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Abstract Objective In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. Methods This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. Results 702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). Conclusions LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Abstract To explore the role of bronchoscopy for the assessment of checkpoint inhibitor pneumonitis (CIP), a retrospective single-center study was conducted to assess patients diagnosed with CIP at grade 2 or above and also underwent bronchoscopy between January 2020 and December 2022. Clinical data and bronchoscopic findings were recorded. The treatment data and prognosis information were collected. Twenty-one patients who underwent bronchoscopy and were diagnosed with CIP were enrolled in this study. All patients underwent bronchoalveolar lavage fluid (BALF) analysis. Of them, T lymphocyte subsets of BALF were tested in 15 cases. Transbronchial cryobiopsy (TBCB) was performed in 8 patients, and transbronchial lung biopsy was performed in 5 patients. 3 patients developed pneumothorax after TBCB and all recovered without serious compilations.14 patients experienced grade 2 CIP, while 7 patients ≥ grade 3 CIP. Symptoms were improved in 19 (90.5%) patients after standard treatment adhering to CIP guidelines. However, 5 patients relapsed during steroid tapering. Factors related to the severity and recurrence of CIP were analyzed. Patients with previous interstitial lung disease (ILD) were more likely to develop high grade CIP than those without [83.3% (5/6) versus 15.4% (3/15), P = 0.011].The odds ratio (OR) was 32.5 (95% CI 2.284–443.145, P = 0.009). Increased BALF lymphocyte percentage was associated with high grade CIP, OR 1.095 (95% CI 1.001–1.197, P = 0.047), and higher possibility of CIP relapse, OR 1.123 (95% CI, 1.005–1.225, P = 0.040). Lymphocyte subsets were tested in 15 patients. CD4/CD8 > 1 was found in 80% (4/5) of relapsed patients and 20% (2/10) of patients without relapse (P = 0.047). The OR was 16.00 (95% CI 1.093–234.24, P = 0.043). In this retrospective study, patients with previous ILD was more likely to develop high grade CIP. Higher lymphocyte percentage in BALF was associated with high grade CIP and susceptibility to relapse during treatment of CIP. A CD4/CD8 ratio greater than 1 in lymphocyte subsets of BALF was associated with higher possibility of CIP relapse. We found that TBCB is a safe procedure in CIP patients.

Abstract Objective The aim of this study is to identify risk factors associated with acute complicated appendicitis (CA) in children aged three years or younger, providing a theoretical foundation for the management and treatment of acute appendicitis (AA). Methods A retrospective analysis was conducted on 135 pediatric patients with AA, admitted to the Department of General Surgery at Anhui Children’s Hospital between December 2020 and December 2023, who underwent successful surgical treatment. Based on the intraoperative and postoperative pathological findings, patients were categorized into two groups: complicated appendicitis (CA) (n = 97 cases) and uncomplicated appendicitis (UA) (n = 38 cases). Clinical data including gender, age, weight, disease duration, preoperative white blood cell count (WCC), neutrophil granulocyte (NEUT) count, C-reactive protein (CRP) levels, total bilirubin (TBil) levels, procalcitonin (PCT) levels, calprotectin (Cal) levels, preoperative ultrasound results indicating the presence or absence of fecaliths, maximum appendix diameter, and pediatric appendicitis sore (PAS) were collected and analyzed. Comparative analysis was performed to investigate the differences between the groups and identify risk factors of CA. Results The CA group exhibited significantly higher values in disease duration, CRP levels, PCT, Cal, presence of appendiceal fecaliths, maximum appendix diameter, and PAS compared to the UA group (P

Objective To explore the influencing factors the combination of acute renal tubular injury （ARTI） in patients with idiopathic membranous nephropathy （IMN） in a multi-ethnic area of Guangxi. Methods From April 2013 to October 2021, 155 patients with IMN diagnosed by renal biopsy and hospitalized at Hechi People's Hospital were recruited. They were assigned into two groups of with ARTI （n = 43） and without （n = 112）. Results Multifactorial Logistic analysis revealed that serum β2 microglobulin （β2-MG） was independently associated with ARTI in IMN patients （OR = 1.06, 95%CI: 1.01 to 1.12, P = 0.014）. AUC value for ROC curve analysis of serum β2 microglobulin for diagnosing ARTI was 0.748. An optimal threshold value of 2.65 mg/L corresponded to a sensitivity of 81.4% and a specificity of 58.04%. According to serum β2 microglobulin level, they were assigned into three groups of low, medium and high. The odds of ARTI spiked 5.01 and 22.89 folds in medium and high groups as compared with low group. And the results of trend test indicated that the odds of ARTI in IMN patients increased with a rising serum β2 microglobulin concentration （P＜0.001）. Stratified interaction test analysis revealed an interaction between serum β2 microglobulin and ARTI in IMN patients among gender, differential degrees of hypoproteinemia and ethnicity （P for interaction ＜0.05）. Conclusion Serum β2 microglobulin is independently associated with ARTI in IMN patients. And an interaction exists between gender, differential levels of hypoproteinemia and ethnicity.

Abstract Background Whether there are invasive components in pure ground glass nodules(pGGNs) in the lungs is still a huge challenge to forecast. The objective of our study is to investigate and identify the potential biomarker genes for pure ground glass nodule(pGGN) based on the method of bioinformatics analysis. Methods To investigate differentially expressed genes (DEGs), firstly the data obtained from the gene expression omnibus (GEO) database was used.Next Weighted gene co-expression network analysis (WGCNA) investigate the co-expression network of DEGs. The black key module was chosen as the key one in correlation with pGGN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were done. Then STRING was uesd to create a protein-protein interaction (PPI) network, and the chosen module genes were analyzed by Cytoscape software.In addition the polymerase chain reaction (PCR) was used to evaluate the value of these hub genes in pGGN patients’ tumor tissues compared to controls. Results A total of 4475 DEGs were screened out from GSE193725, then 225 DEGs were identified in black key module, which were found to be enriched for various functions and pathways, such as extracellular exosome, vesicle, ribosome and so on. Among these DEGs, 6 overlapped hub genes with high degrees of stress method were selected. These hub genes include RPL4, RPL8, RPLP0, RPS16, RPS2 and CCT3.At last relative expression levels of CCT3 and RPL8 mRNA were both regulated in pGGN patients’ tumor tissues compared to controls. Conclusions To summarize, the determined DEGs, pathways, modules, and overlapped hub genes can throw light on the potential molecular mechanisms of pGGN.

Abstract Introduction This study aimed to explore influencing factors and clinical significance of ultra-long-term microischemia following intracranial aneurysm (IA) embolization and establish a theoretical foundation for reducing both the incidence of ultra-long-term microischemia and cognitive dysfunction in patients post embolization. Methods A retrospective analysis was conducted on data from 147 patients who received endovascular treatment for IAs. Patients were categorized into microischemic and control (non-microischemic) groups on the based on the findings of high-resolution magnetic resonance vessel wall imaging (HR-VWI) examinations performed 3 days postoperatively and 6 months postoperatively. Risk factors for the occurrence of ultra-long-term microischemia were determined by univariate analysis and multivariate logistic regression analysis. Results Out of 147 patients included in the study, 51 (34.69%) developed microischemia while the remaining 96 (65.31%) did not experience this condition. Analysis revealed that factors such as sex, age, history of underlying diseases (hypertension, diabetes mellitus), aneurysmal site characteristics, the presence or absence of stenosis in the aneurysm-bearing artery, modified Fisher score at admission, Barthel’s index at discharge, immunoinflammatory index at 3 days postoperatively and at the 6-month follow-up, the presence or absence of aneurysmal wall enhancement, and the presence or absence of aneurysmal lumen showed no statistically significant differences between the two groups (all P > 0.05). By contrast, variables like in operative time, rupture status of the aneurysm before surgery according to World Federation of Neurologic Surgeons (WFNS) grade, aneurysm size, number of stents used, number of guidewires and catheters used, and Evans index between the two groups were found to have statistically significant disparities between those who developed microischemia and those who did not (P 0.3, and the quantity of stents were independent risk factors for the occurrence of ultra-long-term microischemia after aneurysm embolization and provided good predictive performance. Cognitive dysfunction was closely associated with microischemia, with its severity increasing with an increase in the number of ischemic foci.

This work conducted tensile experiments from room temperature to 1100 °C on a new fourth-generation single crystal superalloys along [001]. The effect of temperature on the tensile properties and deformation mechanism of the alloy were investigated. Results showed that the yield strength of the alloy reached its peak value (1017 MPa) at 850 °C. From room temperature to 760 °C, the occurrence of stacking faults (SFs) was observed in the γ matrix channel. From the room temperature to 850 °C, the occurrence of stacking faults was observed in the γʹ phase. The interface dislocation networks appeared at 980 °C and above. At room temperature, stacking faults sheared γʹ phase, in which three types of stacking faults occurred, which controlled deformation process. The main deformation mechanism from 650 °C to 850 °C was the shearing of γʹ phase by stacking faults and super dislocations, and at 850 °C, stacking faults in different directions of propagation corresponded to the formation of Lomer-Cottrell locks (L-C locks), which greatly increased the yield strength. At 980 °C and 1100 °C, dislocation climbing and bypassing and anti-phase boundary (APB) coupled dislocation pair shear γʹ phase became the main deformation mechanism.

Based on the analysis of the demand of U.S. aviation assets to implement of the long-range air-to-air intervention of the great powers high-end war, and combined with the penetrating counter air fighter, collaborative combat aircraft, AIM-260 air-to-air missiles, Long Shot unmanned aerial vehicles and other projects, as well as the latest concept of operations, such as agile combat employment, this paper researches and analyzes three kinds of long range air-to-air intervention operation scenarios: using the next generation stealthy manned fighter to achieve kill chain self-closing, based on stealth manned aircraft and stealth unmanned aircraft to execute distributed air operations, and using existing non-stealth aircraft under the outer information support to carry out long-range air-to-air strikes. In the end, raise three points of view.

Abstract Background Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. Methods Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein–protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. Results Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. Conclusions PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.

BackgroundSpontaneous intracerebral hemorrhage (sICH) is a form of stroke with high mortality rates and significant neurological implications for patients. Abnormalities in lipid metabolism have been implicated in various cardiovascular diseases, yet their relationship with sICH remains insufficiently explored, particularly concerning their association with inflammatory factors.MethodsEmploying a two-sample, two-step Mendelian Randomization approach, combined with data from GWAS datasets, to investigate the causal relationship between plasma lipid levels and sICH. Additionally, the role of inflammatory factors in this relationship was examined, and sensitivity analyses were conducted to ensure the robustness of the results.ResultsThe results indicate a significant causal relationship between 19 plasma lipid metabolites and sICH. Furthermore, mediation analysis revealed that three distinct lipids, namely Sterol ester (27:1/20:2), Phosphatidylcholine (16:0_20:4), and Sphingomyelin (d34:1), exert their influence on sICH through inflammatory factors. TRAIL (OR: 1.078, 95% CI: 1.016–1.144, p = 0.013) and HGF (OR: 1.131, 95% CI: 1.001–1.279, p = 0.049) were identified as significant mediators.ConclusionThis study provides new evidence linking abnormalities in lipid metabolism with sICH and elucidates the role of inflammatory factors as mediators. These findings contribute to a better understanding of the pathogenesis of sICH and offer novel insights and therapeutic strategies for its prevention and treatment.

IntroductionMolecular subgroups influence the vascular architecture within medulloblastomas, particularly the wingless (WNT) subgroup, which contributes to its propensity for primary tumor hemorrhage. Whether this mechanism affects intraoperative blood loss remains unknown. This study aimed to assess the association between WNT medulloblastoma and the predisposition for blood loss.MethodsThis was a retrospective observational study using data from a neuro-oncology center comprising molecular data on patients treated between December 31, 2014, and April 30, 2023. Differences between WNT and other subgroups in the risk of primary outcome-intraoperative blood loss were assessed using multivariable-adjusted linear regression.ResultsOf the 148 patients included in the analysis, 18 patients (12.2%) had WNT, 42 (28.4%) had sonic hedgehog (SHH) TP53-wildtype, 7 (4.7%) had SHH TP53-mutant, and 81 (54.7%) were non-WNT/ non-SHH. The WNT subgroup more frequently underwent primary intratumoral hemorrhage (22% vs. 3.8%; p = 0.011). The median intraoperative blood loss was 400.00 (interquartile range [IQR] 250, 500) mL for WNT and 300.00 [200, 400] mL for the other subgroups (p = 0.136), with an adjusted β of 135.264 (95% confidence intervals [CI], 11.701–258.827; p = 0.032). Similar results were observed in both midline and noninfiltrative margin medulloblastoma.DiscussionWNT medulloblastoma is typically associated with primary intratumoral hemorrhage and intraoperative blood loss. The validity of determining the surgical approach based on predicted molecular subtypes from imaging data is questionable. However, attempting to engage in risk communication with patients in a molecular-specific way is worthwhile to validate.

Abstract The hemorrhagic progression of a contusion (HPC) after Traumatic brain injury (TBI) is one of the important causes of death in trauma patients. The purpose of this meta-analysis was to evaluate the predictive effect of imaging features of Computed tomography (CT) on HPC after TBI. A comprehensive systematic search was performed using PubMed, EMBASE, and WEB OF SCIENCE databases to identify all relevant literature. A total of 8 studies involving 2543 patients were included in this meta-analysis. Meta-analysis showed that subarachnoid hemorrhage (OR 3.28; 95% CI 2.57–4.20), subdural hemorrhage (OR 4.35; 95% CI 3.29–5.75), epidural hemorrhage (OR 1.47;95% CI 1.15–1.89), contrast extravasation (OR 11.81; 95% CI 4.86–28.71) had a predictive effect on the occurrence of HPC. Skull fracture (OR 1.64; 95% CI 0.84–3.19) showed no statistical significance, and midline displacement > 5 mm (OR 4.66; 95% CI 1.87–11.62) showed high heterogeneity. The results of this meta-analysis showed that some imaging features were effective predictors of HPC after TBI. Well-designed prospective studies are needed to more accurately assess the effective predictors of HPC after TBI.

Abstract Brushless direct current motor is widely used in industrial production because of its simple structure, wide speed range and low noise. To improve the operation efficiency of brushless DC motor and reduce the production and application costs, the optimization of brushless DC motor is analyzed by introducing the JAYA algorithm. This method determines the optimal parameters of a brushless DC motor using the theory of electromagnetic structure parameter selection and efficiency calculation. The population diversity of the JAYA algorithm is improved through an empirical learning strategy, and an adaptive strategy is introduced to balance the development ability and search performance of the algorithm. This ensures population diversity and improves convergence speed. The experiment showcases that the improved JAYA algorithm has a lower rank average in unimodal function operations, demonstrating stronger local development ability and better stability. It exhibits strong search ability in many local optima of multimodal functions. Moreover, the motor's average efficiency after optimization is 94.48%. The algorithm reaches the global optimum after approximately 40 iterations and offers faster convergence speed and higher accuracy. The adaptive JAYA algorithm is stable at around 93% when the number of iterations reaches 90, with a maximum efficiency of 95.3%. It is 5–12 percentage points higher than the other three comparison algorithms. The optimal solution of the motor parameters in the adaptive JAYA algorithm is closest to the theoretical parameter optimization value, meeting both the constraints of variables and the constraints of the model. The stator diameter, tooth magnetic induction, winding current density, air gap magnetic induction, and stator yoke magnetic induction values are 201.5 mm, 1.8 T, 2.049 A/mm2, 0.63 T, and 0.91 T, respectively. The research overcomes the problem of parameter optimization in the optimization design of brushless DC motor, improving their economic value of brushless DC motor in industrial production and application.

The isothermal oxidation behavior of fourth-generation nickel-based single crystal superalloys with 2-4 wt% Mo content were studied at 900 °C and 1100 °C.At 1100 °C, the oxide layer can be divided into three layers, the outermost layer is Ni–Co oxide, the intermediate layer is spinel and heavy metal element oxide, and the innermost layer is Al2O3 layer. With the increase of Mo content, the oxide layer accumulates more growth stress, resulting in more severe spallation. At 900 °C, the oxide layer can be divided into three layers, the outermost layer is Ni–Co oxide, the intermediate layer is Cr–Al oxide, and the innermost layer has obvious selective oxidation of Al element. The volatilization of oxide promotes the diffusion of O into the matrix, thus promoting the oxidation of heavy metal elements in the matrix. With the increase of Mo content, this phenomenon is more obvious. The results show that the increase of Mo content of alloy promotes the oxidation of Mo, W and Re elements, which let the volatilization of the oxide and the spalling of the oxide layer more severe, thus decreasing the oxidation resistance of the alloy.

Abstract Scalable, high-capacity, and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks. Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls, hindering them from the sustainable performance improvement and iterative multi-task learning. Referring to another modality of light, photonic computing has been progressively applied in high-efficient neuromorphic systems. Here, we innovate a reconfigurable lifelong-learning optical neural network (L2ONN), for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware co-design. Benefiting from the inherent sparsity and parallelism in massive photonic connections, L2ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field, while incrementally acquiring expertise on various tasks by gradually enlarging the activation. The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths. Extensive evaluations on free-space and on-chip architectures confirm that for the first time, L2ONN avoided the catastrophic forgetting issue of photonic computing, owning versatile skills on challenging tens-of-tasks (vision classification, voice recognition, medical diagnosis, etc.) with a single model. Particularly, L2ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks, and 14× larger capacity than existing optical neural networks while maintaining competitive performance on each individual task. The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme, permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

It is important in production to achieve accurate counting and density estimation of high-density culture fry under the environmental conditions of aquaculture scenarios in an efficient and accurate manner. However, none of the current methods for fry counting works well under the high-density and high-overlap conditions of real aquaculture scenarios. Therefore, in this paper, we propose a high-density farming fry monitoring network model, Super-Resolution GAN Density Estimate Attention Network (SGDAN), which incorporating an image enhancement algorithm and an attention mechanism, and we create a high-density farming fry dataset (HD-FryDataset) based on the environmental conditions of real aquaculture scenarios. The network model is designed to improve and optimize the targeted subnetworks for several key aspects of high-density fish fry monitoring work. Four subnetworks are included for image optimization, feature extraction, attention, and density map estimation. The experimental results show that the SGDAN network model achieved an average counting accuracy of 97.57% on the high-density culture fry dataset, which was 8.23% and 2.06% higher than those of MCNN and CSRNet, respectively. Additionally, the MAE and RMSE of the model were reduced by 71.9% and 67.3% and by 34.3% and 33.2% compared with those of MCNN and CSRNet, respectively. The model proposed in this paper also has a better ability to generate predictive density maps. The density maps generated by SGDAN have values of the evaluation metrics PSNR and SSIM of 20.33 and 0.933, respectively, which are 3.31 and 0.037 and 2.63 and 0.031 higher than those of MCNN and CSRNet. In general, the network model proposed in this paper outperforms existing network models in two applications: accurate counting of fry and generation of density maps for high-density culture in aquaculture. It also provides a good solution for digitizing the number of fry and visualizing the density of high-density culture in intelligent aquaculture systems.

Abstract Background Pure uterine serous carcinoma (p-USC) and mixed tumors with serous component (m-USC) are aggressive subtypes of endometrial cancer associated with high mortality rates. This retrospective study aimed to compare clinicopathologic features and outcomes of p-USC and m-USC in a single center. Methods This study retrospectively reviewed patients diagnosed with USC at Peking University People’s Hospital between 2008 and 2022. T-tests and chi-square tests were used to compare clinicopathological characteristics between p-USC and m-USC. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the impact of clinical and pathological variables on OS and PFS. Results Among the 91 patients who underwent surgery, 65.9% (n = 60) were p-USC, and 34.1% (n = 31) were m-USC. Patients with p-USC had earlier menopause (P = 0.0217), a lower rate of progesterone receptor(PR) expression (P

Abstract Background Patients undergoing carotid endarterectomy (CEA) have a high restenosis rate, which increases the risk of stroke, and there is still a lack of effective treatment for restenosis. The cause of stenosis is related to local inflammatory reactions. Some basic studies have shown that the inflammatory response causing arterial stenosis is closely related to the nerve axons distributed in its outer membrane, and that removal of the nerve is effective in reducing the inflammatory response to prevent arterial stenosis. Therefore, we propose to design a randomized controlled trial to study whether disconnecting the carotid sinus nerve during a CEA operation can reduce carotid arterial restenosis. Method/design This study is a randomized, double-blind, single-center study. We will recruit 276 patients, who will be randomly divided into the experimental group and the control group. Based on the standard CEA operation, the operator will search for the carotid sinus nerve on the surface of the internal carotid artery and will entirely transect it in the experimental group. Both groups will be guided with the same postoperative treatment and will be followed up every 3 months for 3 years after the operation. The main indices observed will be the carotid restenosis rate, incidence and nature of carotid plaque, and carotid blood flow velocity. Other indices will be arrhythmia, blood pressure variability, and biomarkers of atherosclerosis, such as blood lipids, hypersensitive C-reactive protein (hs-CRP), homocysteine, and total bilirubin. Discussion It is expected that carotid sinus nerve transection will significantly reduce the occurrence of restenosis after CEA, decrease the incidence of ischemic stroke, and realize the effective primary prevention of stroke. Trial registration ChiCTR2300073652. Registered on July 18, 2023.

Abstract Background and Aims Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross‐line ICIs therapy is effective in treating non‐small cell lung cancer (NSCLC). Methods We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross‐line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross‐line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061–30.979), 31.643 (95% CI: 23.513–39.774), and 7.997 (95% CI: 3.746–12.247) months, respectively (p = 0.003). The median second progression‐free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276–5.864), 3.530 (95% CI: 0.674–6.386), and 1.570 (95% CI: 0–4.091) months, respectively (p = 0.091). Conclusions Cross‐line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

BackgroundGlioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined.MethodIn this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis.ResultsAfter conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515–0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L– HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004–2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031–1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma.ConclusionOur study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

Modular Multilevel Converter (MMC) is widely used in applications such as High Voltage Direct Current (HVDC) transmission, AC/DC power conversion centers, and large-scale power quality management in electrical grids due to its highly modular structure, strong redundancy and low harmonic content in AC output. The application of the traditional deadbeat predictive current control to MMC enhances the fast tracking ability of the output current, but it still has the problems of low output current accuracy and high dependence on bridge arm inductor. Based on this, this paper proposes an improved two-beat deadbeat synchronous predictive current control based on Newton interpolation method. By improving the two-beat deadbeat synchronous predictive current control strategy, the accuracy of the output current can be further improved and its fast tracking ability can be enhanced. Newton interpolation is introduced to improve the accuracy of the output current while reducing the dependence on the bridge arm inductor. The results show that the control strategy proposed in this paper reduces the output current THD by 2.88% compared with the two-beat deadbeat predictive current control, thus improving the accuracy; the bridge arm inductor value is reduced by 1.28%, thus reducing the dependence; and under the transient environment, the output current can be tracked to its predicted reference value 843 μs in advance, which enhances the fast tracking capability.

Abstract Background The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients. Methods This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS (n = 101) and HA (n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8. Discussion This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment. Trial registration ClinicalTrials.govNCT05682547. Registered on December 05, 2022.

In this paper, a high-yield Hf-modified SiHfBOC ceramic precursor was developed, and a high-pressure assisted impregnation pyrolysis method was proposed to achieve the preparation of 3D PyC–Cf/SiHfBOC composites. This high-pressure assisted impregnation method significantly improves impregnation filling effect of the precursor in and between fiber bundles compared to dozens of traditional impregnation cycles. After undergoing just 9 precursor infiltration pyrolysis (PIP) cycles, the composites achieved relative density of approximately 90% and density of 1.64 g/cm3. The critical temperature difference of the 3D PyC–Cf/SiHfBOC composites after the shock of room temperature (RT)–1000 ℃ is as high as 650 ℃, which is twice that of traditional ceramic materials, showing good thermal shock resistance. Under the effect of Hf modification, a dense HfO2–SiO2 oxide layer (thickness of 93 μm) was formed in situ on the surface of the 3D PyC–Cf/SiHfBOC composites, effectively preventing further erosion of the composite matrix by high-temperature oxidation gas. Even in the ultra-high-temperature oxygen-containing environment at 1800 ℃, it still exhibits an excellent non-ablative result (with a linear ablation rate of 0.83×10−4 mm/s). This work not only enriches the basic research on lightweight ultra-high-temperature ceramic composites converted from Hf ceramic precursors, but also provides strong technical support for their applications in ultra-high-temperature non-ablative thermal protection materials for high-speed aircraft.

Abstract Over the past few years, the rapid development of machine learning (ML) models for weather forecasting has led to state-of-the-art ML models that have superior performance compared to the European Centre for Medium-Range Weather Forecasts (ECMWF)’s high-resolution forecast (HRES), which is widely considered as the world’s best physics-based weather forecasting system. Specifically, ML models have outperformed HRES in 10-day forecasts with a spatial resolution of 0.25∘. However, the challenge remains in mitigating the accumulation of forecast errors for longer effective forecasts, such as achieving comparable performance to the ECMWF ensemble in 15-day forecasts. Despite various efforts to reduce accumulation errors, such as implementing autoregressive multi-time step loss, relying on a single model has been found to be insufficient for achieving optimal performance in both short and long lead times. Therefore, we present FuXi, a cascaded ML weather forecasting system that provides 15-day global forecasts at a temporal resolution of 6 hours and a spatial resolution of 0.25∘. FuXi is developed using 39 years of the ECMWF ERA5 reanalysis dataset. The performance evaluation demonstrates that FuXi has forecast performance comparable to ECMWF ensemble mean (EM) in 15-day forecasts. FuXi surpasses the skillful forecast lead time achieved by ECMWF HRES by extending the lead time for Z500 from 9.25 to 10.5 days and for T2M from 10 to 14.5 days. Moreover, the FuXi ensemble is created by perturbing initial conditions and model parameters, enabling it to provide forecast uncertainty and demonstrating promising results when compared to the ECMWF ensemble.

Here we investigated the nucleation of the Re, Ru-rich δ phase affected by stacking faults in the γ phase in a 4th generation Ni-based single crystal superalloy during the service at 800°C. The stacking faults in the γ phase were rich in Re and Ru, similar to the observed δ phase. And the stacking fault regions possessed a similar structure to the δ phase, promoting the transformation from γ phase to δ phase. Furthermore, the calculation results indicated that Ru had more significant promoting effects on the δ phase precipitation than Re, providing a reference for the alloy design.

To measure the long-range transport of PCDD/Fs, a background sampling site at Mt. Lulin station (Taiwan) was selected based on meteorological information and its location relative to burning events in Southeast Asia. During regular sampling periods, a higher concentration of PCDD/Fs was recorded in 2008 at Mt. Lulin station during La Niña events, with levels reaching 390 fg I-TEQ/m3. In contrast, a higher concentration of 483 fg I-TEQ/m3 was observed in 2013 during biomass burning events. This indicates that La Niña affects the ambient PCDD/F concentrations. The ratio of ΣPCDD/ΣPCDF was 0.59, suggesting significant long-range transport contributions from 2007 to 2023. From 2007 to 2015, the predominant species was 2,3,4,7,8-PCDF, accounting for 25.3 to 39.6% of the total PCDD/Fs. From 2018 onward, 1,2,3,7,8-PCDD became more dominant, accounting for 15.0 to 27.1%. According to the results from the receptor model PMF (n = 150), the sources of PCDD/Fs were identified as dust storms and monsoon events (19.3%), anthropogenic activity (28.5%), and biomass burning events (52.2%). The PSCF values higher than 0.7 highlighted potential PCDD/F emission source regions for Mt. Lulin during biomass burning events, indicating high PSCF values in southern Thailand, Cambodia, and southern Vietnam.

Springback error is a major obstacle in L-bending sheets via cold working. Although thermal processing can effectively reduce the springback phenomenon, it is challenging to heat the sheet globally due to the influence of working conditions. Therefore, this study applied local induction heating to reduce the springback of 45 steel sheets and investigated the effects of bending parameters on springback behavior. Initially, a thermodynamic coupling model and a static model were created utilizing the VOCE hardening model and the von Mises yield criterion in the ANSYS workbench 2022 R2 software. The springback behavior and stress distribution of the sheets were then investigated under different temperatures (room temperature and 800 °C) and bending angles (15°, 30°, 45°, 60°, 75°, and 90°). Simultaneously, the experiments were performed to investigate springback behavior and guarantee the accuracy of the model. The results indicate that the springback reached a minimum value at the 45° bending angle at room temperature while increasing with the increasing bending angle under 800 °C local heating. The springback under local heating can be decreased by 75.2% and the error of the bending angle can improve by 2–7° compared with samples processed in room temperature.

the clinical effectiveness of unilateral/bilateral percutaneous vertebral augmentation (PVA) for the treatment of osteoporotic vertebral compression fractures (OVCF) was assessed to provide guidance for clinical treatment.Through retrospective analysis of data from 107 patients, including preoperative and postoperative visual analogue scale scores, bone cement leakage, adjacent vertebral fractures, vertebral height, and infection.There was no significant difference in preoperative and postoperative scores, Cobb angle, anterior height, and bone cement leakage rate, but the vertebral body height in the bilateral percutaneous vertebral fusion surgery group was significantly higher than that in the unilateral group(P

Pectin methylesterase (PME), a family of enzymes that catalyze the demethylation of pectin, influences seed germination. Phytohormone abscisic acid (ABA) inhibits seed germination. However, little is known about the function of PMEs in response to ABA-mediated seed germination. In this study, we found the role of PME31 in response to ABA-mediated inhibition of seed germination. The expression of PME31 is prominent in the embryo and is repressed by ABA treatment. Phenotype analysis showed that disruption of PME31 increases ABA-mediated inhibition of seed germination, whereas overexpression of PME31 attenuates this effect. Further study found that ABI5, an ABA signaling bZIP transcription factor, is identified as an upstream regulator of PME31. Genetic analysis showed that PME31 functions downstream of ABI5 in ABA-mediated seed germination. Detailed studies showed that ABI5 directly binds to the PME31 promoter and inhibits its expression. In the plants, PME31 expression is reduced by ABI5 in ABA-mediated seed germination. Taken together, PME31 is transcriptionally inhibited by ABI5 and negatively regulates ABA-mediated seed germination inhibition. These findings shed new light on the mechanisms of PMEs in response to ABA-mediated seed germination.

Endometrial cancer (EC) is a common malignant tumor in women worldwide. Although early EC has a good prognosis, advanced endometrial cancer is still associated with the risk of drug resistance and recurrence. Cancer stem cells (CSCs), a category closely related to drug resistance and recurrence, are rarely studied at present. Here, we constructed a risk model containing ten stemness-related prognostic genes. Compared with patients in the low-risk group, patients in the high-risk group had a shorter overall survival time. The accuracy of this model was verified by ROC in the TCGA (AUC = 0.779) and Peking University People's Hospital (PKUPH, AUC = 0.864) cohorts. The risk score and stage were independent risk factors in the multivariate regression analysis, which was subsequently used to construct the nomogram and verified in the TCGA cohort. LGR5 was significantly correlated with overall survival and involvement in the Wnt signaling pathway. In addition, LGR5 was highly expressed in EC tissues and was related to age, stage, histological type, and menopause status in the TCGA database. Overexpression of LGR5 accelerated the proliferation rate of EC cells, which may be related to autophagy activation. Taken together, our study established a prognostic model based on transcription sequencing data from the TCGA database and verified it in the PKUPH cohort, which has prospective clinical implications for the prognostic evaluation of EC. We systematically studied the code gene LGR5 in EC, which may help clinicians make personalized prognostic assessments and effective clinical decisions for EC.

Background: The cachexia index (CXI) has been proposed as a novel biomarker of cancer cachexia. We aimed to investigate the association between CXI and survival outcomes after stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) and brain metastases. Methods: Data from 145 patients with NSCLC, who underwent SRT for brain metastases between April 2016 and August 2020, were retrospectively analyzed. Cachexia index was calculated as skeletal muscle index (SMI) × serum albumin level/neutrophil-to-lymphocyte ratio, whereas SMI was calculated from computed tomography images captured at the L1 level. Kaplan-Meier curves and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). The prognostic values of CXI and other cachexia biomarkers were assessed using receiver operating characteristic (ROC) curve analysis. Results: Lower pretreatment CXI (

The disheveled-associated antagonist of β-catenin homolog 3 (DACT3) has been recognized as a tumor suppressor in various cancers. However, the function of DACT3 on glioma malignant progression along with potential molecular mechanisms is poorly clarified. This research aimed to investigate how DACT3 contributes to suppressing the progression of glioma. In our investigation, a pronounced decrease in DACT3 expression was observed in glioma tissues. Through the overexpression of DACT3, we noted a significant suppression in the proliferation, invasion, and migration of glioma cells, while concurrently observing an increase in cell adhesion. Our exploration into the molecular mechanisms revealed that DACT3 executes its tumor-suppressive role by impeding the expression of notch 1 intracellular domain (NICD) and translocating into the nucleus by downregulating the expression of β-catenin. Consequently, this process leads to the suppression of Notch1 signaling. To summarize, our findings reveal the function of DACT3 to inhibit glioma progression via the Notch1 signaling pathway in β-catenin dependent manner. This study stands as the pioneer in examining the role of DACT3 in glioma progression and comprehensively elucidating its molecular mechanisms in glioma development. Therefore, our results suggest that DACT3 holds promise as both a prognostic factor and a potential biomarker for guiding treatment strategies in glioma patients (Graphical Abstract).

The nucleation and growth of topologically close-packed (TCP) phases in Ni-based single crystal superalloys (SCs) are controlled by composition, temperature, time, interface structure and stress. The formation of TCP phases causes detrimental effects on the mechanical properties of SCs. Therefore, it is crucial to study the formation mechanism and control factors of TCP phases to develop new-generation Ni-based SCs. Different alloying elements influence the TCP phase nucleation by adjusting the chemical driving force. The interface structure determined by interface energy and strain energy mainly affects the growth mechanism and morphology of the TCP phase. Various temperature determines the driving force for TCP nucleation and diffusion rates of elements during TCP phase growth. Holding time is also crucial to the growth and evolution of TCP phases. Applied stress also has an impact on the precipitation of TCP phases. Evolution between different types of TCP phases depends on the temperature, composition and crystal structure of TCP phases. TCP phases damage the mechanical properties mainly by causing stress concentration and weak interface strength. The review aims to establish a link among TCP phase formation, alloy design and microstructure from the macroscopic view to the microscopic view, providing some perspectives for future research.

BackgroundHyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients.MethodsWe conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People’s Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results.ResultsOf the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA.ConclusionOur study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies.

Abstract Objective To observe and evaluate the effectiveness and safety of Esketamine or Sufentanil combined with Dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA) to provide a clinical basis for the optimization of sedation and analgesia in lung tumor PRFA protocols outside the operating room. Methods In this trial, 44 patients aged 37 to 84 undergoing lung tumor PRFA were enrolled and assigned to Group E (n = 22, Esketamine 0.2 mg/kg) or Group S (n = 22,Sufentanil 0.1 μg/kg ). Dexmedetomidine was infused intravenously as a sedative in both groups. The modified observer’s assessment of alertness and sedation scale (MOAAS), physical movement pain scale, intraoperative vital signs, anesthesia recovery time, radiologist and patient satisfaction rates, incidence of respiratory depression, and incidence of postoperative nausea and vomiting were recorded. Results Although there was no significant difference in the physical movement pain scale, blood oxygen saturation or incidence of perioperative adverse events between the two groups during ablation, the MOAAS, mean arterial pressure (MAP) and heart rate (HR) were higher in Group E than in Group S. The anesthesia recovery time was shorter in Group E than in Group S, and radiologist satisfaction was better in Group E than in Group S, but there was no significant difference between the two groups in terms of patient satisfaction. Conclusion Esketamine or Sufentanil combined with Dexmedetomidine is safe for lung tumor PRFA. However, in elderly patients with multiple underlying diseases, low-dose Esketamine combined with Dexmedetomidine has fewer hemodynamic effects on patients, milder respiratory depression, shorter recovery time, and better radiologist satisfaction because of its better controllability of sedation depth. Trial registration Chinese Clinical Trial Registry (Registration number#ChiCTR ChiCTR21000500 21); Date of Registration: 16/08/2021

[Introduction] With the rapid development of power electronic equipment and artificial intelligence and other high-tech, DC (Direct Current) system has been popularized and applied in substations. The grounding fault of the substation DC system has become an important factor affecting the safe and stable operation of the substation. [Method] Firstly, the DC system of the substation was introduced, and its components, typical types of DC ground faults and their adverse effects were analyzed. Then, the principle of five common DC ground fault finding strategies was emphasized. [Result] Based on their respective research status and application scenarios, the advantages and disadvantages of various finding strategy are compared and analyzed. [Conclusion] Combined with the existing problems and technical development trends, the future research directions of DC grounding fault detection at home and abroad are prospected from the perspectives of accurate fault location, complex fault identification, finding accuracy and the improvement of the endurance of portable insulation detection device.

The flexible interconnection AC/DC hybrid system with modular multilevel converter (MMC) as the core interface can comprehend the centralized get right of entry to of different and decentralized resources, decorate the reliability of strength supply, and enhance new energy consumption. However, the intermittence and fluctuation of distributed generations affect the safety and stability of flexible interconnected AC/DC hybrid systems. MMC based on battery energy storage system (MMC-BESS) can stabilize power fluctuations on the AC and DC sides of the system and improve the stability of the system. In order to improve the rapidity and immunity of MMC-BESS, this paper presents an active disturbance rejection control (ADRC) strategy for the bidirectional DC–DC converter of MMC-BESS. The voltage fluctuations of the interface capacitor in the energy storage and the current fluctuations of the inductor in the bidirectional DC–DC converter are discussed. Moreover, ADRC controller is designed for the bidirectional DC–DC converter of MMC-BESS. At last, simulations under different load mutations on the DC side and unbalanced three-phase grid voltage are carried out for verification of the performance of the ADRC control strategy in MMC-BESS. The results show that MMC-BESS based on ADRC strategy has more favorable rapidity and immunity than PI strategy, and is helpful to practical application in flexible interconnected AC/DC hybrid system in the future.

Abstract Introduction Endometrial cancer (EC) is the most common female reproductive system cancer in developed countries with growing incidence and associated mortality, which may be due to the growing prevalence of obesity. Metabolism reprogramming including glucose, amino acid, and lipid remodeling is a hallmark of tumors. Glutamine metabolism has been reported to participate in tumor proliferation and development. This study aimed to develop a glutamine metabolism‐related prognostic model for EC and explore potential targets for cancer treatment. Method Transcriptomic data and survival outcome of EC were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes related to glutamine metabolism were recognized and utilized to build a prognostic model by univariate and multivariate Cox regressions. The model was confirmed in the training, testing, and the entire cohort. A nomogram combing prognostic model and clinicopathologic features was established and tested. Moreover, we explored the effect of a key metabolic enzyme, PHGDH, on the biological behavior of EC cell lines and xenograft model. Results Five glutamine metabolism‐related genes, including PHGDH, OTC, ASRGL1, ASNS, and NR1H4, were involved in prognostic model construction. Kaplan–Meier curve suggested that patients recognized as high risk underwent inferior outcomes. The receiver operating characteristic (ROC) curve showed the model was sufficient to predict survival. Enrichment analysis recognized DNA replication and repair dysfunction in high‐risk patients whereas immune relevance analysis revealed low immune scores in the high‐risk group. Finally, a nomogram integrating the prognostic model and clinical factors was created and verified. Further, knockdown of PHGDH showed cell growth inhibition, increasing apoptosis, and reduced migration. Promisingly, NCT‐503, a PHGDH inhibitor, significantly repressed tumor growth in vivo (p = 0.0002). Conclusion Our work established and validated a glutamine metabolism‐related prognostic model that favorably evaluates the prognosis of EC patients. DNA replication and repair may be the crucial point that linked glutamine metabolism, amino acid metabolism, and EC progression. High‐risk patients stratified by the model may not be sufficient for immune therapy. PHGDH might be a crucial target that links serine metabolism, glutamine metabolism as well as EC progression.

Abstract Wilkes Land and Totten Glacier (TG) in East Antarctica (EA) have been losing ice mass significantly since 1989. There is a lack of knowledge of long-term mass balance in the region which hinders the estimation of its contribution to global sea level rise. Here we show that this acceleration trend in TG has occurred since the 1960s. We reconstruct ice flow velocity fields of 1963–1989 in TG from the first-generation satellite images of ARGON and Landsat-1&4, and build a five decade-long record of ice dynamics. We find a persistent long-term ice discharge rate of 68 ± 1 Gt/y and an acceleration of 0.17 ± 0.02 Gt/y2 from 1963 to 2018, making TG the greatest contributor to global sea level rise in EA. We attribute the long-term acceleration near grounding line from 1963 to 2018 to basal melting likely induced by warm modified Circumpolar Deep Water. The speed up in shelf front during 1973–1989 was caused by a large calving front retreat. As the current trend continues, intensified monitoring in the TG region is recommended in the next decades.

Abstract Background Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. Methods This study is based on patients diagnosed with EC in Peking University People’s Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. Results The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81–0.90) and 0.77 (95% CI: 0.77–0.83), respectively (P

Abstract Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC. Graphical abstract

The magnetic shielding device, made of high-permeability soft magnetic material, is sensitive to external influences and requires a protective steel enclosure. A steel enclosure, being strongly ferrimagnetic, can alter the surrounding magnetic field distribution, thus impacting the shielding effectiveness. This study proposes a novel analytical approach to quantify this effect, which has not been previously researched. The method develops a simplified finite element simulation model based on the structural symmetry of the steel enclosure. By using this model, this study analyzes the impact of steel structures with varying heights, widths, and remanent magnetization values. The validity of the method is confirmed through experimental tests on steel buildings. The findings offer insights into the optimal placement of magnetic shielding systems and provide theoretical guidance for designing large-scale magnetic shielding devices.

Volatile organic compounds (VOCs) play a significant role in influencing the flavor quality of cherry tomatoes (Solanum lycopersicum var. cerasiforme). The scarcity of systematic analysis of VOCs in cherry tomatoes can be attributed to the constraints imposed by detection technology and other contributing factors. In this study, the cherry tomato cultivar var. ‘Zheyingfen1’ was chosen due to its abundant fruit flavor. Two detection technology platforms, namely the commonly employed headspace solid-phase microextraction—gas chromatography–mass spectrometry (HS-SPME-GC-MS) and the most advanced headspace solid-phase microextraction—full two-dimensional gas chromatography–time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS), were employed in the analysis. The VOCs of cherry tomato cultivar var. ‘Zheyingfen1’ fruits at red ripening stage were detected. A combined total of 1544 VOCs were detected using the two aforementioned techniques. Specifically, 663 VOCs were identified by through the HS-SPME-GC-MS method, 1026 VOCs were identified by through the HS-SPME-GC×GC-TOFMS, and 145 VOCs were identified by both techniques. The identification of β-ionone and (E)-2-nonenal as the principal VOCs was substantiated through the application of the relative odor activity value (rOAV) calculation and subsequent analysis. Based on the varying contribution rates of rOAV, the analysis of sensory flavor characteristics revealed that cherry tomato cultivar var. ‘Zheyingfen1’ predominantly exhibited green and fatty attributes, accompanied by elements of fresh and floral flavor characteristics. In conclusion, our study conducted a comprehensive comparison of the disparities between these two methodologies in detecting VOCs in cherry tomato fruits. Additionally, we systematically analyzed the VOC composition and sensory flavor attributes of the cherry tomato cultivar var. ‘Zheyingfen1’. This research serves as a significant point of reference for investigating the regulatory mechanisms underlying the development of volatile flavor quality in cherry tomatoes.

Background Since the Internet dependence of the supply and demand sides of health popularization is increasing, eHealth literacy has become a primary skill that chronic disease patients need to master. Objective To analyze the current situation and existing problems of online health information usage habits and eHealth literacy in middle-aged and elderly residents, and discuss the relationship between online health information usage habits and eHealth literacy, providing a reference for improving the level of eHealth literacy and developing appropriate Internet-based health popularization services for these populations. Methods From June to September 2021, a questionnaire survey was conducted among 1 061 middle-aged and elderly residents in Shanghai communities selected by multistage sampling using the General Information Questionnaire and the Chinese version of the eHealth Literacy Scale (eHEALS-C) to understand their habits of using online health information and levels of eHealth literacy. Stepwise multiple linear regression was used to assess the association of habit of using online health information and other potential candidate factors with the level of eHealth literacy. Results Altogether, 1 019 cases (96.04%) who effectively responded to the survey were included for analysis. Following health care accounts〔411 cases (40.33%) 〕was a major channel used for seeking online health information, followed by the search functionality or engines〔336 cases (32.97%) 〕, while the health apps or mini programs〔254 cases (24.93%) 〕, and online health communities〔65 cases (6.38%) 〕were less used. The online health information was less sourced from medical institutions〔397 cases (38.96%) 〕and medical workers〔187 cases (18.35%) 〕. The average total score of the eHEALS-C for the respondents was (27.62±8.57). The respondents scored lower in item 2〔 (3.36±1.27) points〕and item 6〔 (3.38±1.23) points〕of the eHEALS-C, indicating that they had low awareness of applying online health information to health problems, and low perceived skills at evaluating the online health information. Multiple linear regression analysis showed that age, participation in both basic and commercial medical insurance, using at least two channels for seeking online health information, having at least two sources of online health information, the habit of forwarding and sharing online health information, participation in collective online learning, and having an attitude of acceptance towards online health information were influencing factors of the level of eHealth literacy. Conclusion The eHealth literacy of these middle-aged and elderly residents is at a medium level, which is affected by online health information usage habits and other factors. To help them make better use of online health information and to improve their eHealth literacy, it is suggested to spread integrated authoritative information and retrieval platforms among these populations, give priority to supervision and elderly-oriented transformation of online health information platforms, and mobilize community, family, health associations, and commercial medical insurance institutions to co-deliver health-promotion services targeting these people.

Abstract Background Acute fibrinous and organizing pneumonia (AFOP) is a rare histological interstitial pneumonia pattern characterized by patches of “fibrin balls” distributed within the alveoli and organizing pneumonia. Currently, there is no consensus on the diagnosis and treatment of this disease. Methods We present the case of a 44‐year‐old male with AFOP secondary to Mycobacterium tuberculosis. We have further reviewed organizing pneumonia (OP) and AFOP caused by tuberculosis. Conclusion Tuberculosis secondary to OP or AFOP is rare and challenging to diagnose. We need to constantly adjust the treatment plan based on the patient's symptoms, test results, and response to treatment in order to arrive at an accurate diagnosis and maximize treatment efficacy.

Abstract Objective The objective of this study was to explore the clinical utility of the implementation of expanded carrier screening (ECS) in Chinese population of childbearing age. Materials and methods Based on capillary electrophoresis, a first-generation sequencing technology, a prospective screening study of carriers of 15 single-gene diseases was carried out in 327 subjects in Anhui Province, including 84 couples and 159 women of childbearing age, the disease carrier rate, types of screened pathogenic genes, and incidence of both partners carrying the same pathogenic genes were summarized and analyzed. Results In 320 people with normal phenotypes who underwent ECS for 15 genetic diseases and 7 spouses who underwent targeted gene sequencing, 65 carriers of at least one disease were detected, with a total carrier rate of 20.31% (65/320). Among the 65 carriers, 81.54% (53/65) carried one genetic variant, 16.92% (11/65) carried two genetic variants, and 1.54% (1/65) carried three genetic variants. In this study, the three diseases with the highest carrier rates were hereditary deafness (8.13%, 26/320), Wilson's disease (4.06%, 13/320), and phenylketonuria (3.13%, 10/320). One high-risk couple (1.19%, 1/84) was detected. Conclusions It has certain clinical application value to implement ECS in the population of childbearing age in China.

Abstract Exosomes, the cell-derived small extracellular vehicles, play a vital role in intracellular communication by reciprocally transporting DNA, RNA, bioactive protein, chains of glucose, and metabolites. With great potential to be developed as targeted drug carriers, cancer vaccines and noninvasive biomarkers for diagnosis, treatment response evaluation, prognosis prediction, exosomes show extensive advantages of relatively high drug loading capacity, adjustable therapeutic agents release, enhanced permeation and retention effect, striking biodegradability, excellent biocompatibility, low toxicity, etc. With the rapid progression of basic exosome research, exosome-based therapeutics are gaining increasing attention in recent years. Glioma, the standard primary central nervous system (CNS) tumor, is still up against significant challenges as current traditional therapies of surgery resection combined with radiotherapy and chemotherapy and numerous efforts into new drugs showed little clinical curative effect. The emerging immunotherapy strategy presents convincing results in many tumors and is driving researchers to exert its potential in glioma. As the crucial component of the glioma microenvironment, tumor-associated macrophages (TAMs) significantly contribute to the immunosuppressive microenvironment and strongly influence glioma progression via various signaling molecules, simultaneously providing new insight into therapeutic strategies. Exosomes would substantially assist the TAMs-centered treatment as drug delivery vehicles and liquid biopsy biomarkers. Here we review the current potential exosome-mediated immunotherapeutics targeting TAMs in glioma and conclude the recent investigation on the fundamental mechanisms of diversiform molecular signaling events by TAMs that promote glioma progression.

Accurate ice flow velocity data are essential for studying the mass balance of the Antarctic ice sheet. However, there is a lack of ice velocity maps of 1960s–80s in basin-wide regions or the entire ice sheet. In this study, an enhanced hierarchical network densification approach is developed for basin-wide Antarctic velocity mapping using historical ARGON and Landsat images. The produced multiple historical velocity maps from 1963 to 1989 in the region of the Fimbul and Jelbart ice shelves, East Antarctica, achieved an accuracy better than 29 m a−1. They revealed that the ice flow velocity had no significant changes over the period. Combining the surface mass balance estimate with the ice discharge estimated from our historical velocity maps and recently published velocity maps, we estimated a positive mass balance of 8.6 ± 3.9 Gt a−1 in the study area from 1963 and 2015. Our results indicate that the region's positive mass balance, as estimated in recently published studies, has been maintained since the 1960s. It is also in concordance with the low level of mass balance from 1992 to 2017 in East Antarctica. This suggests that the study area has been stable since the 1960s.

Abstract In this letter, a novel single parity check‐aided minimum sum (SPC‐aided MS) algorithm is proposed. A cascaded compiled code scheme is used to approximate the adaptive belief propagation (ABP) algorithm for Reed–Solomon (RS) codes using the min sum (MS) algorithm. The computational complexity is greatly reduced compared with the previous algorithm. Simulation results show that the SPC‐aided MS algorithm can achieve coding gains of up to 1.1, 0.7, and 0.6 dB for RS (255,239) code compared with the conventional ABP, LRBP, and HD‐P‐ABP algorithms, respectively under the condition of FER=10−3.