Research on the Encapsulation Device for Lunar Samples

The encapsulation of lunar samples is a core research area in the third phase of the Chinese Lunar Exploration Program.The seal assembly,opening and closing mechanism(OCM),and locking mechanism are the core components of the encapsulation device of the lunar samples,and the requirements of a tight seal,lightweight,and low power make the design of these core components difficult.In this study,a combined sealing assembly,OCM,and locking mechanism were investigated for the device.The sealing architecture consists of rubber and an Ag-In alloy,and a theory was built to analyze the seal.Experiments of the electroplate Au coating on the knife-edge revealed that the hermetic seal can be significantly improved.The driving principle for coaxial double-helical pairs was investigated and used to design the OCM.Moreover,a locking mechanism was created using an electric initiating explosive device with orifice damping.By optimizing the design,the output parameters were adjusted to meet the requirements of the lunar explorer.The experimental results showed that the helium leak rate of the test pieces were not more than 5×10^(-11) Pa·m^(3)·s^(-1),the minimum power of the OCM was 0.3 W,and the total weight of the principle prototype was 2.9 kg.The explosive driven locking mechanism has low impact.This investigation solved the difficulties in achieving tight seal,light weight,and low power for the lunar explorer,and the results can also be used to explore other extraterrestrial objects in the future.

基于数据挖掘的含荜拔藏药方剂用药规律及药性研究

目的:探讨含荜拔藏药方剂的用药规律及含该药材方剂的配伍规律,为藏医临床用药及潜在新处方的发现提供参考。方法:以《四部医典》和《藏药晶镜本草》为标准,利用Excel从《藏药方剂大全》中整理和搜集明确含有荜拔的藏药方剂,利用SPSS分析含荜拔方剂中各味药材的配伍规律和高频主治疾病用药规律。结果:共收集含冰片藏药方剂298首,涵盖主治疾病256种,其中出现频次≥10次的有23个,主要为培根病(45次)、痼有不消(30次)、痞硬症(29次)等;涉及药材226味,使用频次≥30次共30味,主要为白豆蔻(111次)、诃子(107次)、石榴(95次)等;共挖掘出常用核心药材组合30个,以荜拔-白豆蔻(123次)、荜拔-诃子-白豆蔻(122次)、荜拔-石榴(116次)、荜拔-干姜(97次)为主,体现了藏药方剂的“主辅配伍”规律。主治疾病的频次有治疗培根病(27次)、痼有不消(22次)、胃火(20次)的含荜拔藏药方剂六味都以辛、甘、苦为主,治疗培根病具有轻、糙、热、锐利效等药性,治疗痼有不消具有轻、锐、热、润效等药性,治疗胃火具有热、稀、锐、糙效等药性。结论:藏药荜拔常与白豆蔻、石榴等温性药材联用,符合藏医清寒性培根病、痼有不消、以及增胃火等标本兼治的治病原则,并与诃子、寒水石、沙棘等配伍是增效温凉平衡机理;同时也体现了藏药凉温兼用的用药规律。

计划生育工作人员咨询服务状况调查

目的:了解计划生育工作人员的咨询服务状况及可能的影响因素,为下一步在该人群中开展咨询培训提供依据。方法:通过结构式问卷,调查了来自于全国31个省、市、自治区和直辖市的271名计划生育工作人员,对他们的咨询服务状况及可能的影响因素进行分析。结果:271名调查对象中,255人曾为服务对象提供过咨询服务。咨询服务相关知识得分最高为100.0分,中位数为76.9分;咨询服务知识得分单因素分析显示,不同年龄组、不同文化程度对象之间的差别有统计学意义(P<0.05);多分类反应变量多元Logistic回归分析显示,文化程度越高,研究对象的咨询服务知识得分越高。结论:计划生育工作人员咨询服务的总体状况良好,但研究对象的年龄,文化程度等因素可能对他们的咨询服务产生影响。建议加强咨询培训的针对性,提高计划生育工作人员的整体素质。

上海市流动人口性病/艾滋病知识状况及影响因素分析

目的:了解上海市流动人口性病/艾滋病相关知识,探讨其影响因素,掌握人群对性病/艾滋病健康教育的需求,为流动人口艾滋病预防及健康教育工作提供科学依据。方法:按照拟定的筛选表,采用多级抽样的方法及知情同意的原则,选取上海市闵行区外来流动人口1000人,通过结构式问卷调查其性病/艾滋病相关知识并进行量化评分,采用方差分析和多元线性回归分析综合知识得分的可能影响因素。结果:流动人口性病/艾滋病综合知识得分仅为50.67±25.40分,在各项知识回答中,关于性病症状和艾滋病症状的得分最低。学历、婚姻状况及月收入是知识得分的主要影响因素。性病/艾滋病知识的主要来源为影视广播、书报杂志、宣传板报和网络。结论:流动人口性病/艾滋病知识水平有待提高,应针对流动人口相关知识的薄弱环节如性病/艾滋病症状等方面开展宣传,加强学历水平较低的未婚人群的健康教育工作。

流动人口宫内节育器使用情况及影响因素分析

目的:了解上海市闵行区流动人口宫内节育器(IUD)的使用情况及影响因素。方法:采用结构式问卷进行调查。结果:本次共调查2001名流动人口,其中采用避孕措施的1300人,使用最多的避孕方式是IUD,占51.08%(664人),但70.63%的调查对象不知道自己使用的IUD种类。以IUD作为避孕方式的主要是已婚的对象,使用的比例为59.57%;30～40岁对象使用比例略高于其他年龄组;初中学历使用比例最高(57.70%);到现居住地后,仅有50.09%的对象进行过IUD复查,大学以上文化程度复查比例最高。结论:计划生育部门应加强有关IUD的宣教和复查服务,特别是对已婚、文化程度较低的流动人口,从而使他们能选择适宜、有效的避孕措施,提高他们的生殖健康水平。

计划生育工作人员的避孕知识状况及影响因素分析

目的通过开展流行病学现况调查,了解计划生育工作人员的避孕节育知识状况及影响因素,为下一步在该人群中开展咨询培训提供依据。方法通过结构式问卷,调查了来自全国31个省/自治区和直辖市的271名计划生育工作者,对他们的避孕节育知识状况及可能的影响因素进行分析。结果271名调查对象的避孕知识平均得分为74.6分,得分>80分的对象占40.2%;单因素分析显示,不同年龄组、不同职业以及不同文化程度对象之间的差别有统计学显著性差异(P<0.05);多因素Logistic回归分析显示,计划生育工作人员的避孕知识得分比管理人员的知识得分高,OR值为2.70,95%CI为1.36～5.35;文化程度越高,研究对象的避孕节育知识得分越高。结论计划生育工作人员的避孕节育知识总体状况良好,但存在职业、文化程度间的差异。今后应加强宣教的针对性,以提高计划生育领域工作者的整体素质,更好地为群众服务。

吸烟对精液DNA指标影响的研究

目的探讨吸烟对精液DNA指标的影响,以促进男性生殖健康。方法选择322例合格的研究对象,其中195例为吸烟者,127例为不吸烟者,通过问卷调查方法收集对象的背景信息、吸烟暴露情况以及可能的混杂因素,同时收集所有研究对象的精液标本,分析吸烟对精液DNA指标的影响。结果吸烟使精液中单倍体精子的比例降低,同时使二倍体细胞以及多倍体细胞的比例升高。结论吸烟对精液质量可能有不良影响,且精液DNA指标可能对烟的作用更为敏感。对大量或长期吸烟者,其影响更为深远,应当广泛提倡戒烟。

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors

BACKGROUND Colorectal laterally spreading tumors(LSTs)with malignant potential require en bloc resection by endoscopic submucosal dissection(ESD),but lesions with deep submucosal invasion(SMI)are endoscopically unresectable.AIM To investigate the factors associated with high-grade dysplasia(HGD)/carcinoma and deep SMI in colorectal LSTs.METHODS The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed.The characteristics of LST subtypes were compared.Risk factors for HGD/carcinoma and deep SMI(invasion depth≥1000μm)were determined using multivariate logistic regression.RESULTS A total of 323 patients with 341 colorectal LSTs were enrolled.Among the four subtypes,non-granular pseudodepressed(NG-PD)LSTs(85.5%)had the highest rate of HGD/carcinoma,followed by the granular nodular mixed(G-NM)(77.0%),granular homogenous(29.5%),and non-granular flat elevated(24.2%)subtypes.Deep SMI occurred commonly in NG-PD LSTs(12.9%).In the adjusted multivariate analysis,NG-PD[odds ratio(OR=16.8,P<0.001)and G-NM(OR=7.8,P<0.001)subtypes],size≥2 cm(OR=2.2,P=0.005),and positive non-lifting sign(OR=3.3,P=0.024)were independently associated with HGD/carcinoma.The NG-PD subtype(OR=13.3,P<0.001)and rectosigmoid location(OR=8.7,P=0.007)were independent risk factors for deep SMI.CONCLUSION Because of their increased risk for malignancy,it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD.Given their substantial risk for deep SMI,surgery needs to be considered for NG-PD LSTs located in the rectosigmoid,especially those with positive nonlifting signs.

Game analysis on constructing the model of an international carbon emissions trading model

Constructing a model for international carbon emissions trading is an effective method to curb global warming through a market mechanism.Although the international carbon emissions market generates substantial profits,the relevant trading mechanism has been far from perfect.The perfect mechanism for international carbon emissions trading should be a revealing preference game.In other words,only if all players in this game truly show their information and preferences can the Nash outcome be Pareto efficient and fair.China should actively participate in the international carbon emissions trading game;promote efficiency,justice,rationality,and the quality of being manipulation-free in the carbon emissions market;and play a more important role in perfecting the international carbon emissions trading mechanism.

Stoichiometric flexibility regulates the co-metabolism effect during organic carbon mineralization in eutrophic lacustrine sediments

Several studies have suggested the pivotal roles of eutrophic lakes in carbon(C)cycling at regional and global scales.However,how the co-metabolism effect on lake sediment organic carbon(OC)mineralization changes in response to integrated inputs of labile OC and nutrients is poorly understood.This knowledge gap hinders our ability to predict the carbon sequestration potential in eutrophic lakes.Therefore,a 45-day microcosm experiment was conducted to examine the dominant mechanisms that underpin the co-metabolism response to the inputs of labile C and nutrients in lacustrine sediments.Results indicate that the labile C addition caused a rapid increase in the positive co-metabolism effect during the initial stage of incubation,and the co-metabolism effect was positively correlated with the C input level.The positive co-metabolism effect was consistently higher under high C input,which was 152%higher than that under low C input.The higherβ-glucosidase activity after nutrient addition,which,in turn,promoted the OC mineralization in sediments.In addition different impacts of nutrients on the co-metabolism effect under different C inputs were observed.Compared with the low nutrient treatments,the largest co-metabolism effect under high C with high nutrient treatment was observed by the end of the incubation.In the high C treatment,the intensity of the co-metabolism effect(CE)under high nitrogen treatment was 1.88 times higher than that under low nitrogen condition.However,in the low C treatment,the amount of nitrogen had limited impact on co-metabolism effect.Our study thus proved that the microorganisms obviously regulate sediment OC turnover via stoichiometric flexibility to maintain a balance between resources and microbial requirements,which is meaningful for evaluating the OC budget and lake eutrophication management in lacustrine sediments.

Quantum Anti-Zeno Effect in Nuclear Decay

The acceleration of decay induced by frequency measurements,namely the quantum anti-Zeno effect(AZE),was first predicted by Kofman and Kurizki [Nature 405(2000) 546].The effect of the frequency measurements on nuclear β decay rate is analyzed based on the time-dependent perturbation theory.We present a detailed calculation of the decay rates of ^(3)H,^(60)Co(β^(-)type),^(22)Na,^(106)Ag(β^(+) type) and ^(18)F,^(57)Co and ^(111)Sn(EC type)under frequency measurements.It is found that the effects of frequency measurements on the decay rates of β^(+)and β^(-)cases are different from the case of EC,and the smaller the β decay energy is,the more favorable it is to observe the AZE in experiment.Based on our analysis,it is suggested that possible experimental candidates should have a small decay energy and a reasonable half life(such as ^(3)H) for observing the AZE in β decay.

数字化转型背景下商业银行“科技-人员-组织”对经营绩效影响的组态研究

数字化转型是银行在数字经济、金融科技发展和商业竞争加剧背景下的重要战略选择,全国性商业银行是我国银行业的重要力量,这些银行的科技、人员、组织等数字化转型投入巨大。这些投入能否切实提升银行经营绩效、其中的具体作用机制是什么是有待研究的关键问题。本研究基于互补机制理论,构建了数字化银行“科技-人员-组织”对绩效影响的研究框架,采用必要条件分析(Necessary Condition Analysis, NCA)与模糊集定性比较分析(Fuzzy-set Qualitative Comparative Analysis, fsQCA)相结合的方法 ,以14家全国性商业银行为案例,探析科技投入、科技投入在营业收入中占比、科技人员数量、科技人员数量在全体员工中占比、金融科技相关机构数量5个前因条件变量与资产收益率(Return on Assets,ROA)代表的绩效结果变量之间的因果复杂关系。研究发现:(1)通过NCA方法分析,科技人员数量构成高ROA的必要条件,其他前因条件不构成高ROA的必要条件;(2)产生高ROA的2种组态均存在高科技人员数量与高金融科技相关机构数量2个核心条件;在此基础上,第一种组态还需与科技投入总量领先组合,而第二种组态还需与科技投入在营业收入中占比、科技人员在全体员工中占比领先组合。其中,第一种组态是产生高ROA的主要路径;(3)产生非高ROA的组态有2种, 2种组态与产生高ROA的2种组态总体上存在非对称关系。本研究为银行和其他相似企业组织合理配置数字化转型要素提供了理论参考和实践启示。

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.

ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells

Glioblastoma(GBM)is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment(TME).In this environment,myeloid cells,such as myeloid-derived suppressor cells(MDSCs),play a pivotal role in suppressing antitumor immunity.Lipometabolism is closely related to the function of myeloid cells.Here,our study reports that acetyl-CoA acetyltransferase 1(ACAT1),the key enzyme of fatty acid oxidation(FAO)and ketogenesis,is significantly downregulated in the MDSCs infiltrated in GBM patients.To investigate the effects of ACAT1 on myeloid cells,we generated mice with myeloid-specific(LyzM-cre)depletion of ACAT1.The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically.The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1(CXCLI)of macrophages(Mo).Overall,our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models

Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently.Here,we showed that IMMH002,a novel orally active S1 P1 modulator,desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus.Using different psoriasis animal models,we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PAS I score and pathological injure evaluation.Mechanistically,IMMH002 regulated CD3+T lymphocytes re-distribution by inducing lymphocytes’homing,thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus.Our results suggest that the novel SIP1 agonist,IMMH002,exert extraordinary capacity to rapidly modulate T lymphocytes distribution,representing a promising drug candidate for psoriasis treatment.

Targeted delivery of chlorogenic acid by mannosylated liposomes to effectively promote the polarization of TAMs for the treatment of glioblastoma

Tumor-associated macrophages(TAMs)generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis,suggesting their potential value as a target in cancer immunotherapy.Chlorogenic acid(CHA)has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype.However,rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials.In this study,mannosylated liposomes are developed for targeted delivery of CHA to TAMs.The immunoregulatory effects of CHA,along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes,are investigated through in vitro and in vivo experiments.The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size,favorable stability,and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects.Further,CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype.Overall,these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.

Iron Aggravates the Depressive Phenotype of Stressed Mice by Compromising the Glymphatic System

Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].

Analysis of risk factors associated with endoscopic retrograde cholangiopancreatography for patients with liver cirrhosis: a multicenter, retrospective, clinical study

Background:Endoscopic retrograde cholangiopancreatography(ERCP)is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases.However,patients with cirrhosis,particularly those with decompensated cirrhosis,are believed to be at increased risk for complications associated with ERCP.There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis.This study aimed to investigate the outcomes of ERCP for cirrhosis patients,especially adverse events,and evaluated its safety and efficacy.Methods:We performed a multicenter,retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University,Xijing Hospital affiliated to Air Force Military Medical University,Beijing Youan Hospital affiliated to Capital Medical University,and the Fifth Medical Center of the People’s Liberation Army General Hospital from June 2003 to August 2019.The adverse events of inpatient ERCP for patients with(n=182)and without liver cirrhosis(controls;n=385)were compared.Results:A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study.Compared to patients without cirrhosis,patients with cirrhosis were at higher risk for postoperative complications(odds ratio[OR],4.172;95%confidence interval[CI],1.232–7.031;P<0.001)such as postoperative pancreatitis(OR,2.026;95%CI,1.002–4.378;P=0.001)and cholangitis(OR,3.903;95%CI,1.001–10.038;P=0.036).The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis(101 cases;55.5%),benign bile duct strictures(46 cases;25.3%),and malignant bile duct strictures(28 cases;15.4%).Among them,23 patients(12.6%)underwent balloon dilation and 79 patients(43.4%)underwent sphincterotomy.Of the patients with cirrhosis,delayed bleeding occurred in ten patients(5.5%),postoperative pancreatitis occurred in 80 patients(44.0%),and postoperative cholangitis occurred in 25 patients(13.7%).An additional multivariate analysis showed that the total bilirubin(TBIL)level(OR,4.58;95%CI,2.37–6.70)and Child-Pugh score of C(OR,3.11;95%CI,1.04–5.37)were risk factors for postoperative complications in patients with cirrhosis.Conclusions:Compared with the general population of patients undergoing ERCP,patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis.TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.

YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients,and their indications are expanding incessantly.Currently,most PD-1/PD-L1 agents are administered intravenously,which may be uncomfortable for some cancer patients.Herein,we develop a novel oral-delivered small molecular,YPD-29B,which specifically targets human PD-L1.Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1,but did not inhibit any other immune checkpoints.Mechanistically,YPD-29B induced human PD-L1 dimerization and internalization,which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro.YDP-29B was modified as the YPD-30 prodrug to improve druggability.Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells,we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo.Taken together,our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.

A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors.Brain metastasis,such as breast cancer and lung cancer,also leads to high mortality.The available medicines are limited due to blood-brain barrier.Abnormal activation of phosphatidylinositol 3-kinases(PI3 K)signaling pathway is prevalent in glioblastoma and metastatic tumors.Here,we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3 K inhibitor with excellent anti-tumor activity against human glioblastoma.XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3 K signaling pathway,induced cell cycle arrest in G1 phase as well.Additionally,XH30 inhibited the migration of glioma cells and blocked the activation of PI3 K pathway by interleukin-17 A(IL-17 A),which increased the migration of U87 MG.Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models.XH30 also repressed tumor growth in brain metastasis models of lung cancers.Moreover,XH30 reduced IL-17 A and its receptor IL-17 RA in vivo.These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.