Gabapentinoids for the treatment of stroke

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.

“两个结合”的思想意蕴

马克思主义基本原理同中国具体实际相结合、同中华优秀传统文化相结合是马克思主义中国化的本质命题与实践要义。从中国共产党创立前后先进知识分子们主张把马克思主义“应用”到中国实境的主张,到马克思主义中国化思想命题提出之际倡导“使马克思主义在中国具体化”,再到领导中国革命、建设、改革进程中强调马克思主义同中国具体实际相结合,中国共产党人提出并践行了与时俱进的马克思主义中国化观。新时代新征程上,中华优秀传统文化的重要性日益擢升,长期包含在“中国具体实际”中的中华优秀传统文化得以独立出来,“两个结合”正式被明确提出。“两个结合”深化了对马克思主义中国化规律的认知,实现了马克思主义与中国古今“双向互动”上的思想进阶。要深入地把握“两个结合”的思想意蕴,有必要对其哲学思想基础进行深层的探究。“两个结合”是体现马克思主义世界观和方法论的哲学命题,在马克思主义本体论、认识论、方法论和价值论上有根本规定性,在实践发展上也有具体要求。“两个结合”作为一个系统工程,是长期的、动态的、全面的结合,也是主动的、科学的、有效的结合。

Localization of Mobile Robot Aided for Large-Scale Construction Based on Optimized Artificial Landmark Map in Ongoing Scene

The effectiveness of mobile robot aided for architectural construction depends strongly on its accurate localization ability.Localization of mobile robot is increasingly important for the printing of buildings in the construction scene.Although many available studies on the localization have been conducted,only a few studies have addressed the more challenging problem of localization for mobile robot in large-scale ongoing and featureless scenes.To realize the accurate localization of mobile robot in designated stations,we build an artificial landmark map and propose a novel nonlinear optimization algorithm based on graphs to reduce the uncertainty of the whole map.Then,the performances of localization for mobile robot based on the original and optimized map are compared and evaluated.Finally,experimental results show that the average absolute localization errors that adopted the proposed algorithm is reduced by about 21%compared to that of the original map.

Tuning the electronic structure of a metal-organic framework for an efficient oxygen evolution reaction by introducing minor atomically dispersed ruthenium

The establishment of efficient oxygen evolution electrocatalysts is of great value but also challenging.Herein,a durable metal–organic framework(MOF)with minor atomically dispersed ruthenium and an optimized electronic structure is constructed as an efficient electrocatalyst.Significantly,the obtained NiRu_(0.08)-MOF with doping Ru only needs an overpotential of 187 mV at 10 mA cm^(-2) with a Tafel slop of 40 mV dec^(-1) in 0.1M KOH for the oxygen evolution reaction,and can work continuously for more than 300 h.Ultrahigh Ru mass activity is achieved,reaching 56.7 Ag^(-1)_(Ru) at an overpotential of 200 mV,which is 36 times higher than that of commercial RuO_(2).X-ray adsorption spectroscopy and density function theory calculations reveal that atomically dispersed ruthenium on metal sites in MOFs is expected to optimize the electronic structure of nickel sites,thus improving the conductivity of the catalyst and optimizing the adsorption energy of intermediates,resulting in significant optimization of electrocatalytic performance.This study could provide a new avenue for the design of efficient and stable MOF electrocatalysts.

论中国共产党的长期执政

长期执政是中国共产党的执政夙愿,也是中国共产党超越其他政党的建党特征和政治信念。中国共产党的长期执政并非出于对政党自身利益的考量,而是为维护和发展民族、国家和人民利益而作出的政治抉择。始终保持政治的、思想的、理论的清醒为中国共产党长期执政提供了逻辑前提和逻辑可能,立党为公、执政为民奠定了中国共产党长期执政的道义基础,领导中华民族站起来富起来强起来的历程契合了中国共产党长期执政的历史规律和实践逻辑,为中国人民谋幸福、为中华民族谋复兴、为人类世界谋大同充实了中国共产党长期执政的目标使命,为中国特色社会主义共同理想和共产主义远大理想奋斗的价值选择延续了中国共产党长期执政的思想活力和实践空间。经过百年来领导中国革命、建设、改革和复兴的艰辛奋斗,中国共产党的长期执政已经实现了党的夙愿和人民期待的高度统一,也达到了执政应然和实然、政治作为合目的性与合规律性的有机结合,为未来长期执政奠定了坚实基础。

Analysis of Multi-AGVs Management System and Key Issues: A Review

Multiple Automatic Guided Vehicle(multi-AGVs)management systems provide an effective solution to ensuring stable operations of multi-AGVs in the same scenario,such as flexible manufacturing systems,warehouses,container terminals,etc.This type of systems need to balance the relationship among the resources of the system and solve the problems existing in the operation to make the system in line with the requirement of the administrator.The multi-AGVs management problem is a multi-objective,multi-constraint combinatorial optimization problem,which depends on the types of application scenarios.This article classifies and compares the research papers on multi-AGVs management in detail.Firstly,according to the different dimensions of the problem,the multi-AGVs management system is analyzed from three perspectives,namely,1)task dimensiondispatch,2)spatial dimension-path,and 3)time dimension-scheduling.The detailed comparison between the three dimensions and their respective solutions are discussed in detail as well.Secondly,according to their utility,the multi-AGVs management problems are divided into three categories:1)cost reduction,resource-oriented,2)efficiency improvement,problem-oriented,3)personalized demand,goal-oriented.The algorithm and methods of the different utility-oriented are analyzed and discussed.The related literature is summarized and corresponds to the composition of the multi-AGVs management system and the multi-AGVs management problems.Finally,according to the literature review,suggestions are made for further research.

Cultivating Contemporary Chinese People’s Global Consciousness from the Perspective of a Community with a Shared Future for Mankind

Building a community with a shared future for mankind calls for contemporary Chinese people’s understanding of the future of the community of mankind.Chinese people must also be encouraged to engage in the practices of global governance.Given their historical traditions,cultura thoughts and our nation’s current conditions,contemporary Chinese people must enhance their understanding of the development of the modern world especially the intertwined fate and differentiated interests of humans within such a community.Chinese people must arm themselves with a better globa view,cultivate a global consciousness,consolidate the concept of community and participate with a more open view,a more inclusive mind and more sensible strategies in the campaign initiated by the CPC to build an open inclusive,clean,and beautiful world that enjoys lasting peace,universa security,and common prosperity.Grand-scale education must be launched and relevant policy must be introduced to enhance people’s enthusiasm for global governance.International cooperation and communications mus be expanded so that Chinese people’s awareness of the community can be strengthened.Then a community with a shared future for mankind tha follows the rules of the development of China and the world,and that respects the historical trends and serves multiple interests can be constructed.

Metabolic reprogramming of proinflammatory macrophages by target delivered roburic acid effectively ameliorates rheumatoid arthritis symptoms

Rheumatoid arthritis(RA)is a common chronic inflammatory disorder that usually affects joints.It was found that roburic acid(RBA),an ingredient from anti-RA herb Gentiana macrophylla Pall.,displayed strong anti-inflammatory activity.However,its medical application is limited by its hydrophobicity,lack of targeting capability and unclear functional mechanism.Here,we constructed a pH responsive dual-target drug delivery system hitchhiking RBA(RBA-NPs)that targeted both CD44 and folate receptors,and investigated its pharmacological mechanism.In rat RA model,the nanocarriers effectively delivered RBA to inflammatory sites and significantly enhanced the therapeutic outcomes compared with free RBA,as well as strongly reducing inflammatory cytokine levels and promoting tissue repair.Following analysis revealed that M1 macrophages in the joints were reprogrammed to M2 phenotype by RBA.Since the balance of pro-and anti-inflammatory macrophages play important roles in maintaining immune homeostasis and preventing excessive inflammation in RA,this reprogramming is likely responsible for the anti-RA effect.Furthermore,we revealed that RBA-NPs drove M1-to-M2 phenotypic switch by down-regulating the glycolysis level via blocking ERK/HIF-1α/GLUT1 pathway.Thus,our work not only developed a targeting delivery system that remarkably improved the anti-RA efficiency of RBA,but also identified a potential molecular target to reversely reprogram macrophages though energy metabolism regulation.

免疫组化技术在氯胺酮诱导致精神分裂症中的应用进展

本文阐述了精神分裂症的发病机制,提出了用新型毒品氯胺酮建立精神分裂症SD大鼠动物模型,并提出用免疫组化技术对大鼠海马及前额叶皮质区的精神分裂症阳性细胞进行定位的方法,同时也讲述了免疫组化技术的应用,这将为精神分裂症的鉴定及个性化治疗提供依据。

民族文化禀赋与建设中华民族现代文明

建设中华民族现代文明,是党和人民在新时代新的文化使命。挖掘民族文化禀赋,理解和理顺民族文化禀赋与建设中华民族现代文明的基本原则、主要路径之间的内在机理,是建设中华民族现代文明的必然要求。中华民族文化禀赋既表现为把礼仪文明作为民族认同的基本标准,又展现为遵道尚德和求仁崇义的德性文明特质,还蕴含于近代中国建立容纳古今中西优秀文化要素的新文明形态的革命诉求中。这种民族文化禀赋,一方面有利于坚持价值主体性原则、历史主动性原则、综合创新性原则,依据以人民为中心、主动运用文明发展规律和促进不同文化的综合创新来建设中华民族现代文明;另一方面有利于夯实建设中华民族现代文明的主要路径,即以实事求是为原则推进“两个结合”,既弘扬爱国主义精神,建设中华民族共有精神家园,彰显中华民族现代文明的民族特性,又立足民族复兴伟业,推动构建人类命运共同体,彰显中华民族现代文明的世界意义。

DNA crosslinking and recombination-activating genes 1/2(RAG1/2)are required for oncogenic splicing in acute lymphoblastic leukemia

Background:Abnormal alternative splicing is frequently associated with carcinogenesis.In B-cell acute lymphoblastic leukemia(B-ALL),double homeobox 4 fused with immunoglobulin heavy chain(DUX4/IGH)can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript(ERGalt)and other splicing variants.However,the molecular mechanism underpinning this process remains elusive.Here,we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia.Methods:The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients.X-ray crystallography,small angle X-ray scattering(SAXS),and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element(DRE)-DRE sites.The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity.To check whether recombination-activating gene 1/2(RAG1/2)was required for DUX4/IGH-driven splicing,the proximity ligation assay,co-immunoprecipitation,mammalian two hybrid characterizations,in vitro RAG1/2 cleavage,and shRNA knock-down assays were performed.Results:We reported previously unrecognized intron retention events in Ctype lectin domain family 12,member A abnormal transcript(CLEC12Aalt)and chromosome 6 open reading frame 89 abnormal transcript(C6orf89alt),where also harbored repetitive DRE-DRE sites.Supportively,X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain(HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites.Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt,CLEC12Aalt,and C6orf89alt biogenesis,resulting in marked alleviation of its inhibitory effect on B-cell differentiation.Furthermore,we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes.Supportively,shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt,CLEC12Aalt,and C6orf89alt.Conclusions:All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites,catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.

SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed peptide microarrays to map linear peptide epitopes(LPEs)recognized following SARS-CoV-2 infetion and vaccination.LPEs detected by nonhuman primate(NHP)and patient IgMs after SARS-CoV-2 infection extensively overlapped,localized to functionally important virus regions,and aligned with reported neutralizing antibody binding sies.Similar LPE overlap occurred atfter infection and vaccination,with LPE clusters specifc to each stimulus,where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function.Vaccine-specifc LPEs tended to map to sites known or likely to be afected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein.Mapping LPEs to regions of known functional importance in this manner may acelerate vaccine evaluation and discovery of targets for sile secific therapeutic interventions.

CONVERGENCE AND OPTIMALITY OF ADAPTIVE MIXED METHODS FOR POISSON’S EQUATION IN THE FEEC FRAMEWORK

Finite Element Exterior Calculus (FEEC) was developed by Arnold, Falk, Winther andothers over the last decade to exploit the observation that mixed variational problems canbe posed on a Hilbert complex, and Galerkin-type mixed methods can then be obtained bysolving finite-dimensional subcomplex problems. Chen, Holst, and Xu (Math. Comp. 78(2009) 35–53) established convergence and optimality of an adaptive mixed finite elementmethod using Raviart–Thomas or Brezzi–Douglas–Marini elements for Poisson’s equationon contractible domains in R^2, which can be viewed as a boundary problem on the deRham complex. Recently Demlow and Hirani (Found. Math. Comput. 14 (2014) 1337–1371) developed fundamental tools for a posteriori analysis on the de Rham complex.In this paper, we use tools in FEEC to construct convergence and complexity resultson domains with general topology and spatial dimension. In particular, we construct areliable and efficient error estimator and a sharper quasi-orthogonality result using a noveltechnique. Without marking for data oscillation, our adaptive method is a contractionwith respect to a total error incorporating the error estimator and data oscillation.

PML nuclear body biogenesis and oligomerization-driven leukemogenesis

PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly.The productive RBCC oligomerization allows subsequent PML biogenesis steps,including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions.In promyelocytic leukemia,the oncoprotein PML/RARa(P/R)inhibits PML NBs assembly and leads to a full-fledged leukemogenesis.In this review,we review the recent progress in PML and acute promyelocytic leukemia fields,highlighting the protein oligomerization as an important direction of future targeted therapy.

中国共产党人对劳动精神的弘扬和培育

中国共产党是代表工人阶级和广大劳动群众根本利益的政党,党的阶级属性决定了其带领劳动群众争取劳动权益、植根劳动群众组织劳动运动、唤醒劳动者革命意识和觉悟的政治使命。中国共产党人对劳动精神的弘扬和培育体现为:明确无产阶级的劳动属性,声明党作为劳动阶级先进代表的政治本色;支持劳工运动,伸张劳工权益,唤起劳动者觉悟;保障劳动者权利,开展革命劳动教育,培育劳动观念;明确劳动者主人翁地位,规范劳动者角色,增强劳动者意识;继承劳动传统,提倡劳动精神,启动新时代劳动教育。

新时代加强李大钊研究的若干思考

李大钊研究是中共党史和马克思主义中国化研究领域中的重要内容。自李大钊就义不久,各界就实质性地开始了对李大钊生平、思想和贡献的研究。近百年来,国内外李大钊研究取得重要成就,出版了李大钊传记、文集、全集、年谱等标志性成果,发表了大量研究著述。面向未来,新时代李大钊研究应在前人研究的基础上,实现政治性研究与思想性研究的新融合、价值性研究与关系性研究的新开拓、单向度研究与多维度研究的新交叉、问题式研究与命题式研究的新结合、经辨式研究与史辨式研究的新整理、传统性研究与现代化研究的新协作。新时代李大钊研究应从中共党史大视野、马克思主义中国化史大进程、社会主义发展史大探索以及海外研究大关系角度,加强李大钊政治思想、建党思想、马克思主义中国化思想、社会主义思想以及海外李大钊研究与海外中国共产党研究关系领域的研究。

Six sigma robust design optimization for thermal protection system of hypersonic vehicles based on successive response surface method

Lightweight design is important for the Thermal Protection System(TPS) of hypersonic vehicles in that it protects the inner structure from severe heating environment. However, due to the existence of uncertainties in material properties and geometry, it is imperative to incorporate uncertainty analysis into the design optimization to obtain reliable results. In this paper, a six sigma robust design optimization based on Successive Response Surface Method(SRSM) is established for the TPS to improve the reliability and robustness with considering the uncertainties. The uncertain parameters related to material properties and thicknesses of insulation layers are considered and characterized by random variables following normal distributions. By employing SRSM, the values of objective function and constraints are approximated by the response surfaces to reduce computational cost. The optimization is an iterative process with response surfaces updating to find the true optimal solution. The optimization of the nose cone of hypersonic vehicle cabin is provided as an example to illustrate the feasibility and effectiveness of the proposed method.

Recent advances in vacancy engineering of metal-organic frameworks and their derivatives for electrocatalysis

The efficient electrocatalysis plays the key role in the development of electrochemical energy conversion technologies to alleviate energy crisis.Given their multiple active sites and large specific surface areas as electrocatalysts,metalorganic frameworks(MOFs)and their derivatives have attracted considerable interests in recent years.Specially,exploring the roles of the enhanced active sites inMOFs and their derivatives is significant for understanding and developing new effective electrocatalysts.Recently,the vital role of vacancies has been proven to promote electrocatalytic processes(such as H2 or O2 evolution reactions,O2 reduction reactions,and N2 reduction reactions).In order to in-depth exploring the effect of vacancies in electrocatalysts,the vacancies classification,synthetic strategy,and the recent development of various vacancies inMOFs and their derivatives for electrocatalysis are reviewed.Also,the perspectives on the challenges and opportunities of vacancies inMOFs and their derivatives for electrocatalysis are presented.

Effect of GR24 Stereoisomers on Plant Development in Arabidopsis

Dear Editor,Strigolactones （SLs） are a group of carotenoid-derived terpenoid lactones with similar structures. They can promote symbiotic interactions of plants with soil microbes （Akiyama et al., 2010）, stimulate the germination of parasitic weeds Striga and Orobanche （Cook et al., 1966; Johnson et al., 1976）, and regulate plant growth and development, including inhibition of shoot （tiller） outgrowth （Gomez-Roldan et al., 2008; Umehara et al., 2008）, suppression of hypocotyl elongation in Arabidopsis （Scaffidi et al., 2014）, and regulation of root architecture （Koltai, 2011）.

Analysis of tritium activity concentrations in urine and internal dose assessment for nuclear power plant workers

Objective:To investigate the activity concentration of tritium in urine of nuclear power plant(NPP)workers,in order to evaluate the occupational exposure levels.Methods:Three chosen NPPs were respectively located in southern,southeastern and northeastern China.Workers involved in operating,service,nuclear cleaning,chemical analysis,health physics,technical support,among others were randomly selected as the research targets,and 69 urine samples of no less than 50 mL were collected.The oxidative distillation method was used to pretreat the urine samples,and the activity concentration of tritium in distillate was then measured using liquid scintillation counter.The formula for the committed effective dose was also applied used to estimate the internal doses.Results:The highest tritium activity concentrations in urine samples from three NPPs were 2412.7,6351.4,and 478.7 Bq/L,respectively.Correspondingly,the internal doses due to tritium intake were 1.8,4.8 and 0.4μSv,respectively.Conclusions:The urine tritium activity concentration of workers varied greatly dependent on their job categories.The values for urine tritium radioactivity concentrations of workers involved in health care,nuclear cleaning and maintenance were generally higher than those for other job categories.The difference in urine tritium activity concentration mainly came from the different exposure time and tritium concentrations.From the dose assessment results,the internal dose caused by tritium intake did not exceed the public annual effective dose limit.