mRNA expression of Rho GTPase-related signaling molecules during rat hippocampal development

BACKGROUND:Rho GTPase family members have been shown to participate in neurite growth by regulating the neuronal cytoskeleton.However,there are very few reports of developmental roles of signaling molecules related to Rho GTPases. OBJECTIVE:To investigate messenger ribonucleic acid mRNA expression of signaling molecules associated with Rho GTPases,including Rho-A,Rac-1,collapsin response mediator protein 1(CRMP-1),and tubulin(53(Tubβ3) during rat hippocampus development. DESIGN,TIME AND SETTING:A non-randomized,controlled,animal experiment,based on different developmental stages of the rat hippocampus,was performed at the Guangdong Key Laboratory of Tissue Construction and Detection,Institute of Clinical Anatomy,Southern Medical University between December 2005 and July 2007. MATERIALS:Trizol reagent was purchased from Invitrogen,USA.RNA PCR kit(AMV) Ver 3.0 and 150 bp DNA Ladder Marker were purchased from TaKaRa,Japan.Unless otherwise specified,all other reagents were purchased from Sigma-Aldrich,USA. METHODS:Twenty-five Sprague Dawley rats were assigned to five groups(n = 5) according to developmental stages:embryonic(embryonic 15 days),neonatal(postnatal 5 days),juvenile (postnatal 1 month),adult(postnatal 3 months),and senile(postnatal 18 months). MAIN OUTCOME MEASURES:Detection of mRNA expression of Rho-A,Rac-1,CRMP-1,and Tubβ3 during various hippocampal developmental stages by reverse-transcription polymerase chain reaction. RESULTS:Hippocampal mRNA expression of Rho-A,as well as Rac-1,reached peak levels at embryonic,juvenile,and senile stages,and was relatively less during neonatal and adult stages. mRNA expression of Rac-1 was greater than Rho-A during each hippocampal developmental stage. CRMP-1 mRNA expression levels were as follows:embryonic>neonatal>juvenile>adult<senile, while Tubβ3 mRNA expression was embryonic>neonatal>juvenile>adult = senile. CONCLUSION:Rho-A and Rac-1 shared similar expression profiles,which demonstrated similar variations during the entire rat hippocampus developmental process.However,Rac-1 mRNA expression remained greater than Rho-A.Both CRMP-1 and Tubβ3 mRNA expression profiles gradually declined during hippocampal development from embryonic to adult stages.Tubβ3 mRNA expression arrested during the adult stage,and CRMP-1 mRNA expression increased during the senile stage.

Macrophage-derived matrix metalloproteinase-1 enhances aortic aneurysm formation in transgenic rabbits

Increased expression of matrix metalloproteinase-1(MMP-1)has been observed in the lesions of atherosclerosis and aneurysms;however,it is not fully understood whether macrophage-derived MMP-1 affects these diseases.To investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases,we generated transgenic(Tg)rabbits expressing human MMP-1 in the monocyte/macrophage lineage under the control of the human scavenger receptor enhancer/promoter.Tg rabbits exhibited no visible abnormalities throughout their bodies.Western blotting analysis revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg rabbits.For the first experiment,Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks,and aortic and coronary atherosclerosis were evaluated.The gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly different from that in non-Tg rabbits,but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic examination.For the second experiment,we generated aortic aneurysms by incubating with elastase.Compared with non-Tg rabbits,Tg rabbits exhibited a significantly greater aortic dilation.Increased macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and aneurysms.These results demonstrate that MMP-1 plays a different role in the pathogenesis of atherosclerosis and aneurysms.

Elite sd1 alleles in japonica rice and their breeding applications in northeast China

The Green Revolution gene sd1 has been used extensively in modern rice breeding,especially in indica cultivars.However,elite sd1 alleles and related germplasm resources used for japonica rice breeding have not been identified,and extensive efforts are needed for japonica rice breeding to obtain new dwarfing sources.Data from MBKbase-Rice revealed seven sd1 haplotypes in indica and four in japonica rice.Two new sd1 alleles were identified in indica rice.In 295 japonica accessions from northeast Asia,except for the weak functional allele SD1-EQ,sd1-r was the major allele,reducing plant height in comparison with SD1-EQ.Japonica germplasm resources carrying reported sd1 alleles were identified by genotype searching and further verified by literature search,genealogical analysis,and d Caps markers.Pedigrees and geographic distribution showed that sd1-r is an excellent allele widely used in northern China and Tohoku in Japan,and sd1-j is commonly used in east China and Kyushu in Japan.Dongnong-and Xiushui-series cultivars carrying sd1-r and sd1-j,respectively,are essential branches of the backbone parents of Chinese japonica rice,Akihikari and Ce21,with the largest number of descendants and derived generations.In semi-dwarf japonica rice breeding,sd1-d was introgressed into Daohuaxiang 2(DHX2).Dwarf and semi-dwarf lines carrying sd1-d were selected and designated as 1279 and 1280,respectively,after withstanding typhoon-induced strong winds and heavy rains in 2020,and are anticipated to become useful intermediate materials for future genetic research and breeding.This work will facilitate the introduction,parental selection,and marker-assisted breeding,and provide a material basis for the next step in identifying favorable genes that selected together with the sd1 alleles in japonica backbone parents.

Genome engineering technologies in rabbits

The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome manipulations in rabbit has been stalled for decades,severely limiting its applications in biomedical research.Novel genome editing technologies,especially CRISPR/Cas9,have remarkably enhanced precise genome manipulation in rabbits,and shown their superiority and promise for generating rabbit models of human genetic diseases.In this review,we summarize the brief history of transgenic rabbit technology and the development of novel genome editing technologies in rabbits.

Compressive Mechanical Properties of Normalized 10^#Low Carbon Steel

Compressive mechanical properties of 10~# lowcarbon steel with normalizing heat treatment are studied. A Gleeble system is adopted to analyze the quasi-static properties and thermal softening effects of heat treated 10~# steel,while a Hopkinson bar apparatus is used to investigate its dynamic characteristics under different strain rates. The results showthat yield stress of heat treated 10~# steel is more than that of untreated one at room temperature. When the specimens are tested at different temperatures,yield stresses decrease with increasing temperature except 573 K. Moreover,the influence of strain rate on yield stress are verified,which shows that the yield stress increases sharply from 500 s^(-1) to 1 890 s^(-1),while it changes a little from 1 890 s^(-1)to 4 850 s^(-1). The results indicate that yield stress is mainly influenced by hardening effect at lowstrain rate and controlled by both thermal softening effect and strain rate hardening effect at high strain rate.

Observability conditions of switched linear singular systems

observability 问题切换线性单个(SLS ) 系统在这篇论文被学习。基于 observability 定义，交换法律给的 unofyservable 潜水艇空格在所有分系统是常规的条件下面被调查。为 SLS 系统的 observability 的一个必要条件和一个足够的条件被给。observability 和可控制性为有循环切换的法律的一些特殊 SLS 系统是双的，这被显示出。这里开发的方法对正常交换线性系统的 observability 分析适用。

Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical–Electrical Anisotropic Microenvironment for Heart Repair

The biomimetic construction of a microstructural–mechanical–electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction(MI).Inspired by the 3D anisotropic characteristic of the natural fish swim bladder(FSB),a novel flexible,anisotropic,and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural,conductive,and mechanical features of the native cardiac extracellular matrix.The results revealed that the originally stiff,homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel,enabling its potential as a functional engineered cardiac patch(ECP).In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity,maturation,elongation,and orientation of cardiomyocytes(CMs),and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis,thereby promoting cell retention,myogenesis,and vascularization,as well as improving electrical integration.Our findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.

CONSENSUS CONTROL FOR LEADER-FOLLOWING MULTI-AGENT SYSTEMS WITH MEASUREMENT NOISES

This work is concerned with consensus control for a class of leader-following multi-agentsystems (MASs).The information that each agent received is corrupted by measurement noises.Toreduce the impact of noises on consensus,time-varying consensus gains are adopted,based on whichconsensus protocols are designed.By using the tools of stochastic analysis and algebraic graph theory,asufficient condition is obtained for the protocol to ensure strong mean square consensus under the fixedtopologies.This condition is shown to be necessary and sufficient in the noise-free case.Furthermore,by using a common Lyapunov function,the result is extended to the switching topology case.

ON FORMABILITY OF LINEAR CONTINUOUS-TIME MULTI-AGENT SYSTEMS

这份报纸集中于多代理人系统(质量) 的 formability。这个问题涉及有能力驾驶包含到需要的形成的 MAS 的一个协议的存在，并且这样，具有在设计形成协议的必要重要性。Formability 一妈取决于几个关键因素：动态结构，连接拓扑学，需要的形成的性质和可被考虑的控制设置了的代理人。这里考虑的团的代理人被一个将军描述连续线性时间不变(LTI ) 当模特儿。由使用矩阵分析和代数学的图理论， LTI 团的 formability 上的一些必要、足够的条件被获得。这些条件关于一些典型、广泛地使用的可被考虑的协议集合在某感觉描绘 formability，连接拓扑学，形成性质和代理人动力学的关系。

Effect of cooling rate upon the microstructure and mechanical properties of in-situ TiC reinforced high entropy alloy CoCrFeNi

Three types of in-situ TiC(5 vol%,10 vol%and 15 vol%)reinforced high entropy alloy CoCrFeNi matrix composites were produced by vacuum induction smelting.The effect of two extreme cooling conditions(i.e.,slow cooling in fu rnace and rapid cooling in copper crucible)upon the microstructure and mechanical properties was examined.In the case of slow cooling in the furnace,TiC was found to form mostly along the grain boundaries for the 5 vol%samples.With the increase of TiC reinforcements,fibrous TiC appeared and extended into the matrix,leading to an increase in hardness.The ultimate tensile strength of the composites shows a marked variation with increasing TiC content;that is,425.6 MPa(matrix),372.8 MPa(5 vol%),550.4 MPa(10 vol%)and 334.3 MPa(15 vol%),while the elongation-to-failure(i.e.,ductility)decreases.The fracture pattern was found to transit from the ductile to cleavage fracture,as the TiC content increased.When the samples cooled rapidly in copper crucible,the TiC particles formed both along the grain boundaries and within the grains.With the increase of TiC volume fraction,both the hardness and ultimate tensile strength of the resulting composites improved steadily while the elongation-to-failure declined.Therefore,the fast cooling can be used to drastically improve the strength of in-situ TiC reinforced CoCrFeNi.For example,for the 15 vol%TiC/CoCrFeNi composite cooled in the copper crucible,the hardness and ultimate tensile strength can reach as high as 595 HV and 941.7 MPa,respectively.

青藏高原“大湖期”的时空复杂性

As the"Asian Water Tower"and the source of many major rivers in Asia,the Tibetan Plateau(TP)significantly affects human societies in densely-populated Asia[1].Lakes in the TP have a total area of^5×10^4 km^2 and hence they comprise an important component of the"Asian Water Tower".These lakes are sensitive to climate changes and have exhibited an overall trend of rapid expansion during recent decades[2].

SysFinder：A customized platform for search,comparison and assisted design of appropriate animal models based on systematic similarity

Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not transferable to human.To address these issues,we developed SysFinder(http://lifecenter.sgst.cn/SysFinder),a platform for scientists to find appropriate animal models for translational research.SysFinder offers a "topic-centered" approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal models.Scientific topic can be a certain disease,drug,gene function or biological pathway.SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics.Meanwhile,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models.Furthermore,SysFinder provides a userfriendly platform for determination of short guide RNAs(sgRNAs) and homology arms to design a new animal model.Case studies illustrate the ability of SysFinder in helping experimental scientists.SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.

HDL quality features revealed by proteome–lipidome connectivity are associated with atherosclerotic disease

Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.

Gene editing therapy ready for cardiovascular diseases: opportunities, challenges, and perspectives

Gene editing nucleases(GENs),represented by CRISPR/Cas9,have become major tools in biomedical research and offer potential cures for many human diseases.Gene editing therapy(GETx)studies in animal models targeting genes such as proprotein convertase subtilisin/kexin type 9(PCSK9),apolipoprotein C3(APOC3),angiopoietin Like 3(ANGPTL3)and inducible degrader of the low-density lipoprotein receptor(IDOL)have demonstrated the benefits and advantages of GETx in managing atherosclerosis.Here we present our views on this brand new therapeutic option for cardiovascular diseases(CVD).