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Abstract Background Price levels of medical services may vary across regions with different income levels, which would raise concerns about the equal access to medical services. This study aimed to estimate the spatial price index of medical services to measure price levels across 31 provincial regions in China. Methods Price data were collected from medical service price schedule in each region. Two methods based on the Purchasing Power Parities were used to estimate the spatial price index and measure price differences across regions. The two-way fixed effects models were used to examine the association between medical service price levels and income levels, and further investigate the impacts of price differences on utilization of medical services and medical expenditure. Results The consistent estimation results were given by two methods. Medical service price level in the highest-price region was found to be 74% higher than the lowest. There was a significant negative correlation between price levels and income levels, as well as price levels and the utilization of outpatient services. Moreover, we also found a 1% increase in medical service price level was significantly associated with a 0.34% and 0.24% increase in the medical service expense per outpatient visit and per inpatient respectively. Conclusions Regions in China had significant gaps in medical service price levels. Policymakers should pay more attention to regional price differences and take great measures such as enhancing financial protection to ensure the equal access to medical services and better achieve the universal health coverage.

Abstract Background Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. Methods To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. Results Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p

Partial discharge at the oil-paper interface is one of the main reasons for the failure of oil-paper insulation in oil-immersed transformers. In this article, based on the numerical model of multi-branching streamer discharge, a multi-branching streamer discharge model in oil-paper insulation system is constructed by further considering the charge transport characteristics of oil-paper interface. The surface discharge characteristics under the influence of the dielectric constant ratio between natural ester insulating oil and insulating paper, and the spacing between needle electrode and paperboard are studied by finite element method, respectively. The results show that the distance between the needle electrode and the paperboard, and the dielectric constant ratio of insulating oil and insulating paper both significantly affect the streamer branching. The smaller the clearance between the needle electrode and paper-board is, the more serious the inhibition of streamer branches at the oil-paper interface is, which resulting in the streamers near the oil-paper interface are more significant effect on the propagation of the z-axis streamer. When the dielectric constant of the insulating oil is larger than that of the paperboard, the development and branching of the streamer in the oil will be more significant. On the contrary, the streamer is more likely to develop along the surface of the paperboard and accumulate charge at the oil-paper interface.

ObjectiveTo screen biomarkers for forensic identification of acute myocardial infarction （AMI） by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI.MethodsThe rat models of the sham surgery group, AMI group and hyperlipidemia + acute myocardial infarction （HAMI） group were established. Ultra-high performance liquid chromatography-mass spectrometry （UPLC-MS） was used to analyze the changes of urine metabolic spectrometry in AMI rats. Principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites.ResultsA total of 40 and 61 differential metabolites associated with AMI and HAMI were screened, respectively. Among them, 22 metabolites were common in both rat models. These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways. Within the 95% confidence interval, the area under the curve （AUC） values of receiver operator characteristic curve for N8-acetylspermidine, 3-methylhistamine, and thymine were greater than 0.95.ConclusionN8-acetylspermidine, 3-methylhistamine, and thymine can be used as potential biomarkers for AMI diagnosis, and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI. This study can provide reference for the mechanism and causes of AMI identification.

Abstract Machine learning algorithms are frequently used to clinical risk prediction. Our study was designed to predict risk factors of prolonged intra-aortic balloon pump (IABP) use in patients with coronary artery bypass grafting (CABG) through developing machine learning-based models. Patients who received perioperative IABP therapy were divided into two groups based on their length of IABP implantation longer than the 75th percentile for the whole cohort: normal (≤ 10 days) and prolonged (> 10 days) groups. Seven machine learning-based models were created and evaluated, and then the Shapley Additive exPlanations (SHAP) method was employed to further illustrate the influence of the features on model. In our study, a total of 143 patients were included, comprising 56 cases (38.16%) in the prolonged group. The logistic regression model was considered the final prediction model according to its most excellent performance. Furthermore, feature important analysis identified left ventricular end-systolic or diastolic diameter, preoperative IABP use, diabetes, and cardiac troponin T as the top five risk variables for prolonged IABP implantation in patients. The SHAP analysis further explained the features attributed to the model. Machine learning models were successfully developed and used to predict risk variables of prolonged IABP implantation in patients with CABG. This may help early identification for prolonged IABP use and initiate clinical interventions.

Abstract In this study, we concentrate on the seismic signature of subducted sediments and suggest the formation of the L‐discontinuity beneath the ancient craton related to migrated sediment dehydration. We first determined the single‐crystal elasticity of topaz, the product of sediment dehydration, at high pressures and temperatures by Brillouin scattering. Using the derived elastic parameters, we establish the velocity and density profiles of subducted sediments in the upper mantle. According to our modeling results, 8.5–17.5 vol.% sediments intruding into the upper mantle will induce a 2%–4% low‐VS anomaly at 210–260 km. Meanwhile, continuous heating will lead to the dehydration of phengite in sediments. The dehydration of this amount sediments can generate a 3%–6% ISS with negative Clapeyron slopes, satisfying the observed L‐discontinuity in northern Finland and northern America without the anisotropy changes but accompanied by low‐velocity anomalies. Our study thus provides new insights into the origin of the L‐discontinuity.

Abstract Background Medical service prices play a crucial role in cost containment in China. This study aimed to assess the change in medical service price levels at the macro level and the relationship with relevant macroeconomic factors. Methods Data from the 2022 China Statistics Yearbook, the 2022 China Health Statistics Yearbook, and the 2020 China National Health Accounts Report were used. Time trends of health price levels, utilization, and health expenditure were examined. A time-series regression model was employed to measure the impact of service utilization and medical service prices on total medical service expenditure growth from 2000 to 2021. The Johansen cointegration test was conducted to test the cointegrating relationship between medical service price levels and total medical service expenditure, average wage of employees and CPI. The Granger causality test was performed to observe the direction of causality. Results Descriptive analyses showed consistent growth in utilization and medical service price levels from 2000 to 2021. The time-series model indicated that medical service expenditure was influenced by the rise in inpatient admissions and price levels of medical service and medicine. The Johansen cointegration test identified a long-term equilibrium relationship between medical service price levels and total medical service expenditure, average wage and CPI. The change in medical service price levels was the Granger cause of the change in medical service expenditure, but it had no impact on average wage and CPI. However, the change in medical service price levels was influenced by these three macroeconomic factors. Conclusions The growth of medical service expenditure in China was driven by inpatient use and price level. There was a long-term equilibrium relationship between medical service price levels and relevant macroeconomic factors. However, medical service price levels only affected medical service expenditure and have no impact on average wage and CPI. It is necessary to improve the value transmission mechanism of medical service prices.

Objective To investigate the effect of quality control circle (QCC)activities to reduce the risk of defects in the intra-hospital transport of critically ill ICU patients. Methods A QCC team was established, and factors influencing quality of the intra-hospital transport of critically ill ICU patients were analyzed. Improvement goals were set and following countermeasures were carried out to reduce the risk of defects in the intra-hospital transport. Results The rate of defects in the intra-hospital transport of critically ill ICU patients was decreased form 31. 75%beforeimplementation of QCC activities to 10. 66% after implementation of QCC activities. Conclusion The QCC activity is effective to reduce the risk of defects in the intra-hospital transport of critically ill ICU patients. It helps to regulate the management of first aid materials and modified the intra-hospital transport process. (目的 探讨品管圈在降低危重患者院内转运缺陷中的作用, 从而提高转运质量, 确保患者安全。方法 2022年8月—2023年2月成立品管圈小组, 选定“降低危重患者院内转运缺陷率”为主题, 现状调查影响院内转运质量的因素, 设定目标, 分析原因制定对策并实施。结果 危重患者院内转运缺陷率由品管圈活动实施前的31. 75%下降到实施后的10. 66%。结论 运用品管圈活动有效降低了危重患者院内转运缺陷的发生率, 有助于规范转运急救物品的管理, 完善转运流程。)

Abstract We propose an autoregressive weighted network (ARWNet) time series forecasting model inspired by the idea of ensemble learning. The model adopts the classical autoregressive analysis to optimize weak learners. Meanwhile, the combined weight optimization method is used to construct an efficient, strong learner. With these methodological foundations, the scalability of the framework is greatly enhanced by the possibility of experimenting with other learners to assist in decision‐making. Machine learning can provide great utility and acceptable cost in the prediction process of electricity transformers. Over the years, many research papers on time series prediction have been reported. This work will focus on the analysis using the potential properties in the series: long‐term, continuity, periodicity, and delay. In our experiments, the ETT‐small dataset is used to compare the prediction accuracy of ARWNet and other mainstream models. All results suggest that the proposed ARWNet model demonstrates strong generalization ability and high predicting accuracy with delay characteristics, which outperform current popular time‐series prediction methods.

An UPLC Quadrupole Orbitrap high resolution mass Spectrometry method for accurate quantification of aflatoxins in grains and oils was established, which were purified by automatic immunoaffinity column. The sample was extracted with 84/16(V/V) acetonitrile/water and centrifuged. The supernatant was diluted 10 times with 0.1% PBST. Aflatoxin immunoaffinity column without background and recovery greater than 90% was chosen for purification automatically. UPLC-Quadrupole Orbitrap HRMS was used for quantitative analysis. Results showed that recoveries for aflatoxins were 84.7%~104.6%. The intra-day relative standard deviations were 1.7%~9.4%, and the intra-day precision were 0.7%~8.4%. The developed method can minimize the workload, improve work efficiency and avoid the result deviation caused by operation manually. It is suitable for the accurate determination of aflatoxins in grains and oils, and meet the requirement of the daily test and monitoring aflatoxins.

The research on terahertz wave manipulation based on metasurfaces has gradually deepened, and the number of functions or electromagnetic control dimensions in a single device is constantly increasing. For the spatial dimension of terahertz field regulation, its design degrees of freedom have been expanded from a single transverse plane to the propagation path. In this paper, we propose a novel circularly polarization multiplexed metasurface for dual channel terahertz wave transmission control. Based on the spatial integration of two heterogeneous meta-atoms, which are spin-decoupled and isotropic, respectively, there are four phase channels that can be used at the same time, thus achieving different switching between vector and scalar beams in different circularly polarization channels along the optical path. For linearly polarized wave incidence, the device exhibits conversion between different vector beams longitudinally. To control more electric field components, we combine focused wavefront design with vector or scalar fields and utilize the focusing induced spin–orbit coupling effect, then complex amplitude switching of longitudinal electric field components is obtained. This article extends the manipulation of terahertz waves along the propagation trajectory based on metasurface from single to dual channel for the first time, providing a reference for the design of multifunctional meta-device in terahertz band.

Objective To explore the potential active components and anti-inflammation mechanism of a Chinese herb from Dong ethnic minority, Madeng'ai (MDA). Methods UPLC-Q-TOF-MS was taken to analyze and identify the major components of MDA. The potential active targets of MDA were retrieved in the Swiss Target Prediction database, and the disease-related targets were searched in the Omim, Disgene and Genecards databases. The common targets of active components and inflammation were obtained for the potential targets of MDA in the treatment against inflammation. The "drug-disease-target" network and protein-protein interaction (PPI) network were separately constructed by Cytoscape 3.9.1 and String database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping targets were performed through David database. Finally, RT-qPCR and Western blotting were conducted to determine the mRNA levels of several inflammation-related factors and the possible signaling pathways in RAW264.7 cells after LPS treatment. Results There were 29 compounds identified by UPLC-Q-TOF/MS, and the top 5 were tormentic acid, ellagic acid, procyanidin C1, epicatechin and procyanidin B1. There were 104 core targets of MDA docking inflammation through database retrieval and after duplicate removal, and TNF-α, IL-6, AKT1 and ALB might be the core targets. A total of 761 GO items were enriched, including 600 items concerning biological processes, 52 items on cell components, and 109 items involving molecular functions. KEGG analysis screened out 160 signal pathways, mainly focusing on NF-κB, MAPK, PI3K-AKT and so forth signaling pathways. Compared with the normal control group, the mRNA levels of TNF-α, IL-6, IL-1β and CCL2 were increased significantly in the model group (LPS treatment group)(P < 0.05), and the phosphorylation levels of p38, ERK and JNK were obviously up-regulated (P < 0.05). While, MDA treatment notably declined the mRNA levels of TNF-α, IL-6, IL-1β and CCL2 (P < 0.05), and down-regulated the phosphorylation levels of p38, ERK and JNK when compared with the model group (P < 0.05). Conclusion Our study forecasts that the water extract of MDA, a Chinese traditional herb from Dong minority, has the potential active ingredients in treatment of inflammation, and shows anti-inflammatory effects through multiple pathways, such as MAPK pathway.

Abstract Background Price differences of medical services across regions may affect equity in health financing. This study aimed to estimate the spatial price index of medical services to measure price levels across regions in the Yangtze River Delta, China. Methods Gini-Éltetö-Köves-Szulc method and minimum spanning tree method based on the purchasing power parities were used in this study. Results According to the Gini-Éltetö-Köves-Szulc method, Shanghai and Anhui province had price levels that are 127.55% and 103.45% respectively of the price level in Zhejiang province, whereas in Jiangsu medical services were priced at 92.71% of that in Zhejiang province. The spatial price index of medical services in the Yangtze River Delta based on the minimum spanning tree method provided similar results. Conclusions Regions in the Yangtze River Delta had significant gaps in medical services price levels. And the price levels tended to not correlate with socioeconomic levels. It is necessary to promote the regional coordination of medical services price and better achieve equity in health.

Abstract Dispersion curves for surface wave recordings are required input for many surface wave inversion methods to image subsurface shear wave velocity distribution, while the conventional extraction of dispersion curves requires significant amount of human interaction. This step impedes efficiency enhancement of surface wave analysis and its automation. In this paper, we present an unsupervised learning scheme to achieve efficient automatic picking of dispersion curves of the fundamental mode for surface wave gathers. This scheme is composed of four major steps: computing a frequency velocity(f‐v) spectrum for the surface wave gather using a high‐resolution Tau‐p transform improved by the iteratively shrinkage Thresholding algorithm (ISTA) algorithm, generating clusters points along the dispersion energy in the f‐v spectrum via a weighted Kmeans algorithm, filtering these cluster points by principal component analysis (PCA) and Local Outlier Factor (LOF) algorithms to remove the erroneous clusters, and fitting the remaining clusters to form the dispersion curve. Tests with synthetic and field noisy surface wave recordings demonstrated the effectiveness of this approach and its potential in automatic processing of noisy surface wave data sets.

Abstract. Background:. Non-transport unintentional injuries (NTUIs) are major public concerns, especially among children and adolescents in low- and middle-income countries. With environmental and cognitive changes, a recent systematic description of global trends and regional differences concerning NTUIs is urgently needed for the global agenda of relevant policy-making and intervention target findings. Methods:. We used mortality, population, and socio-demographic-index (SDI) data from Global Burden of Disease 2019 to analyze the trends of NTUIs mortality. We applied the slope index of inequality (SII) and relative index of inequality (RII) to measure the absolute and relative inequality between countries and territories. The concentration curve and concentration index (CI) were also used to measure the inequality. We conducted a sensitivity analysis to make our findings credible. Results:. In 2019, there were 205,000 deaths due to NTUIs among children and adolescents aged 5 to 24 years, which decreased from 375,000 in 1990. In 2019, the age-standardized mortality rate (ASMR) was 8.13 per 100,000, ranging from the lowest in the Netherlands (0.90 per 100,000) to the highest in the Solomon Islands (29.34 per 100,000). The low-middle SDI group had the highest ASMR of NTUIs, while the low SDI group had the slowest decrease. After excluding the death caused by “exposure to forces of nature” and “other unintentional injuries”, drowning accounted for the most deaths in almost every SDI group, gender, and age group, but the major causes of death varied in different subgroups. For example, animal contact was a major cause in low and low-middle SDI groups but less in high SDI groups, while high and high-middle SDI groups had a higher proportion of deaths for foreign body and poisonings. The SII showed a declining trend, but the RII and CI did not, which might indicate that inequality was persistent. Similar results were found in the sensitivity analysis. Conclusions:. Despite the declining trend of the mortality rate and the narrowing gap between countries, there were still a large number of children and adolescents dying from NTUIs, and those experiencing social-economic disadvantages remained at high mortality. Embedding the prevention of NTUIs into sustainable development goals might contribute to the progress of reducing death and inequalities, which ensures that no one is left behind.

C19H14N4O11, monoclinic, C2/c (no. 15), a = 17.855(4) Å, b = 18.214(4) Å, c = 14.193(3) Å, β = 124.32(3)°, V = 3812.3(17) Å3, Z = 8, R gt(F) = 0.0639, wR ref(F 2) = 0.1897, T = 100.01(10) K.

Abstract Objectives Doctors who wish to become general practitioners (GPs) in China are required to attend and complete general practice resident training. In the early stages of the standardized GP training system, GP training supervisors play important roles. This study aims to explore how GP residents perceive their GP supervisors, factors that affect GP residents’ satisfaction level, as well as to offer suggestions based on the implications of this study. Design We conducted a mixed quantitative and qualitative study. Firstly, with respect to the quantitative research, we conducted a survey to investigate training satisfaction through questionnaires, then extracted and analyzed the factors that influence training satisfaction. In the qualitative study, we conducted in-depth, semistructured interviews using qualitative research criteria (COREQ)––a 32-item checklist for interviews. Participants Participants in the quantitative survey included 1172 GPs whose training time wasbetween 2008 and 2017. Afterwards, 100 participants were selected from this sample , filtered by stratified random sampling and by having provided extreme answers on the quantitative survey (less than 5% of the total sample). They were chosen for the qualitative research to conduct a more detailed investigation., This stratified random sampling was based on residents’ grades, regions, and training levels (city level or county level). Extreme answers were identified as answers of “extremely good” or “extremely bad” to questions from the initial comprehensive survey of 1172 participants. Consequently, 30 participants with extreme answers were found, while the remaining 70 participants in the interviews were selected by stratified random sampling. Ultimately, this sample of participants met our information collection and sample estimation requirements. Results The results show that satisfaction with GP theoretical training supervisors, GP hospital-based training supervisors, and GP community-based training supervisors differed. Considering long-term averages, the hierarchy of satisfaction is as follows: GP theoretical training supervisors > GP community-based training supervisors > GP hospital-based training supervisors. GP hospital-based training supervisors need to improve their conception of GPs, teaching methods and conscientiousness. GP community-based training supervisors need to improve their teaching methods, knowledge of clinical theory and practice ability. Conclusions On the one hand, teams of GP supervisors in China have gradually been established over time. On the other hand,the satisfaction tendencies of residents with respect to their GP supervisors are quite different, and teams of GP supervisors must be promoted and improved.

Abstract Background The effective components contained in compound Kushen injection (CKI) and the genes and signalling pathways related to gastric cancer (GC) were analyzed through the network pharmacology method of traditional Chinese medicine, and various possible mechanisms by which CKI affects the proliferation, differentiation, survival, and metastasis of GC cells were discussed. The PI3K/AKT signalling pathway is considered to be one of the most important pathways targeted by CKI in the regulation of GC cells. The implementation of related cell experiments also confirmed the information we revealed. Methods Effective drug components of Kushen and Baituling in CKI were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). Genes related to GC were identified using the GENECARD and OMIM databases. The common target genes related to the effective components of the drug and GC were identified using the intersection method and visualized using software. A protein–protein interaction network (PPI) was established using STRING online software to confirm the key genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the key pathways of CKI in GC treatment. BGC-803 and MKN-28 GC cells were used to verify the signalling pathway. Cell proliferation, apoptosis, migration ability, and invasion ability were assessed using CCK8, flow cytometry, scratch, and transwell assays. Immunofluorescence assays and western blotting were used to detect the expression of related proteins. Results CKI regulated GC cells through 35 effective drug components of GC-related target genes. In total, 194 genes were common targets of CKI and GC. The most significant function of the enriched genes was DNA-binding transcription activator activity as demonstrated by GO enrichment analysis. The metabolic pathway with the highest enrichment was the PI3K/AKT signalling pathway as demonstrated by KEGG enrichment analysis. Our cell experimental evidence also shows that CKI inhibits GC cell growth and migration and induce GC cell apoptosis. In addition, CKI inhibits the EMT process in GC cells through the PI3K/AKT signalling pathway. Conclusion AKT1 is a key gene for CKI treatment of GC. CKI inhibited GC cell growth and migration and induced GC cell apoptosis. In addition, CKI regulated the EMT process in GC cells through the PI3K/AKT signalling pathway.

Mediation analysis has been used in many disciplines to explain the mechanism or process that underlies an observed relationship between an exposure variable and an outcome variable via the inclusion of mediators. Decompositions of the total effect (TE) of an exposure variable into effects characterizing mediation pathways and interactions have gained an increasing amount of interest in the last decade. In this work, we develop decompositions for scenarios where two mediators are causally sequential or non-sequential. Current developments in this area have primarily focused on either decompositions without interaction components or with interactions but assuming no causally sequential order between the mediators. We propose a new concept called natural mediated interaction (MI) effect that captures the two-way and three-way interactions for both scenarios and extends the two-way MIs in the literature. We develop a unified approach for decomposing the TE into the effects that are due to mediation only, interaction only, both mediation and interaction, neither mediation nor interaction within the counterfactual framework. Finally, we compare our proposed decomposition to an existing method in a non-sequential two-mediator scenario using simulated data, and illustrate the proposed decomposition for a sequential two-mediator scenario using a real data analysis.

Abstract Differentiation states of glioma cells correlated with prognosis and tumor-immune microenvironment (TIME) in patients with gliomas. We aimed to identify differentiation related genes (DRGs) for predicting the prognosis and immunotherapy response in patients with gliomas. We identified three differentiation states and the corresponding DRGs in glioma cells through single-cell transcriptomics analysis. Based on the DRGs, we separated glioma patients into three clusters with distinct clinicopathological features in combination with bulk RNA-seq data. Weighted correlation network analysis, univariate cox regression analysis and least absolute shrinkage and selection operator analysis were involved in the construction of the prognostic model based on DRGs. Distinct clinicopathological characteristics, TIME, immunogenomic patterns and immunotherapy responses were identified across three clusters. A DRG signature composing of 12 genes were identified for predicting the survival of glioma patients and nomogram model integrating the risk score and multi-clinicopathological factors were constructed for clinical practice. Patients in high-risk group tended to get shorter overall survival and better response to immune checkpoint blockage therapy. We obtained 9 candidate drugs through comprehensive analysis of the differentially expressed genes between the low and high-risk groups in the model. Our findings indicated that the risk score may not only contribute to the determination of prognosis but also facilitate in the prediction of immunotherapy response in glioma patients.

Discrete Dislocation Dynamics (DDD) simulations are a powerful simulation methodology that can predict a crystalline material’s constitutive behavior based on its loading conditions and micro-constituent population/distribution. In this paper, a 3D DDD model with spiral dislocation sources is developed to study size-dependent plasticity in a pure metal material (taken here as Aluminum). It also shows, for the first time, multipole simulations of spirals and how they interact with one another. In addition, this paper also discusses how the free surface of a crystalline material affects the plasticity generation of the spiral dislocation. The surface effect is implemented using the Distributed Dislocation Method. One of the main results from this work, shown here for the first time, is that spiral dislocations can result in traditional Frank–Read sources (edge or screw character) in a crystal. Another important result from this paper is that with more dislocation sources, the plastic flow inside the material is more continuous, which results in a lowering of the flow stress. Lastly, the multipole interaction of the spiral dislocations resulted in a steady-state fan-shaped action for these dislocation sources.

Despite the growing knowledge of T cell responses in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Here, with a predicted peptide library from SARS-CoV-2 S and N proteins, we found that specific CD8+ T cell responses were identified in over 75% of COVID-19 convalescent patients (15/20) and an epitope from the N protein, N361-369 (KTFPPTEPK), was the most dominant epitope from our selected peptide library. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity that were independent of the CD8 co-receptor. These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants, as to the wild-type epitope. Further, the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells (DCs) and the lung organoid model. We found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells, to elicit successful activation and effective cytotoxicity of CD8+ T cells ex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, and illuminated potential ways of viral clearance in COVID-19 patients. These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells. Additionally, this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains.

Abstract Valvuloplasty for rheumatic aortic valve disease remains controversial. We conducted this study to explore whether aortic valvuloplasty is appropriate for the rheumatic population. A comprehensive search was conducted, and 7 eligible retrospective studies were identified from PubMed, Embase, Medline and Cochrane (up to April 7, 2020) according to the inclusion and exclusion criteria. The data for hospital mortality, 5-year survival, 5-year reoperation, aortic insufficiency grade (AIG) and aortic valve gradient (AVG) were extracted by 2 independent reviewers and were analysed to evaluate the safety and availability of aortic valvuloplasty for rheumatic patients. The heterogeneity of the results was estimated using the Q test and I2 statistics. The fixed pooling model was used when I2 ≤ 50%; otherwise, the random pooling model was selected. 7 articles with 418 patients were included. The pooled hospital mortality, 5-year survival and 5-year reoperation rates were 3.2%, 94.5% and 9.9%, respectively. The heterogeneities of the weighted mean differences (WMD) values of the AIG and AVG between preoperation and postoperation were extremely high (I2 = 81.5%, p

Although statins are shown to have cardiac pleiotropic effects independent of lowering cholesterol, the underlying mechanism remains unclear. Mitochondrial dysfunction induced by increased fatty acid oxidation (FAO) is the culprit in the development of cardiac hypertrophy and dysfunction. This study was to explore whether the cardiac pleiotropic effects of atorvastatin were associated with FAO regulation, with a specific focus on carnitine palmitoyltransferase 1 (CPT1). High-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated neonatal rat primary cardiomyocytes (NRCMs) were treated with atorvastatin, with or without FAO modulators, signal transducer and activator of transcription 3 (STAT3) agonist, and inhibitor. Atorvastatin (3 mg/kg) did not reduce serum cholesterol levels in HFD-fed mice but ameliorated mitochondrial dysfunction and cardiac hypertrophy. In vitro, atorvastatin and the FAO inhibitor alleviated PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy. However, the FAO enhancer eliminated atorvastatin’s protective effects. Furthermore, atorvastatin decreased CPT1 and FAO levels and prevented STAT3 phosphorylation and nuclear translocation. STAT3 inhibitor had the same inhibitory effects as atorvastatin on CPT1, FAO levels, and cardiomyocyte hypertrophy, whereas STAT3 agonist disrupted these effects of atorvastatin. Our results demonstrate that atorvastatin decreases myocardial FAO by inactivating the p-STAT3/CPT1 signaling pathway, which improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy in a cholesterol-independent manner. This is the first study to explore the cardiac pleiotropic effects of atorvastatin with respect to FAO. However, whether atorvastatin regulates FAO in the cardiac hypertrophy model induced by other variables has not been investigated in this work, and this is expected to be performed in the future.

Neutralizing antibodies are currently one versatile strategy to treat SARS-CoV-2 infection. Here, Li et al. characterize three monoclonal antibodies neutralizing authentic virus infection in vitro and in vivo by targeting the receptor binding domain as evidenced by Cryo-EM.

Summary: The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.

BMP10 signaling has been implicated in regulation of cardiovascular cell fate determination and diseases, while the underlying molecular mechanism still remains uncertain. Here, the human embryonic stem cell line (H7-BMP10del) with homozygous deletion of BMP10 was generated by CRISPR/Cas9 method. Thus, the crosstalk related to BMP10 signaling could be investigated in cell fate determination and the molecular pathogenesis of cardiovascular disease.

C15H15N1O3, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 7.1053(11) Å, b = 8.3014(12) Å, c = 11.0297(16) Å, α = 85.810(2)°, β = 79.896(2)°, γ = 87.055(2)°, V = 638.28(16) Å3, Z = 2, R gt(F) = 0.0371, wR ref(F 2) = 0.1062, T = 296(2) K.

Background: Due to the highly variable prognosis of low-grade gliomas (LGGs), it is important to find robust biomarkers for predicting clinical outcomes. Aging cancer-associated fibroblasts (CAFs) within the senescent stroma of a tumor microenvironment (TME) have been recently reported to play a key role in tumor development. However, there are few studies focusing on this topic in gliomas.Methods and Results: Based on the transcriptome data from TCGA and CGGA databases, we identified aging CAF-related genes (ACAFRGs) in LGGs by the weighted gene co-expression network analysis (WGCNA) method, followed by which LGG samples were classified into two aging CAF-related gene clusters with distinct prognosis and characteristics of the TME. Machine learning algorithms were used to screen out eight featured ACAFRGs to characterize two aging CAF-related gene clusters, and a nomogram model was constructed to predict the probability of gene cluster A for each LGG sample. Then, a powerful aging CAF scoring system was developed to predict the prognosis and response to immune checkpoint blockage therapy. Finally, the ACAFRGs were verified in two glioma-related external datasets. The performance of the aging CAF score in predicting the immunotherapy response was further validated in two independent cohorts. We also confirmed the expression of ACAFRGs at the protein level in glioma tissues through the Human Protein Atlas website and Western blotting analysis.Conclusion: We developed a robust aging CAF scoring system to predict the prognosis and immunotherapy response in LGGs. Our findings may provide new targets for therapeutics and contribute to the exploration focusing on aging CAFs.

The structures of social networks with power laws have been widely investigated. People have a great interest in the scale-invariant generating mechanism. We address this problem by introducing a simple model, i.e., a heuristic probabilistic explanation for the occurrence of a power law. In particular, the proposed model can be used to explain the generative mechanism that leads to the scale-invariant of the degree distribution with a power exponent of τ>2. Furthermore, a stochastic model (the pure birth points process) is used to describe the cumulative growth trend of edges of a temporal social network. We applied our model to online temporal social networks and found that both the degree distribution scaling behaviors and the growth law of edges can be quantitatively reproduced. We gained further insight into the evolution nature of scale-invariant temporal social networks from the empirical observation that the power exponent τ gradually decreases and approaches 2 or less than 2 over evolutionary time.

In the high-speed rotating state, the experimental study on the vibration characteristics of high-pressure turbine rotor blade and the vibration reduction effect of flange damping device is beneficial to the later design iteration and obtain the real blade vibration situation.With high pressure turbine rotor simulator as an object, simulating the turbine blade periodic pneumatic excitation by non-contact atomizing oil excitation, the vibration characteristics test system of high rotational speed high pressure turbine rotor blades is designed and created. The component level test is between the fixed blade test and the direct test of the core turbine aero-engine system. The test system excites the rotor blades under operation status, obtains data of blade vibration characteristics successfully, and verifies the vibration reduction level of the platform damper. Research shows under 10 000~19 000 r/min operating rotating speed at the normal temperature, the platform damper device can reduce the vibration of rotor blades by about 40%, and frequency of the rotor blade with higher damping mass is higher.

Objective To evaluate and compare the efficacy and safety of different managements for women with cesarean scar pregnancy based on a ultrasonographic scoring system. Methods A total of 299 pregnant women with cesarean scar undergoing delivery surgeries in our department from November 2018 to December 2019 were recruited retrospectively. According to the preoperative results of the ultrasonographic scoring system, they were divided into low-risk group (score ≤4) and high-risk group (score > 4). The patients in the low-risk group were treated with ultrasound-guided curettage. And those of the other group were treated with uterine artery embolization and ultrasound-guided curettage. The basic information, perioperative data and postoperative follow-up data of the patients were collected and analyzed. Results There was no statistical difference in the amount of intraoperative blood loss between the 2 groups (P > 0.05), neither the incidence of secondary uterine artery embolization between them (P > 0.05). But significant difference was found in the incidence of secondary laparoscopic procedure for removing scar tissues between the 2 groups (P < 0.05). What's more, there were obvious differences in the length of hospital stay and total cost, the time of postoperative serum β-HCG level dropping to normal, the time of disappearance of the abnormal echoes in the lower segment of the uterus, and the restoration of normal menstruation between the 2 groups (P < 0.05). However, there was no statistical significance of the outcome of the second pregnancy between them after treatment. Conclusion According to the preoperative ultrasonographic scoring system for cesarean scar pregnancy, patients in different treatment methods.

ObjectivesCerebral ischemic complications are common after revascularization in patients with moyamoya disease (MMD). Risk factors from specific laboratory variables have only been assessed by limited research. This study was to investigate the association between postoperative cerebral ischemia and nutritional blood parameters and examine predictive values of such risk factors in adults.MethodsPreoperative demographics and nutritional blood parameters of patients with MMD who received revascularization at our institution from 2012 to 2021 were retrospectively reviewed. Univariate analysis and multivariable logistic regression were used to identify independent risk factors for the onset of postoperative cerebral ischemic complications. Predictive values were tested and a model incorporating these independent risk factors was created using the R program. Area under the receiver operating characteristic curve (AUC) was used for testing its discriminability.ResultsPostoperative cerebral ischemic complications occurred in 32 patients of 100 included procedures. Surgery on the left hemisphere, lower admission modified Rankin Scale (mRS) score, aberrant nutritional parameters including low white blood cell (WBC), and high total cholesterol (TC) were significantly associated with cerebral ischemic complications after revascularization. The intriguing role of WBC might be explained by altered immunomodulation. The AUC of this model with novel nutritional parameters yielded a value of 0.811, presenting better predictive accuracy. Additionally, the model was visualized in the form of a nomogram and translated into a user-friendly calculator to generate individual risk.ConclusionsSurgical side, admission mRS score, WBC, and TC were independent risk factors for postoperative cerebral ischemic complications. The model composed of these four parameters was promising to be adopted in clinical practice.

Background: Due to high heterogeneity and mortality of low-grade gliomas (LGGs), it is of great significance to find biomarkers for prognosis and immunotherapy. Pyroptosis is emerging as an attractive target in cancer research for its effect on tumor immune microenvironment (TIME). However, the investigation of pyroptosis in LGGs is insufficient.Methods: LGG samples from TCGA and CGGA database were classified into two pyroptosis patterns based on the expression profiles of 52 PRGs using consensus clustering. A prognostic model was constructed by using the LASSO-COX method. ESTIMATE algorithm and single sample gene set enrichment analysis (ssGSEA) were used to characterize the TIME. Based on the differentially expressed genes between two pyroptosis patterns, favorable and unfavorable pyroptosis gene signatures were determined. Pyroptosis score scheme was constructed to quantify the pyroptosis patterns through gene set variation analysis (GSVA) method. Two external datasets and immunotherapy cohort from CGGA and GEO database were used to validate the predictive value of the pyroptosis score. The Human Protein Atlas website and Western blotting were utilized to confirm the expression of the selected genes in the prognostic model in LGGs.Results: Distinct overall survival and immune checkpoint blockage therapeutic responses were identified between two pyroptosis patterns. A low pyroptosis score in LGG patients implies higher overall survival, poor immune cell infiltration, and better response to immunotherapy of immune checkpoint blockage.Conclusion: Our findings provided a foundation for future research targeting pyroptosis and opened a new sight to explore the prognosis and immunotherapy from the angle of pyroptosis in LGGs.

Carbon / epoxy composites are widely used in aviation due to their high strength, fatigue resistance and corrosion resistance. Aiming at the damage of carbon / epoxy composites during aircraft lightning strikes, a three-dimensional finite element model of carbon / epoxy composite laminates protected by copper mesh and aluminum mesh was established, and the lightning ablative element of composite structure was treated by element deletion method. The lightning protection effect of copper mesh and aluminum mesh was verified under different current peaks and different grid spacing, and the relationship between the weight change of the metal mesh and the lightning protection effect was studied. The test results show that the ablation area and damage depth of the composite laminate with metal mesh protection are significantly reduced. The denser the grid spacing is, the better the lightning protection effect is. The copper mesh composite laminate has better protection effect than the aluminum mesh. With the weight of the metal mesh increases, the degree of lightning damage to the composite laminate decreases.

BACKGROUND Heavy metal pollution caused by the exploitation of mineral resources in the social development has caused serious threats to the ecosystem and human health. Hyperaccumulating plants have super-enrichment and super-tolerance capabilities for heavy metals, which is an effective way to reduce environmental heavy metal pollution, protect human health, and realize green mineral exploration. It has been widely used in phytoremediation, plant mining and plant prospecting. OBJECTIVES To better understand the enrichment and tolerance mechanisms of hyperaccumulating plants, reveal the principles of heavy metal-plant interactions, and improve the ability of plants to accumulate heavy metals. METHODS Based on a brief description of the effects of heavy metals on plants, the focus of this article is the accumulation mechanism of heavy metal hyperaccumulation plants, and a review of the progress in the fields of detoxification and tolerance mechanisms. RESULTS (1) The root exudates of hyperaccumulator and microorganisms work together to promote the dissolution of heavy metals. After being absorbed by the symplastic and apoplastic pathways, the heavy metals are transported upwards to aerial parts through xylem, and segregated in vacuoles, achieving the hyperaccumulation of heavy metals. (2) Concentration of free metal ions in cytoplasm can be reduced by combining heavy metals with small molecular organic acids, cell walls, phytochelatins and vacuole isolation, which increases plant tolerance. (3) Under heavy metal stress, plants activate a variety of specific antioxidant enzymes to resist oxidative stress and achieve hypertolerance on heavy metals. (4) A possible mechanism is suggested that arsenic-induced oxidative stress in plants should be composed of arsenic reduction and methylation, and Haber-Weiss reaction. CONCLUSIONS In-depth research on the physiological and biochemical processes involved in hyperaccumulation and hypertolerance of hyperaccumulator reveals key factors and related principles. Finding effective ways to improve their specific accumulation and indication capabilities will contribute to the research and application of hyperaccumulators to develop in depth.

At present, ablation is still considered as one of the most effective, reliable, mature and economical thermal protection methods, which is widely used in thermal protection systems (TPS) of aerospace flight vehicles. Recent years, series of advanced lightweight ablative composites (LAC) were developed driven by major projects such as manned space flight, lunar exploration program, deep space exploration, and near space flight vehicles. Particularly, material's developing, engineering application and corresponding applied basic research of LACs filled in honeycombs and new LAC integrated ablation & insulation were emphatically introduced. Furthermore, complicated ablative mechanisms and synergistic effects of multiple thermal protection methods were explored. With the development of advanced TPS demand, multi-functionalization, compatibility and integration are the main development tendency of LAC for earth reentry or atmospheric entry aerospace flight vehicles.

The combustion characteristics of ammonia/hydrogen premixed laminar flow and the effect of hydrogen on the combustion performance of ammonia fuel were studied. First, the corresponding model of ammonia/ hydrogen premixed laminar combustion is established by using GRI3.0 mechanism, Konnov mechanism, Mei mechanism, Okafor mechanism, and Otomo mechanism respectively. Second, the simulation results are compared with the experimental results. It is found that the Mei mechanism and Okafor mechanism are more suitable for ammonia/ hydrogen premixed laminar combustion. On this basis, the effects of equivalent ratio, hydrogen ratio, and initial temperature on laminar flame velocity, maximum combustion temperature, and NO mole fraction were studied. The results show that the laminar flame velocity, the maximum combustion temperature, and the mole fraction of NO first increase and then decrease with the increase of the equivalent ratio, and the laminar flame velocity reaches the maximum when the equivalent ratio is 1.1. At the same time, with the increase of hydrogen ratio and initial temperature, the maximum combustion temperature increases first and then decreases. The mole fraction of NO increased with the increase of hydrogen ratio and initial temperature. The results show that mixing hydrogen in ammonia can improve the combustion characteristics of ammonia.

Facing the imminent need for vaccine candidates with cross-protection against globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we present a conserved antigenic peptide RBD9.1 with both T-cell and B-cell epitopes. RBD9.1 can be recognized by coronavirus disease 2019 (COVID-19) convalescent serum, particularly for those with high neutralizing potency. Immunization with RBD9.1 can successfully induce the production of the receptor-binding domain (RBD)-specific antibodies in Balb/c mice. Importantly, the immunized sera exhibit sustained neutralizing efficacy against multiple dominant SARS-CoV-2 variant strains, including B.1.617.2 that carries a point mutation (SL452R) within the sequence of RBD9.1. Specifically, SY451 and SY454 are identified as the key amino acids for the binding of the induced RBD-specific antibodies to RBD9.1. Furthermore, we have confirmed that the RBD9.1 antigenic peptide can induce a S448-456 (NYNYLYRLF)-specific CD8+ T-cell response. Both RBD9.1-specific B cells and the S448-456-specific T cells can still be activated more than 3 months post the last immunization. This study provides a potential vaccine candidate that can generate long-term protective efficacy over SARS-CoV-2 variants, with the unique functional mechanism of activating both humoral and cellular immunity.

The Paris Agreement, with its target of net-zero emissions by 2050, has forced the concrete industry to reduce its energy consumption and carbon emissions. Therefore, the development of green concrete with a lower environmental impact is urgently required. In this case study, alum sludge was used as both sand and cement replacement in concrete blocks, and the compressive behaviour of concrete blocks and constructed masonry walls was first investigated. For cement replacement, the strength of blocks decreased with increasing alum sludge ash (ASA) content when the cement replacement ratio was higher than 10% by weight. These results were attributed to the fact that the filler effect and pozzolanic reaction of ASA compensated for the cement dilution effect at a moderate replacement ratio. However, the cement dilution effect dominated the mechanism with further ASA addition. For sand replacement, 10% oven-dried alum sludge addition degraded the mechanical performance of blocks significantly due to high organic content, which might hinder cement hydration. The compression behaviour of masonry walls was also influenced by alum sludge, and the testing results showed that the sludge addition increased ductility of the masonry wall but decreased the strength insignificantly. Therefore, the sludge-derived blocks were suitable for masonry application. Furthermore, a life cycle assessment model was developed based on the designed sludge-derived cement supply chain in South Australia. The obtained results indicate that the annual reduced greenhouse gas emissions were around 1,3339,549 tons, which equaled to the amount of greenhouse gas released from 28,898 passenger vehicles driven for a year.

A better understanding of the role of T cells in the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is helpful not only for vaccine development but also for the treatment of COVID-19 patients. In this study, we determined the existence of SARS-CoV-2-specific T cells in the blood of COVID-19 convalescents. Meanwhile, the specific T cell response in the non-RBD region was stronger than in the RBD region. We also found that SARS-CoV-2 S-specific reactive CD4+ T cells exhibited higher frequency than CD8+ T cells in recovered COVID-19 patients, with greater number of corresponding epitopes presented. Importantly, we isolated the SARS-CoV-2-specific CD4+ T cell receptors (TCRs) and inserted the TCRs into allogenic CD4+ T cells. These TCR-T cells can be activated by SARS-CoV-2 spike peptide and produce IFN-γ in vitro. These results might provide valuable information for the development of vaccines and new therapies against COVID-19.

Objective: The participation of general practice (GP) residents in COVID-19 prevention and control tasks touched workload participation in public health and disease prevention and control and was also a rare, valuable training experience for the residents and research material for medical education. This experience contributed to the understanding of three key points: First, was the content of the COVID-19 prevention task suited to them, or did it overload them in the present? Second, their competence in the COVID-19 prevention task reflected whether the early medical school training was sufficient or not. Third, what can be drawn from this study to promote public health training in the future? This study aimed to explore these issues by conducting a real epidemic situated training (REST) program.Methods: A situated cognition study was designed that included situational context design, legitimate peripheral participation, and the construction of a community of practice. The Task Cognitive Load Scale (NASA-TLX Scale) and self-developed questionnaires were adopted to conduct a questionnaire survey of resident doctors in a GP training program from West China Hospital of Sichuan University, and 183 questionnaires were collected. SPSS 23.0 statistical software was used for the statistical analysis of data.Results: The NASA scale showed that the intensity of field epidemic prevention and control (training) was tolerable. In particular, there was statistical difference in the cognitive load intensity of training before and after the epidemic occurred at different time points (P < 0.05). This shows that they were early trained and well-prepared before sudden outbreak of the COVID-19. Before the outbreak of the epidemic, the public health knowledge and training received came from undergraduate education (83.16%), early residents program training (69.47%), online self-study (49.16%), and continuing education (20.53%).Conclusion: Former medical school education and training at the regulatory training stage have a good effect and enable residents to master the skills required for epidemic prevention and control and to physically and mentally prepare for the task. After this stage, epidemic prevention and control training in real situations will make important contributions to the self-assessment and performance improvement of public health training.

Objective: A reliable prediction of clinical outcome is important for clinicians to set appropriate medical strategies in treating patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aim to establish a perioperative nomogram involving serum lipid signatures for predicting poor outcomes at 3 months in patients with aSAH following endovascular therapy.Methods: Data of patients with aSAH receiving endovascular therapy were collected. Univariable and multivariable analyses were performed to screen independent predictors related to unfavorable outcomes defined by the modified Rankin Scale (mFS) ≥3. A novel nomogram based on these significant features was conducted. The clinical application of this nomogram was assessed by decision curve analysis (DCA) and clinical impact curve.Results: A total number of patients included in this study were 213 (average age 58.9 years, 65.7% female), representing a poor 3-month outcome rate of 48.8%. Free fatty acid (FFA) levels on admission were efficient in predicting poor outcomes compared with other contents in serum lipids. Univariable and multivariable analyses revealed advanced age (P = 0.034), poor Hunt Hess (HH) (odds ratio, OR = 3.7, P < 0.001) and mFS (OR = 6.0, P < 0.001), aneurysms in the posterior circulation (OR = 4.4, P = 0.019), and higher FFA levels on admission (OR = 3.1, P = 0.021) were negative independent predictors of poor 3 months outcome. A novel nomogram composed of these significant features presented a concordance index (C-index) of 0.831 while the practical benefit was validated by DCA and clinical impact curve. An online calculator based on R programming promoted the clinical application of this nomogram.Conclusion: Nomogram involving age, HH grade, mFS, aneurysm location, and serum FFA levels was sufficient to provide an individualized prediction of 3-month poor outcome for each patient with aSAH who underwent endovascular therapy.

Aiming at the problem of insufficient endurance performance of flapping wing aircraft, a stable attitude control algorithm based on energy optimization and ESO (extended state observer) is designed, which effectively reduces the energy consumption in cruise phase. Firstly, the longitudinal dynamic model of flapping wing aircraft is established, and then the uncertain part of the system and various unknown external disturbances are taken as the total disturbance. ESO module is introduced to observe and track the total disturbance in real time. Therefore, the system is transformed into a series integral system through the total disturbance feedback, and then the energy optimal control law is designed on the base of the transformed system. The numerical simulation results show that, compared with the traditional PID control method, the designed energy optimal control method reduces the average energy consumption by 35.28%.

Objective To retrospectively analyze the reproductive outcome of patients after undergoing uterine artery chemoembolization (UACE) due to cesarean scar pregnancy (CSP), and to explore the risk factors for CSP. Methods The clinical data and follow-up information were retrospectively collected from the women who had diagnosed with CSPs and treated by UACE combined with evacuation in our hospital between January 2010 and December 2017. Their conditions of pregnancy and reproductive outcome were analyzed. The clinical manifestations and ultrasonographic features were compared between these pregnant women and those with normal pregnancy. Results Of the 396 cases with follow-up data, 118 cases (29.8%) wished to give a birth again and finally 96 cases (88.1%) were successfully pregnant, with a total of 104 pregnancies. Among them, 62 pregnancies (59.6%) were intrauterine pregnancy while 26 pregnancies (25.0%) were RCSP. Although 278 cases (70.2%) had no pregnancy plans, there were 42 cases (16.9%) having subsequent pregnancies, with a total of 47 pregnancies. Among them, 2 pregnancies (4.3%) were intrauterine pregnancy while 6 pregnancies (12.7%) were RCSP. In all pregnancies, the incidence of RCSP was 21.2% (32/151). Between the intrauterine pregnancy and RCSP groups, the latter group had older gestational age (P=0.020), thinner remnant myometrial thickness of lower uterine segment of previous CSP (P=0.010) and larger times of abortion (P=0.029). Conclusion Women with CSP could be pregnant again after UACE combined with evacuation. It is apt to form RCSP in the subsequent pregnancy after the previous CSP. The gestational age and the remnant myometrial thickness of lower uterine segment of the previous CSP and the number of abortions are associated with RCSP.

Abstract Background Metabolic rewiring is a common feature of many cancer types, including prostate cancer (PCa). Alterations in master genes lead to mitochondrial metabolic rewiring and provide an appealing target to inhibit cancer progression and improve survival. Phospholipase C (PLC)ε is a regulator of tumor generation and progression. However, its role in mitochondrial metabolism remains unclear. Methods The GEO, The Cancer Genome Atlas, and the GTEx databases were used to determine Twist1 mRNA levels in tumors and their non-tumor counterparts. Fifty-five PCa and 48 benign prostatic hypertrophy tissue samples were tested for the presence of PLCε and Twist1 immunohistochemically. An association between PLCε and Twist1 was determined by Pearson’s correlation analysis. PLCε was knocked down with a lentiviral short hairpin RNA. Mitochondrial activity was assessed by measuring the oxygen consumption rate. Western blotting analyses were used to measure levels of PPARβ, Twist1, phosphorylated (p)-Twist1, p-MEK, p-ERK, p-P38, and p-c-Jun N-terminal kinase (JNK). Cells were treated with inhibitors of MEK, JNK, and P38 MAPK, and an agonist and inhibitor of peroxisome proliferator activated receptor (PPAR) β, to evaluate which signaling pathways were involved in PLCε-mediated Twist1 expression. The stability of Twist1 was determined after blocking protein synthesis with cycloheximide. Reporter assays utilized E-cadherin or N-cadherin luciferase reporters under depletion of PLCε or Twist1. Transwell assays assessed cell migration. Finally, a nude mouse tumor xenograft assay was conducted to verify the role of PLCε in tumor formation. Results Our findings revealed that the expression of PLCε was positively associated with Twist1 in clinical PCa samples. PLCε knockdown promoted mitochondrial oxidative metabolism in PCa cells. Mechanistically, PLCε increased phosphorylation of Twist1 and stabilized the Twist1 protein through MAPK signaling. The transcriptional activity of Twist1, and the Twist1-mediated epithelial-to-mesenchymal transition, cell migration, and transcription regulation, were suppressed by PLCε knockdown and by blocking PPARβ nuclear translocation. The tumor xenograft assay demonstrated that PLCε depletion diminished PCa cell tumorigenesis. Conclusions These findings reveal an undiscovered physiological role for PLCε in the suppression of mitochondrial oxidative metabolism that has significant implications for understanding PCa occurrence and migration.