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Jun-Qi Li,1,* Qian-Ting Wang,1,2,* Ying Nie,2 Yun-Peng Xiao,3 Tao Lin,2 Ru-Jin Han,2 Zhe Li,2 Yu-Ying Fan,2 Xiao-Hui Yuan,1 Yue-Ming Wang,4 Jian Zhang,2 You-Wen He,5 Hua-Xin Liao1 1Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, National Engineering Research Center of Genetic Medicine, Guangzhou 510632, People’s Republic of China; 2Guangdong 999 Brain Hospital, Guangzhou 510510, People’s Republic of China; 3Guangzhou Trinomab Biotechnology Co., Ltd, Guangzhou 510632, People’s Republic of China; 4Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai 519040, People’s Republic of China; 5Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA*These authors contributed equally to this workCorrespondence: Hua-Xin LiaoCollege of Life Science and Technology, 704 2nd Science and Engineering Building, Jinan University, 601 Huang Pu Avenue West, Guangzhou 510632, People’s Republic of ChinaTel/Fax +86 20 8522 2062Email tliao805@jnu.edu.cnYou-Wen HeDepartment of Immunology, Duke University Medical Center, Durham NC 27710, USATel/Fax +1 919 613 7870Email youwen.he@duke.eduPurpose: Glioblastoma multiforme (GBM) is a highly malignant tumor of the central nervous system. Although primary GBM patients receive extensive therapies, tumors may recur within months, and there is no objective and scientific method to predict prognosis. Adoptive immunotherapy holds great promise for GBM treatment. However, the expression profiles of the tumor-associated antigens (TAAs) and tumor immune microenvironment (TME) genes used in immunotherapy of GBM patients have not been fully described. The present study aimed to develop a predictive tool to evaluate patient survival based on full analysis of the expression levels of TAAs and TME genes.Methods: Expression profiles of a panel of 87 TAAs and 8 TME genes significantly correlated with poor prognosis were evaluated in 44 GBM patients and 10 normal brain tissues using quantitative real-time polymerase chain reaction (qRT-PCR). A linear formula (the LASSO algorithm based in the R package) weighted by regression coefficients was used to develop a multi-element expression score to predict prognosis; this formula was cross-validated by the leave-one-out method in different GBM cohorts.Results: After analysis of gene expression, clinical features, and overall survival (OS), a total of 8 TAAs (CHI3L1, EZH2, TRIOBP, PCNA, PIK3R1, PRKDC, SART3 and EPCAM), 1 TME gene (FOXP3) and 4 clinical features (neutrophil-to-lymphocyte (NLR), number of basophils (BAS), age and treatment with standard radiotherapy and chemotherapy) were included in the formula. There were significant differences between high and low scoring groups identified using the formula in different GBM cohorts (TCGA (n=732) and GEO databases (n=84)), implying poor and good prognosis, respectively.Conclusion: The multi-element expression score was significantly associated with OS of GBM patients. The improve understanding of TAAs and TMEs and well-defined formula could be implemented in immunotherapy for GBM to provide better care.Keywords: glioblastoma, gene expression score, prognosis, TAAs, TME

Objective: The aim of this work was to estimate the present periodontal problems of people in China, based on an epidemiological investigation of adults. Material and Methods: The data were collected from the northwest, southwest, northeast and east regions (400 subjects from each region) of China. All subjects were over 25 years of age. About half of the subjects were farmers and about half were urban professionals. Everyone was asked to fill out a questionnaire and to undergo a professional oral examination. Periodontal health status was evaluated by a simplified oral hygiene index (OHI-S), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PD), clinical attachment loss (CAL), and tooth mobility. Results: Of the 1590 subjects enrolled in this investigation, 45.7% were male, 45.5% were farmers, and the remaining were urban professionals, and 27.7% of the subjects were smokers. There was a significant difference in the educational background but not smoking between the rural and urban groups. While 34.9% of the subjects in the urban group brushed only once per day, 56.1% of the subjects in the rural group did so. The prevalence of bleeding during brushing was 71.1%, while about 61.4% of the subjects know nothing about scaling. All periodontal indices were significantly higher in males than in females and higher in the rural group than in the urban group. PD, CAL and tooth mobility increased with age. The percentage of sites with CAL>3 mm in the rural group (49.5%) was significantly higher than that in the urban group (37.5%). Both current and former smokers showed increased CAL than non-smokers. Conclusion: Gingivitis and periodontitis are common findings in China. Most Chinese have no knowledge of common periodontal prevention and treatment and very few have regular dental care. The data of this study suggest that age, smoking, and limited education are significantly associated with Chinese adult periodontal attachment loss. Preventive periodontal care and education should be reinforced in the future by establishing relevant oral health projects. [ABSTRACT FROM AUTHOR]

Background: The availability of mechanical thrombectomy (MT) for acute ischemic stroke is limited, and vast disparities exist between countries. We aim to create a MT access score to measure the drivers of access to help quantify and accelerate treatment worldwide., Methods: We used a systematic review complemented by a modified Delphi method. In the first of 3 rounds, 4 independent investigators performed a systematic literature review using key search terms that drive MT access, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In the second round, a panel of 6 anonymous international experts selected key attributes needed for scoring. In the final round, a total of 12 attributes were selected on consensus, each given a score on a 0 to 3 scale. An ultimate MT access score (range, 0-36) was proposed as a new tool to use in identifying barriers to MT access and assist in providing an initial framework for public health interventions., Results: Of 2864 abstracts screened, 121 studies were included in the final systematic review. A total of 34 attributes that potentially drive MT access were initially identified. In the final round, 12 attributes were selected by the expert panel: public awareness, emergency medical services transportation, prehospital large vessel occlusion screening, interhospital transfer policy, emergency department protocols, stroke imaging protocols, emergency department stroke expertise or telestroke availability, interventionalists, MT-capable centers, device availability, and insurance coverage. These attributes were weighted as part of the final score of 0 to 36., Conclusions: The MT access score represents the first tool to quantify barriers to global MT access. Its implementation stands not just as an academic achievement but as a beacon of hope for improving stroke care and outcomes worldwide, bringing us a step closer to bridging the gap in stroke treatment disparities.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS ( p = 0.042) and OS ( p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups ( p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV ( p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peng, Wang, Wang, Li, Lin and He.)

Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by gland fibrosis. We previously found a close correlation between gland fibrosis and the expression of G protein-coupled receptor kinase 2 (GRK2). In this study we explored the pathological and therapeutic significance of GRK2 in SS. Submandibular gland (SMG) antigen-induced SS mouse model was established in WT and GRK2 +/- mice. We showed that the expression levels of GRK2 were significantly up-regulated in glandular tissue and positively correlated with fibrotic morphology in SS patients and mice. Hemizygous knockout of GRK2 significantly inhibited the gland fibrosis. In mouse salivary gland epithelial cells (SGECs), we demonstrated that GRK2 interacted with Smad2/3 to positively regulate the activation of TGF-β-Smad signaling with a TGF-β-GRK2 positive feedback loop contributing to gland fibrosis. Hemizygous knockout of GRK2 attenuated TGF-β-induced collagen I production in SGECs in vitro and hindered gland fibrosis in murine SS though preventing Smad2/3 nuclear translocation. Around 28 days post immunization with SMG antigen, WT SS mice were treated with a specific GRK2 inhibitor paroxetine (Par, 5 mg·kg -1 ·d -1 , i.g. for 19 days). We found that Par administration significantly attenuated gland fibrosis and alleviated the progression of SS in mice. We conclude that genetic knockdown or pharmacological inhibition of GRK2 significantly attenuates gland fibrosis and alleviates the progression of SS. GRK2 binds to Smad2/3 and positively regulates the activation of TGF-β-Smad signaling. A TGF-β-GRK2 positive feedback loop contributes to gland fibrosis. Our research points out that GRK2 could be a promising therapeutic target for treating SS., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro , providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods: According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results: Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects ( t= 8.88, P< 0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group ( F= 3.86, P< 0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group ( F= 35.25, P< 0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation ( F= 39.95, P< 0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group ( F= 88.24, P< 0.001). Conclusions: Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

Fifteen bibenyls and four fluorenones, including five new bibenzyl-phenylpropane hybrids, were isolated from the aerial part of Dendrobium nobile Lindl. Their structures were determined by spectroscopic methods. Bioassay on the LPS-induced proliferations of mouse splenic B lymphocytes, and Con A-induced T lymphocytes showed that compounds 1, 2, and 14 showed excellent immunosuppressive activities with IC 50 values of 1.23, 1.01, and 3.87 μM, respectively, while compounds 3-4, 7, 10, 13, and 15 exhibited moderate immunosuppressive activities with IC 50 values ranging from 6.89 to 14.2 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background and Importance: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process., Methods: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]., Conclusion: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Patient-based real-time quality control (PBRTQC), a laboratory tool for monitoring the performance of the testing process, has gained increasing attention in recent years. It has been questioned for its generalizability among analytes, instruments, laboratories, and hospitals in real-world settings. Our purpose was to build a machine learning, nonlinear regression-adjusted, patient-based real-time quality control (mNL-PBRTQC) with wide application., Methods: Using computer simulation, artificial biases were added to patient population data of 10 measurands. An mNL-PBRTQC was created using eight hospital laboratory databases as a training set and validated by three other hospitals' independent patient datasets. Three different Patient-based models were compared on these datasets, the IFCC PBRTQC model, linear regression-adjusted real-time quality control (L-RARTQC), and the mNL-PBRTQC model., Results: Our study showed that in the three independent test data sets, mNL-PBRTQC outperformed the IFCC PBRTQC and L-RARTQC for all measurands and all biases. Using platelets as an example, it was found that for 20 % bias, both positive and negative, the uncertainty of error detection for mNL-PBRTQC was smallest at the median and maximum values., Conclusions: mNL-PBRTQC is a robust machine learning framework, allowing accurate error detection, especially for analytes that demonstrate instability and for detecting small biases., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Patients with rheumatoid arthritis (RA) have a much higher incidence of cardiac dysfunction, which contributes to the high mortality rate of RA despite anti-arthritic drug therapy. In this study, we investigated dynamic changes in cardiac function in classic animal models of RA and examined the potential effectors of RA-induced heart failure (HF). Collagen-induced arthritis (CIA) models were established in rats and mice. The cardiac function of CIA animals was dynamically monitored using echocardiography and haemodynamics. We showed that cardiac diastolic and systolic dysfunction occurred in CIA animals and persisted after joint inflammation and that serum proinflammatory cytokine (IL-1β, TNF-α) levels were decreased. We did not find evidence of atherosclerosis (AS) in arthritic animals even though cardiomyopathy was significant. We observed that an impaired cardiac β 1 AR-excitation contraction coupling signal was accompanied by sustained increases in blood epinephrine levels in CIA rats. Furthermore, serum epinephrine concentrations were positively correlated with the heart failure biomarker NT-proBNP in RA patients (r 2  = +0.53, P < 0.0001). In CIA mice, treatment with the nonselective βAR blocker carvedilol (2.5 mg·kg -1 ·d -1 , for 4 weeks) or the specific GRK2 inhibitor paroxetine (2.5 mg·kg -1 ·d -1 , for 4 weeks) effectively rescued heart function. We conclude that chronic and persistent β-adrenergic stress in CIA animals is a significant contributor to cardiomyopathy, which may be a potential target for protecting RA patients against HF., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer., Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3 -under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR., Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues., Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3 . Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-490/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objective: To analyze the mortality trend of hypertension in Xinjiang Uygur Autonomous Region, Qinghai Province, Shaanxi Province, Gansu Province, Ningxia Hui Autonomous Region and Inner Mongolia Autonomous Region (6 provinces) in northwestern China, from 2013 to 2021, and evaluate the influence of hypertension on people's life expectancy. Methods: Based on national death surveillance data and demographic data in the 6 provinces from 2013 to 2021, the mortality rate, standardized mortality rate, life expectancy, cause eliminated life expectancy (CELE), potential gains in life expectancy (PGLEs) and life loss rate of hypertension were calculated. Software Joinpoint was used to analyze the mortality trends and calculate average annual percentage change (AAPC) and annual percentage change (APC) in hypertension deaths. Results: From 2013 to 2021, the overall standardized mortality rate of hypertension in the 6 provinces showed a downward trend (AAPC=-1.82%, P= 0.050). The mortality rate in rural area was always higher than that in urban area, and showed an increasing trend after 2016 (APC=4.74%, P =0.003), and the mortality rate in men was always higher than that in women. The incidence trend of deaths of different types of hypertension were different, and the deaths caused by hypertensive heart disease accounted for the highest proportion (72.69%). In 2021, the life expectancy of the population in the 6 provinces increased by 1.01 years, the CELE increased by 0.93 years, the PGLEs decreased by 0.08 years, and the life loss rate decreased by 0.11% compared with 2013. Conclusions: The overall standardized mortality rate of hypertension showed a decreasing trend in the 6 northwestern provinces from 2013 to 2021, but it showed an increasing trend in rural area after 2016. Prevention of hypertension should be further strengthened in rural area, men and elderly population.

Many advances have been made recently in the field of cancer immunotherapy, particularly with the development of treatments such as immune checkpoint inhibitors and adoptive cellular immunotherapy. The efficacy of immunotherapy is limited, however, owing to high levels of tumor heterogeneity and the immunosuppressive environments of advanced malignant tumors. Therefore, therapeutic anticancer vaccines have gradually become powerful tools for inducing valid antitumor immune responses and regulating the immune microenvironment. Tumor vaccines loaded in nanocarriers have become an indispensable delivery platform for tumor treatment because of their enhanced stability, targeting capability, and high level of safety. Through a unique design, cancer nanovaccines activate innate immunity and tumor-specific immunity simultaneously. For example, the design of cancer vaccines can incorporate strategies such as enhancing the stability and targeting of tumor antigens, combining effective adjuvants, cytokines, and immune microenvironment regulators, and promoting the maturation and cross-presentation of antigen-presenting cells (APCs). In this review, we discuss the design and preparation of nanovaccines for remodeling tumor antigen immunogenicity and regulating the immunosuppressive microenvironment., (© 2023 Wiley-VCH GmbH.)

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4 + and CD8 + T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted., Competing Interests: You-Wen He and Shi-You Li are co-founders of Tricision Biotherapeutics Inc., and the contribution of You-Wen He in this project was through his scientific advisor to tricision Biotherapeutic Inc. Sheng-Nan Sun, Jun Jiang, Qian-Ting Wang, and Shi-You Li are full-time employees of Tricision Biotherapeutics Inc. You-Wen He and Jun O. Liu are co-inventors of the TriVac technology patented by Duke University and Johns Hopkins University and co-founders of TriVac Inc. TriVac technology used by Tricision Biotherapeutics Inc. was licensed by Duke/JHU through TriVac Inc. Other authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

By maintaining the cell integrity of waste activated sludge (WAS), structural extracellular polymeric substances (St-EPS) resist WAS anaerobic fermentation. This study investigates the occurrence of polygalacturonate in WAS St-EPS by combining chemical and metagenomic analyses that identify ∼22% of the bacteria, including Ferruginibacter and Zoogloea, that are associated with polygalacturonate production using the key enzyme EC 5.1.3.6. A highly active polygalacturonate-degrading consortium (GDC) was enriched and the potential of this GDC for degrading St-EPS and promoting methane production from WAS was investigated. The percentage of St-EPS degradation increased from 47.6% to 85.2% after inoculation with the GDC. Methane production was also increased by up to 2.3 times over a control group, with WAS destruction increasing from 11.5% to 28.4%. Zeta potential and rheological behavior confirmed the positive effect which GDC has on WAS fermentation. The major genus in the GDC was identified as Clostridium (17.1%). Extracellular pectate lyases (EC 4.2.2.2 and 4.2.2.9), excluding polygalacturonase (EC 3.2.1.15), were observed in the metagenome of the GDC and most likely play a core role in St-EPS hydrolysis. Dosing with GDC provides a good biological method for St-EPS degradation and thereby enhances the conversion of WAS to methane., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant ( P <0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times ( OR =1.73, 95% CI :1.51-1.97), 1.13 times ( OR= 1.13, 95% CI :1.03-1.24), 1.25 times ( OR= 1.25, 95% CI :1.14-1.38), 1.41 times ( OR= 1.41, 95% CI :1.24-1.60), 1.81 times ( OR= 1.81,95% CI :1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep ( OR =4.89, 95% CI : 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population ( OR =2.12, 95% CI : 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times ( OR =2.31, 95% CI : 1.64-3.26) higher than that in the average population. Tea drinking ( OR =0.73, 95% CI : 0.54-0.98) and physical exercise ( OR =0.67, 95% CI : 0.49-0.90) seemed to be protective factors for depression in elderly MS patients ( P <0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.

Background: Tuberculosis (TB) is a serious infectious disease that is one of the leading causes of death worldwide. This study aimed to investigate the spatial and temporal distribution patterns and potential influencing factors of TB incidence risk, and to provide a scientific basis for the prevention and control of TB., Methods: We collected reported cases of TB in 38 districts and counties in Chongqing from 2014 to 2020 and data on environment, population characteristics and economic factors during the same period. By constructing a Bayesian spatio-temporal model, we explored the spatio-temporal distribution pattern of TB incidence risk and potential influencing factors, identified key areas and key populations affected by TB, compared the spatio-temporal distribution characteristics of TB in populations with different characteristics, and explored the differences in the influence of various social and environmental factors., Results: The high-risk areas for TB incidence in Chongqing from 2014 to 2020 were mainly concentrated in southeastern and northeastern regions of Chongqing, and the overall relative risk (RR) of TB showed a decreasing trend during the study period, while RR of TB in main urban area and southeast of Chongqing showed an increasing trend. The RR of TB was relatively high in the main urban area for the female population and the population aged 0-29 years, and the RR of TB for the population aged 30-44 years in the main urban area and the population aged 60 years or older in southeast of Chongqing had an increasing trend, respectively. For each 1 μg/m 3 increase in SO 2 and 1% increase in the number of low-income per 1000 non-agricultural households (LINA per 1000 persons), the RR of TB increased by 0.35% (95% CI: 0.08-0.61%) and 0.07% (95% CI: 0.05-0.10%), respectively. And LINA per 1000 persons had the greatest impact on the female population and the over 60 years old age group. Although each 1% increase in urbanization rate (UR) was associated with 0.15% (95% CI: 0.11-0.17%) reduction in the RR of TB in the whole population, the RR increased by 0.18% (95% CI: 0.16-0.21%) in the female population and 0.37% (95% CI: 0.34-0.45%) in the 0-29 age group., Conclusion: This study showed that high-risk areas for TB were concentrated in the southeastern and northeastern regions of Chongqing, and that the elderly population was a key population for TB incidence. There were spatial and temporal differences in the incidence of TB in populations with different characteristics, and various socio-environmental factors had different effects on different populations. Local governments should focus on areas and populations at high risk of TB and develop targeted prevention interventions based on the characteristics of different populations., (© 2023. The Author(s).)

This study analyzes the impact of echinacoside(ECH) in the proliferation, metastasis and adriamycin(ADR) resistance of breast cancer(BC) MCF-7 cells via the modulation of aldo-keto reductase family 1 member 10(AKR1B10)/extracellular signal-regulated kinase(ERK) pathway. The chemical structure of ECH was firstly confirmed. MCF-7 cells were treated with different concentration(0, 10, 20, 40 μg·mL~(-1)) of ECH for 48 h. Western blot was used to analyze expression of AKR1B10/ERK pathway-associated proteins and cell counting kit-8(CCK-8) assay to determine cell viability. MCF-7 cells were collected and classified into control group, ECH group, ECH + Ov-NC group, and ECH + Ov-AKR1B10 group. Then Western blot was employed to analyze the expression of AKR1B10/ERK pathway-associated proteins. CCK-8 and 5-ethynyl-2'-deoxyuridine(EdU) assay were used to examine cell proliferation. Cell migration was appraised with scratch assay, Transwell assay, and Western blot. Eventually, MCF-7 cells were treated with ADR for 48 h to induce ADR resistance. Cell viability was tested by CCK-8 assay and cell apoptosis was estimated based on terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay and Western blot. Based on Protein Data Bank(PDB) and molecular docking, the binding affinity of ECH to AKR1B10 was assessed. Various doses of ECH decreased the expression of AKR1B10/ERK pathway-associated proteins in a dose-dependent manner and declined cell viability compared with the control group. Compared with the control group, 40 μg·mL~(-1) ECH blocked the AKR1B10/ERK pathway in MCF-7 cells and inhibited the proliferation, metastasis and ADR resistance of the cells. Compared with the ECH + Ov-NC group, ECH + Ov-AKR1B10 group showed the recovery of some biological behaviors of MCF-7 cells. ECH also targeted AKR1B10. ECH can inhibit the proliferation, metastasis, and ADR resistance of BC cells by blocking AKR1B10/ERK pathway.

Background: Global warming and increasing extreme weather have become a severe problem in recent years, posing a significant threat to human health worldwide. Research exploring the link between injury as one of the leading causes of death globally and ambient temperature was lacking. Based on the hourly injury emergency ambulance dispatch (IEAD) records from 2019-2021 in the main urban area of Chongqing, this study explored the role of temperature extremes on the pathogenesis of injury by different mechanisms and identified sensitive populations for different mechanisms of injury., Methods: In this study, we collected hourly injury emergency ambulance dispatch (IEAD) records from Chongqing Emergency Dispatch Center in the main urban area of Chongqing from 2019 to 2021, and used a distributed lagged nonlinear model (DLNM) with quasi-Poisson distribution to evaluate the association between ambient temperature and IEADs. And the stratified analysis was performed by gender, age and different injury mechanisms to identify susceptible groups. Finally, the attributable burden of ambient extreme temperatures was also investigated., Results: The risk for total IEADs increased significantly at high temperature (32 °C) compared with optimal temperature (9 °C) (CRR: 1.210; 95%CI[1.127,1.300]). The risks of traffic accident injury (CRR: 1.346; 95%CI[1.167,1.552]), beating injury (CRR: 1.508; 95%CI[1.165,1.952]), fall-height injury (CRR: 1.871; 95%CI[1.196-2.926]) and injury of sharp penetration (CRR: 2.112; 95%CI[1.388-3.213]) were significantly increased. At low temperature (7 °C), the risk of fall injury (CRR: 1.220; 95% CI [1.063,1.400]) increased significantly. Lag for 24 hours at extreme low temperature (5 °C), the risk of 18-45 years (RR: 1.016; 95%CI[1.009,1.024]) and over 60 years of age (RR: 1.019; 95%CI[1.011,1.025]) increased significantly. The effect of 0 h delay in extreme high temperature (36 °C) on males aged 18-45 years (RR: 1.115; 95%CI[1.071,1.162]) and 46-59 years (RR: 1.069; 95%CI[1.023,1.115]) had significant impact on injury risk., Conclusions: This study showed that ambient temperature was significantly related to the risk of injury, and different mechanisms of injury were affected differently by extreme temperature. The increasing risk of traffic accident injury, beating injury, fall-height injury and sharp penetrating injury was associated with extreme heat, while fall injury was associated with extreme cold. The risk of injury in high temperature environment was mainly concentrated in males and young adults. The results of this study can help to identify the sensitive population with different injury mechanisms in extreme temperature environment, and provide reference for public health emergency departments to respond to relevant strategies in extreme temperature environment to minimize the potential risk to the public.

Species of the genus Russula are key components of ectomycorrhizal ecosystems worldwide, some of which are famous edible fungi. Although many new species have been described in China, their diversity in North China is still poorly known. Based on the morphology observation of specimens and molecular phylogenetic analyses, combined with the current classification frame of Russula , six new species of Russula subgenus Russula are proposed from the Yanshan Mountains in northern Beijing and northern Hebei Province of China in this study: viz. Russula miyunensis (subsection Chamaeleontinae ), R . plana (subsection Chamaeleontinae ), R. sinoparva (subsection Puellarinae ), R. sinorobusta (subsection Puellarinae ), R. subversatilis (subsection Roseinae ), and R. yanshanensis (subsection Puellarinae ). This is the first report of the species of Russula subgenus Russula from the Yanshan Mountains. This study enriches the species diversity of Russula in North China and provides new data support for the systematic study of Russula in subsequent research, including research and development on edibility.

Nagrajomyces ( incertae sedis , Ascomycota ) is a monotypic genus with a previously unknown systematic position. In this report, two new species are proposed, Nagrajomycesfusiformis and Nagrajomyceslaojunshanensis. These new taxa are proposed based on morphological characteristics evident via light microscopy and molecular data. Multi-locus phylogenetic analyses (ITS rDNA, nrLSU rDNA, RPB2 , and TEF1-α ) show that specimens recently collected in Yunnan Province, China are closely related to Gnomoniaceae . Both new species and known species were discovered repeatedly in their asexual developmental form exclusively on twigs of Rhododendron spp. ( Ericaceae ). This indicates a host specificity of Nagrajomyces spp. for species of Rhododendron ., (Lan Zhuo, Mei-Jun Guo, Qiu-Tong Wang, Hao Zhou, Meike Piepenbring, Cheng-Lin Hou.)

Background: Patient-based real-time quality control (PBRTQC), a complement to traditional QC, may eliminate matrix effect from QC materials, realize real-time monitoring as well as cut costs. However, the accuracy of PBRTQC has not been satisfactory as physicians expect till now. Our aim is to set up a artificial intelligence-based QC for small error detection in real laboratory settings. Taking tPSA as our unique research subject, data extraction, data stimulation, data partition, model construction and evaluation were designed., Methods: 84241 deidentified results for tPSA were extracted from Laboratory Information System of Aviation General Hospital. The data set was accumulated by way of data simulation. Independent training and test datasets were separated. After three classification models (RF, SVM and DNN) in ML constructed and weighted by information entropy, a multi-model fusion algorithm was generated. Performance of the fusion model was evaluated by comparing with optimal PBRTQC., Results: For 4 PBRTQC methods, MovSO showed overall better performance for 0.2 μg/L bias and optimal MNPed was equal to 200. For the fusion model, MNPeds were less than 12 for all biases, and ACC surpassed MovSO nearly 100 times. Except for 0.01 μg/L bias, ACC was more than 0.9 for the rest of biases. FPR was apparently lower than MovSO, only 0.2% and 0.1%., Conclusion: The fusion model shows outstanding performance and reduces incorrect and omitting error detection, adaptable for the real settings., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the changes of liver cancer mortality and the effect of liver cancer on life expectancy in key areas of four provinces in China from 2008 to 2018 and provide the basis for the evaluation of comprehensive prevention and control of cancer and promotion of the rational allocation of health resources. Methods: Based on the national cause-of-death surveillance in key areas of the 4 provinces from 2008 to 2018, we analyzed the mortality of liver cancer, cause eliminated life expectancy (CELE) and potential gains in life expectancy (PGLEs). Software Joinpoint 4.9.0.0 was used to calculate the average annual percentage change (AAPC). Arriaga's decomposition method was used to estimate the contribution of the changes of liver cancer mortality in each age group to life expectancy. Results: The standardized mortality of liver cancer in key areas of the 4 provinces showed a downward trend from 2008 to 2018 (AAPC=-4.37%, P <0.001). The changes of liver cancer mortality had a positive effect on the increase of life expectancy, with a contribution value of 0.240 years and a contribution degree of 5.62%. The positive effect was greatest in age group 45-49 years (0.041 years, 0.96%), and the negative effect was greatest in age group 50-54 years (-0.015 years, -0.35%). Compared with 2008, the life expectancy increased by 4.27 years (AAPC=0.59%, P <0.001), the liver cancer CELE increased by 4.20 years (AAPC=0.58%, P <0.001), the PGLEs decreased by 0.07 years (AAPC=-0.62%, P <0.001), and life loss rate decreased by 0.13% (AAPC=-1.18%, P =0.001). The liver cancer PGLEs increased in Yongqiao district, Anhui province (0.09 years), and decreased in other districts (counties), with the largest decline was in Fugou county, Henan province (-0.21 years). Conclusions: From 2008 to 2018, the standardized mortality rate of liver cancer in key areas of the 4 provinces decreased gradually, contributing to the growth of life expectancy. The life loss caused by liver cancer decreased gradually, but the PGLEs varied with districts (counties).

The electricity production via psychrophilic microbial fuel cell (PMFC) for wastewater treatment in cold regions offers an alternative to avoid the unwanted methane dissolution of traditional anaerobic fermentation. But, it is seldom reported by mixed-culture, especially closed to 0 °C. Thus, a two-chamber mixed-culture PMFC at 4 °C was successfully operated in this study using acetate as an electron donor. The main results demonstrated a good performance of PMFC, including the maximum voltage of 513 mV at 1000 Ω, coulombic efficiency of 53%, and power density of 689 mW/m 2 . The cyclic voltammetry curves of enriched biofilm showed a direct electron transfer pathway. These good performances of mixed-culture PMFC were due to the high psychrophilic activity of enriched biofilm, including exoelectrogens genera of Geobacter (6.1%), Enterococcus (17.5%), and Clostridium&#95;sensu&#95;stricto&#95;12 (3.8%). Consequently, a mixed-culture PMFC provides a reasonable strategy to enrich exoelectrogens with high activity. For low-temperature regions, the mixed-culture PMFC involved biotechnologies shall benefit energy generation and valuable chemical production in the future. KEY POINTS: • PMFC showed a maximum voltage of around 513 mV under a resistance of 1000 Ω. • The coulombic efficiency was 53% and the max power density was 689 mW/m 2 . • Geobacter, Enterococcus, and Clostridium&#95;sensu&#95;stricto&#95;12 were key exoelectrogens., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A new functionalized graphenylene-based structure was designed by adsorbing of alkali metals M 3 and superalkali M 3 O (M = Li, Na, K) on graphenylene (BPC) surface. The spectral data show that the spectral properties of the M 3 O@BPC system are very similar because the two-dimensional material plays a major role in the main transition. However, for M 3 @BPC system, the spectral shapes of the three systems show significant changes compared to each other because the different alkali metals play a major role in the main transition process. The calculation results show that the introduction of superalkali does not significantly increase the first polarizability; however, the introduction of alkali metals can obtain considerable nonlinear optical materials. For M 3 @BPC system, the first hyperpolarizability increases significantly when heavier alkali metal is introduced into the two-dimensional structure, which is found to be 866,290.9 au for K 3 @ BPC. A two-level model and first hyperpolarizability density can explain the large first polarizability of these systems., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Caproate production from organic wastes is deemed as a novel strategy in mixed culture fermtation (MCF). However, producing caproate from natural sugar of xylose by MCF is seldom reported and the metabolic pathway is still unclear. Thus, the caproate production from xylose was investigated in this study by mesophilic MCF. The results showed that the caproate concentration from xylose (10 g/L) was 1.2 ± 0.17 g/L (equal to 2.7 gCOD/L) under pH 5.0. Dosing extra ethanol of 5 g/L could slightly increase the caproate production by ∼ 30% (i.e., 1.6 g/L). While dosing extra acetate of 5 g/L negatively affected the caproate production, which was just 0.2 g/L. The microbial analysis illustrated that genus Caproiciproducens was a main identified caproate producer, occupying over 80% of enriched mixed culture. The fatty acid biosynthesis pathway was identified via metagenomic analysis. These unexpected differences extended the understanding of caproate production from organic wastes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture., Methods: From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge)., Results: Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups ( P =0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation( P >0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation ( P =0.049). There was no significant difference in DVT formation between group A and group B( P >0.05). However, the formation of DVT in group A was significantly higher than that in group B( P =0.012)., Conclusion: Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.

Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Objective: To analyze the prevalence and risk factors of self-reported cancer in adults in China in 2015. Methods: The data used in this study were from China Chronic Disease and Risk Factors Surveillance in 2015. The frequency and proportion of the classified variables were analyzed by descriptive statistics, the disordered classified variables were compared by χ 2 test, and the possible risk factors of cancer patients were screened by univariate and multivariate logistic regression analyses. Results: In 2015, there were 1 809 self-reported tumors patients in China, including 689 males (0.63%), 1 120 females (1.03%), 769 (0.71%) in the eastern region, 465 (0.43%) in the central region and 575 (0.53%) in the western region. The patients were mainly distributed in people aged 45- and 55- years old, being overweight or obese, living in eastern urban area, having low education level, being married, having low annual household income and being occupational population. The results of multivariate logistic regression showed that compared with the western region, the prevalence rate of cancer was higher in the eastern region ( OR =1.05, 95% CI : 1.04-1.06), while lower in the central region ( OR =0.94, 95% CI : 0.93-0.95); the risk for cancer in people with family history of malignancy was higher than that in people without family history of malignancy ( OR =1.95, 95% CI :1.94-1.96) the risk for cancer in people with an annual household income of less than 10 000 yuan or between 10 000 and 50 000 yuan was higher than that in people with an annual household income of more than 50 000 yuan (<10 000 yuan: OR =1.59, 95% CI : 1.58-1.60; between 10 000 and 50 000 yuan: OR =1.27, 95% CI : 1.26-1.28); and the risk for cancer in people living urban areas was lower than that in people living in rural areas ( OR =0.98, 95% CI : 0.97-0.99). In terms of personal behavior and diet, the risk for cancer in smokers was 1.25 times higher than that in non-smokers ( OR =1.25, 95% CI : 1.24-1.26), and the risk for cancer in alcoholics was 1.16 times higher than that in non-alcoholics ( OR =1.16, 95% CI : 1.15-1.17), the risk for cancer in people with insufficient vegetable and fruit intakes was 1.29 times and 1.03 times higher than those in people with sufficient intakes of vegetables and fruits, respectively ( OR =1.29, 95% CI : 1.28-1.30; OR =1.03,95% CI : 1.02-1.04). People with low frequency of high-intensity exercise had a higher risk for cancer compared with those with high frequency of high-intensity exercise ( OR =1.32, 95% CI : 1.31-1.33), the risk for cancer was higher in people with low frequency of moderate exercise than in people with high frequency of moderate exercise ( OR =1.08, 95% CI : 1.07-1.09). The risk for cancer in people with sedentary time less than 2 hours was higher than that in those with sedentary time more than 2 hours ( OR =1.69, 95% CI : 1.68-1.70), and the risk for cancer in people who ate moderate amount of red meat was lower than that in people who ate excessive amount of red meat ( OR =0.86, 95% CI : 0.85-0.87). Conclusions: The number of female self-reported cancer was more than that in males, and the number of self-reported cancer in the eastern region was higher than that in the central and western regions. Living in eastern region, with family history of malignancy, having low annual household income, smoking, drinking, insufficient vegetable intake, insufficient fruit intake and low frequency of high-intensity exercise and low frequency of moderate intensity exercise were the main risk factors for cancer, while living in central region, living in urban area and low red meat intake were protective factors.

Objectives: Delta check (DC) is widely used for detecting sample mix-up. Owing to the inadequate error detection and high false-positive rate, the implementation of DC in real-world settings is labor-intensive and rarely capable of absolute detection of sample mix-ups. The aim of the study was to develop a highly accurate DC method based on designed deep learning to detect sample mix-up., Methods: A total of 22 routine hematology test items were adopted for the study. The hematology test results, collected from two hospital laboratories, were independently divided into training, validation, and test sets. By selecting six mainstream algorithms, the Deep Belief Network (DBN) was able to learn error-free and artificially (intentionally) mixed sample results. The model's analytical performance was evaluated using training and test sets. The model's clinical validity was evaluated by comparing it with three well-recognized statistical methods., Results: When the accuracy of our model in the training set reached 0.931 at the 22nd epoch, the corresponding accuracy in the validation set was equal to 0.922. The loss values for the training and validation sets showed a similar (change) trend over time. The accuracy in the test set was 0.931 and the area under the receiver operating characteristic curve was 0.977. DBN demonstrated better performance than the three comparator statistical methods. The accuracy of DBN and revised weighted delta check (RwCDI) was 0.931 and 0.909, respectively. DBN performed significantly better than RCV and EDC. Of all test items, the absolute difference of DC yielded higher accuracy than the relative difference for all methods., Conclusions: The findings indicate that input of a group of hematology test items provides more comprehensive information for the accurate detection of sample mix-up by machine learning (ML) when compared with a single test item input method. The DC method based on DBN demonstrated highly effective sample mix-up identification performance in real-world clinical settings., (© 2021 Rui Zhou et al., published by De Gruyter, Berlin/Boston.)

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being ( p = 0.003), functional well-being ( p = 0.006), breast cancer subscale ( p = 0.038), and FACT-B Total scores ( p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Yu, Jia, Cui, Tian, Fan, Geng, Cao, Yang, Wang, Liang, Wang, Jiang, Duan, Wang, Li, Wang, Zhang, Jin, Tang, Li, Zhu, Zuo, Wang, Zhou, Xiang, Guo, Wang, Huang, Liu and Yu.)

Objective: To investigate whether bone marrow mesenchymal stem cells (BMMSCs) derived apoptotic extracellular vesicles (ApoEVs) could regulate the polarization of mouse macrophage cell line RAW264.7 and whether BMMSCs derived ApoEVs could attenuate pro-inflammatory condition of RAW264.7 induced by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS), so as to provide experimental evidence and theoretical basis for using BMMSCs derived ApoEVs as a method to treat periodontitis. Methods: The Operetta CLS high-content analysis system was used to observe the time-dependent apoptosis process of BMMSCs. Besides, field emission scanning electron microscopy (FESEM), dynamic light scattering technology and streaming potential method were used to measure the surface characteristics of BMMSCs derived ApoEVs. The Operetta CLS high-content analysis system was used to observe the process of RAW264.7 phagocyting 5-carboxy-tetramethylrhodamine, succinimidyl ester (5-TAMRA-SE) labeled ApoEVs. Real-time quantitative PCR was used to detect the mRNA expression of arginase-1 (Arg-1). Cell immunofluorescence and Western blotting were used to detect the number of inducible nitric oxide synthase (iNOS)(+) macrophages and iNOS protein expression level in each experiment group. Enzyme linked immunosorbent assay was used to detect tumor necrosis factro-α (TNF-α) level in the Pg-LPS induced pro-inflammatory macrophage culture supernatant in each experiment group. Results: After treating with 0.5 μmol/L staurosporine for 12 hours, mouse BMMSCs underwent shrinking with obvious vesicles structure around. The FESEM showed the ApoEVs were in spherical shapes. The size range of ApoEVs was about 100-1 000 nm and the average Zeta potential was -16.6 mV. The Operetta CLS high-content analysis system showed RAW264.7 could phagocytose 5-TAMRA-SE labeled ApoEVs by pseudopodia. The relative mRNA expression of Arg-1 was significantly increased in RAW 264.7 after being treated with interleukin 4 (IL-4) and ApoEVs (261.97±15.91) compared to that with IL-4 alone (115.29±15.42) ( P <0.01). Cell immunofluorescence showed that ApoEVs could reduce the number of iNOS(+) macrophages induced by Pg-LPS (39.33±4.70) comparing to those without ApoEVs (95.33±4.70) ( P =0.007). In the meanwhile, ApoEVs could also down-regulate the iNOS protein level of macrophages induced by Pg-LPS (5.84±1.05) comparing to those without ApoEVs (14.91±3.87) ( P <0.01). Besides, ApoEVs could also reduce the TNF-α secretion in the culture supernatant of pro-inflammatory macrophages induced by Pg-LPS [(21 899.71±409.73) ng/L] comparing to those without ApoEVs [(71 296.50±2 344.22) ng/L] ( P =0.003). Conclusions: BMMSCs derived ApoEVs could regulate the polarization of macrophages and could also attenuate the pro-inflammatory condition of macrophages induced by Pg-LPS.

Background: Accumulating evidence indicates that miRNAs are involved in multiple cellular functions and participate in various cancer development and progression, including breast cancer., Methods: We aimed to investigate the role of miR-381-3p in breast cancer. The expression level of miR-381-3p and EMT transcription factors was examined by quantitative real-time PCR (qRT-PCR). The effects of miR-381-3p on breast cancer proliferation and invasion were determined by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. The regulation of miR-381-3p on its targets was determined by dual-luciferase analysis, qRT-PCR, and western blot., Results: We found that the expression of miR-381-3p was significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-381-3p inhibited breast cancer proliferation and invasion, whereas knockdown of miR-381-3p promoted cell proliferation and invasion in MDA-MB-231 and SKBR3 cells. Mechanistically, overexpression of miR-381-3p inhibited breast cancer epithelial-mesenchymal transition (EMT). Both Sox4 and Twist1 were confirmed as targets of miR-381-3p. Moreover, transforming growth factor-β (TGF-β) could reverse the effects of miR-381-3p on breast cancer progression., Conclusions: Our observation suggests that miR-381-3p inhibits breast cancer progression and EMT by regulating the TGF-β signaling via targeting Sox4 and Twist1., (© 2021. The Author(s).)

The main active ingredients of the fruiting bodies of Shiraia bambusicola and Rubroshiraia bambusae are Hypocrellins, belonging perylenequinones with potential photodynamic activity against cancer and microbial diseases. However, the strains of S. bambusicola and R. bambusae do not produce hypocrellins in culture, so resource exploitation of natural products was seriously restricted. In this study, a series of novel Shiraia -like fungal endophyte strains, with varying sporulation ability and synthesizing diverse secondary metabolites, was isolated from different bamboos. Based on phylogenetic analyses and morphological characteristics of the endophytes, Pseudoshiraia conidialis gen. et sp. nov. is proposed. The secondary metabolites of different fruiting bodies and strains have been comprehensively analyzed for the first time, finding that the endophytic strains are shown not only to produce hypocrellins, but also other perylenequinonoid compounds. It was noteworthy that the highest yield of total perylenequinone production and hypocrellin A appeared in P. conidialis CNUCC 1353PR (1410.13 mg/L), which was significantly higher than any other wild type P. conidialis strains in published reports. In view of these results, the identification of Shiraia -like endophytes not only confirm the phylogenetic status of similar strains, but will further assist in developing the production of valuable natural products.

Objective: To investigate the effect of low dose lipopolysaccharide (LPS)-treated human periodontal ligament stem cells (HPDLSC) on the expression of macrophage pro-inflammatory factors and the mechanism involved. Methods: The primary HPDLSCs were obtained from healthy third molar periodontal ligament tissue. Phosphate buffer saline (PBS), 100 μg/L or 10 mg/L of LPS were used to treat HPDLSCs for 48 h, and their conditioned media were respectively co-cultured with THP-1-derived macrophages for 48 h. The corresponding experimental groups were PBS-treated HPDLSC-derived conditioned medium (CM-C) group, low dose LPS-treated HPDLSC-derived conditioned medium (CM-L) group, and high dose LPS-treated HPDLSC-derived conditioned medium (CM-H) group. Quantitative real-time PCR was performed to explore the mRNA expressions of macrophage interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α) in the CM-C, CM-L and CM-H groups, and the expressions of nuclear factor (erythroid-derived 2)-like 2 (NRF2), glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H quinone dehydrogenase 1 (NQO1) and heme oxygenase 1 (HO-1) in the CM-C and CM-L groups. Meanwhile, Western blotting was used to detect the change of nuclear and cytoplasmic NRF2 and the levels of GCLC and HO-1 in the CM-C and CM-L groups. The 2', 7'-dichlorofluorescein probe was adopted to detect the reactive oxygen species (ROS) levels of macrophages in the CM-C and CM-L groups and the data were characterized by the mean fluorescent intensity (MFI). Results: The mRNA expressions of macrophage pro-inflammatory factors IL-6, IL-8, IL-12 and TNF-α in the CM-H group (2.332±0.594, 3.601±0.639, 2.120±0.677 and 2.468±0.236) were significantly upregulated compared with those in the CM-C group (1.000±0.321, 1.000±0.151, 1.000±0.059 and 1.000±0.095) ( P <0.05); while the relative mRNA levels of IL-6, IL-12 and TNF-α in the CM-L group (0.056±0.002, 0.215±0.024 and 0.567±0.071) were much lower than those in the CM-C group (1.000±0.209, 1.000±0.220 and 1.000±0.220) ( P <0.05). At the mRNA level, the expression of NRF2 was significantly increased in the CM-L group (1.864±0.198) compared with that in the CM-C group (1.000±0.094) ( P <0.05). At the protein level, the cytoplasmic NRF2 and nuclear NRF2 were increased in CM-L group (1.175±0.104 and 1.308±0.082) compared with those in the CM-C group (1.000±0.025 and 1.000±0.049) ( P <0.05). Furthermore, the antioxidative genes, i.e. GCLC and NQO1, localized in NRF2 downstream, were significantly upregulated in the CM-L group (1.786±0.278 and 1.444±0.078) compared with the CM-C group (1.000±0.139 and 1.000±0.226) ( P <0.05). The protein levels of GCLC and HO-1 were augmented in the CM-L group (1.159±0.036 and 1.412±0.075) in contrast with those in the CM-C group (1.000±0.050 and 1.000±0.013) ( P <0.05). In addition, the MFI in the CM-L group (123 419±1 302) was significantly lower than that in the CM-C group (139 193±1 241) ( P <0.05). Conclusions: Low-dose LPS-treated HPDLSCs could regulate oxidative stress response through activating the NRF2 signaling pathway of macrophages and further downregulating the expressions of macrophage pro-inflammatory factors.

MicroRNAs are important for the regulation of multiple cellular functions and are involved in the initiation and progression of various types of cancer, including breast cancer. Although microRNA (miR)‑454‑3p is reported to function as an oncogene in several types of human cancer, the role of miR‑454‑5p in breast cancer remains unknown. The present study demonstrated that miR‑454‑5p was upregulated in breast cancer and was associated with a poor prognosis in patients with breast cancer. Overexpression of miR‑454‑5p promoted breast cancer cell viability, migration and invasion in vitro , whereas silencing of miR‑454‑5p inhibited breast cancer proliferation, migration and invasion in vitro and suppressed tumor growth in vivo . Mechanistically, forkhead box J2 (FoxJ2) was shown to be a target of miR‑454‑5p and transactivated E‑cadherin expression. Moreover, silencing of miR‑454‑5p reversed the epithelial‑mesenchymal transition phenotype through upregulation of the FoxJ2/E‑cadherin axis. Collectively, the present findings suggested that miR‑454‑5p may serve as a novel therapeutic target and prognostic predictor for patients with breast cancer.

[Figure: see text].

β-arrestin2 (β-arr2) is, a key protein that mediates desensitization and internalization of G protein-coupled receptors and participates in inflammatory and immune responses. Deficiency of β-arr2 has been found to exacerbate collagen antibody-induced arthritis (CAIA) through unclear mechanisms. In this study we tried to elucidate the molecular mechanisms underlying β-arr2 depletion-induced exacerbation of CAIA. CAIA was induced in β-arr2 -/- and wild-type (WT) mice by injection of collagen antibodies and LPS. The mice were sacrificed on d 13 after the injection, spleen, thymus and left ankle joints were collected for analysis. Arthritis index (AI) was evaluated every day or every 2 days. We showed that β-arr2 -/- mice with CAIA had a further increase in the percentage of plasma cells in spleen as compared with WT mice with CAIA, which was in accordance with elevated serum IgG1 and IgG2A expression and aggravating clinical performances, pathologic changes in joints and spleen, joint effusion, and joint blood flow. Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in β-arr2 -/- mice as compared with WT mice. LPS treatment induced membrane distribution of toll-like receptor 4 (TLR4) on B lymphocytes, accordingly promoted the nuclear translocation of NF-κB and the transcription of Blimp1. Immunofluorescence analysis confirmed that more TLR4 colocalized with β-arr2 in B lymphocytes in response to LPS stimulation. Depletion of β-arr2 restrained TLR4 on B lymphocyte membrane after LPS treatment and further enhanced downstream NF-κB signaling leading to additional increment in plasma cell formation. In summary, β-arr2 depletion exacerbates CAIA and further increases plasma cell differentiation and antibody production through inhibiting TLR4 endocytosis and aggravating NF-κB signaling.

Recently, the antibacterial properties of oestrogen and progestogen were discovered. The aim of this study was to find the cross-sectional association between oral contraceptive use and Helicobacter pylori seroprevalence. Data were obtained from the US National Health and Nutrition Examination Survey (NHANES). The H. pylori immunoglobulin G (IgG) enzyme-linked immunosorbent assays were used to categorise participants as seropositive or seronegative. The study population included 799 female participants who had information on H. pylori seroprevalence and all other covariates and had not been taking any medications (except oral contraceptives). The bivariate Rao-Scott chi-square test indicated a significant association between H. pylori seroprevalence and contraceptive use (P < 0.01). The variables of race, education, poverty income ratio, smoking, and blood lead and cadmium levels were also significantly associated with H. pylori seroprevalence (P < 0.01). Multiple logistic regression analysis of the age-adjusted model revealed that contraceptive users are 65% less likely of being H. pylori seropositive as compared to non-contraceptive users (odds ratio (OR): 0.35, 95% confidence interval (CI): 0.18-0.68). This association is stronger with the final multivariate model (OR: 0.46, 95% CI: 0.23-0.89). Conclusions: This finding reveals the potential protective effect of oral contraceptives against H. pylori infection and serves as a foundation study for further investigations.

Objective: To investigate the effect and mechanism of periodontal ligament stem cell (PDLSC) from inflammatory environment on the secretion of interleukin-1β (IL-1β) by macrophages. Methods: PDLSCs were pretreated with lipopolysaccharide (LPS) in order to simulate the inflammatory environment. Human monocyte cell line (THP-1) cells were treated with conditioned media collected from healthy and inflammatory PDLSCs respectively and divided into conditioned medium of health PDLSC (CM-H) group and conditioned medium of LPS-PDLSC (CM-LPS) group. After 24 h of co-culture, the condition media were abandoned and THP-1 cells were then cultured for another 24 h. The expression of IL-1β in THP-1 cells supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real time-PCR (qRT-PCR) was used to detect the expression of glucose regulated protein 78 (GRP78), activating transcription factor-6 (ATF6), inositol requiring enzyme 1 (IRE1), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT enhancer binding protein homologous protein (CHOP), activating transcription factor-4 (ATF4) and X box binding protein 1 spliced (XBP1s), which were all related with endoplasmic reticulum stress (ERS), in THP-1 cells. The expressions of proteins GRP78 and CHOP were detected by Western blotting. Furthermore, THP-1 cells, which pretreated with ER inhibitor 4-phenylbutyrate (4-PBA) for intervention experiments were grouped by various concentrations of 4-PBA including groups 0 (control group), 1, 10 and 20 mmol/L and treated with condition medium of inflammatory PDLSC. ELISA was used to detect IL-1β expression and qRT-PCR to detect expression of ERS related genes. Results: ELISA results showed that the expression of IL-1β in THP-1 cells of group CM-LPS [(31.35±2.11) ng/L] was significantly higher than group CM-H [(8.19±1.51) ng/L] ( t= 12.60, P< 0.01). qRT-PCR results showed that the relative expressions of GRP78, ATF6, IRE1, PERK, CHOP, ATF4 and XBP1s genes in THP-1 cells of group CM-LPS (1.782±0.070, 1.387±0.204, 1.404±0.119, 1.777±0.187, 1.325±0.156, 1.295±0.066 and 1.137±0.149, respectively) were significantly higher than those in group CM-H ( P< 0.05). In the 4-PBA intervention experiment, compared with group 0 mmol/L, the expressions of GRP78, IRE-1, ATF-6, PERK and CHOP were significantly lower in group 1, 10 and 20 mmol/L ( P< 0.05). Moreover, compared with control group [(31.23±1.98) ng/L], the expression of IL-1β in THP-1 cells were significantly lower in group 10 mmol/L [(21.20±0.37) ng/L] and group 20 mmol/L [(23.85±1.80) ng/L] ( P< 0.05) with ERS inhibited. Conclusions: PDLSC from inflammatory environment could promote IL-1β secretion of macrophages through upregulating macrophages ERS.

Objective: To describe the clinical, laboratory, temporal, radiographic, and outcome features of acute Intracranial Hemorrhage (ICH) in COVID-19 patients., Methods: Retrospective, observational, consecutive case series of patients admitted with ICH to Maimonides Medical Center from March 1 through July 31, 2020, who had confirmed or highly suspected COVID-19. Demographic, clinical, laboratory, imaging, and outcome data were analyzed. ICH rates among all strokes were compared to the same time period in 2019 in two-week time intervals. Correlation of systolic blood pressure variability (SBPV) and neutrophil-to-lymphocyte ratio (NLR) to clinical outcomes were performed., Results: Of 324 patients who presented with stroke, 65 (20%) were diagnosed with non-traumatic ICH: 8 had confirmed and 3 had highly suspected COVID-19. Nine (82%) had at least one associated risk factor for ICH. Three ICHs occurred during inpatient anticoagulation. More than half (6) suffered either deep or cerebellar hemorrhages; only 2 were lobar hemorrhages. Two of 8 patients with severe pneumonia survived. During the NYC COVID-19 peak period in April, ICH comprised the highest percentage of all strokes (40%), and then steadily decreased week-after-week (p = 0.02). SBPV and NLR were moderately and weakly positively correlated to discharge modified Rankin Scale, respectively., Conclusions: COVID-19 associated ICH is often associated with at least one known ICH risk factor and severe pneumonia. There was a suggestive relative surge in ICH among all stroke types during the first peak of the NYC pandemic. It is important to be vigilant of ICH as a possible and important manifestation of COVID-19., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction., Methods: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models., Results: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (p trend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (p interaction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (p interaction  = 0.0497). However, these interactions became insignificant after Bonferroni correction., Conclusion: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Among the staff of Beijing Chao-Yang Hospital, Capital Medical University, who received the inactivated SARS-CoV-2 vaccine on January 30 in 2021, 28 recipients were selected for this research. Samples for nucleic acid tests were collected from the surface of the recipients' both hands before and after vaccination. The hemostatic stickers used after the inoculation were also collected for nucleic acid tests. The nucleic acid tests of the samples collected from the surface of both hands of the 28 recipients before vaccination were all negative. After vaccination, the nucleic acid tests of the samples collected from the surface of both hands of recipients were positive in 3 cases, and suspicious in 8 cases, with a positive rate of 10.7%. A total of 25 hemostatic stickers used were collected, 24 of them had positive nucleic acid tests, and the rest one had suspicious nucleic acid test result, with a positive rate of 96%. The hemostatic stickers used after the inoculation have the risk of nucleic acid contamination.

Twenty-seven Colletotrichum isolates associated with asymptomatic tissues of bamboo (Bambusoideae, Gramineae) were isolated from Anhui, Beijing, and Guangxi in China. Based on multilocus (internal transcribed spacer [ITS], glyceraldehyde-3-phosphate dehydrogenase [ GAPDH ], chitin synthase [ CHS ], actin [ ACT ], beta-tubulin [ TUB2 ]) phylogenetic analyses and morphological characteristics, three species were distinguished, including two novel species, C. bambusicola and C. guangxiense , and one known species, C. metake , which is a first report for China. These species have hitherto only been discovered on Bambusoideae, indicating that they probably have host preference.

A new series of corannulene derivatives with two mixed π-conjugated bridge have been theoretically designed and investigated by means of density functional theory. It is found that all molecules exhibit large energy gaps. The holes and electrons analysis show that charge transfer from long-chain connected with NH 2 to long-chain connected with NO 2 . The small transition energy brings corannulene derivatives larger first hyperpolarizabilities. Furthermore, the polarization scan of the hyper-Rayleigh scattering (HRS) intensity indicates that all studied compounds belong to dipolar characteristic. The results indicate that employing two mixed π-conjugated bridge can significantly increase the first hyperpolarizability.