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This research was designed to analyze the composition of immune cells in obesity and identify novel and potent drugs for obesity management by epigenetic and transcriptomic conjoint analysis. DNA methylation data set (GSE166611) and mRNA expression microarray (GSE18897) were obtained from the Gene Expression Omnibus database. A total of 72 objects (35 obese samples and 37 controls) were included in the study. Immune cell composition analysis, drug repositioning, and gene set enrichment analysis (GSEA) were performed using CIBERSORT, connectivity map (CMap), and GSEA tools. Besides, we performed a single-cell RNA-seq of the immune cells from whole blood samples obtained from one obese patient and one healthy control. mRNA levels of drug target genes were analyzed by qPCR assay in blood samples from six patients and six healthy controls. Immune cell composition analysis found that CD8 + T cells and NK cells were significantly lower in the obese group. 11 drugs/compounds are considered to possess obesity-control potential, such as atorvastatin. Moreover, the expression of drug targets ( STAT3, MCL1, PMAIP1, SOD2, FOX O 3, FOS, FKBP5 ) in obese patients were higher than those in controls. In conclusion, immune cells are potential therapeutic targets for obesity. Our results also contribute to accelerate research on drug development of obesity., 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 Liu, Liu, Fu, Qiu, Jiang, Huang, Zhu and Li.)

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10 -3  mmHg -1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

The level of triglyceride (TG) ≥ 2. 3 mmol/L is suggestive of marked hypertriglyceridemia (HTG) and requires treatment with a triglyceride-lowering agent in high-risk and very high-risk patients as recommended by the 2019 ESC/EAS guidelines for the management of dyslipidemia. However, the optimal cutoff value required to diagnose non-fasting HTG that corresponds to the fasting goal level of 2.3 mmol/L in Chinese subjects is unknown. This study enrolled 602 cardiology inpatients. Blood lipid levels, including calculated non-high-density lipoprotein cholesterol (non-HDL-C) and remnant cholesterol (RC), were measured at 0, 2, and 4 h after a daily Chinese breakfast. Of these, 482 inpatients had TG levels of <2.3 mmol/L (CON group) and 120 inpatients had TG levels of ≥2.3 mmol/L (HTG group). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values for postprandial HTG that corresponded to a target fasting level of 2.3 mmol/L. Marked hypertriglyceridemia (≥2.3 mmol/L) was found in 120 (19.9%) patients in this study population. The levels of non-fasting TG and RC increased significantly in both groups and reached the peak at 4 h after a daily meal, especially in the HTG group ( p < 0.05). The optimal cutoff value of TG at 4 h, which corresponds to fasting TG of ≥2.3 mmol/L, that can be used to predict HTG, was 2.66 mmol/L. According to the new non-fasting cutoff value, the incidence of non-fasting HTG is close to its fasting level. In summary, this is the first study to determine the non-fasting cutoff value that corresponds to a fasting TG of ≥2.3 mmol/L in Chinese patients. Additionally, 2.66 mmol/l at 4 h after a daily meal could be an appropriate cutoff value that can be used to detect non-fasting marked HTG in Chinese subjects., 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 Guo, Zhu, Xu, Xie, Xiang, Jiang, Tan and Liu.)

A high optoelectronic performance ReS 2 /ReSe 2 van der Waals (vdW) heterojunction phototransistor utilizing thin hafnium oxide (HfO 2 ) as a local-back-gate dielectric layer was prepared and studied. The heterojunction-based phototransistor exhibits a superior electrical performance with a large rectification ratio of ∼10 3 . Furthermore, unlike diode-like heterojunction devices, the innovative introduction of a local-back-gate in this phototransistor provides an outstanding gate-tunable capability with an ultra-low off-state current of 433 fA and a high on/off current ratio of over 10 6 . And under optical excitation of a wide spectrum from 400 to 633 nm, an excellent photodetection responsivity at the 10 4 A W -1 level and the maximum normalized detectivity of 1.8 × 10 15 Jones @ 633 nm have been demonstrated. Such high performances are attributed to the band alignment of the type-II heterojunction and the suppression of dark current by the local-back-gate. This work provides a promising reference for two-dimensional (2D) Re-based heterojunction optoelectronic devices.

Invasion and metastasis are the main causes of colorectal cancer (CRC)-related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1-driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p-paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p-paxillin, MMP-2, and vimentin was enhanced in SphK1-overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E-cadherin was suppressed in SphK1-overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1-overexpressed CRC cells, indicated that SphK1-driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1-driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The present study aims to assess the relationship between red blood cell distribution width (RDW) and clinically significant prostate cancer (csPCa)., Methods: A total of 458 patients with prostate-specific antigen (PSA) ≤ 10 ng/ml, who subsequently underwent 11-core transperineal template-guided prostate biopsy from June 15, 2015 to November 24, 2020, were included in the present study. Receiver-operating characteristic (ROC)-derived area under the curve analysis was performed to evaluate the predictive accuracy. In addition, univariate and multivariate logistic regression analysis was carried out to determine the association between RDW and csPCa detection., Results: A total of 89 patients were diagnosed with csPCa, and these patients presented with higher median RDW. The optimal RDW cut-off was set at 12.35%, which gained the maximal Yuden's index. In addition to csPCa, RDW demonstrated a positive correlation with age (r = 0.210, P < 0.001). It was observed that RDW was independent of prostate-specific antigen density for csPCa detection. Compared with the low-RDW group, patients in the high-RDW group had a 1.586-fold increased risk of being diagnosed with csPCa (OR = 2.586, P = 0.007). In the ROC analysis, the accuracy level increased by 3.1% for the prediction of csPCa, when RDW was added to the multivariate logistic model., Conclusion: A high-RDW value is an independent risk factor for csPCa detection. However, more large-scale studies are needed to confirm these findings. If validated, RDW can become an inexpensive, non-invasive, and convenient indicator for csPCa prediction., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

SARS-CoV-2 is the novel coronavirus behind the COVID-19 pandemic. Since its emergence, the global scientific community has mobilized to study this virus, and an overwhelming effort to identify COVID-19 treatments is currently ongoing for a variety of therapeutics and prophylactics. To better understand these efforts, we compiled a list of all COVID-19 vaccines undergoing preclinical and clinical testing using the WHO and ClinicalTrials.gov database, with details surrounding trial design and location. The most advanced vaccines are discussed in more detail, with a focus on their technology, advantages and disadvantages, as well as any available recent clinical findings. We also cover some of the primary challenges, safety concerns and public responses to COVID-19 vaccine trials, and consider what this can mean for the future. By compiling this information, we aim to facilitate a more thorough understanding of the extensive COVID-19 clinical testing vaccine landscape as it unfolds, and better highlight some of the complexities and challenges being faced by the joint effort of the scientific community in finding a prophylactic against COVID-19., (© 2020 British Pharmacological Society.)

Background: Xuezhikang, an extract of red yeast rice, effectively lowers fasting blood lipid levels. However, the influence of Xuezhikang on the non-fasting levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) has not been explored in Chinese patients with coronary heart disease (CHD). Methods: Fifty CHD patients were enrolled and randomly divided into two groups ( n = 25 each) to receive 1,200 mg/d of Xuezhikang or a placebo for 6 weeks as routine therapy. Blood lipids were repeatedly measured before and after 6 weeks of treatment at 0, 2, 4, and 6 h after a standard breakfast containing 800 kcal and 50 g of fat. Results: The serum LDL-C levels significantly decreased, from a fasting level of 3.88 mmol/L to non-fasting levels of 2.99, 2.83, and 3.23 mmol/L at 2, 4, and 6 h, respectively, after breakfast ( P < 0.05). The serum non-HDL-C level mildly increased from a fasting level of 4.29 mmol/L to non-fasting levels of 4.32, 4.38, and 4.34 mmol/L at 2, 4, and 6 h post-prandially, respectively, and the difference reached statistical significance only at 4 and 6 h after breakfast ( P < 0.05). After 6 weeks of Xuezhikang treatment, the patients had significantly lower fasting and non-fasting serum levels of LDL-C and non-HDL-C ( P < 0.05) than at pretreatment. The LDL-C levels were reduced by 27.8, 28.1, 26.2, and 25.3% at 0, 2, 4, and 6 h, respectively, and the non-HDL-C levels were reduced by 27.6, 28.7, 29.0, and 28.0% at 0, 2, 4, and 6 h, respectively, after breakfast. No significant difference was found in the percent reductions in the LDL-C and non-HDL-C levels among the four different time-points. Conclusions: Six weeks of Xuezhikang treatment significantly decreased LDL-C and non-HDL-C levels, with similar percent reductions in fasting and non-fasting states in CHD patients, indicating that the percent change in non-fasting LDL-C or non-HDL-C could replace that in the fasting state for evaluation the efficacy of cholesterol control in CHD patients who are unwilling or unable to fast., 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 Zhu, Wen, Xiang, Guo, Xu, Zhao and Liu.)

Learning motivation is a significant factor that ensures quality in medical education, and might affect the academic performance and well-being of medical students. This study aimed to explore the status of achievement goal orientations among medical students in China and to further identify the association among academic performance, academic well-being, and achievement goal orientations. Data were collected through a cross-sectional, anonymous survey conducted with 3,511 respondents (effective response rate = 81.7%), from four medical universities in China, and demographic factors, achievement goal orientations, academic performance, and academic well-being were assessed. The average score of achievement goal orientations of Chinese medical students suggested a difference in demographic factors, including sex, year of study, experience of leadership cadre, and family income. Both mastery and performance-avoidance goals were associated with academic performance, subjective academic stress, subjective learning adaptability, subjective sleep quality, and subjective well-being. Performance-approach goals were related to academic performance, subjective academic stress, and subjective learning adaptability. The achievement goal orientations of the medical students in this study were at a middle level. The findings emphasize the importance of mastery goals for promoting the academic performance and well-being of medical students. More care and attention toward achievement goal orientations can be beneficial for the improvement of the academic performance and well-being among medical students., 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 Li, Zhao, Tian, Sun, Zhao, Guo, Zhu, Gao, Yang, Cao and Zhang.)

Background: MUC5AC was recently identified to play important roles in the proliferation and metastasis of malignant mucinous lung tumor cells. Resveratrol (Res), a natural compound with anticancer effects in lung cancer cells, has been reported to inhibit mucin production in airway epithelial cells. This study aimed to investigate the inhibitory effect of Res on MUC5AC expression in lung mucinous adenocarcinoma cells and the potential mechanisms., Methods: Mucus-producing A549 human lung carcinoma cells were used to test the effects of Res on SPDEF and MUC5AC expression. Gene and protein expression was assessed by real-time quantitative PCR (qPCR), immunofluorescence and western blotting assays. SPDEF lentivirus was used to upregulate SPDEF expression levels in mucus-producing A549 human lung carcinoma cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay., Results: Res decreased MUC5AC expression in an SPDEF-dependent manner in mucus-producing A549 human lung carcinoma cells, and this change was accompanied by decreased ERK expression and AKT pathway activation. Moreover, SPDEF was found to be overexpressed in lung adenocarcinoma (LUAD), especially in mucinous adenocarcinoma. In-vitro functional assays showed that overexpression of SPDEF reduced the chemosensitivity of A549 cells to cisplatin (DDP). In addition, Res treatment increased A549 cell chemosensitivity to DDP by inhibiting the SPDEF-MUC5AC axis., Conclusion: Our results indicate that the SPDEF-MUC5AC axis is associated with DDP sensitivity, and that Res decreases SPDEF and MUC5AC expression by inhibiting ERK and AKT signaling in A549 cells, which provides a potential pharmacotherapy for the prevention and therapeutic management of mucinous adenocarcinoma., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Metabolic regulation strategies have been developed to redirect metabolic fluxes to production pathways. However, it is difficult to screen out target genes that, when repressed, improve yield without affecting cell growth. Here, we report a strategy using a quorum-sensing system to control small RNA transcription, allowing cell-density-dependent repression of target genes. This strategy is shown with convenient operation, dynamic repression, and availability for simultaneous regulation of multiple genes. The parameters A i , A m , and R A (3-oxohexanoyl-homoserine lactone [AHL] concentrations at which half of the maximum repression and the maximum repression were reached and value of the maximum repression when AHL was added manually, respectively) are defined and introduced to characterize repression curves, and the variant LuxR I58N is identified as the most suitable tuning factor for shake flask culture. Moreover, it is shown that dynamic overexpression of the Hfq chaperone is the key to combinatorial repression without disruptions on cell growth. To show a broad applicability, the production titers of pinene, pentalenene, and psilocybin are improved by 365.3%, 79.5%, and 302.9%, respectively, by applying combinatorial dynamic repression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glioma is the most common and malignant primary brain tumor. Patients with malignant glioma usually have a poor prognosis due to drug resistance and disease relapse. Cancer stem cells contribute to glioma initiation, progression, resistance, and relapse. Hence, quick identification and efficient understanding of glioma stem cells (GSCs) are of profound importance for therapeutic strategies and outcomes. Ideally, therapeutic approaches will only kill cancer stem cells without harming normal neural stem cells (NSCs) that can inhibit GSCs and are often beneficial. It is key to identify the differences between cancer stem cells and normal NSCs. However, reports detailing an efficient and uniform protocol are scarce, as are comparisons between normal neural and cancer stem cells. Here, we compared different protocols and developed a fast and efficient approach to obtaining high-purity glioma stem cell by tracking observation and optimizing culture conditions. We examined the proliferative and differentiative properties confirming the identities of the GSCs with relevant markers such as Ki67, SRY-box containing gene 2, an intermediate filament protein member nestin, glial fibrillary acidic protein, and s100 calcium-binding protein (s100-beta). Finally, we identified distinct expression differences between GSCs and normal NSCs including cyclin-dependent kinase 4 and tumor protein p53. This study comprehensively describes the features of GSCs, their properties, and regulatory genes with expression differences between them and normal stem cells. Effective approaches to quickly obtaining high-quality GSCs from patients should have the potential to not only help understand the diseases and the resistances but also enable target drug screening and personalized medicine for brain tumor treatment., 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 Han, Cai, Yu, Wang, Hu, Ren, Zhang, Zhu, Zhang, Huang, He and Gao.)

Background: Roux-en-Y gastric bypass (RYGB) has been widely used for type 2 diabetes (T2D) patients with overweight or obesity. However, the long-term outcomes of RYGB versus medical therapy have not been well compared., Objectives: To evaluate the long-term outcomes of RYGB versus medical therapy for patients with T2D., Setting: University-affiliated hospital, China., Methods: Four electronic databases-PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov-were searched for articles published through February 2021. Eligible studies were randomized controlled trials., Results: Of 7 randomized controlled trials (15 articles), 477 patients were included: 239 were randomly divided into RYGB groups and 238 to medical therapy groups. Statistically higher rates of T2D remission were observed in RYGB groups at 1 year (relative risk [RR], 18.01; 95% confidence interval [CI], 4.53- 71.70; P < .0001), 3 years (RR, 29.58; 95% CI, 5.92-147.82; P < .0001), and 5 years (RR, 16.92; 95% CI, 4.15-69.00; P < .0001). Meanwhile, statistically higher rates of achieving the American Diabetes Association's (ADA's) treatment goal were observed in RYGB groups at 1 year (RR, 3.99; 95% CI, 1.01-15.82; P = .05), 2 years (RR, 2.98; 95% CI, 1.62- 5.48; P = .0004), 3 years (RR, 3.16; 95% CI, 1.33-7.49; P = .009), and 5 years (RR, 6.18; 95% CI, 1.69-22.68; P = .006)., Conclusion: This meta-analysis indicated that RYGB led to higher rates of T2D remission than medical therapy at 1, 3, and 5 years, as well as higher rates of achieving ADA's composite goal at 1, 2, 3, and 5 years., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) affects millions of people worldwide. Chemoresistance seriously impairs the therapeutic effects. Lipid droplets (LDs) abnormally accumulate in CRC supported chemoresistance. Exploring the mechanism of LD-induced chemoresistance is extremely important for improving prognosis of CRC patients. The expression of PTMA was increased in both CRC tissues and cells, which was positively correlated with LD production. PTMA facilitated chemoresistance to gemcitabine by inducing LD production in CRC cells. PTMA enhanced LD biogenesis and chemoresistance to gemcitabine by promoting SREBP-1-mediated lipogenesis and STAT3 activation in CRC., (Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Aim: Diabetic foot has become the main cause of non-traumatic amputation. Stem cell therapy, especially mesenchymal stem cells (MSCs), holds a great promise as a therapy for diabetic foot with ischemia limb arterial disease. The aim of this pilot study is to evaluate the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment for diabetic patients with critical limb ischemia (CLI)., Methods: Four eligible diabetic patients with CLI were consecutively enrolled in this pilot study. On the base of the standard-of-care treatment, these patients accepted P-MSCs treatment by intramuscular injection for successive 3 times at an interval of 4 weeks, and the safety and efficacy of placenta-derived MSCs (P-MSCs) treatment were evaluated., Results: There were no serious adverse events during the period of P-MSCs injection and the 24-weeks follow-up period. The clinical ischemic features of patients were improved 24 weeks after P-MSCs treatment. The scores of resting pain and limb coldness significantly decreased, and pain-free walking distance significantly increased from baseline to 24 weeks after P-MSCs therapy. The resting ankle brachial index increased, but no statistically significant difference was found. The findings of magnetic resonance angiography showed the increase of collateral vessel formation in one patient, but there were no significant changes observed in the other patients., Conclusions: The data in this pilot study indicated that multiple intramuscular P-MSCs injections may be a safe and effective alternative therapy for diabetic patients with CLI, and larger, placebo-controlled, perspective studies are needed to prove these results., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Compartmentalization is a defining characteristic of eukaryotic cells, and partitions distinct biochemical processes into discrete subcellular locations. Microscopy 1 and biochemical fractionation coupled with mass spectrometry 2-4 have defined the proteomes of a variety of different organelles, but many intracellular compartments have remained refractory to such approaches. Proximity-dependent biotinylation techniques such as BioID provide an alternative approach to define the composition of cellular compartments in living cells 5-7 . Here we present a BioID-based map of a human cell on the basis of 192 subcellular markers, and define the intracellular locations of 4,145 unique proteins in HEK293 cells. Our localization predictions exceed the specificity of previous approaches, and enabled the discovery of proteins at the interface between the mitochondrial outer membrane and the endoplasmic reticulum that are crucial for mitochondrial homeostasis. On the basis of this dataset, we created humancellmap.org as a community resource that provides online tools for localization analysis of user BioID data, and demonstrate how this resource can be used to understand BioID results better.

Background: To investigate the influence factors of infection complications of transrectal ultrasound-guided transperineal prostate biopsy., Methods: A total of 2192 patients who underwent prostate biopsy under transperineal prostate biopsy were analyzed retrospectively from December 2010 to May 2020.We collected the clinical characteristics and the incidence of complications, and used univariate and multivariate logistic regression analyses to analyze independent risk factors for infection complications after transperineal prostate biopsy., Results: Univariate analysis showed that the following factors were associated with the infection complications: diabetes, bacterial prostatitis, history of urinary retention, history of urinary infection, and number of cores. Furthermore, multivariate logistic analysis revealed that diabetes (OR 2.037, 95% CI 1.143-3.572, P = 0.021) and history of urinary retention (OR 2.563, 95% CI 1.284-3.901, P = 0.013) were independent risk factors for infection complications after transperineal prostate biopsy., Conclusions: Patients with diabetes and history of urinary retention were more likely to have infection complications after transperineal prostate biopsy., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Optical vortex, typically characterized by a helical phase front, results in a possession of orbital angular momentum. In recent years, teleportation of the vortex mode using novel beams with peculiar features has gained great interest. Here, we experimentally demonstrate the propagation dynamics for a new class of the auto-focusing vortex circular Pearcey beam (VCPB), which is theoretically described by delivering the coaxial or off-axial spiral phases into the circular Pearcey beam (CPB), forming the crescent or bottle-like focal structure with self-rotation. Notably, such a hybrid beam with various types is experimentally obtained through a digital micromirror device (DMD) with the binary amplitude holography, and this DMD-based modulation scheme combined with controllable vortex modes enables dynamic switching among the VCPBs. We also measure the topological phase by interferometry and we explain the beam property on the basis of Poynting vector, showing a good agreement with the simulations. Further, the number, location and mode of embedded vortices could offer multiple dimensions of flexibility for target beam modulation, thus the experimentally controllable VCPBs will bring potential to high-speed optical communications and particle manipulations that require dynamic shaping.

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.

To study the material basis and mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease(AD) based on GC-MS and network pharmacology. Ingredients of volatile oil from A.oxyphylla were analyzed by GC-MS. Targets of those ingredients were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Relevant targets of AD were obtained through such databases as DrugBank, STITCH, OMIM. Intersection targets of ingredients and diseases were obtained by Online Venny map, and PPI network was established by STRING to screen out core targets. Gene ontology(GO) functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID. The &quot;ingredients-target-pathway&quot; network was constructed by software Cytoscape 3.8.1 to screen out potential active ingredients of volatile oil from A.oxyphylla in the treatment of AD. The results showed that a total of 6 active ingredients were screened from the volatile oil of A.oxyphylla by GC-MS, 17 targets corresponding to 6 active ingredients were found in TCMSP database, and 3 448 AD targets were found in DrugBank database. &quot;Ingredients-target-pathway&quot; network and PPI network showed there were 4 potential active ingredients in the treatment of AD and 4 core targets. GO analysis and KEGG analysis showed 34(P&lt;0.05) and 5(P&lt;0.05) pathways, respectively, including nerve ligand receptor interaction, calcium signaling pathway, cholinergic synapse and 5-hydroxytryptaminergic synapse. This suggested that volatile oil from A.oxyphylla could synergistically treat AD by regulating calcium balance, cholinergic balance and phosphorylation. This study provided reference and guidance for further study of volatile oil from A.oxyphylla in the treatment of AD.

NOD-like receptor protein 3 (NLRP3) promotes the inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. A high-fat and calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3 -/- mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS + ) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3 -/- mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-α and MCP-1 and infiltration of iNOS + M1 macrophages were increased in the liver of Nlrp3 -/- mice under control diet. NLRP3 deficiency did not attenuate, but instead aggravated NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3 -/- mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH.

Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo , we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs., 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 Gu, Zhu, Xu and Shen.)

Mg-Li based alloys have been widely used in various fields. However, the widespread use of Mg-Li based alloys were restricted by their poor properties. The addition of rare earth element in Mg-Li can significantly improve the properties of alloys. In the present work, different electrochemical methods were used to investigate the electrochemical behavior of Y(iii) on the W electrode in LiCl-KCl melts and LiCl-KCl-MgCl 2 melts. In LiCl-KCl melts, typical cyclic voltammetry was used to study the electrochemical mechanism and thermodynamic parameters for the reduction of Y(iii) to metallic Y. In LiCl-KCl-MgCl 2 melts, the formation mechanism of Mg-Y intermetallic compounds was investigated, and the results showed that only one kind of Mg-Y intermetallic compound was formed under our experimental conditions. Mg-Li-Y alloys were prepared via galvanostatic electrolysis, and XRD and SEM equipped with EDS analysis were used to analyze the samples. Because of the restrictions of EDS analysis, ICP-AES was used to analyze the Li content in Mg-Li-Y alloys. The microhardness and Young's modulus of the Mg-Li-Y alloys were then evaluated., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study aimed to compare the percentage attainment of fasting and non-fasting LDL-C and non-HDL-C target levels in coronary heart disease (CHD) patients receiving short-term statin therapy. This study enrolled 397 inpatients with CHD. Of these, 197 patients took statins for <1 month (m) or did not take any statin before admission (CHD1 group), while 204 patients took statins for ≥1 m before admission (CHD2 group). Blood lipid levels were measured at 0, 2, and 4 h after a daily breakfast. Non-fasting LDL-C and non-HDL-C levels significantly decreased after a daily meal ( P < 0.05). Both fasting and non-fasting LDL-C or non-HDL-C levels were significantly lower in the CHD2 group. The percentage attainment of LDL-C <1.4 mmol/L at 2 and 4 h after a daily breakfast was significantly higher than that during fasting ( P < 0.05), but the percent attainment of non-fasting non-HDL-C <2.2 mmol/L was close to its fasting value ( P > 0.05). Analysis of c-statistic showed that non-fasting cut-off points for LDL-C and non-HDL-C were 1.19 and 2.11 mmol/L, corresponding to their fasting goal levels of 1.4 and 2.2 mmol/L, respectively. When post-prandial LDL-C and non-HDL-C goal attainments were re-evaluated using non-fasting cut-off points, there were no significant differences in percentage attainment between fasting and non-fasting states. Non-HDL-C is more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. If we want to use LDL-C to assess the percent attainment of post-prandial blood lipids, we may need to determine a lower non-fasting cut-off point., 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 Guo, Chen, Lin, Tian, Xiang, Zhu, Xu, Wen and Liu.)

Identifying the quantitative source and hazardous areas of heavy metals in soils plays a pivotal role in soil pollution research, and can provide a basis for regional soil risk monitoring and environmental management. For this purpose, a total of 175 samples were collected in topsoils from Linzi, a typical petrochemical industrial city in Shandong Province. Positive matrix factorization (PMF) and factor analysis with non-negative constraints (FA-NNC) receptor models were applied to analyze the sources of the heavy metals. Based on the multivariate statistical simulation methods of min/max autocorrelation factors (MAF) and sequential Gaussian simulation (SGS), the distribution of heavy metal and potential pollution areas were determined. As, Co, Cr, and Mn were mainly affected by natural sources, their concentrations were dominated by the parent materials, and the high-value areas were distributed in the south of the study area. Hg was the most serious pollution element among the 10 heavy metals analyzed in Linzi and originated from atmosphere deposition from industrial emissions and coal combustion, and the highest values were distributed in the northeast of the study area. Cd, Cu, Ni, Pb, and Zn were dominated by natural sources and human activities. The hot-spot areas were mainly concentrated in the middle of the study area. The potentially contaminated areas of Cd and Hg were 580.80 km 2 and 666.60 km 2 , about 85.04% and 97.59% of the total area, and should require more attention. The potential pollution area of most elements was small and scattered across the study area, accounting for less than 1%.

Background: Venous thromboembolism is a severe preventable complication among orthopaedic surgical patients. Integrating therapeutic guidelines into clinical practice can help improve patient safety and reduce the burden of this pathology. Improving the quality of patient care is important for bridging the gap between the prophylaxis for venous thromboembolism and therapeutic guidelines., Objectives: This study aimed at evaluating the knowledge, attitude, and venous thromboembolism and prophylaxis practices of Chinese orthopaedic nurses to guide quality care improvements., Methods: The data used in this study are secondary data obtained from a multicentric survey. An anonymous questionnaire was used to measure the attitude and knowledge of venous thromboembolic prophylaxis among orthopaedic nurses. VTE prophylactic practices were extracted from medical records within the electronic case report form immediately after the nurses' investigations. The STROBE statement for observational studies was applied., Results: Results indicated that although 94.0% of the responding nurses had attended training courses in their wards, a majority of them (68.9%) achieved a median knowledge score of 7 points or below (range 0-9). Knowledge regarding the proper use of prophylaxis, identification of risk factors, signs and symptoms for pulmonary embolism was limited. Self-reported attitudes underestimate the relationships between venous thromboembolism and low-quality nursing care. Pharmacological prophylaxis was highly used (90.9%), while the utilisation of mechanical prophylaxis and its proper use was relatively low., Conclusions: Chinese orthopaedic nurses demonstrated enthusiasm for venous thromboembolism and prophylaxis. Their knowledge needs to be improved, including the proper use of prophylaxis, identification of risk factors, signs and symptoms. Mechanical prophylaxis practice for VTE prevention after THA and TKA surgical procedures is not optimistic. Further studies should analyse the causes from multiple perspectives, including the availability of resources, the knowledge and attitude of doctors, nurses and patients., Relevance to Clinical Practice: The findings from this study can be used to develop and implement interventions for venous thromboembolism after orthopaedic surgery., (© 2020 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Introduction: Venous thromboembolism (VTE) occurs in up to 40%-80% of patients after hip and knee arthroplasty. Clinical decision-making aided by guidelines is the most effective strategy to reduce the burden of VTE. However, the quality of guidelines is dependent on the strength of their evidence base. The objective of this article is to critically evaluate the quality of VTE prevention guidelines and the strength of their recommendations in VTE prophylaxis in patients undergoing hip and knee arthroplasty., Methods: Relevant literature up to 16 March 2020 was systematically searched. We searched databases such as Web of Science, PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature, China National Knowledge Infrastructure and WanFang and nine guidelines repositories. The identified guidelines were appraised by two reviewers using the Appraisal of Guidelines for Research and Evaluation II and appraised the strength of their recommendations independently. Following quality assessment, a predesigned data collection form was used to extract the characteristics of the included guideline., Results: We finally included 15 guidelines. Ten of the included guidelines were rated as 'recommended' or 'recommended with modifications'. The standardised scores were relatively high in the domains of Clarity of Presentation, and Scope and Purpose. The lowest average standardised scores were observed in the domains of Applicability and Stakeholder Involvement. In reference to the domains of Rigour of Development and Editorial Independence, the standardised scores varied greatly between the guidelines. The agreement between the two appraisers is almost perfect (intraclass correlation coefficients higher than 0.80). A considerable proportion of the recommendations is based on low-quality or very-low-quality evidence or is even based on working group expert opinion., Conclusions: In summary, the majority of the recommendations are based on low-quality evidence, and further confirmation is needed. Furthermore, guideline developers should pay more attention to methodological quality, especially in the Stakeholder Involvement domain and the Applicability domain., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The accumulation of senescent adipose-derived mesenchymal stem cells (AMSCs) in subcutaneous white adipose tissue (WAT) is the main cause for the deterioration of WAT and the subsequent age-related disorders in obesity. The number of AMSCs staining positively for senescence-associated-β-galactosidase (SA-β-Gal) increased significantly after incubation with postprandial triglyceride-rich lipoproteins (TRL), accompanied by an impaired cell proliferation capacity and increased expression of inflammatory factors. Besides, the expression of anti-aging protein, silent mating-type information regulation 2 homolog 1 (SIRT1), was downregulated significantly, while those of acetylated p53 (Ac-p53), total p53, and p21 proteins were upregulated significantly during postprandial TRL-induced premature senescence of AMSCs. Furthermore, the production of intracellular reactive oxygen species (ROS) in the TRL group increased significantly, while pretreatment with the ROS scavenger N-acetyl-L-cysteine effectively attenuated the premature senescence of AMSCs by decreasing ROS production and upregulating SIRT1 level. Thus, postprandial TRL induced premature senescence of AMSCs through the SIRT1/p53/Ac-p53/p21 axis, partly through increased oxidative stress.

Residual levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in karst groundwater in Nanshan Laolongdong were measured using a gas chromatograph equipped with a micro- 63 Ni electron capture detector to determine the residual characteristics including concentration, distribution, and source of OCPs and PCBs. Results revealed that the total concentration range of OCPs was 34.8-623.2 ng·L -1 , and the mean value was 215.6 ng·L -1 , among which the total concentration ranges of HCHs, DDTs, and other OCPs were 8.2-23.6, 4.5-363.7, and 22.2-235.9 ng·L -1 , respectively, and the mean values were 15.9, 104.5, and 95.3 ng·L -1 ; the total concentration range of PCBs was 6.0-40.7 ng·L -1 , and the mean value was 16.8 ng·L -1 . Overall, the pollution of OCPs and PCBs was above average; the results of multiple comparisons revealed that statistically significant differences occurred in the concentration of some OCPs and PCBs. The pollution levels in the water of each sampling point in the study area were quite different; however, the seasonal distribution of OCPs and PCBs was relatively uniform. Source analyses revealed that HCHs' source was the input of lindane in the surrounding environment, DDTs recently originated from illegal use of industrial DDT, other OCPs originated from atmospheric deposition and agricultural input, and PCBs' sources included both historical remains and enterprise production processes. The results of Pearson correlation analyses revealed that some organo-halogen pollutants were homologous or had similar sources and decomposition mechanisms. According to health risk assessment model, drinking water in the study area would not cause obvious harm to human health, but children were more sensitive to pollutants than adults.

Developing alternatives to antibiotics is an urgent need in livestock production. Antimicrobial peptides (AMPs) are regarded as powerful antibiotic substitutes (ASs) because AMPs have broad-spectrum antimicrobial activities and growth-promoting ability. Here, we aimed to comprehensively assess the effects of AMPs on the growth performance, diarrhea rate, intestinal morphology and immunity of healthy or challenged piglets, compared with an antibiotics group or negative control group. We performed a set of meta-analyses of feeding trials from database inception to 27 May 2019. Among the 1379 identified studies, 20 were included in our meta-analyses (56 arms and 4067 piglets). The meta-analyses revealed that (1) compared with the negative control group, AMPs significantly improved the healthy piglets' average daily gain (ADG), average daily feed intake (ADFI), gain : feed ratio (G/F), levels of immune globulin (Ig) IgM and IgG, and intestinal villus height : crypt depth ratio (V/C) (P < 0.05). Meanwhile, AMPs significantly increased the challenged piglets' ADG, ADFI, G/F and V/C of the jejunum and ileum, and notably deceased the diarrhea rate (P < 0.05); (2) compared with antibiotics group, the effects of AMPs were slightly weaker than those of antibiotics in the healthy piglets, but AMPs have similar effects to those of antibiotics in challenged piglets. In a higher purity, the optimal dose of AMPs may be approximately 0.01%. Our findings indicate that AMPs can improve piglet growth performance, enhance immunity, benefit intestinal morphology and decrease the diarrheal rate. AMPs could be great ASs especially under infection conditions.

Purpose: To study the effect of hypoxia induced by cobalt chloride (CoCl2) on viability and oxidative stress of genioglossus myoblast, and to explore the mechanism of the protective effect of conditioned medium (CM) on human dental pulp stem cells (hDPSCs)., Methods: The hDPSCs were isolated and cultured, and the conditioned medium was prepared by ultrafiltration concentration. Mouse genioglossus myoblasts were isolated and divided into control group, CM group, CoCl2 group and CoCl2+CM group. The cell viability of genioglossus myoblasts was detected by CCK-8. The intracellular and mitochondrial ROS levels were evaluated by DCFH-DA and MitoSOX, respectively. The expression level of mitochondria-related genes in NRF-1 and NRF-2 were analyzed by real-time PCR. The expression of PGC-1α, p-AMPK and total AMPK protein was detected by Western blot. Statistical analysis was performed using SPSS 22.0 software package., Results: The proliferation of genioglossus myoblasts was significantly decreased after 200 μmol/L CoCl2 treatment for 24 h (P<0.05), and the levels of reactive oxygen species (ROS) were significantly increased in intracellular and mitochondria (P<0.05). Compared with CoCl2 group, the proliferation ability of hDPSCs-CM was dramatically raised (P<0.05), and the intracellular and mitochondrial ROS content was remarkably decreased(P<0.05). hDPSCs-CM up-regulated the protein expression levels of pAMPK and PGC-1α in genioglossus myoblasts and mitochondrial downstream effectors of PGC-1α, including mRNA expression levels of NRF-1, NRF-2 (P<0.05)., Conclusions: Human dental pulp stem cells conditioned medium can alleviate hypoxia injury induced by CoCl2 in genioglossus myoblasts, and its mechanism may be related to AMPK/PGC-1α signaling pathway.

Purpose: To examine insomnia disorder and its association with sociodemographic factors and poor mental health in 2019 novel coronavirus (COVID-19) inpatients in Wuhan, China., Design: and Methods: A total of 484 COVID-19 inpatients in Wuhan Tongji Hospital were selected and interviewed with standardized assessment tools. Insomnia disorder was measured by the Chinese version of the Insomnia Severity Index (ISI-7), a total score of 8 or more was accepted as the threshold for diagnosing insomnia disorder., Results: The prevalence of insomnia disorder in the whole sample was 42.8%. Binary logistic regression analysis revealed that female gender, younger age, and higher fatigue and anxiety severity were more likely to experience insomnia disorder., Conclusion: Given the high rate of insomnia disorder status among COVID-19 inpatients in Wuhan, China, and its negative effects, follow-up assessments and appropriate psychological interventions for insomnia disorder are needed in this population., (Copyright © 2020. Published by Elsevier B.V.)

Background: Our study aims to evaluate the anesthetic efficacy of multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion-guided targeted periprostatic nerve block (PNB) for transperineal template-guided prostate biopsy (TTPB)., Methods: The patients who underwent mpMRI/TRUS fusion-guided prostate biopsy from May 2018 to March 2019 were randomized into two groups using a random number table. The intervention group (n=47) and the control group (n=45) received targeted PNB and traditional PNB, respectively. Visual analog scale (VAS) and visual numeric scale (VNS) scores were used to assess the patients' pain and quantify their satisfaction., Results: The total detection rate for prostate cancer was 45.7%, with a comparable positive rate between the intervention group (42.6%) and the control group (48.9%), which meant there was no significant difference between the groups (P=0.542). Patient age, prostate-specific antigen, prostate volume, suspicious lesions on mpMRI, number of cores, operation time, and biopsy time were comparable between the groups. The VAS scores during biopsy were significantly lower in the intervention group than in the control group [2 (1 to 3) vs . 2 (1 to 4), P=0.019]. Conversely, the VNS scores during biopsy were higher in the intervention group [3 (2 to 4) vs . 3 (2 to 3), P=0.015]. There were no significant differences in the pain scores or the satisfaction scores at 30 min after the procedure between the two groups. There were no significant differences between the groups for complications, such as hematuria, urinary retention, infection, hemospermia, and vasovagal reaction (P>0.05)., Conclusions: Targeted PNB significantly relieved the pain and did not increase the incidence of complications for patients when compared with traditional PNB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-369). The authors have no conflicts of interest to declare, (2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Introduction: High risk of mental health problems is associated with Coronavirus Disease 2019 (COVID-19). This study explored the prevalence of depressive symptoms (depression hereafter) and its relationship with quality of life (QOL) in clinically stable patients with COVID-19., Methods: This was an online survey conducted in COVID-19 patients across five designated isolation hospitals for COVID-19 in Hubei province, China. Depression and QOL were assessed with standardized instruments., Results: A total of 770 participants were included. The prevalence of depression was 43.1% (95%CI: 39.6%-46.6%). Binary logistic regression analysis found that having a family member infected with COVID-19 (OR=1.51, P = 0.01), suffering from severe COVID-19 infection (OR=1.67, P = 0.03), male gender (OR=0.53, P<0.01), and frequent social media use to obtain COVID-19 related information (OR=0.65, P<0.01) were independently associated with depression. Patients with depression had lower QOL than those without., Conclusion: Depression is highly prevalent in clinically stable patients with COVID-19. Regular screening and appropriate treatment of depression are urgently warranted for this population., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.

(Aim) COVID-19 pandemic causes numerous death tolls till now. Chest CT is an effective imaging sensor system to make accurate diagnosis. (Method) This article proposed a novel seven layer convolutional neural network based smart diagnosis model for COVID-19 diagnosis (7L-CNN-CD). We proposed a 14-way data augmentation to enhance the training set, and introduced stochastic pooling to replace traditional pooling methods. (Results) The 10 runs of 10-fold cross validation experiment show that our 7L-CNN-CD approach achieves a sensitivity of 94.44±0.73, a specificity of 93.63±1.60, and an accuracy of 94.03±0.80. (Conclusion) Our proposed 7L-CNN-CD is effective in diagnosing COVID-19 in chest CT images. It gives better performance than several state-of-the-art algorithms. The data augmentation and stochastic pooling methods are proven to be effective.

Objective: To explore the correlation between prostate imaging report and data system (PI-RADS) score and international society of uological pathology (ISUP) grade of prostate cancer (PCa) and the role of PI-RADS score in predicting the pathological features of clinically significant PCa (csPCa), positive surgical margin and pathological upgrade. Methods: The pathologically positive patients with multi-parameter magnetic resonance image (mpMRI) were included in this study. The patients with prostate specific antigen (PSA)<100 μg/L were divided into two groups: biopsy group ( n= 523) and RP group ( n= 215). The correlation between PI-RADS score and ISUP grade and the accuracy of predicting csPCa in the two groups were evaluated. In the RP group, the correlation between PI-RADS score and postoperative pathological grade or degradation and positive incisal margin was further discussed. The patients with PSA≥100 μg/L (171cases in biopsy group and 6 cases in RP group) were not included in the statistical analysis, and the results were simply described. Results: The age, prostate volume, and PSA level of biopsy group and RP group was (72±8) years vs (68±7) years, 48.3 (32-57) cm(3) vs 47.2 (32-54) cm(3), and 26.3(10.2-34.2)μg/L vs 21.7 (9.24-23.95)μg/L, respectively. The PI-RADS scores ≤ 3,4, and 5 in the biopsy group were 109,97, and 317 respectively, and those in the RP group were 61,55, and 99 respectively. There were significant differences in the composition of ISUP grades of different PI-RADS scores between the two groups ( P< 0.001), and there was a positive correlation between the two groups ( r= 0.493 in the biopsy group, r= 0.671 in the RP group, both P< 0.001). Using PI-RADS score to predict csPCa, biopsy group (AUC=0.764, P< 0.001, 95 %CI :0.710-0.819) and RP group (AUC=0.807, P< 0.001, 95 %CI :0.735-0.879) had certain accuracy. The PI-RADS score combined with PSA could improve the accuracy of csPCa prediction in the biopsy group (AUC=0.795, P< 0.001, 95 % CI: 0.746-0.843) and the RP group (AUC=0.852, P< 0.001, 95 %CI :0.789-0.915). Compared with the pathological results of biopsy in the RP group, 52.6% of the patients showed upgrade and degrade of ISUP, and there was insignificant difference in the composition of PI-RADS scores between upgraded and degraded patients ( P> 0.05). However, 41.7%(27/65) of the patients with ISUP grade 1 biopsies had pathological upgrades that the patients with PI-RADS ≤ 3 accounted for 33.3%, while the patients with PI-RADS>3 accounted for 66.7%, and there was significant difference between the two groups ( P< 0.05). After RP, 43.3% of the patients had positive surgical margins, and the patients with PI-RADS score ≤ 3, 4 and 5 were 13 (14%), 24 (25.8%) and 56 (60.2%), respectively, while the PI-RADS scores of patients with negative surgical margin were 48 (39.3%), 31(25.4%) and 43(35.2%), respectively. There was significant difference between the two groups ( P< 0.001). The higher the PI-RADS score, the greater the possibility of the positive surgical margin. For the patients with PSA ≥ 100 μg/L, 98.8% (169/171) patients in the biopsy group had a PI-RADS score 5. The pathological results of all patients were csPCa, of which 85.4% (146/171) had ISUP grade ≥ 4. Among them, 6 cases underwent RP, 5 cases had ISUP grade ≥ 4, all surgical margin were positive, 5 cases had seminal vesicle invasion, 3 cases had capsule invasion and 3 cases had positive pelvic lymph nodes. Conclusion: ThePI-RADS score is correlated with the ISUP grade of PCa. Combined with PSA can accurately predict csPCa. At the same time, the higher PI-RADS score, the more likely the patients with positive incisal margin after RP and Gleason score of 3+3=6 at the time of puncture will be upgraded pathologically.

Several brain tumors is closely related to the disorder of chromatin histone modification, whereas the epigenetic mechanisms of the incidence of highly malignant adult glioma is not yet deeply studied. Deletion or mutation of the MEN1 gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance of MEN1 in the nervous system remains poorly understood. Menin expression was robustly activated in 44.4% of adult gliomas. Abnormally high expression of menin was closely related to a shorter median survival time of 20 months, a larger tumor volume and a higher percentage of Ki67 staining. Interestingly, menin expression was also activated in the cytoplasm of tumor cells (38.8%) and was also closely related to the poor prognosis of patients with glioma. Importantly, in a screening of 96 types of small-molecule targeted histone modification regulators, menin inhibitors were found to significantly block the proliferation of adult glioma cells. Our findings confirm that menin is a potential biomarker of poor prognosis in adult gliomas, independent of the WHO grade. Targeting menin may effectively inhibit certain gliomas, and this information provides novel insight into therapeutic strategies for glioma.

Objective: To compare the postoperative functional prognosis of transanal mesorectal excision (taTME) and conventional total mesorectal excision (TME) in rectal cancer. Methods: Totally 49 patients underwent taTME and 478 patients underwent conventional TME at Department of Gastroenterological Surgery, Peking University People's Hospital from January 2015 to December 2019 were retrospectively collected. Propensity score matching method was used to perform 1 versus 1 matching between the taTME and conventional TME groups, and 36 pairs of patients were successfully matched. After matching, the median age of patients in taTME group and conventional TME group was 60.5 (16.0) years and 60.5 (13.0) years ( M ( Q(R) )), respectively, and the proportion of male patients was 66.7% (24/36) and 55.6% (20/36) , respectively. EORTC QLQ-C30 scale was used to assess quality of life, low anterior resection syndrome (LARS) scale and Wexner constipation score were used to evaluate anal function, international prostate symptom score (IPSS) was used to evaluate urinary function,international index of erectile function (IIEF) -5 and female sexual function index (FSFI) score were used to evaluate male and female sexual function, respectively, and generalized anxiety disorder (GAD-7) and patient health questionnaire (PHQ-9) scale were used to evaluate psych function. The t test, Mann-Whitney U test, χ(2) test, and Fisher exact test were used for comparison between groups, and Wilcoxon rank sum test or McNemar test was used for comparison between paired data. Results: There were no significant differences in surgery time, postoperative hospital stays, conversion rate, morbidity rate, surgery cost, and numbers of lymph node yield between the two groups (all P> 0.05). Compared with the conventional TME group, the intraoperative blood loss in the taTME group was significantly higher (100 (100) ml vs . 80 (50) ml, U =424.5, P= 0.010), the prophylactic stoma rate was significantly higher (96.9%(31/36) vs . 63.6%(21/36), χ(2)=11.218, P< 0.01), the total hospitalization cost was significantly lower (74 297.7 (16 746.4) CNY vs . 91 781.3 (26 228.4) CNY, U =413.0, P= 0.008). There were no significant differences in anal and urinary function between the two groups (LARS scalescore: Z= -0.513, P= 0.608, Wexner constipation score: Z= -0.992, P= 0.321, IPSS: Z= -1.807, P= 0.071). In terms of psych function, significant difference in GAD-7 scale was seen between the two groups ( Z= -2.311, P= 0.021), patients with generalized anxiety disorder accounting for 26.7% (8/30) and 46.9% (15/32), respectively. Conclusions: Compared with conventional TME surgery, taTME has a significantly increased blood loss and prophylactic stoma rate. There are no significant difference in the incidence of postoperative anal, urinary, and sexual dysfunction between taTME and conventinal TME. taTME can alleviate the financial burden and general anxiety disorder to a certain extent.

Purpose: To investigate the biological characteristics of human periodontal stem cells (hPDLSCs) modified with platelet derived growth factor BB(PDGFBB) gene, and to explore its influence on proliferation, migration and osteogenic induction of hPDLSCs., Methods: hPDLSCs were isolated and amplified, and immunofluorescence staining was performed to identify cell surface markers and osteogenic differentiation ability. hPDLSCs were transfected with PDGFBB gene by lentivirus vector, and the effects on cell proliferation and migration were detected by CCK-8 and scratch test after transfection. Real-time PCR was performed to analyze the mRNA expression levels of osteogenic and angiogenic genes in hPDLSCs cells transfected with PDGFBB gene. Statistical analysis was performed using SPSS 22.0 software package., Results: hPDLSCs were successfully obtained by tissue mass culture and finite dilution method. Compared with the blank virus group and non-transfected group, the proliferation and migration ability of the cells in the transfection group were significantly increased, and the mRNA expression levels of OPN, COL-1 and VEGF were significantly up-regulated(P<0.05)., Conclusions: Lentiviral vector can transfer PDGFBB gene into hPDLSCs in vitro and obtain continuous and stable expression. PDGFBB can promote proliferation and migration of hPDLSCs cells and up-regulate expression of osteogenic and angiogenic genes.

Background: In recent years, health monitoring systems (HMS) have aroused great interest due to their broad prospects in preventive medicine. As an important component of HMS, flexible force sensors (FFS) with high flexibility and stretch-ability can monitor vital health parameters and detect physical movements., Aim of Review: In this review, the novel materials, the advanced additive manufacturing technologies, the selective sensing mechanisms and typical applications in both wearable and implantable HMS are discussed., Key Scientific Concepts and Important Findings of Review: We recognized that the next generation of the FFS will have higher sensitivity, wider linear range as well as better durability, self-power supplied and multifunctional integrated. In conclusion, the FFS will provide powerful socioeconomic benefits and improve people's quality of life in the future., Competing Interests: 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., (© 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Medulloblastomas (MBs) are currently divided into 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Among them, Group 3 MB has the worst prognosis, and 40%-50% of Group 3 cases are already metastatic at the time of diagnosis. Emerging evidence indicates that exosomes drive tumor invasion, but very little is known about exosomes in MBs. In this study, we initially discovered that exosomes isolated from Group 3 MB cell lines altered in vitro behaviors of a less invasive SHH MB cell line and yielded a much more aggressive phenotype. RNA-sequencing analysis revealed 7 exosomal miRNAs with markedly different expression levels between the SHH and Group 3 MB cell lines. They were all predicted to be related to the Ras/MAPK pathway according to the Kyoto Encyclopedia of Genes and Genomes data analysis. Increased expression of miR-181a-5p, miR-125b-5p, and let-7b-5p was further confirmed in Group 3 MB cells with real-time PCR and was shown to increase in vitro invasion and migratory abilities of tumor cells through the activation of ERK in Ras/MAPK pathway. Collectively, our findings suggest that exosomal miRNAs have a critical role in MB progression in vitro and might serve as diagnostic biomarkers and therapeutic targets., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

Beyond their widespread application as genome-editing and regulatory tools, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems also play a critical role in nucleic acid detection due to their high sensitivity and specificity. Recently developed Cas family effectors have opened the door to the development of new strategies for detecting different types of nucleic acids for a variety of purposes. Precise and efficient nucleic acid detection using CRISPR-Cas systems has the potential to advance both basic and applied biological research. In this review, we summarize the CRISPR-Cas systems used for the recognition and detection of specific nucleic acids for different purposes, including the detection of genomic DNA, nongenomic DNA, RNA, and pathogenic microbe genomes. Current challenges and further applications of CRISPR-based detection methods will be discussed according to the most recent developments., (© 2020 Wiley Periodicals, Inc.)

Background: No FDA-approved medications are available for the treatment of nonalcoholic steatohepatitis (NASH). The present study aimed to assess the effects of Hepalatide, a sodium taurocholate cotransporting polypeptide (NTCP) receptor-binding agent, on metabolic and histopathologic changes of a mouse model of NASH caused by high fat/calorie diet plus high fructose/glucose in drinking water (HFCD-HF/G) for 16 weeks., Methods: Male mice were randomly divided into 4 groups: controls (normal diet), HFCD-HF/G group, HFCD-HF/G plus low or high dose of Hepalatide (20 or 60 mg/kg, LH or HH, s.c. from 9 to 16 weeks)., Results: Compared to HFCD-HF/G-fed mice, serum triglyceride and cholesterol levels in mice fed HFCD-HF/G plus LH or HH were decreased. The treatment with Hepalatide decreased serum alanine aminotransferase levels significantly. Liver histology and TUNEL staining showed that Hepalatide remarkably attenuated inflammation, hepatocellular steatosis and apoptosis. Hepalatide treatment decreased fasting blood glucose, serum insulin and HOMA insulin resistance index in the HH group. Moreover, Masson's staining, semi-quantitative score of fibrosis, and hydroxyproline content demonstrated that Hepalatide mitigated fibrotic progression in this murine NASH model. Additionally, most components of liver and few serum bile acids were increased in mice treated with HH., Conclusion: Hepalatide effectively alleviated the pathological process, metabolic profile, hepatocellular steatosis and injury, insulin resistance, halted hepatic fibrotic progression in a mouse model of NASH, most likely through the increase of serum bile acids., Competing Interests: Declaration of Competing Interest The current study is supported by a service contract between Fudan University and Shanghai Hep Pharmaceutical Co., Ltd, Shanghai 201203, China., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

We had previously demonstrated that the calcitonin gene-related peptide (CGRP) suppresses the oxidative stress and vascular smooth muscle cell (VSMC) proliferation induced by vascular injury. A recent study also indicated that CGRP protects against the onset and development of angiotensin II (Ang II)-induced hypertension, vascular hypertrophy and oxidative stress. However, the mechanism behind the effects of CGRP on Ang II-induced oxidative stress is unclear. CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II-induced VSMCs. The Ang II-stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre-treatment with H-89 or CGRP 8-37 also blocked the CGRP inhibitory effects against Ang II-induced oxidative stress. Additionally, both in vitro and in vivo analyses show that CGRP treatment inhibited Ang II-induced VSMC proliferation and hypertrophy, accompanied by a reduction in ROS generation. Collectively, these results demonstrate that CGRP exhibits its antioxidative effect by blocking the Src/STAT3 signalling pathway that is associated with Ang II-induced VSMC hypertrophy and hyperplasia., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The magnetic vortex, as one of the most interesting magnetic solitons, has attracted great interest over the past two decades. A fast and reliable method to switch vortex polarity and chirality is one of the key issues for various applications. Based on micromagnetic simulation, here we report a fast, low energy cost and deterministic switching of a vortex core, by the designing of a notch structure in disks and the use of out-of-plane current geometry. We demonstrate that with such a design, the multiple switching problems found in notch disk systems can be avoided. Furthermore, the switching time can be reduced by more than 50% compared with disks without notches.

Development of high-performance ammonia (NH 3 ) sensor is imperative for monitoring NH 3 in the living environment. In this work, to obtain a high performance NH 3 gas sensor, structurally well-defined WO 3 @SnO 2 core shell nanosheets with a controllable thickness of SnO 2 shell layer have been employed as sensing materials. The prepared core shell nanosheets were used to obtain a miniaturized gas sensor based on micro-electro-mechanical system (MEMS). By tuning the thickness of SnO 2 layer via atomic layer deposition, a series of WO 3 @SnO 2 core-shell nanosheets with tunable sensing properties were realized. Particularly, the sensor base on the fabricated WO 3 @SnO 2 nanosheets with 20-nm SnO 2 shell layer demonstrated superior gas sensing performance with the highest response (1.55) and selectivity toward 15 ppm NH 3 at 200 °C. This remarkable enhancement of NH 3 sensing ability could be ascribed to the formation of unique WO 3 -SnO 2 core-shell heterojunction structure. The detailed mechanism was elucidated by the heterojunction-depletion model with the help of specific band alignment., 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 © 2020 Elsevier Inc. All rights reserved.)