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Abstract Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

Abstract Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P

Abstract. Background:. Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. Methods:. Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results:. A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. Conclusions:. PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Summary: Photoacoustic imaging (PAI) with co-registered ultrasound (US) is a hybrid non-invasive imaging modality that enables visualization and quantification of tumor hypoxia in live animals. Here, using a breast tumor xenograft model as an example, we present a stepwise protocol describing animal preparation, positioning, instrument setup, and US-PAI image acquisition procedures. This protocol also guides through detailed data analysis, explains functional readouts obtained from PAI, and discusses the potential application of the technology to study the hypoxic tumor microenvironment.For complete details on the use and execution of this protocol, please refer to Dai et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Injuries to axons within the central nervous system (CNS) pose a substantial clinical challenge due to their limited regenerative capacity. This study investigates the therapeutic potential of Cell-free fat extract (CEFFE) in CNS injury. CEFFE was injected intravitreally after the optic nerve was crushed. Two weeks post-injury, quantification of regenerated axons and survival rates of retinal ganglion cells (RGCs) were performed. Subsequently, comprehensive gene ontology (GO) an-notation elucidated the cellular origins and functional attributes of CEFFE components. Molecular mechanisms underlying CEFFE’s therapeutic effects were explored through Western blotting (WB). Additionally, levels of inflammatory factors within CEFFE were determined using enzyme-linked immunosorbent assay (ELISA), and histological staining of microglia was conducted to assess its impact on neuroinflammation. CEFFE demonstrated a significant capacity to promote axon re-generation and enhance RGCs survival. GO annotation revealed the involvement of 146 proteins within CEFFE in axonogenesis and neurogenesis. WB analysis unveiled the multifaceted pathways through which CEFFE exerts its therapeutic effects. Elevated levels of inflammatory factors were detected through ELISA, and CEFFE exhibited a modulatory effect on microglial activation in the retinal tissue following optic nerve crush (ONC). The present study highlights the therapeutic promise of CEFFE in the management of CNS injuries, exemplified by its ability to foster axon regeneration and improve RGCs survival.

Bayesian network (BN) inference is an important statistical tool with additive symmetry. However, BN inference cannot deal with the uncertain, fuzzy, random, and conflicting information from experts’ knowledge in the process of conducting a risk assessment. To tackle this issue, a new fuzzy BN inference approach for risk assessments was proposed based on cloud model (CM), interval type-2 fuzzy set (IT2 FS), interval type-2 fuzzy logic system (IT2 FLS), modified Dempster–Shafer (D-S) evidence theory (ET), and Latin hypercube sampling (LHS) methods along the following lines. Firstly, CM was integrated into IT2 FS, and CM-based IT2 FS (CM-IT2 FS) was defined in the IT2 FLS. Secondly, modified D-S ET was utilized to determine the CM-IT2 FS-based a priori probabilities, and the CM-IT2 FS-based BN model was established. Thirdly, the CM-IT2 FS-based a priori probabilities were reduced to the CM-IT1 FS-based ones using a type reducer in the IT2 FLS, LHS was applied to propose a new fuzzy BN inference algorithm, and then, the new algorithm was used in a typical case to perform the fuzzy BN positive inference for risk prediction and the fuzzy BN reverse inference for risk sensitivity analysis. Finally, the BN inference results were analyzed using the proposed algorithm and the two common BN inference algorithms, and the effectiveness of the proposed approach was validated. It can be concluded that the proposed approach was both accurate and promising.

Ghrelin has been well known as an orexigenic hormone that regulates appetite and energy metabolism in animals. Recent studies imply the regulatory function of ghrelin on ovary development, however, the mechanism about the effects of ghrelin on key hormonal receptors in ovary is far away from systematically understood. The present study aimed to analyze the tissue distribution of ghrelin and related genes and elucidate the regulation of ghrelin on key hormonal receptors in ovary of grass carp (Ctenopharyngodon idella). High expression of ghrelin and ghrelin O-acyltransferase (GOAT) was found in the ovary compared to heart, kidney, spleen, muscle, brain, liver, gill and intestine. To understand the regulatory function of ghrelin on ovarian development, the effects of ghrelin on the key hormone receptors participated in ovarian maturation were determined by ghrelin, acyl-ghrelin and octanoic acid (substrate in the ghrelin acylation system) treatments with 1, 10 and 100 nM concentration. The in vivo study showed that all the 1, 10 and 100 nM ghrelin treatment stimulated follicle-stimulating hormone receptor (FSHR) expression compared to the control. Estrogen Receptor-α (ERα) was depressed by 10 nM acyl-ghrelin compared to the control, while ERβ1 and ERβ2 could be inhibited by 1 nM and 10 nM octanoic acid treatment compared to the control, respectively. The present results for the first time provided novel information about the regulatory role of ghrelin on key hormonal receptors in ovarian of grass carp providing potential new ideas for cultivating of grass carp broodstock.

With the extensive integration of the Internet, social networks and the internet of things, the social internet of things has increasingly become a significant research issue. In the social internet of things application scenario, one of the greatest challenges is how to accurately recommend or match smart objects for users with massive resources. Although a variety of recommendation algorithms have been employed in this field, they ignore the massive text resources in the social internet of things, which can effectively improve the effect of recommendation. In this paper, a smart object recommendation approach named object recommendation based on topic learning and joint features is proposed. The proposed approach extracts and calculates topics and service relevant features of texts related to smart objects and introduces the “thing-thing” relationship information in the internet of things to improve the effect of recommendation. Experiments show that the proposed approach enables higher accuracy compared to the existing recommendation methods.

Quickly recognizing the real-time operating states will be helpful to identify the instantaneous and permanent power loss of the renewable energy station, so as to realize the continuous operation under the influence of the instantaneous disturbances caused by faults. This paper proposes a state recognition method for renewable energy units based on sparse stacked auto-encoder (SSAE) feature extraction and improved k-nearest neighbor (KNN) algorithm. The characteristics of this method is that the electrical parameters of the unit port are collected directly without relying on the unit’s supervisory control and data acquisition (SCADA) system, whose acquisition speed is too slow to meet the recognition accuracy requirement, and that the unit operation states can be recognized quickly and accurately. Firstly, operation states of renewable energy unit are divided, and the framework for the unit’s state recognition is proposed. Moreover, improved strategies for state recognition of renewable energy unit are proposed. Finally, the power system analysis software package (PSASP) is used to obtain the electrical parameters of renewable energy units and the improved KNN algorithm is used to recognize operation states after extracting features based on SSAE. By comparing the method proposed with the traditional KNN algorithm, the effect of the proposed method for states recognition is shown to be the best, with an accuracy of 98.16% and computing time of 50ms. The results show the validity of the proposed method.

Abstract Background Impaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure. Methods This was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR. Results A total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p

Context S-Propargyl-cysteine (SPRC), an endogenous H2S modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis.Objective To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms.Materials and methods Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting.Results SPRC reduced the levels of AST (p

Ghrelin is a growth-promoting hormone produced by the gastrointestinal tract that plays a crucial role through the ghrelin-growth hormone secretagogue receptor (GHS-R) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. To explore the effect of ghrelin on the transcriptomic profile of tilapia liver, the hepatic transcriptome of tilapia was sequenced for two groups, including saline-injected control (CL) and ghrelin-injected (GL; 2 μg/g body weight) tilapia. The transcriptome of livers from the two groups was sequenced using an Illumina HiSeqTM 2000 platform and yielded approximately 310.53 million raw reads. Subsequently, approximately 308.51 million clean reads were obtained from the total raw reads using in-house Perl scripts. Approximately 92.36% clean reads were mapped to the Nile tilapia genome using RSEM. Using the DESeq package, 250 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment of two pathways related to RNA transcription (ribosome biogenesis in eukaryotes pathway and RNA transport pathway), with a total of 14 functional DEGs. ATP-binding and muscle contraction terms were identified as enriched using Gene Ontology (GO), yielding a total of 28 DEGs. Finally, real-time quantitative PCR (RT-qPCR) was used to confirm the accuracy of the transcriptomic results. The results of RT-qPCR were highly consistent with the RNA-seq, indicating that results of RNA-seq were valid. The differences in gene expression between the groups indicated that ghrelin-injection altered energy metabolism and RNA transcription in the tilapia liver, which provides new information to help promote the growth of tilapia.

BackgroundChronic comorbidity has become a major challenge in chronic disease prevention and control. This issue is particularly pronounced in rural areas of developing countries, where the prevalence of chronic disease comorbidity is high, especially among middle-aged and older adults populations. However, the health status of middle-aged and older adults individuals in rural areas of China has received inadequate attention. Therefore, it is crucial to investigate the correlation among chronic diseases to establish a reference basis for adjusting health policies aimed at promoting the prevention and management of chronic diseases among middle-aged and older adults individuals.MethodsThis study selected 2,262 middle-aged and older adults residents aged 50 years or older in Shangang Village, Jiangsu Province, China, as the study population. To analyze the chronic comorbidity of middle-aged and older adults residents with different characteristics, we used the χ2 test with SPSS statistical software. Data analysis was conducted using the Apriori algorithm of Python software, set to mine the strong association rules of positive correlation between chronic disease comorbidities of middle-aged and older adults residents.ResultsThe prevalence of chronic comorbidity was 56.6%. The chronic disease comorbidity group with the highest prevalence rate was the lumbar osteopenia + hypertension group. There were significant differences in the prevalence of chronic disease comorbidity among middle-aged and older adults residents in terms of gender, BMI, and chronic disease management. The Apriori algorithm was used to screen 15 association rules for the whole population, 11 for genders, and 15 for age groups. According to the order of support, the most common association rules of comorbidity of three chronic diseases were: {lumbar osteopenia} → {hypertension} (support: 29.22%, confidence: 58.44%), {dyslipidemia} → {hypertension} (support: 19.14%, confidence: 65.91%) and {fatty liver} → {hypertension} (support: 17.82%, confidence: 64.17%).ConclusionThe prevalence of chronic comorbidity among middle-aged and older adults rural residents in China is relatively high. We identified many association rules among chronic diseases, dyslipidemia is mostly the antecedent, and hypertension is primarily the result. In particular, the majority of comorbidity aggregation patterns consisted of hypertension and dyslipidemia. By implementing scientifically-proven prevention and control strategies, the development of healthy aging can be promoted.

Polyetheretherketone (PEEK) is a potential implant material for dental application due to its excellent mechanical properties. However, its biological inertness and poor osteoinductive ability limited its clinical application. Based on a lay-by-layer self-assembly technique, here we incorporated casein phosphopeptide (CPP) onto PEEK surface by a simple two-step strategy to address the poor osteoinductive ability of PEEK implants. In this study, the PEEK specimens were positively charged by 3-ammoniumpropyltriethoxysilane (APTES) modification, then the CPP was adsorbed onto the positively charged PEEK surface electrostatically to obtain CPP-modified PEEK (PEEK-CPP) specimens. The surface characterization, layer degradation, biocompatibility and osteoinductive ability of the PEEK-CPP specimens were studied in vitro. After CPP modification, the PEEK-CPP specimens had a porous and hydrophilic surface and presented enhanced cell adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. These findings indicated that CPP modification could significantly improve the biocompatibility and osteoinductive ability of PEEK-CPP implants in vitro. In a word, CPP modification is a promising strategy for the PEEK implants to achieve osseointegration.

Based on global cobalt technology patents, this paper uses patent data mining and co-occurrence methods to identify technology application trends, key technology areas, key technology layouts, and technology roadmap. According to the development trend, the development of co-cobalt technology is divided into slow and rapid development stages. The conclusion are: 1) In terms of key technologies, E35-V (Cobalt compound) is the long-term R&D focus in the field of cobalt, and X16-B01F1 (Lithium-based) is the most important key technology area at present. 2) China, Japan, the United States, and South Korea are the main contributors to key cobalt technologies, mainly focusing on the R&D layout of L03-E01B5B (Lithium electrode) technology in the field of X16-B01F1 (Lithium-based). 3) Regarding the cooperation relationship between patent applicants, cooperation between groups is relatively close, cooperation between different countries is less, and transnational cooperation is mainly concentrated in developed countries, among which the United States has the most transnational partners. 4) In the field of cobalt’s most important electrode material technology LG Chemical Co., Ltd. (Korea) and Sumitomo Metal Mining Corporation (Japan) are the two companies with clear technology lines, while Univ Cent South (China) has a late technology development. Finally, we make suggestions for the development of cobalt technology: focus on core technology for R&D and innovation, actively study the technology status and innovation mode of leading companies, and strengthen the cooperation among different R&D institutions.

New study finds cobalt-free batteries and recycling progress can significantly alleviate long-term cobalt supply risks, however a cobalt supply shortage appears inevitable in the short- to medium-term, even under the most technologically optimistic scenario.

Background: It is currently the most cost-effective management model to have multiple professionals from relevant institutions collaborate so as to provide integrated chronic disease management services. The “classified, color-coded, hierarchical and regionalized” chronic disease management model in Youxi County, Fujian Province is a typical case in China. However, related research is limited. This paper aims to analyze the practice measures and lessons learned in Youxi County, focusing on the professional integration of service providers. Methods: From January to March 2021, interviews with 15 key informants in Youxi County were conducted to collect qualitative data, which was analyzed by the thematic framework method as well as the policy data, using the professional integration dimension in the evaluation framework of the integrated healthcare system. Results: A series of measures were taken, such as improving the professional division and collaboration mechanism, establishing the incentive and restraint mechanism geared toward chronic disease management, formulating norms and standards of chronic disease management for patients with different color labels, and promoting the compatibility of inter-professional value and culture under the governmental institutional supply and the organizational support of the tight county healthcare alliance in Youxi County, to prompt professionals of different levels and types to collaborate in order to provide integrated chronic disease management services. However, some problems remained, such as limited capacity of primary health care, the relatively narrow range and weak effect of the incentive and restraint mechanism, inadequate implementation of the norms and standards, and so forth. Conclusions: Our findings provide reference for other regions in China and other low- and middle-income countries in exploring the integrated chronic disease management model. Long-term follow-up surveys and mixed research designs are required in the future to enrich relevant evidence.

Background: Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Methods: Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR (△ = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. Results: We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), △HR, △QRS interval, △QT interval, and △QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and △QRS interval remained significant independent risk factors after adjusting for potential confounds. Conclusions: Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and △QRS interval.

Abstract Background The Coronavirus Disease 2019 (COVID-19) pandemic has rapidly spread across the whole world and brought strong psychological impact. This study aimed to evaluate the prevalence of post-traumatic stress disorders (PTSD) in the general people of southwestern China and associated factors 1 month after the outbreak of the COVID-19. Methods This study was started on 4–10 Feb 2020 based on online survey. The present work was carried out in the provinces of southeastern China, including Sichuan Province, Guizhou Province, Yunnan Province, and Chongqing City.1593 respondents aged 18 years and above administered to this study. Data on whether they have experienced confirmed or suspected COVID-19 of themselves/family members/acquaintances were also collected, and based on ‘yes’ answers, the number of affected individuals (via COVID-19) were categorized into four exposure levels i.e., non-affected, less, moderately, or significantly affected. The civilian version of the PTSD checklist and the self-reported information about COVID-19 were used. Results The prevalence of PTSD was approximately 25.2%(n = 401/1593). The chances of developing PTSD were 6.053(OR = 6.053, 95% CI 1.394 to 26.280) or 3.673(OR = 3.673, 95% CI 1.738 to 7.765) times higher among respondents who had been significantly and moderately affected than those who had not been affected, accordingly. Male (OR = 1.484, 95% CI 1.147 to 1.920),younger age individuals (40 ~ 49 age group/

BackgroundVillage doctors (VDs) in China undertook arduous primary healthcare missions. However, they received little attention in comparison to doctors in urban public secondary and tertiary hospitals. There is an urgent need to explore the overall situation of turnover intention and job burnout among VDs to evaluate and adjust current health manpower policy.MethodsIn this study, seven databases like PubMed, EMBASE, Web of Science (WOS), WanFang, China Science and Technology Journal Database (VIP), Chinese BioMedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) were systematically searched, relevant experts were consulted, and empirical research on job burnout and turnover intention among VDs in international publications was evaluated. Therefore, we evaluated the prevalence of job burnout among VDs in general, across all dimensions and different severity levels, as well as the scores of each category. For turnover intention, we assessed the prevalence of different groups and their overall situation and also identified significant contributors.ResultsIn this study, we integrated 20 research evidences on job burnout and turnover intention among 23,284 VDs from almost all provinces in China, and the prevalence of turnover intention among VDs in China was as high as 44.1% [95% confidence interval (CI): 34.1–54.2], which was two to four times that of primary health workers in high-income countries, but not much different from some developing countries. Simultaneously, VDs with the highest risk of turnover intention were men [odds ratio (OR): 1.22 (1.05–1.43)], those with a monthly income below USD 163.4 [OR: 0.88 (0.78–0.98)], those with a high educational level [OR: 0.88 (0.78–0.98)], and those

Background: Basal-like breast cancer (BLBC) is an important subtype of breast cancer. Twist1 is a key transcription factor in BLBC metastasis, which serves a key role in tumorigenesis. The potential mechanism of Twist1 in BLBC remains to be elucidated. Here, we explored the role and molecular mechanism of Twist1 in BLBC. Methods: The levels of CBX7, Twist1 and EphA2 in BLBC tissues and cells were determined by Western blot. ChIP and dual-luciferase reporter assays confirmed the interaction between CBX7, Twist1 and EphA2 promoter. The cellular functions were analyzed by CCK-8, colony formation, wound healing and Transwell assays. Expression of EMT related proteins was analyzed by Western blot. IHC measured the expression of CBX7, Twist1 and EphA2 in tumor tissues. Results: CBX7 was down-regulated in BLBC tissues and cells, whereas Twist1 and EphA2 were up-regulated. Twist1 silencing inhibited the cell migration, invasion and cancer metastasis of BLBC through targeting EphA2 and regulating EphA2 expression. Additionally, CBX7 blocked the binding of Twist1 to EphA2 promoter and inhibited EphA2 expression and suppressed BLBC growth and metastasis via Twist1/EphA2 axis. Conclusion: CBX7 suppresses BLBC growth and metastasis through Twist1/EphA2 pathway. Our study may provide evidence and new therapeutic targets for the comprehensive treatment of BLBC.

BackgroundVillage doctors are the health “gatekeepers” of rural residents in most developing countries. They undertake a series of strenuous but pivotal missions, including prevention, diagnosis, and treatment of complicated diseases, sanitation services and management, and preventive healthcare and education tasks. Hence, it is of great importance to evaluate the village doctors’ job satisfaction status, which is one of the most important indicators that can reflect the current working state, to provide guidelines for the healthcare policies.MethodsLiterature search was conducted in 7 authoritative databases, including PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI). Experts in the field of social medicine were consulted to achieve supplement and obtain relevant literature. China was selected as a representative of the village doctor system for the in-depth analysis. Building on the previous literature, we modified and proposed a novel strategy that can transform and integrate the outcome indicators to conduct a meta-based and quantitative assessment on job satisfaction.ResultsA total of 37 publications and 23,595 village doctors were included in this research. The meta-analysis showed that the overall job satisfaction score of village doctors was 3.1858 (total score: 5.00), 95% CI: 2.9675–3.404, which represented the level of “neither satisfied nor dissatisfied.” However, in the subsequent adjustment of publication bias, this score reduced to 2.7579, 95% CI: 2.5254–2.9904, which indicated a direct “dissatisfied” level. To discover the underlying causes, a holistic analysis of each dimension and influencing factors of job satisfaction was conducted, and the results demonstrated that “Financial Rewards” (2.49) was the most important factor causing dissatisfaction among village doctors, followed by “Job Security (2.52)” and “Work Stress (3.05).” Several important themes were also identified and assessed to explore the factors related to this topic.ConclusionThis study indicated that there is an urgent need to improve the working status of health workers in rural and remote areas, especially in the middle- and low-income countries. Health policy makers should not only improve the current remuneration and subsidies of village doctors but also guide the professional development and give them more job security to enhance the work stability of this group. More specifically, in the context of the COVID-19 pandemic, further surveys on job satisfaction of village doctors should be carried out to take targeted measures.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021289139].

Mango (Mangifera indica L.) is famous for its sweet flavor and aroma. China is one of the major mango-producing countries. Mango is known for variations in flowering intensity that impacts fruit yield and farmers' profitability. In the present study, transcriptome and metabolome analyses of three cultivars with different flowering intensities were performed to preliminarily elucidate their regulatory mechanisms. The transcriptome profiling identified 36,242 genes. The major observation was the differential expression patterns of 334 flowering-related genes among the three mango varieties. The metabolome profiling detected 1,023 metabolites that were grouped into 11 compound classes. Our results show that the interplay of the FLOWERING LOCUS T and CONSTANS together with their upstream/downstream regulators/repressors modulate flowering robustness. We found that both gibberellins and auxins are associated with the flowering intensities of studied mango varieties. Finally, we discuss the roles of sugar biosynthesis and ambient temperature pathways in mango flowering. Overall, this study presents multiple pathways that can be manipulated in mango trees regarding flowering robustness.

Delignification pretreatment with alkali under various conditions (25–160 °C for 1–12 h) or sodium chlorite at 75 °C for 4 h was applied to improve the enzymatic digestibility of sugarcane bagasse by removing hemicellulose and lignin. Compared with the elimination of hemicellulose, delignification contributed more in achieving a higher glucose yield. In addition, the characterization of untreated and pretreated sugarcane bagasse was conducted to determine the influence of hemicellulose and lignin degradation on subsequent enzymatic digestibility. Furthermore, Polysorbate 80 was added to reduce the enzyme loading, shorten the hydrolysis time, and enhance the efficiency of enzymatic hydrolysis, suggesting that the glucose yield of 92.2% was obtained with enzyme loading of 5 FPU/g substrate. However, the increased yield of glucose with Polysorbate 80 occurred with an increased lignin content and a reduction of enzyme loading, and the yield decreased sharply as the hydrolysis time was prolonged from 6 h to 24 h.

IntroductionRural health workers (RHWs) play an irreplaceable role in ensuring and improving the health level of rural residents as the most basic and extensive medical service providers in rural areas. However, rural health institutions are facing significant worker shortages worldwide, not only in low- and middle-income countries but also in developed countries. As an important variable to explain RHWs' work status and predict turnover behavior, job satisfaction has received more and more attention currently.MethodsPublications from 1 January 1995 to 31 December 2021 were identified from the Science Citation Index Expanded (SCI-Expanded), the Social Sciences Citation Index (SSCI), and the Emerging Sources Citation Index (ESCI) of the Web of Science Core Collection (WoSCC); CiteSpace, VOSviewer, and R software were applied to conduct this study.ResultsA total of 251 publications were obtained from the WoSCC database. The number of publications had a statistically significant increase in the study period. Ranking in the top three of the most productive countries or regions in this field was the United States, the United Kingdom, and China. “Health Care Sciences & Services,” “Nursing,” and “Public, Environmental & Occupational Health” seemed to be the major subjects. According to the reference co-citation analysis, “motivation,” “rural and remote areas,” and “work environment” were three noteworthy topics during the development of the research field. Moreover, through the keyword analysis, the underlying relationship among “job satisfaction,” “job burnout,” and “turnover intention” was explored.ConclusionPublications about job satisfaction associated with RHWs had remarkably indicated that this research field had great development potential and broad prospects. As an emerging topic related to RHWs' job status, job satisfaction and its related affected factors were systematically summarized by cluster and keywords analysis. We also highlighted that job satisfaction had a negative predictive effect on RHWs' job burnout and turnover intention, and job burnout played a positive role in predicting turnover intention. In addition, the job satisfaction and working environment of RHWs under the COVID-19 pandemic should receive more attention in the future.

We presented an antibiotic-loaded γ-cyclodextrin metal-organic framework that delivered antibiotics suitable for the treatment of bacterial infections. The γ-cyclodextrin metal-organic framework was developed using γ-cyclodextrin and potassium ion via the ultrasonic method. The antibiotic (florfenicol and enrofloxacin) was primarily encapsulated into the pore structures of γ-CD-MOF, which allowed the sustained release of antibiotics over an extended period of time in vitro and in vivo. Notably, antibiotics-loaded γ-CD-MOF showed much superior activity against bacteria than free antibiotics (lower MIC value) and displayed better long-lasting activity (longer antibacterial time). The antibiotics-loaded γ-CD-MOF showed nontoxic and perfect biocompatibility to mammalian cells and tissues both in vitro and in vivo. These materials thus represent a novel drug-delivery device suitable for antibiotic therapy. This research is of great significance for reducing the generation of bacterial resistance and providing new ideas for the application of γ-CD-MOF.

It is urgently needed to develop novel adjuvants for improving the safety and efficacy of vaccines. Metal-organic frameworks (MOFs), with high surface area, play an important role in drug delivery. With perfect biocompatibility and green preparation process, the γ-cyclodextrin metal-organic framework (γ-CD-MOF) fabricated with cyclodextrin and potassium suitable for antigen delivery. In this study, we modified γ-CD-MOF with span-85 to fabricate the SP-γ-CD-MOF as animal vaccine adjuvants. The ovalbumin (OVA) as the model antigen was encapsulated into particles to investigate the immune response. SP-γ-CD-MOF displayed excellent biocompatibility in vitro and in vivo. After immunization, SP-γ-CD-MOF loaded with OVA could induce high antigen-specific IgG titers and cytokine secretion. Meanwhile, SP-γ-CD-MOF also significantly improved the proliferation of spleen cells and activated and matured the bone marrow dendritic cells (BMDCs). The study showed the potential of SP-γ-CD-MOF in vaccine adjuvants and provided a novel idea for the development of vaccine adjuvants.

The distributed assembly scheduling problem with a hybrid-flow shop for fabrication is seldom studied, and some real-life constraints such as factory eligibility are seldom handled. In this study, a distributed assembly hybrid-flow shop-scheduling problem (DAHFSP) with factory eligibility is investigated, which has some symmetries on machines. A shuffled frog-leaping algorithm with cooperations (CSFLA) is applied to minimize makespan. A problem-related feature is used. Memeplexes are evaluated, and group 1, with the two best memeplexes, and group 2, with the two worst memeplexes, are formed. A new cooperation between memeplexes and an adaptive search strategy are implemented in groups 1 and 2, respectively. An adaptive cooperation between groups 1 and 2 is also given. Population shuffling is executed every T generations. A number of computational experiments are conducted. Computational results demonstrate that new strategies are effective and CSFLA is a very competitive algorithm for DAHFSP with factory eligibility.

Polyetheretherketone (PEEK) is a potential implant material for dental application due to its excellent mechanical properties and low elasticity modulus. However, its biological inertia results in weak osseointegration between implants and bone tissue, which limited its clinical application. In this study, amino groups were covalently grafted on the PEEK surface using a simple facile self-assembly method to address its poor osteogenic ability. The surface characterization, cell adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells on bare PEEK and amino-modified PEEK (PEEK-APTES) were studied. After grafting amino groups onto the PEEK, the surface morphology changed, the contact angle decreased significantly. The PEEK-APTES showed boosted cell adhesion, proliferation, alkaline phosphate (ALP) activity, extracellular matrix (ECM) mineralization, and expression of osteogenic genes in MC3T3-E1 cells. These findings suggested that amino modification significantly improved the biocompatibility and osteogenic ability of PEEK in vitro .

An MoSi2–borosilicate glass coating with high emissivity and oxidation resistance was prepared on the surface of the fiber-reinforced C/SiO2 aerogel composite by the slurry method combined with the embedding sintering method under the micro-oxygen atmosphere. The microstructure and phase composition of the coatings with different MoSi2 contents before and after static oxidation were investigated. This composite material has both excellent radiating properties and outstanding oxidation resistance. The total emissivity values of the as-prepared coatings are all above 0.8450 in the wavelength of 300∼2,500 nm. Meanwhile, the as-prepared M40 coating also has superior thermal endurance after the isothermal oxidation of 1,200°C for 180 min with only 0.27% weight loss, which contributes to the appropriate viscosity of the binder to relieve thermal stress defects. This material has broad application prospects in thermal protection.

Background: Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca2+ channels, and cell depolarization. This study aimed to investigate PIEZO2’s role in breast cancer. Methods: The clinical relevance of PIEZO2 expression in breast cancer patient was analyzed in a publicly available dataset. Utilizing PIEZO2 overexpressed breast cancer cells, and in vitro and in vivo experiments were conducted. Results: High expression of PIEZO2 was correlated with a worse survival in triple-negative breast cancer (TNBC) but not in other subtypes. Increased PEIZO2 channel function was confirmed in PIEZO2 overexpressed cells after mechanical stimulation. PIEZO2 overexpressed cells showed increased motility and invasive phenotypes as well as higher expression of SNAIL and Vimentin and lower expression of E-cadherin in TNBC cells. Correspondingly, high expression of PIEZO2 was correlated with the increased expression of epithelial–mesenchymal transition (EMT)-related genes in a TNBC patient. Activated Akt signaling was observed in PIEZO2 overexpressed TNBC cells. PIEZO2 overexpressed MDA-MB-231 cells formed a significantly higher number of lung metastases after orthotopic implantation. Conclusion: PIEZO2 activation led to enhanced SNAIL stabilization through Akt activation. It enhanced Vimentin and repressed E-cadherin transcription, resulting in increased metastatic potential and poor clinical outcomes in TNBC patients.

Abstract Background To understand the attitudes and opinions of directors of large public hospitals in China on reform policies of public hospital. Method A cross-sectional survey utilizing questionnaires of the Survey of Attitudes to Public Hospital Reform by Directors was conducted in 2014. The respondents were randomly selected in 100 tertiary public hospitals in 62 cities of 31 provinces in China by stratified multistage random cluster sampling method. 178 directors and associate directors working in tertiary public hospitals were involved. Standard descriptive statistics were used to describe and summarize the data. Results The measure of increasing government subsidies ranked first in the list of concerns expressed by responders (N = 149, 83.7%); while implementing clinical pathways ranked lowest in the list of concerns (N = 34, 19.7%). More associate directors (N = 64, 70.3%) were concerned over the measures of removing drug mark-ups than directors (N = 45, 51.7%) (χ2 = 6.49, p = 0.01). In addition, 75.8% of responders were concerned over the policy of salary system reform, while only 14.5% of them were satisfied with their current income level. What’s more, more than half responders were concerned over the policy of adjusting pricing policies (N = 127, 71.4%) and removing drug markups (N = 109, 61.2%). Conclusion In healthcare reform, the financial security for the hospitals should be considered as a priority by the policy-makers, without the reform goals cannot be achieved. Thus, an incentive mechanism needs to be established in China to guide the director to focus on the medical quality.

Citation recommendation has gained increasing attention in recent years. In practice, researchers usually prefer to cite the most topic-relevant articles. Nevertheless, how to model the implicit correlations between topics and citations is still a challenging task. In this paper, we propose a novel citation recommendation model, called TopicCite, which mines such fine-grained correlations. We extract various citation features from citation network, and integrate the learning process of feature regression with topic modeling. At the recommendation stage, we expand the folding-in process by adding the topic influence of papers that correlated with user-provided information. TopicCite can also be considered a technique for extracting topic-related citation features from manually defined citation features, which can essentially improve the granularity of pre-extracted features. In addition, the unsupervised topic model is supervised and mutually reinforced by abundant citation features in TopicCite; thus, the proposed model can also extract more reliable topic distributions from citation data, which brings a new perspective to topic discovery on linked data. The experimental results on the AAN and DBLP datasets demonstrate that our model is competitive with the state-of-the-art methods.

With the increasing number of scientific papers, researchers find it more and more difficult to obtain relevant and appropriate papers to cite. Citation recommendation aims to overcome this problem by providing a reference paper list for a given manuscript. In this paper, we propose a bibliographic network representation (BNR) model, which simultaneously incorporates bibliographic network structure and content of different kinds of objects (authors, papers, and venues) for efficient recommendation. The proposed model also makes personalized citation recommendation possible, which is a new issue that a few papers addressed in the past. When conducting experiments on the ACL Anthology Network and DBLP datasets, the results demonstrate that the proposed BNR-based citation recommendation approach is able to achieve considerable improvement over other network representation-based citation recommendation approaches. The performance of the personalized recommendation approach is also competitive with the non-personalized recommendation approach.

Automatic image annotation is an effective and straightforward way to facilitate many applications in computer vision. However, manually annotating images is a computation-expensive and labor-intensive task. To address these problems, this paper proposes a novel approach by using a cograph regularized collective nonnegative matrix factorization method to annotate images, which is referred to as CG-CNMF; CG-CNMF maximizes the annotation consistency for each image and minimizes the semantic gap for good annotation performance. To reduce the computation cost, this method formulates the annotation problem as a recommending issue and uses nonnegative matrix factorization (NMF) to recover the image-to-label relation for the testing images. Moreover, to find the most similar latent image features and latent label features during the matrix factorization, it exploits the image-to-image relation and label-to-label relation by utilizing the visual content information of images and the semantic cooccurrence information of labels, respectively. To reduce the semantic gap between the image visual content and semantic concepts, both the semantic features and convolutional neural networks (CNNs)-based visual features are considered. Moreover, to address the label-imbalance and incomplete-label problems, the visual-based label cooccurrence information is also considered. In this way, visually similar images are highly correlated with the true semantics of the test images. The experimental results for three multilabel image datasets demonstrate the effectiveness and the efficiency of the proposed method.

In order to research the flow characteristics of mixed flow pump as turbine (MF-PAT) with different rotation speeds, a hydraulic model of mixed flow pump was established based on a pumped storage power station. The k-ε turbulent model was used to simulate internal flow fields with three rotation speeds by SMPLEC algorithms. Subsequently, theoretical calculations and experiments were carried out to verify the precision of numerical simulation. The results showed that the rotation speed of MF-PAT has a significant impact on its performance. Both numerical calculations and experimental test presented that all efficiency curves consist of ascending and descending stages, while the shaft power and head increase nonlinearly from 1000 to 2000 r/min. When the MF-PAT deviates from the rated environment, increase in speed is positive to the energy recovery efficiency in the high water period and negative in the dry season. This work could provide a reference for further study of MF-PAT.

BackgroundActivity-dependent neuroprotective protein (ADNP), which is involved in embryonic development and neurogenesis, has been proven to be upregulated in some human tumors. However, its role in bladder cancer (BC) has never been studied.ObjectiveWe aimed to investigate the mechanisms by which ADNP promotes the progression of BC.MethodsADNP expressions in BC cell lines and paired BC and adjacent normal tissues were measured by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. Colony formation, Cell Counting Kit-8 (CCK-8), trypan blue exclusion assay, flow cytometry, and nude mice tumorigenesis assay were performed to explore the effects of ADNP on growth of BC in vivo and in vitro. The impacts of ADNP on AKT signaling pathways were measured by Western blot.ResultsThe expression of ADNP mRNA and protein was significantly upregulated in BC tissues compared with adjacent normal tissues. Immunohistochemical analysis of 221 BC and 51 adjacent normal tissue paraffin sections indicated that ADNP expression was significantly associated with histological classification and pathological T and N stages. Survival analysis revealed that patients with high ADNP expression have worse prognosis with respect to overall survival and progression-free disease. ADNP knockdown markedly delayed propagation of BC in vitro and the development of BC in vivo. ADNP overexpression showed the opposite effect. In addition, ADNP can markedly promote G1-S cell cycle transition in BC cells. On the molecular level, we confirmed that ADNP mediated acceleration of G1-S transition was associated with activation of the AKT pathways in BC.ConclusionADNP is overexpressed in BC and promotes BC growth partly through AKT pathways. ADNP is crucial in predicting the outcome of BC patients and may be a potential therapeutic target in BC.

The rapid growth of scientific papers makes it difficult to find relevant and appropriate citations. Context-aware citation recommendation aims to overcome this problem by providing a list of scientific papers given a short passage of text. In this paper, we propose a long-short-term memory (LSTM)based model for context-aware citation recommendation, which first learns the distributed representations of the citation contexts and the scientific papers separately based on LSTM, and then measures the relevance based on the learned distributed representation of citation contexts and the scientific papers. Finally, the scientific papers with high relevance scores are selected as the recommendation list. In particular, we try to incorporate author information, venue information, and content information in scientific paper distributed vector representation. Furthermore, we integrate author information of the given context in citation context distributed vector representation. Thus, the proposed model makes personalized context-aware citation recommendation possible, which is a new issue that few papers addressed in the past. When conducting experiments on the ACL Anthology Network and DBLP data sets, the results demonstrate the proposed LSTM-based model for context-aware citation recommendation is able to achieve considerable improvement over previous context-aware citation recommendation approaches. The personalized recommendation approach is also competitive with the non-personalized recommendation approach.

With the rapid growth of scientific publications, it is hard for researchers to acquire appropriate papers that meet their expectations. Recommendation system for scientific articles is an essential technology to overcome this problem. In this paper, we propose a novel low-rank and sparse matrix factorization-based paper recommendation (LSMFPRec) method for authors. The proposed method seamlessly combines low-rank and sparse matrix factorization method with fine-grained paper and author affinity matrixes that are extracted from heterogeneous scientific network. Thus, it can effectively alleviate the sparsity and cold start problems that exist in traditional matrix factorization based collaborative filtering methods. Moreover, LSMFPRec can significantly reduce the error propagated from intermediate outputs. In addition, the proposed method essentially captures the low-rank and sparse characteristics that exist in scientific rating activities; therefore, it can generate more reasonable predicted ratings for influential and uninfluential papers. The effectiveness of the proposed LSMFPRec is demonstrated by the recommendation evaluation conducted on the AAN and CiteULike data sets.

In this work, we synthesized a pair of positional isomers by attaching a small electron-donating pyrrolidinyl group at ortho- and para-positions of a conjugated core. These isomers exhibited totally different fluorescent properties. PDB2 exhibited obvious aggregation-induced emission properties. In contrast, PDB4 showed the traditional aggregation-caused quenching effect. Their different fluorescent properties were investigated by absorption spectroscopy, fluorescence spectroscopy, density functional theory calculations and single-crystal structural analysis. These results indicated that the substituent position of the pyrrolidinyl groups affects the twisted degree of the isomers, which further induces different molecular packing modes, thus resulting in different fluorescent properties of these two isomers. This molecular design concept provided a new accurate strategy for designing new aggregation-induced emission luminogens.

Convolutional Neural Networks (CNNs) have been widely used in video super-resolution (VSR). Most existing VSR methods focus on how to utilize the information of multiple frames, while neglecting the feature correlations of the intermediate features, thus limiting the feature expression of the models. To address this problem, we propose a novel SAA network, that is, Scale-and-Attention-Aware Networks, to apply different attention to different temporal-length streams, while further exploring both spatial and channel attention on separate streams with a newly proposed Criss-Cross Channel Attention Module (C3AM). Experiments on public VSR datasets demonstrate the superiority of our method over other state-of-the-art methods in terms of both quantitative and qualitative metrics.

The temperature distribution of the submarine cable is an important parameter during the operation. In order to lift the efficiency of heat dissipation during the high-voltage direct current (HVDC) cable thermal cycling test, this study presents a method of cooling the cable using a cooling pipe with circulating water. A three-dimensional mode based on the thermal-fluid coupled model was established for 500 kV HVDC submarine cable by using finite element simulation software COMSOL Multiphysics and Fluent. The temperature field distribution and carrying ampacity of the HVDC submarine cables were analysed and compared under two cooling modes including bipolar double pipe and bipolar single pipe. The results indicate that both cooling modes can lift the current carrying ampacity of the cable; the bipolar double tube cooling mode performs better in cooling, a tiny circulating water velocity can significantly reduce the temperature of the submarine cable. Thus both suitable cooling mode and circulating water velocity were determined to accelerate the heat dissipation of the submarine cable during the thermal cycling test.

Background: The New Rural Cooperative Medical Scheme (NCMS) has been further adjusted and optimized to reduce the financial burden of rural residents and to achieve universal coverage for them. In this study, we aimed to explore the impact of NCMS on medical service utilization and medical expense of inpatients in recent years. Methods: The research data of Hainan Province were extracted from the Chinese NCMS platform from 2012 to 2014. Detailed information included total expenditure, average inpatients costs, average out-of-pocket payments, actual reimbursement rate, and average annual growth rate of the above indicators. Descriptive analysis was used to gauge the effects of NCMS. Results: In the utilization of medical services, NCMS inpatients in tertiary hospital decreased from 25.49% in 2012 to 20.39% in 2014, inpatients in county hospitals increased from 39.49% to 55.92%, simultaneously. The total expenditure in county hospitals rose steadily from 28.46% to 46.66%, meanwhile, the total expenditure in tertiary hospitals fell from 60.44% to 44.51%.The average out-of-pocket costs of rural inpatients remained stable over the years. Furthermore, the compensation fund of NCMS inpatients grew significantly. The actual inpatient reimbursement rate at township health centers increased from 76.93% to 84.04%. Meanwhile, the rate at county hospitals and tertiary hospitals increased slightly from 59.37% and 46.10% to 61.25% and 47.71%, respectively. Conclusions: With the improvement of the reimbursement ability, especially after the new health care reform in 2009, the NCMS have been playing a prominent role in alleviating the economic burden of farmers' medical treatment. Meanwhile, more patients go to primary hospitals than tertiary hospitals, and the capability of primary hospitals has been greatly improved.

The China Fusion Engineering Test Reactor (CFETR) is a tokamak device to validate and demonstrate fusion engineering technology. In CFETR, the breeding blanket is a vital important component that is closely related to the performance and safety of the fusion reactor. Neutronics/thermal-hydraulics (N/TH) coupling effect is significant in the numerical analysis of the fission reactor. However, in the numerical analysis of the fusion reactor, the existing coupling code system mostly adopts the one-way coupling method. The ignorance of the two-way N/TH coupling effect would lead to inaccurate results. In this paper, the MCNP/FLUENT code system is developed based on the 3D-1D-2D hybrid coupling method. The one-way and two-way N/TH coupling calculations for two typical blanket concepts, the helium-cooled solid breeder (HCSB) blanket and the water-cooled ceramic breeder (WCCB) blanket, are carried out to study the two-way N/TH coupling effect in CFETR. The numerical results show that, compared with the results from the one-way N/TH coupling calculation, the tritium breeding ration (TBR) calculated with the two-way N/TH calculation decreases by −0.11% and increases by 4.45% for the HCSB and WCCB blankets, respectively. The maximum temperature increases by 1 °C and 29 °C for the HCSB and WCCB blankets, respectively.

Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (NR3C1). We hypothesized that not only cancer cells, but even immune cells in the tumor microenvironment (TME) may contribute to GR expression in bulk tumor and influence prognosis. To test this, mRNA expression data was accessed from METABRIC and TCGA. “High” and “low” expression was based on highest and lowest quartiles of NR3C1 gene expression, respectively. Single-cell sequencing data were obtained from GSE75688 and GSE114725 cohorts. Computer algorithms CIBERSORT, Gene Set Enrichment Analysis and TIMER were used. GR-high BC has better median disease-free and disease-specific survival. Single cell sequencing data showed higher GR expression on immune cells compared to cancer and stromal cells. Positive correlation between GR-high BC and CD8+ T-cells was noted. In GR-high tumors, higher cytolytic activity (CYT) with decreased T-regulatory and T-follicular helper cells was observed. High GR expression was associated with lower proliferation index Ki67, enriched in IL-2_STAT5, apoptosis, KRAS, TGF-β signaling, and epithelial-to-mesenchymal transition. Immune cells significantly contribute to GR expression of bulk BC. GR-high BC has a favorable TME with higher CYT with favorable outcomes.