Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

Long noncoding RNA Pvt1 promotes the proliferation and migration of Schwann cells by sponging microRNA-214 and targeting c-Jun following peripheral nerve injury

Research has shown that long-chain noncoding RNAs(lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.

NEDD4L和ULK1在非小细胞肺癌中的表达及预后价值

目的研究非小细胞肺癌(NSCLC)组织中NEDD4样E3泛素蛋白连接酶(NEDD4L)、UNC-51样激酶1(ULK1)的表达及临床意义。方法选取2017年1月—2018年1月三二〇一医院收治的88例NSCLC患者作为研究对象。应用R语言分析癌症基因组图谱(TCGA)数据库中NSCLC及癌旁组织中NEDD4L和ULK1 mRNA的表达差异,免疫组织化学法分析癌组织和癌旁组织中NEDD4L和ULK1蛋白的表达,Kaplan-Meier法分析NEDD4L、ULK1表达与患者生存预后的关系,单因素及多因素Cox回归分析影响NSCLC患者生存预后的危险因素。结果癌组织NEDD4L mRNA相对表达量低于癌旁组织(P<0.05),ULK1 mRNA相对表达量高于癌旁组织(P<0.05)。癌组织NEDD4L的阳性表达率低于癌旁组织(P<0.05),ULK1的阳性表达率高于癌旁组织(P<0.05)。有无淋巴结转移、不同TNM分期患者的癌组织NEDD4L、ULK1阳性表达率比较,差异有统计学意义(P<0.05)。Spearman相关性分析结果显示,NSCLC患者癌组织中NEDD4L与ULK1的表达呈负相关(r_(s)=-0.587,P<0.05)。NEDD4L阴性表达患者3年总体生存率较阳性表达患者低(P<0.05),NEDD4L阳性表达患者平均生存时间较阴性表达患者长(P<0.05)。ULK1阳性表达患者3年总体生存率较阴性表达患者低(P<0.05),LK1阳性表达患者平均生存时间较阴性表达患者长(P<0.05)。单因素Cox回归分析结果显示,肿瘤TNM分期Ⅲ期[HR^(^)=1.898(95%CI:1.320,2.729)]、NEDD4L阴性表达[HR^(^)=1.654(95%CI:0.921,2.588)]和ULK1阳性表达[HR^(^)=1.692(95%CI:0.860,2.650)]是NSCLC患者预后的影响因素(P<0.05)。多因素Cox回归分析结果显示,NEDD4L阴性表达[HR^(^)=1.878(95%CI:0.961,2.995)]、ULK1阳性表达[HR^(^)=1.679(95%CI:0.785,2.884)]及肿瘤TNM分期Ⅲ期[HR^(^)=1.937(95%CI:1.131,3.317)]是NSCLC患者不良预后的独立危险因素(P<0.05)。结论NSCLC中NEDD4L表达降低,ULK1表达升高,NEDD4L、ULK1的表达与肿瘤TNM分期、淋巴结转移有关,NEDD4L阴性表达、ULK1阳性表达是NSCLC患者不良预后的独立危险因素。

Impact of Tobacco Smoking on Health Care Utilization and Medical Costs in Chronic Obstructive Pulmonary Disease,Coronary Heart Disease and Diabetes

Objective To determine the impact of smoking on disease-specific health care utilization and medical costs in patients with chronic non-communicable diseases(NCDs).Methods Participants were middle-aged and elderly adults with chronic NCDs from a prospective cohort in China.Logistic regressions and linear models were used to assess the relationship between tobacco smoking,health care utilization and medical costs.Results Totally,1020 patients with chronic obstructive pulmonary disease(COPD),3144 patients with coronary heart disease(CHD),and 1405 patients with diabetes were included in the analysis.Among patients with COPD,current smokers(β:0.030,95%CI:−0.032-0.092)and former smokers(β:0.072,95%CI:0.014-0.131)had 3.0%and 7.2%higher total medical costs than never smokers.Medical costs of patients who had smoked for 21-40 years(β:0.028,95%CI:−0.038-0.094)and≥41 years(β:0.053,95%CI:−0.004β0.110)were higher than those of never smokers.Patients who smoked≥21 cigarettes(β:0.145,95%CI:0.051-0.239)per day had more inpatient visits than never smokers.The association between smoking and health care utilization and medical costs in people with CHD group was similar to that in people with COPD;however,there were no significant associations in people with diabetes.Conclusion This study reveals that the impact of smoking on health care utilization and medical costs varies among patients with COPD,CHD,and diabetes.Tobacco control might be more effective at reducing the burden of disease for patients with COPD and CHD than for patients with diabetes.

植物生物质构建钠离子电池负极材料研究进展

以废弃植物生物质为基材制备的高值化钠离子电池负极纳米复合碳材料,工艺简单、成本低廉,有望成为传统石墨负极材料的替代品。本文系统梳理了废弃植物生物质应用于钠离子电池负极材料的最新研究现状,具体归纳了木质纤维素类废弃植物生物质(乔木类、秸秆类、干质果壳类)和多糖淀粉类废弃植物生物质(种子类)的生物模板法制备过程,深入阐释了其诸多电化学性能和独特形态结构形成的钠离子存储机理及构效关系,客观探讨了植物生物质基钠离子电池负极材料目前存在的一些问题,简要分析与非植物基钠离子电池负极材料的性能对比优势及未来发展方向,为植物生物质固废物这一大自然中储量巨大的可再生能源的高值化利用提供了新思路和新方法。

Functional monodisperse microspheres fabricated by solvothermal precipitation co-polymerization

Simultaneous achievement in high solid content and high microsphere yield is deemed a challenge in the fabrication of monodisperse microspheres by precipitation polymerization.We herein demonstrate that micro-sized monodisperse poly(methacrylic monomer-divinylbenzene)microspheres containing epoxy,lauyl,carboxyl and hydroxyl functions can be fabricated by solvothermal precipitation copolymerization at 20%(mass)monomer loading with over 94%microsphere yield.The morphology and porosity of the obtained particles can be readily tuned by cosolvent-acetonitrile binary solvents.Addition of a small amount of cosolvent that has similar solubility parameter to that of the functional monomer can significantly improve the monodispersity of the obtained microspheres.When tetrahydrofuran was used as the co-solvent,the surface area of the highly porous microspheres achieved higher than 400 m^(2)·g^(-1).Solvothermal precipitation co-polymerization can be expected in scale-up fabrication of various monodisperse functional microspheres free of any surfactant and additive.

Bibliometric analysis about compassion fatigue based on Web of Science database

Objective: To analyze the related foreign literature about compassion fatigue (CF) and to provide the basis for further improving the level of research in this field. Methods: Based on the Web of Science core database and its own analysis function, HistCite analysis software was used to study the diploma research about CF. Results: A total of 652 paper were retrieved, the output of literature showed an increasing trend year by year. The United States ranked first, and China ranked eleventh. The “Oncology Nursing Forum” had the largest number of articles (4.0%). The main research direction was in nursing (29.6%), and the main research output was from articles (73.2%). The key words highly cited were “compassion” and “fatigue”. Figley was the author of the high-yield field, and mainly research institutions were universities. The highly cited article was entitled “Compassion fatigue: Psychotherapists’ chronic lack of self-care”. Conclusions: In recent years, the related heat of CF has been high fever. Our research in this field is still in the primary stage, and it needs to be further excavated and promoted.

基于ROBOGUIDE软件的机器人离线编程研究

机器人离线编程方法已得到较为广泛的应用,但由于工件几何外形的多样性,坐标系标定操作非常不便。基于ROBOGUIDE软件对机器人离线编程进行了研究。在研究中,以轮毂法兰盘打磨为例,推导了利用外轮廓多点进行机器人用户坐标系标定的算法。运用这一算法,可以解决由于轮毂装夹偏差造成的离线程序无法复用的问题。通过仿真试验,验证了基于ROBOGUIDE软件的机器人离线编程的有效性。

钣金零件全自动连续折弯工艺的研究

将智能制造应用于传统钣金零件折弯行业,对钣金零件全自动连续折弯工艺进行研究。在研究中,编排了工艺路线,确认了靠边距离,并通过三维仿真、尺寸设定、现场修正对折弯进行过程控制,同时给出了现场应用情况。采用钣金零件全自动连续折弯工艺,可以实现自动化、数字化、精细化生产和管理。

Reference satellite selection method for GNSS high-precision relative positioning

Selecting the optimal reference satellite is an important component of high-precision relat/ve positioning because the reference satellite directly influences the strength of the normal equation. The reference satellite selection methods based on elevation and positional dilution of precision （PDOP） value were compared. Results show that all the above methods cannot select the optimal reference satellite. We introduce condition number of the design matrix in the reference satellite selection method to improve structure of the normal equation, because condition number can indicate the ill condition of the normal equation. The experimental results show that the new method can improve positioning accuracy and reliability in precise relative positioning.

儿童慢食行为与身体质量指数的神经影像学关联:基于中国儿童大脑结构常模的研究

中国儿童超重肥胖比率不断增长,危害儿童身心健康.因此,有必要关注儿童肥胖问题,探究儿童饮食行为与肥胖的脑结构关联.慢食行为是儿童饮食行为中潜在的重要关键因素,在增强饱腹感的同时减少能量摄入,能够有效预防和改善肥胖问题,但已有研究未深入探讨其脑结构基础.本研究选取99名儿童,年龄范围为9~12岁,平均年龄为10.476±0.855岁,通过儿童饮食行为量表的慢食维度测量儿童的慢食行为,使用磁共振成像仪采集脑影像数据,获取脑区皮层体积并映射到中国儿童脑体积常模上,进一步得到儿童脑区皮层体积在常模上的相对位置参数.相关分析结果表明,身体质量指数(body mass index,BMI)与慢食行为(r=-0.383,P<0.001)呈负相关,与舌回皮层体积(r=0.304,P=0.002)和后扣带回皮层体积呈正相关(r=0.392,P<0.001),慢食行为与后扣带回皮层体积呈负相关(r=‒0.221,P=0.028).中介模型表明后扣带回皮层体积在儿童慢食行为与身体质量指数之间存在中介作用,中介效应值为‒0.088.后扣带回具有重要的奖赏和执行控制功能,引导注意力焦点(进食体验、进食过程)和支持内部导向认知(奖赏状态、饱腹状态).慢食行为的儿童感知进食过程并识别饱腹信号,适时停止进食行为,而快速进食的儿童在进食体验带来的奖赏中忽视了饱腹状态,往往与过度进食产生肥胖有关.本研究提供了儿童慢食行为和身体质量指数稳健的脑结构基础证据,并且为从减缓餐内饮食速度入手改善儿童肥胖问题提供理论参考.

Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive chemotherapy.To explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days.The complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),respectively.With a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),respectively.The most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of treatment.Tumor proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment.In conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage NKTCL.Dysregulated lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

Core shift limitation in investment casting process of hollow turbine blade

The deviation in wall thickness caused by core shift during the investment casting process significantly impacts the strength and service life of hollow turbine blades.To address this issue,a core shift limitation method is developed in this study.Firstly,a shift model is established based on computational fluid dynamics and motion simulation to predict the movement of the ceramic core in investment casting process.Subsequently,utilizing this model,an optimization method for fixturing layout inside the refractory ceramic shell is devised for the ceramic core.The casting experiment demonstrates that by utilizing the optimized fixture layout,not only can core shift during the investment casting pouring process be effectively controlled,but also the maximum wall thickness error of the blade can be reduced by 42.02%.In addition,the core shift prediction is also validated,with a prediction error of less than 26.9%.

RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway

Gliomas are the most common central nervous system tumours;they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.

煤基活性炭表面改性对稀土负载型CeO_2/AC低温脱硝性能的影响

以煤基活性炭(AC)为载体,在不同温度下分别采用空气热氧化和硝酸浸渍对其进行预氧化表面改性处理,然后将稀土金属Ce3+负载在预氧化改性后的活性炭载体上,经煅烧而制得改性Ce O2/AC低温SCR脱硝剂。并采用N2等温吸附脱附测试、X射线光电子能谱等表征手段考察了2种不同预氧化改性方式对基炭孔结构和表面物化性质的影响。同时研究了不同预氧化方式、稀土负载量、煅烧温度对脱硝剂的低温脱硝性能的影响。结果表明:空气热氧化预处理的AC相对于原炭而言,比表面积没有明显损失,且基炭表面官能团得到了明显丰富;而经硝酸氧化的活性炭,比表面积有明显下降。制备Ce O2/AC低温脱硝剂的最佳工艺为:在350?C下,采用空气热氧化预处理,稀土负载量为5%(质量分数),500?C N2保护煅烧温度下,所得到的Ce O2/AC脱硝剂具有最佳低温脱硝活性。该脱硝剂在脱硝温度为150?C即可达到100%的脱硝率。

Natural Polyphenol Inspired Polycatechols for Efficient siRNA Delivery

There is a continuing quest to rationally fabricate polymeric biomaterials with both high transfection efficiency and minimal toxicity for the emerging opportunities in small interfering RNA(siRNA)delivery.Recently,this goal was promoted highly by developing a robust and efficient strategy to facilitate polymer-mediated RNAi using natural polyphenols with multiple phenol groups that could condense siRNA effectively into negatively charged nanoparticles(NPs).Further coating of these NPs with cationic polymers of low molecular weight enabled their intracellular siRNA delivery.Inspired by the structural and functional features of natural polyphenols,we aimed to further the development of low molecular weight polycatechols as a new class of efficient and biocompatible polymers for siRNA delivery in our current study.The fabricated polycatechols have benefits of requiring only one-step fabrication toward efficient siRNA nanoformulations.Moreover,they could deliver siRNA into cells and silence target genes both in vitro and in vivo.The resulting polycatechol/siRNA formulations were also functionally competent,demonstrating a successful,profound downregulation of a proinflammatory enzyme to attenuate chronic intestinal inflammation in an intestinal injury model.This study provides a new approach in chemistry for the development of efficient synthetic polymers for therapeutic siRNA delivery.

Effects of scalp cluster needling on cognition and oxidative stress in a rat model of schizophrenia

Objective:To analyze the effects of cluster needling at scalp acupoints(CNSA)on behavioral performance and expression of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)in the hippocampus of rats with schizophrenia,and therefore,to shed light on the mechanism of action of CNSA in attenuating schizophrenia.Methods:Thirty-six Wistar rats were randomly divided into the control,model,risperidone,and CNSA groups(9 rats per group).The schizophrenia model was prepared by injecting 0.1 mg/mL dizocilpine maleate(MK-801)for 14 consecutive days.Subsequently,rats in the risperidone and CNSA groups were subjected to the following therapy for 14 consecutive days:(1)Risperidone group:intragastric administration of risperidone suspension(0.4 mg/kg);(2)CNSA group:the"Bǎihuì(百会GV 20)""Qiándǐng(前顶GV21)""Shéntíng(神庭GV24)"Xìnhuì(囟会GV 22)""Tōngtiā(通天BL7)""Luòquè(络却BL8)""Qūchā(曲差BL4)"and"Wǔchù(五处BL 5)"acupoints were selected for needle positioning.Following14-day intervention period,the Morris water maze experiment and open field experiment were performed.Finally,hippocampal tissue specimens were collected and SOD,CAT,and GSH-Px expression levels were measured by ELISA.Results:(1)Morris water maze experiment:Following the 14-day model construction period,the model,risperidone,and CNSA groups showed a significant increase in escape latency(all P<0.05)and a significant decrease in the number of platform crossings(all P<0.05)compared with the control group,indicating successful induction of schizophrenia in the rat model.At the end of the intervention period(28 d),the risperidone and CNSA groups showed a significant decrease in escape latency(both P<0.05),and the CNSA group showed a significant increase in the number of platform crossings(P<0.05)compared with the model group.(2)Open field experiment:At 14 d,the model,risperidone and CNSA groups exhibited a significant decrease in the travelled distance and amount of time spent in the central zone(all P<0.05)compared with the control group(all P<0.05).At 28 d,the risperidone and CNSA groups showed a significant increase in the travelled distance and percentage of time spent in the central zone(P<0.05 or P<0.01).(3)Antioxidant enzyme expression:At 28 d,the model group exhibited significant decreases in the hippocampal SOD,CAT,and GSH-Px levels,compared with the control group(P<0.01 or P<0.001).Conclusion:CNSA enabled the attenuation of cognitive impairment and enhancement of memory and learning abilities in the rat model of schizophrenia,plausibly through inhibition of the expression of oxidative stress factors in the hippocampus.

Ca_(2)Nb_(2)O_(7)as a Novel Open-framework Anode Material for Potassium-ion Batteries

Potassium-ion batteries(KIBs)are a promising alternative to Lithium-based energy storage systems owning to the low cost and rich abundance of potassium resources,but are facing challenges in designing low-cost hosts that can reversibly accommodate large-size K^(+)with fast diffusion kinetics.Herein,we report a novel 3D inorganic open framework of Ca_(2)Nb_(2)O_(7)(CNO)as an anode for KIBs.The open framework structure affords interstitial vacancies available for storing K^(+)and allows a facile diffusion of K^(+),thus resulting in excellent structural stability and fast reaction kinetics.The CNO electrode delivers a reversible specific capacity of 65.3 and 52.2 mAh/g at 5 and 10 mA/g,respectively.Moreover,CNO exhibits excellent long-term cyclability with 92.53%capacity retention over 700 cycles at 10 mA/g.This will trigger more investigations into open-framework-based materials for stable and fast KIBs.

The 2009 pandemic A/Wenshan/01/2009 H1N1 induces apoptotic cell death in human airway epithelial cells

In 2009,a novel swine-origin H1N1 influenza virus emerged in Mexico and quickly spread to other countries,including China.This 2009 pandemic H1N1 can cause human respiratory disease,but its pathogenesis remains poorly understood.Here,we studied the infection and pathogenesis of a new 2009 pandemic strain,A/Wenshan/01/2009 H1N1,in China in human airway epithelial cell lines compared with contemporary seasonal H1N1 influenza virus.Our results showed that viral infection by the A/Wenshan H1N1 induced significant apoptotic cell death in both the human nasopharyngeal carcinoma cell line CNE-2Z and the human lung adenocarcinoma cell line A549.The A/Wenshan H1N1 virus enters both of these cell types more efficiently than the seasonal influenza virus.Viral entry in both cell lines was shown to be mediated by clathrin-and dynamin-dependent endocytosis.Therefore,we discovered that the 2009 pandemic H1N1 strain,A/Wenshan/01/2009,can induce apoptotic cell death in epithelial cells of the human respiratory tract,suggesting a molecular pathogenesis for the 2009 pandemic H1N1.