A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis

Hypoxia-inducible factor 1 （HIF-1） attenuates amyloid-beta protein neurotoxicity and decreases apoptosis induced by oxidative stress or hypoxia in cortical neurons. In this study, we construct-ed a recombinant adeno-associated virus （rAAV） vector expressing the human HIF-1αgene （rAAV-HIF-1α）, and tested the assumption that rAAV-HIF-1αrepresses hippocampal neuronal apoptosis induced by amyloid-beta protein. Our results conifrmed that rAAV-HIF-1αsigniifcant-ly reduces apoptosis induced by amyloid-beta protein in primary cultured hippocampal neurons. Direct intracerebral rAAV-HIF-1αadministration also induced robust and prolonged HIF-1αproduction in rat hippocampus. Single rAAV-HIF-1αadministration resulted in decreased apoptosis of hippocampal neurons in an Alzheimer＇s disease rat model established by intrace-rebroventricular injection of aggregated amyloid-beta protein （25-35）. Our in vitro and in vivo ifndings demonstrate that HIF-1 has potential for attenuating hippocampal neuronal apoptosis induced by amyloid-beta protein, and provides experimental support for treatment of neurode-generative diseases using gene therapy.

Study on urban spatial structure and morphology of Guangzhou-Foshan metropolitan coordinating region compared with Randstad,Netherlands

In recent years,regional integration of Chinese cities has gradually developed.Meanwhile,metropolitan areas and urban agglomerations have taken shape.On the one hand,the development of the metropolitan area has brought about urban spatial expansion,as well as population and economic growth.On the other hand,it has led to problems such as the urban sprawl and suburbanization,increasing pressure on environmental resources,and the decline of urban central areas.Under this background,the Guangdong-Hong Kong-Macao Greater Bay Area Development Plan Outline proposes to accelerate the integration of Guangzhou-Foshan(Guang Fo)Metropolitan Coordinating Region(MCR),and to construct a networked space pattern driven by urban poles and shafts.Based on the academic research of Metropolitan Coordinating Region(MCR),as well as the theory of urban spatial structure and morphology,this study focus on urban spatial patterns and elements in different scales,from two individual cites(Guangzhou and Foshan),Guang Fo MCR,to Guangdong-Hong Kong-Macao(GHM)Greater Bay Area.With GIS and the mapping method,the spatial elements such as green space,water system,built-up area,road network,rail transit network and main pivot points of the Guang Fo MCR are classified,laid out individually and again overlaid in order to figure out the relationship of these elements.At the same time,through the comparative case study of the Randstad MCR in the Netherlands,the enlightenment of solving the development problem of MCR is hopefully to be obtained.As delta cities,the Guang Fo MCR is cut by the multi-channel water network,while the urban built-up area is concentrated in the middle of the MCR and spread out along the traffic corridor to the suburban district.The traffic structure of the Guang Fo MCR is characterized by the outward radiation of the central area of Guangzhou and Foshan.Simultaneously,the traffic connection between Guangzhou and Foshan is relatively weak.Compared with the polycentric spatial structure,which is called Decentralized Compact pattern of Randstad MCR,the Guang Fo MCR presents a city form with little hierarchy but homogeneity,and its urban space is disorderly spread.The bluegreen system of water and vegetation is fragmented because of the urban invasion in Guang Fo MCR,while the green heart in central Randstad is well preserved.As a result,it is well advised to explore a more resilient and ecological urban development in Guang Fo MCR.

Prediction of Enthalpies of Fusion for Divalent Rare Earth Halides Based on Modeling by Artificial Neural Networks and Pattern Recognition

The artificial neural network (ANN) and the pattern recognition were applied to study the correlation of enthalpies of fusion for divalent rare earth halides with their microstructural parameters,such as ionic radius and electronegativity. The model,represented by a back-propagation netal network, was trained with a 12 set of published data for divalent rare earth halides and then was used to predict the unknown ones. Also the criterion equations were ptesented to determine the enthalpies of fuSion for divalent rare earth halides using pattern recognition in mis work. The results from the model in ANN and criterion equations are in very good agreement with reference data.

Multiscale design of stiffening and ROS scavenging hydrogels for the augmentation of mandibular bone regeneration

Although biomimetic hydrogels play an essential role in guiding bone remodeling,reconstructing large bone defects is still a significant challenge since bioinspired gels often lack osteoconductive capacity,robust mechanical properties and suitable antioxidant ability for bone regeneration.To address these challenges,we first engineered molecular design of hydrogels(gelatin/polyethylene glycol diacrylate/2-(dimethylamino)ethyl methacrylate,GPEGD),where their mechanical properties were significantly enhanced via introducing trace amounts of additives(0.5 wt%).The novel hybrid hydrogels show high compressive strength(>700 kPa),stiff modulus(>170 kPa)and strong ROS-scavenging ability.Furthermore,to endow the GPEGD hydrogels excellent osteoinductions,novel biocompatible,antioxidant and BMP-2 loaded polydopamine/heparin nanoparticles(BPDAH)were developed for functionalization of the GPEGD gels(BPDAH-GPEGD).In vitro results indicate that the antioxidant BPDAH-GPEGD is able to deplete elevated ROS levels to protect cells viability against ROS damage.More importantly,the BPDAH-GPEGD hydrogels have good biocompatibility and promote the osteo differentiation of preosteoblasts and bone regenerations.At 4 and 8 weeks after implantation of the hydrogels in a mandibular bone defect,Micro-computed tomography and histology results show greater bone volume and enhancements in the quality and rate of bone regeneration in the BPDAH-GPEGD hydrogels.Thus,the multiscale design of stiffening and ROS scavenging hydrogels could serve as a promising material for bone regeneration applications.

Delivering Microrobots in the Musculoskeletal System

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy.Patients often suffer chronic pain and might eventually have to undergo end-stage surgery.Therefore,future treatments should focus on early detection and intervention of regional lesions.Microrobots have been gradually used in organisms due to their advantages of intelligent,precise and minimally invasive targeted delivery.Through the combination of control and imaging systems,microrobots with good biosafety can be delivered to the desired area for treatment.In the musculoskeletal system,microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body.Compared to traditional biomaterial and tissue engineering strategies,active motion improves the efficiency and penetration of local targeting of cells/drugs.This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system.We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.

MXene在电化学传感器中的应用

过渡金属碳化物或氮化物(MXene)作为一种新型的二维层状材料,由于具有良好的导电性、水中分散性、高的生物相容性和稳定性等,在电化学传感领域具有巨大的应用潜力。将MXene与其他纳米材料复合,可以扬长避短,在性能上实现优势协同和功能互补,有效提高电化学传感器的灵敏度和选择性。本文按照检测物的种类进行分类,综述了基于MXene材料构建的电化学传感平台在生物标记物和环境污染物检测中的应用,并讨论了MXene材料在电化学传感领域未来研究发展和应用中所面临的挑战。

大规模中药转录组研究揭示中药抑制新冠肺炎细胞因子风暴的分子机制

中药抑制新冠肺炎相关细胞因子风暴的分子机制尚不清晰.本文首先通过HTS2技术,在基因表达层面上,大规模检测了578味中药提取物对与细胞因子风暴紧密相关的信号通路的调控作用,发现53味中药对这些通路具有显著抑制作用;评估了国家及地方新冠肺炎诊疗方案中出现的338个方剂,发现理中汤、六君子汤、黄连解毒汤、清肺排毒汤在抑制细胞因子风暴方面排在前列;鉴别了相关中药的潜在活性成分,进一步揭示了中药抑制新冠肺炎相关细胞因子风暴的化学基础.本研究系统探究了中药调节新冠相关细胞因子风暴的分子机制,为中药治疗新冠肺炎药效机制的解析提供了科学依据.

Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders,including Huntington disease[caused by expanded CAG repeats(CAGr)in the HTT gene],and amyotrophic lateral sclerosis[ALS,possibly caused by expanded GGGGCC repeats(G4C2r)in the C9ORF72 gene],of which the molecular mechanisms remain unclear.Here,we demonstrated that lowering the Drosophila homologue of tau protein(dtau)significantly rescued in vivo neurodegeneration,motor performance impairments,and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r.Expression of human tau(htau4 R)restored the disease-related phenotypes that had been mitigated by the loss of dtau,suggesting an evolutionarily-conserved role of tau in neurodegeneration.We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome-lysosome fusion,possibly due to lowering the level of BAG3,a regulator of autophagy and tau.Taken together,our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism.Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.

Crystallization of Al-based Amorphous Alloys in Good Conductivity Solution

The corrosion-induced crystallization of Al94 exNixGd6（x=6 and 10, in at.%） metallic glasses as well as phase separation, oxidation and cracking in good conductivity solution has been investigated by various techniques.The transmission electronic microscopy（TEM） result reveals that crystalline intermetallics and oxides present on the electrochemically thinned hole edge, and the phase separation occurs in the matrix of the as-spun ribbons with the circumferential speed Rcof 29.3 m/s. In addition, the bending and cracking of the samples occur after corrosion. The influence of Ni content on the phase separation, bending and cracking can be explained by the fact that the percolation of the backbone clusters in the amorphous alloy melts and glasses is enhanced by increasing the composition of Ni.

On global controllability for a class of polynomial affine nonlinear systems

In this paper, a necessary and sufficient condition of the global controllability for a class of low dimensional polynomial affine nonlinear systems with special structure is obtained. The condition is imposed on the coefficients of the system only and the methods are based on Green＇s formula and the trajectory analysis of planar linear system. Furthermore, I point out that the global controllability does not hold for the corresponding high dimensional polynomial system.