score was 0.64 (0.62, 0.66) for infectious diseases, 0.72 (0.60, 0.86) for respiratory infectious diseases, and 0.66 (0.62, 0.71) for digestive infectious diseases. Stratified factors including duration of hypertension did not modify the associations between the health score and infectious diseases. In addition, biomarkers including inflammation and renal function collectively explained 46.60% of the associations between the combined lifestyle factors and infectious disease risk among individuals with hypertension. Conclusions and relevance Ideal management of combined modifiable risk factors was associated with lower risks of infectious diseases and might produce profound changes in blood biomarkers among individuals with hypertension. Additionally, specific biomarkers appeared to serve as an intermediate between combined lifestyle factors and infectious diseases. These insights highlighted the important role of a combination of healthy lifestyle and favorable cardiometabolic status in reducing disease burden and facilitated the understanding of biological mechanisms underlying modifiable risk factors with infectious diseases.

Abstract In recent years, with the application of Internet of Things (IoT) and cloud technology in smart industrialization, Industrial Internet of Things (IIoT) has become an emerging hot topic. The increasing amount of data and device numbers in IIoT poses significant challenges to its security issues, making anomaly detection particularly important. Existing methods for anomaly detection in the IIoT often fall short when dealing with data imbalance, and the huge amount of IIoT data makes feature selection challenging and computationally intensive. In this paper, we propose an optimal deep learning model for anomaly detection in IIoT. Firstly, by setting different thresholds of eXtreme Gradient Boosting (XGBoost) for feature selection, features with importance above the given threshold are retained, while those below are ignored. Different thresholds yield different numbers of features. This approach not only secures effective features but also reduces the feature dimensionality, thereby decreasing the consumption of computational resources. Secondly, an optimized loss function is designed to study its impact on model performance in terms of handling imbalanced data, highly similar categories, and model training. We select the optimal threshold and loss function, which are part of our optimal model, by comparing metrics such as accuracy, precision, recall, False Alarm Rate (FAR), Area Under the Receiver Operating Characteristic Curve (AUC-ROC), and Area Under the Precision–Recall Curve (AUC-PR) values. Finally, combining the optimal threshold and loss function, we propose a model named MIX_LSTM for anomaly detection in IIoT. Experiments are conducted using the UNSW-NB15 and NSL-KDD datasets. The proposed MIX_LSTM model can achieve 0.084 FAR, 0.984 AUC-ROC, and 0.988 AUC-PR values in the binary anomaly detection experiment on the UNSW-NB15 dataset. In the NSL-KDD dataset, it can achieve 0.028 FAR, 0.967 AUC-ROC, and 0.962 AUC-PR values. By comparing the evaluation indicators, the model shows good performance in detecting abnormal attacks in the Industrial Internet of Things compared with traditional deep learning models, machine learning models and existing technologies.

Abstract Background Vital pulp therapy (VPT) is recommended as an alternative treatment to root canal therapy (RCT) for management of teeth with carious pulp exposure. This randomized clinical trial aimed to compare the outcomes and postoperative pain, and to evaluate the time and cost after full pulpotomy (FP) and RCT in mature molar teeth with irreversible pulpitis (IP). Methods A total of 160 mature molar teeth with IP were randomly divided into two treatment groups. The FP group (test group) was treated with FP using iRoot BP Plus by an endodontist, the RCT group (control group) was treated with RCT using iRoot SP as sealer by the same endodontist. Pain was recorded preoperatively and daily until day 7 postoperatively. The treatment time and cost were recorded. Clinical and radiographic assessments were collected, and pulp sensibility tests were done by electric pulp test (EPT) at 3-, 6-, 12- month postoperatively. Data were analyzed through chi-square test, Mann-Whitney U test, Fisher exact and independent t test. Results FP and RCT had comparable success rates (Clinical, 97.3% vs. 98.6%; radiographic, 93.3% vs. 94.6%) (P > 0.05). Pain levels decreased over time from day 1 to day 7 postoperative in both groups, and the FP group had larger reductions in pain intensity than RCT at day 1 (P

Abstract Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Abstract Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins. Graphical abstract

In previous research, gamified classroom management has been found to improve high school students' classroom participation. This study applied gamification classroom management through a "Class of Oz" in an elementary school to cultivate students' learning. Two classes were randomly assigned to the experimental group, and the other two were randomly assigned to the control group. Eighty-three valid samples were retained after deleting incomplete data from the pre- and post-test. After 11 weeks of gamified classroom management, the results indicated that the experimental group experienced a higher value and emotion of learning motivation than the control group. However, there were no differences between the Chinese and mathematics scores of the two groups. In addition, qualitative observations showed that gamified classroom management attracted students' attention and improved their learning motivation. These results revealed that role-play gamified classroom management could enhance students' learning motivation without affecting their academic performance.

Abstract Background The positioning error of femoral tunnel was the key factor leading to the failure of anterior cruciate ligament (ACL) reconstruction. This study aimed to propose a new femoral tunnel classification to guide revision ACL reconstruction. Methods Totals of 150 patients with ACL reconstruction failure from 2017 to 2023 were enrolled in this retrospective study. According to the tunnel diameter, shape, posterior wall and the positioning relationship with the Lateral Intercondylar Ridge on the three-dimensional CT imaging, we divided the femoral tunnels into four types: Type I off-target type, Type II straddled type, Type III anatomical type, and Type IV irregular type. Finally, explored the inter-observer reliability within two groups of doctors (Group A, 12 high seniorities; Group B, 12 low seniorities), and evaluated the intra-observer reliability within 6 doctors after two months. Clinical evaluation was performed using the Lysholm score, Tenger activity score, Pivot Shift and anterior knee laxity measurements. Results Among 150 cases of femoral tunnel three-dimensional CT reconstructed imaging, 144 cases were successfully included in the classification system, and 6 cases were confirmed as uncertain type. We measured the Kappa (κ) coefficient of group A was significantly higher than that of group B (κ 0.72 VS 0.68), and the κ coefficient of group A was still higher than group B (κ 0.69 VS 0.62) after further dividing Type III anatomical type into three subtypes. In addition, the κ coefficients of intra-observer reliability were all exceeded 0.73. Clinical follow-up showed that 9 patients had good knee joint motor function and stability after operation. Conclusion The new femoral tunnel classification was reliable and had clinical guiding significance based on three-dimensional CT imaging. Level of evidence Level III.

Abstract The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

Abstract Background Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear. Methods This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies. Results A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB

Abstract Background Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. Methods An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. Results GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P 0.05). Conclusions GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

Abstract Purpose This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133+) ovarian cancer (OC) stem-like cells. Methods CD133+ (CD133 positive) OVCAR4 and CD133 negative (CD133−) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133+OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-β1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). Results The performance of CD133+OVCAR4 cells was much better than that of CD133−OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133−OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133+OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133+OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133+OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. Conclusion The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133+OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-β1/SMAD4 signaling pathway.

In this paper, bathymetry retrieval is combined with the Depth Invariant Index (DII) substrate cluster to acquire more accurate water depth. DIIs are calculated through the selected samples that are in bright and dark pixels firstly. Then, substrates are clustered with DIIs by using the K-MEANS cluster algorithm. Last, in-situ data and Genetic Algorithm (GA) are applied to solve the models’ parameters of the Stumpf model and the Legleiter model. The feasibility of this method is investigated in the Xia Shan Reservoir, Shandong Province, China. The experimental results show that (1) When there are various bottom types in the study area, the substrates cluster before bathymetry retrieval can significantly improve the retrieval accuracy. For example, in the without cluster case, the R2 values are both around 0.72 in the GF-2 image and the R2 values are both 0.53 in the Sentienl-2 image, and the minimum RMSE and RRMSE values are 1.09 m and 19.36 % respectively. When substrates are clustered into two clusters and three clusters, R2 values have all increased and RMSE and RRMSE values decreased. (2) Clustering substrates into more clusters may not necessarily improve retrieval accuracy. For our research area, it’s better to divide the substrate into two clusters. For the two clusters case, the bathymetry result using the Legleiter model has a higher retrieval accuracy, which RMSE is 0.76 m, R2 is 0.9 and RRMSE is 11.76 %. Compared with the three clusters case, the bathymetry retrieval accuracy of the two clusters case improves more obviously.

ObjectiveThis study aims to investigate the complex welding residual stress of high-strength steel thick plate with multi-pass welding, and examines the influence of such stress on the fracture behavior of welded joints. MethodsTaking 75 mm thick Q690 high-strength steel thick plate as the research object, multi-pass butt welding and a corresponding welding experiment are carried out, and the longitudinal residual stress on the middle cross section is then measured by the contour method after cooling. Based on effective thermal elastic-plastic FE computation, properties such as the thermal cycle and microstructure evolution during the multi-pass welding of thick steel plate are represented. The uniaxial tension test and GTN damage model are combined to obtain the parameters of GTN model for Q690 high-strength steel plate, which are then used to examine the fracture behavior and stress-strain curves of the base metal and welded joint specimens.ResultsThe predicted shape of the weld pool and the content of the metallographic phase show good agreement with the measured data. After considering the solid phase transformation during welding and initial stress due to rolling, the longitudinal and transverse residual stresses are in good agreement with the measured results. Moreover, the fracture behavior of the welded joints is also investigated while considering welding micro defects and transverse residual stress, and the mechanical mechanism of welding residual stress is clarified.ConclusionThe results of this study can provide valuable references for the evaluation of the residual stress and fracture behavior of welded joints in high-strength steel thick plate .

Abstract The realization and control of exchange bias (EB) are highly desirable for spintronic applications. All-oxide heterostructures comprised of ferromagnetic and antiferromagnetic/multiferroic oxides provide an ideal platform to enable the electric-field control of EB, promising for energy-efficient memory and logic devices. However, the low block temperature (TB) and small bias field (HEB) hinder further advances towards room-temperature applications. Here, we report an alternative approach to enhance the interface-induced EB by using ferrimagnetic double-perovskite with B-site cation ordering. In heterostructures comprised of double-perovskite Sr2FeReO6 (SFRO) and LaFeO3 (LFO), a high TB (about 250 K) and large HEB are observed, which is significantly larger than the counterparts with LFO and ferromagnetic oxides. Further analysis suggests that the cation-ordering and ferrimagnetic spin structure of the double-perovskite could contribute significantly to the enhanced exchanged bias when interfacing with G-type antiferromagnets. Our results open a new avenue for developing all-oxides heterostructures for future magnetic technologies.

Abstract Our study focuses on the relationship between inflammatory biomarkers and hypertension among sedentary adults in the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We categorized 24,614 participants into two groups based on their daily sedentary time: 9607 individuals in the sedentary group (≥7 h) and 15,007 in the non‐sedentary group (

Abstract Background Advanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients. Materials and methods This study prospectively enrolled 51 eligible treatment-naive patients with unresectable PC to receive GEMOX treatment via PAI or IVC (1:1 ratio randomization) from December 2015 to December 2019. Cycles were repeated monthly, and each process consisted of two treatments administered bi-weekly. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-year survival, 6-month survival, tumor-site subgroup survival, and incidences of adverse events were compared. Results The median OS of the PAI and IVC groups were 9.93 months and 10.07 months, respectively (p = 0.3049). The median PFS of the PAI and IVC groups were 5.07 months and 4.23 months (p = 0.1088). No significant differences were found in the ORR (11.54% vs. 4%, p = 0.6312), DCR (53.85% vs. 44%, p = 0.482), and 1-year OS rate (44% vs. 20.92%, p = 0.27) in PAI and IVC groups. The 6-month OS rate was significantly higher in the PAI group (100%) than in the IVC group (83.67%) (p = 0.0173). The median OS of patients in PAI group with pancreatic head and neck tumors were significantly higher than those of body and tail tumors (12.867 months vs. 9 months, p = 0.0214). The incidences of hematologic disorders, liver function disorders, and digestive disorders in the IVC group were higher than in the PAI group (p < 0.05). Conclusion GEMOX PAI therapy presented a higher 6-month OS rate and fewer adverse events than IVC in advanced pancreatic adenocarcinoma patients. Those with pancreatic head and neck tumors may yield a superior treatment outcome from PAI treatment. Trial registration number NCT02635971. Date of registration 21/12/2015.

Binge-eating disorder (BED) is a type of eating disorder characterized by recurrent episodes of binge eating. Patients with BED have recurrent impulsive and out-of-controlled binge eating behavior, which can lead to gastrointestinal disorders, obesity, and the resulting metabolic and functional disorders of various systems and other physical problems; and it is also often co-morbid with affective disorder, anxiety disorders, substance use disorders, and other mental disorders, which need to be taken seriously. However, the recognition of BED in China was late, and it is difficult to achieve early identification and diagnosis, resulting in a prolonged course of disease. Therefore, under the organization of the Eating Disorders Coordination Group of the Psychosomatic Medicine Society of the Chinese Medical Association, together with the Eating Disorders Research Collaboration Group of the Psychiatric Medicine Society of the Chinese Medical Association, an expert group composed of 15 psychiatrists and evidence-based medicine experts, and 2 internal medicine experts, formulated this expert consensus based on evidence-based medical evidence, domestic and foreign guidelines and expert consensus, and expert experiences. The aim of this study is to improve the recognition, diagnosis and treatment of BED by psychiatrists, internists and general practitioners in China.

Abstract The prevalence of non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers, with the Wnt/β-catenin signaling pathway exhibiting robust activation in this particular subtype. The expression of FAM83A (family with sequence similarity 83, member A) has been found to be significantly upregulated in lung cancer, leading to the stabilization of β-catenin and activation of the Wnt signaling pathway. In this study, we conducted a screening of down-regulated miRNAs in lung cancer with FAM83A as the target. Ultimately, we identified miR-1 as a negative regulator of FAM83A and confirmed that FAM83A is a direct target gene of miR-1 through dual luciferase reporter assays. The overexpression of miR-1 significantly attenuated the expression level of FAM83A and suppressed the Wnt signaling pathway, leading to a reduction in the expression levels of downstream target genes AXIN2, CyclinD1, and C-MYC. Additionally, it decreased the nuclear translocation of β-catenin. In addition, overexpression of miR-1 accelerated the degradation of β-catenin by inhibiting FAM83A, promoted the assembly of β-catenin degradation complex, and inhibited the proliferation, migration and invasion of NSCLC cells. In summary, miR-1 may be a potential candidate miRNA for the treatment of NSCLC.

Recent explosions have prompted researchers to investigate the vulnerability of civil structures, leading to an increased demand for blast-resistant buildings. Laminated glass (LG) panels in glazed facades boost resilience, yet understanding glass fragment interaction with interlayers remains incomplete. This paper presents an integrated experimental-computational study on strain localization in LG polymeric interlayers to accurately simulate their response, addressing this gap. Uniaxial tensile tests were performed on the polymeric interlayer materials polyvinyl butyral (PVB) and SentryGlas® (SG), commonly used in the design of LG in blast-resistant glazing systems. Digital image correlation was used to characterize strain localization within the material. The experimental results were used to calibrate material model parameters to be used in the modeling of LG systems. A three-network viscoplastic (TNV) material model for SG interlayer was calibrated using PolymerFEM software. Yeoh hyperelastic material model parameters were calibrated for the quasistatic response of PVB. A finite element computational model was developed using Ansys LS-DYNA software and validated with experimental data. The study results showcase finite element modeling's ability to accurately predict both the hyperelastic response of PVB and the post-peak large strain behavior of SG interlayer materials by 8% and 3.6%, respectively.

The subspecies Abrus pulchellus subsp. mollis exhibits pharmacological properties akin to the traditional Chinese medicinal plant Abri Herba (A. pulchellus subsp. cantoniensis (Hance) Verdc.). In this report, we unveil the plastid genome of A. pulchellus subsp. mollis. The genome spans 156,322 base pairs (bp), comprising a large single-copy (LSC) region of 86,633 bp, a small single-copy (SSC) region of 18,219 bp, and two distinct inverted repeat regions (IRs) of 25,735 bp each. Annotation process cataloged a total of 111 genes within this genome, including 77 protein-coding genes, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. The overall guanine-cytosine (GC) content of the plastome is 35.5%. Phylogenetic analysis utilizing maximum-likelihood (ML) based on 16 complete plastid genomes reveals a close clustering of three Abrus taxa, namely A. pulchellus subsp. mollis, A. pulchellus subsp. cantoniensis, and A. precatorius. Notably, A. pulchellus subsp. cantoniensis clusters with A. precatorius as a sister group, distinct from A. pulchellus subsp. mollis. These findings highlight significant differences between the plastid genomes of the two subspecies, laying the foundation for future research on the identification of medicinal herbs and germplasm resources related to these subspecies.

Abstract tRNA is the RNA type that undergoes the most modifications among known RNA, and in recent years, tRNA methylation has emerged as a crucial process in regulating gene translation. Dysregulation of tRNA abundance occurs in cancer cells, along with increased expression and activity of tRNA methyltransferases to raise the level of tRNA modification and stability. This leads to hijacking of translation and synthesis of multiple proteins associated with tumor proliferation, metastasis, invasion, autophagy, chemotherapy resistance, and metabolic reprogramming. In this review, we provide an overview of current research on tRNA methylation in cancer to clarify its involvement in human malignancies and establish a theoretical framework for future therapeutic interventions targeting tRNA methylation processes.

Abstract Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment.

In order to compare the microstructures and tribological properties of films, pure Mo2N, pure MoS2, 3-layer and 13-layer MoS2/Mo2N gradient films were deposited by reactive magnetron sputtering. The crystalline structure, surface and cross-section morphologies, 3D surface topography, binding energy, hardness and tribological properties of films were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), atom force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), nanoindenter, and wear tester, respectively. The results indicate that the preferred orientation of MoS2 in gradient films has changed. The surface and cross-section structures of gradient films become denser with increasing the number of gradient layers. Average surface roughness (Ra) of pure MoS2 film is the highest, and Ra of 13-layer film is the lowest. The binding energy of MoS2 in the composite layer of gradient film has changed. The hardness of gradient film is higher than that of MoS2 and lower than that of Mo2N. The wear resistance of gradient films is much better than that of pure MoS2, and this phenomenon is more obvious under high load conditions. The improvement in the wear resistance of gradient films is attributed to the increase of dense, hardness, H/E and H3/E2. In the initial stage of friction, the 3-layer gradient film can maintain low friction coefficient (≤0.15), which is attributed to the thick MoS2 surface layer. The wear resistance of 13-layer is much better than that of 3-layer gradient film, because it has higher hardness, higher H/E and H3/E2 than 3-layer gradient film.

Prioritizing multiple potentially unstable slopes based on varying levels of criticality is an essential approach when resources are limited. This study presents a framework for planning the prioritization of unstable rock slope remediation. The prioritization of mitigation measures for these slopes is determined using deformation values derived from indirect information, such as rock classification systems. To demonstrate the application of this framework, a case study involving unstable rock slopes in southwestern China is presented. Initially, the most appropriate estimation model was chosen from among six candidates for estimating the deformation modulus of the unstable rock mass in the slope, utilizing indirect information. Subsequently, the deformation modulus, updated through Bayesian analysis, was employed to generate the corresponding deformation distributions for the rock slopes. Compared to traditional quantitative methods, the proposed framework is adaptable to various working conditions and yields more definitive results. The indirect data used in this framework are cost-effective, enabling the assessment of all unstable slopes. Moreover, the effect of the amount of indirect data and prior information on slope remediation prioritization is discussed. The proposed framework offers a valuable tool for decision-makers in planning and prioritizing mitigation measures.

Methods In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation.Results AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894–0.934) and 0.923 (95% CI, 0.895–0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model’s favorable clinical applicability.Conclusion We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Abstract Lithium–sulfur (Li–S) battery is attracting increasing interest for its potential in low‐cost high‐density energy storage. However, it has been a persistent challenge to simultaneously realize high energy density and long cycle life. Herein, we report a synergistic strategy to exploit a unique nitrogen‐doped three‐dimensional graphene aerogel as both the lithium anode host to ensure homogeneous lithium plating/stripping and mitigate lithium dendrite formation and the sulfur cathode host to facilitate efficient sulfur redox chemistry and combat undesirable polysulfide shuttling effect, realizing Li–S battery simultaneously with ultrahigh energy density and long cycle life. The as‐demonstrated polysulfide‐based device delivers a high areal capacity of 7.5 mAh/cm2 (corresponds to 787 Wh/L) and an ultralow capacity fading of 0.025% per cycle over 1000 cycles at a high current density of 8.6 mA/cm2. Our findings suggest a novel strategy to scale up the superior electrochemical property of every microscopic unit to a macroscopic‐level performance that enables simultaneously high areal energy density and long cycling stability that are critical for practical Li–S batteries.

IntroductionAlcanivorax, a typical alkane-degrading bacterium, has demonstrated the ability to utilize inorganic electron donor in some reports. However, a comprehensive analysis of its potentiality to utilize inorganic electron donor is still lacking.MethodsIn this study, genomic and phylogenetic analyzes were used to explore the potential oxidative capacity of inorganic compounds in Alcanivorax. And its functions were verified through physiological experiments.ResultsThe sulfur oxidation-related genes sqr and tsdA are prevalent and have various evolutionary origins. Potential genes for CO oxidation were present in 39 strains, whereas genes associated with iron, hydrogen, and ammonia oxidation were either rare or absent. The physiological functions of Sqr and TsdA were confirmed in six representative strains under heterotrophic conditions. Adding thiosulfate enhanced Alcanivorax growth. However, Alcanivorax bacteria perform sulfide detoxification through Sqr rather than by gaining energy via sulfide oxidation Although no strain was confirmed to be chemoautotrophs, we discovered that the two clades, A. xenomutans and A. profundimaris, can grow under conditions with very low organic matter.DiscussionThe ability to utilize inorganic compounds as a supplementary energy source and adapt to carbon oligotrophic growth may contribute to the prevalence of Alcanivorax in marine ecosystems.

Resumo Fundamento A hipertrofia cardíaca patológica (HC) sustentada é um fator de risco independente para aumento da incidência e mortalidade de eventos cardiovasculares. Objetivos Esta pesquisa foi projetada para desvendar o papel do RNA não codificante longo (LncRNA) CCAT2 na progressão da HC. Métodos Procedimentos de constrição aórtica transversal (TAC) foram conduzidos para construir um modelo de HC in vivo induzido por sobrecarga de pressão. O tratamento com angiotensina II (Ang II) foi utilizado para induzir células hipertróficas de cardiomiócitos de rato H9c2. Resultados Os resultados in vivo mostraram que o silenciamento de CCAT2 reduziu a área de superfície dos cardiomiócitos, aliviou a fibrose cardíaca e diminuiu os níveis de β-MHC, ANP e BNP em modelos de camundongos HC. Os resultados in vitro revelaram que o knockdown de CCAT2 reduziu a área de superfície celular e atenuou os níveis de β-MHC, ANP e BNP em células hipertróficas H9c2. Além disso, o silenciamento de CCAT2 diminuiu os níveis de β-catenina ativa, GSK-3β fosforilada e genes alvo Wnt (c-Myc, ciclinaD1 e c-Jun) em camundongos HC e células H9c2 hipertróficas. É importante ressaltar que o tratamento com o ativador da via Wnt / β-catenina LiCl reverteu a supressão do knockdown de CCAT2 na área de superfície celular H9c2 e nos níveis de MHC, ANP e BNP. Conclusões Coletivamente, o silenciamento do CCAT2 desempenha um papel protetor contra a HC através da inativação da sinalização Wnt/β-catenina, o que sugere que o CCAT2 pode se tornar um alvo terapêutico promissor para o HC.

A growing body of evidence exhibits the ubiquitous presence and accumulation of micro- and nanoplastics (MNPs) in the air, drinking water, food, and even inside the body, which has raised concerns about their potential impact on reproductive and developmental health. To comprehensively examine the current state of knowledge regarding MNPs-induced reproductive and developmental toxicity, we conducted this systematic review by focusing on the prevalence of MNPs determined in reproductive tissues and their influences on parental reproduction and offspring development. Our findings demonstrate the detection of MNPs in various human reproductive tissues, including semen, placenta, and ovarian follicular fluid, as well as in reproductive tissues of diverse animal species. We show a potential relationship between MNP exposure and increased prevalence of infertility and adverse pregnancy outcomes based on the fact that MNPs exert detrimental effects on reproductive parameters, including sperm quality, ovarian function, and steroidogenesis. In male reproductive systems, MNPs disrupt testicular tissue structure, impair reproductive endocrinology, and reduce sperm quality. In females, MNPs affect ovarian tissue structure and function, interfere with hormone secretion, and impact the endometrium and embryo implantation. Additionally, MNPs cause developmental toxicity in animal models, affecting embryonic development and offspring health, and produce transgenerational effects. Notably, in-depth literature study suggests a crucial role for oxidative stress, inflammation, and epigenetic modification in MNPs-induced toxicity. In conclusion, we integrated systematic knowledge on MNPs-induced reproductive and developmental toxicity, and the systematic finding underscores future study to fully elucidate the risks posed by MNPs to reproductive and developmental health and to inform policy decisions and public health interventions aimed at mitigating their harmful effects.

Inositol-requiring enzyme 1 (IRE1), a mediator of the unfolded protein response, shows the highest degree of evolutionary conservation. Vertebrates express two IRE1 paralogs: IRE1α, which is universally expressed and IRE1β, which shows specific expression within mucus secreted cells in respiratory and gastrointestinal tracts. The biological properties and regulation of the two IRE1 duplicates show evolutionary differences. As recently suggested, IRE1β-deficient mice display impairment in secreted protein expression and mucosal homeostasis. Abnormal changes in IRE1β caused by external and internal factors can disrupt mucosal homeostasis and further lead to respiratory and gastrointestinal diseases. Here, we highlight the physiological functions of IRE1β in the respiratory and gastrointestinal tracts in response to environmental microbes, viruses, toxins, and food components.

The dual carbon goal is a systematic project involving the entire society and has a leading and systematic role in the green and low-carbon development of China. In this study, we used the CiteSpace software to visualize and analyze 5809 documents from the core database of Web of Science from 1995 to 2023, covering four aspects: descriptive statistics, network collaboration, research hotspots, and thematic evolution analysis. The number of studies in the field of dual carbon is in an explosive growth stage and China and the Chinese Academy of Sciences have become the core country and institution for research, respectively, in this field. Major high-impact journals include Cleaner Production, Energy, Renewable and Sustainable Energy Review, Applied Energy, and Energy Policy. Relevant research has mainly focused on carbon neutralization, CO2 emissions, impact factors, energy, and emission reduction performance. Research hotspots primarily include carbon dioxide electrocatalytic reduction technology, sustainable energy transition strategies, and green financial policy tools. The government should further support for the research and development of carbon-neutral technologies, particularly for the industrialization and application of CO2 electrocatalytic reduction technology. Meanwhile, investment in renewable energy should be increased to optimize the energy structure and promote energy transition. In addition, green financial policy tools must be improved to promote the healthy development of the green financial market. The transparency and efficiency of the carbon trading market can be improved using digital technology and big data analysis, thus promoting the deep integration of the digital economy, with the goal of carbon neutrality.

Summary: Pain has become a major symptom of long COVID-19 without effective therapy. Apart from viral infection pathological process, SARS-CoV-2 membranal proteins (envelope [S2E], spike [S2S] and membrane [S2M]) also present pro-inflammatory feature independently. Here, we aim to uncover the neuroinflammatory mechanism of COVID-pain induced by SARS-CoV-2 membranal proteins. We detected the three proteins in both peripheral sensory ganglions and spinal dorsal horn of COVID-19 donors. After intradermal and intrathecal injection, only S2E triggered pain behaviors, accompanied with upregulated-phosphorylation nuclear factor kappa B (NF-κB), which was significantly attenuated by minocycline in mice. We further identified Toll-like receptor 2 (TLR2) among TLRs as the target of S2E to evoke inflammatory responses leading to COVID-pain. This study identified the nociceptive effect of S2E through directly interacting with macrophage/microglia TLR2 and inducing the following NF-κB inflammatory storm. Clearing away S2E and inhibiting macrophage/microglia TLR2 served as perspective therapeutic strategies for COVID-19 pain.

ABSTRACT: Duck hepatitis A virus type 3 (DHAV-3) is an infectious virus that is highly fatal to ducklings and causes significant economic losses in the duck industry worldwide. Biosecurity and vaccination are required to control the pathogen. In the present study, we attenuated a lowly pathogenic DHAV-3 clinical isolate, named as HB, by serial passaging in duck embryos, and followed by several adaptive proliferations in specific-pathogen-free (SPF) chicken embryos. The virulence of DHAV-3 at different passages was assessed by infecting 3-day-old ducklings. We found that the HB strain lost pathogenicity to ducklings from the 55th passage onwards. The 80th passage strain (HB80), which achieved good growth capacity in duck embryos with a viral titer of 108.17 50% egg lethal dose per milliliter (ELD50/mL), was selected as a live attenuated vaccine candidate. The HB80 strain did not induce clinical symptoms or pathological lesions in 3-day-old ducklings and showed no virulence reversion after 5 rounds of in vivo back-passage. The minimum effective dose of HB80 was determined to be 104.5 ELD50 by hypodermic inoculation of the neck. Importantly, a single dose of HB80 elicited good immune responses and provided complete protection against challenge with the lethal DHAV-3 strain. Compared with the genomic sequence of the parental HB strain, HB80 had 7 amino acid substitutions, two of them are in the hypervariable region of the VP1 and polymerase-encoding 3D regions, which may play a role in virulence attenuation. Our data suggest that the attenuated HB80 strain is a promising vaccine candidate for the prevention of DHAV-3 infections in China. HB80 has been registered as a New Veterinary Drug Registration Certificate by the Chinese Ministry of Agriculture and Rural Affairs (MARA), and is the first live attenuated DHAV-3 vaccine strain to be officially licensed in China.