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Pathway analysis for genome-wide genetic variation data:Analytic principles,latest developments,and new opportunities

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Journal of Genetics and Genomics 2021年第3期48卷 173-183页

作者： Micah Silberstein Nicholas Nesbit Jacquelyn cai Phil h.Lee Center for Genomic Medicine Massachusetts General HospitalBostonMA 02114USA Department of Psychiatry Harvard Medical SchoolBostonMA 02115USA Stanley Center for Psychiatric Research Broad Institute of MIT and HarvardCambridgeMA 02142USA

Pathway analysis,also known as gene-set enrichment analysis,is a multilocus analytic strategy that integrates a priori,biological knowledge into the statistical analysis of high-throughput genetics data.Originally developed for the studies of gene expression data,it has become a powerful analytic procedure for indepth mining of genome-wide genetic variation data.Astonishing discoveries were made in the past years,uncovering genes and biological mechanisms underlying common and complex disorders.however,as massive amounts of diverse functional genomics data accrue,there is a pressing need for newer generations of pathway analysis methods that can utilize multiple layers of high-throughput genomics data.In this review,we provide an intellectual foundation of this powerful analytic strategy,as well as an update of the state-of-the-art in recent method developments.The goal of this review is threefold:(1)introduce the motivation and basic steps of pathway analysis for genome-wide genetic variation data;(2)review the merits and the shortcomings of classic and newly emerging integrative pathway analysis tools;and(3)discuss remaining challenges and future directions for further method developments.

关键词： Pathway analysis Set-based association analysis Gene-set enrichment analysis Genome-wide association study Multilocus association analysis

Microstructural evolution and superelastic properties of ultrafine-graine d NiTi-base d shape memory alloy via sintering of amorphous ribbon precursor

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Journal of Materials Science & Technology 2023年第7期138卷 80-92页

作者： W.S.cai h.Z.Lu h.Z.Li Z.Liu h.B.Ke W.h.Wang C.Yang National Engineering Research Center of Near-net-shape Forming for Metallic Materials Guangdong Provincial Key Laboratory for Processing and Forming of Advanced Metallic MaterialsSouth China University of TechnologyGuangzhou 510640China Songshan Lake Materials Laboratory Dongguan 523808China Institute of Physics Chinese Academy of SciencesBeijing 100190China

NiTi-based shape memory alloys(SMAs)are considered as cutting-edge intelligent functional materials.however,it remains a great challenge to obtain ultrafine-grained(UFGed)bulk materials with mm-scale size as well as outstanding superelastic properties.here,UFGed bulk Ti_(35)Zr_(15)Ni_(35)Cu_(15)NiTi-based SMA is successfully prepared via spark plasma sintering of amorphous ribbon precursor at different sintering temperatures,and microstructural evolution and superelastic properties are symmetrically investigated.It is found that its grain size ranges from UFG to micro-grain with increased sintering temperature regard-less of the predominant B2 matrix in all bulk samples.Interestingly,the orientation relationships between B2 matrix and nano-scale fcc(Ti,Zr)_(2)Ni precipitate evolve from coherent to incoherent.Consequently,the UFGed samples exhibit perfect superelasticity with the high recoverable strain of∼5.8%,the stable recov-ery rate above 99%,and the great critical stress inducing martensitic transformation higher than 1 GPa,far superior to the corresponding ones of suction-cast micro-grained TiZrNiCu SMAs.Fundamentally,the perfect superelasticity is attributed to the good resistance to dislocation slip or grain boundary slip by residual nano-scale amorphous phase or secondary phase of coherent and semi-coherent fcc(Ti,Zr)_(2)Ni precipitate.In addition,the gentle superelastic plateau is associated to the favorable transfer stress and the strong ability to accommodate dislocation movement,which is generated by the coherent interface between nano-scale fcc(Ti,Zr)_(2)Ni and UFGed B2 matrix.These results suggest that spark plasma sintering of amorphous alloy precursor is a feasible route to obtaining excellent superelasticity in NiTi-based SMAs.

关键词： Shape memory alloy Amorphous alloy Microstructure Superelasticity

A distributed VSG control method for a battery energy storage system with a cascaded h-bridge in a grid-connected mode

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Global Energy Interconnection 2022年第4期5卷 343-352页

作者： Yichi cai Donglian Qi Electrical and Electronic Engineering Department Zhejiang UniversityNo.38.Zheda Rd.Hangzhou310027ZhejiangP.R.China

With the high penetration of renewable energy,new challenges,such as power fluctuation suppression and inertial support capability,have arisen in the power sector.Battery energy storage systems play an essential role in renewable energy integration.In this paper,a distributed virtual synchronous generator(VSG)control method for a battery energy storage system(BESS)with a cascaded h-bridge converter in a grid-connected mode is proposed.The VSG is developed without communication dependence,and state-of-charge(SOC)balancing control is achieved using the distributed average algorithm.Owing to the low varying speed of SOC,the bandwidth of the distributed communication networks is extremely slow,which decreases the cost.Therefore,the proposed method can simultaneously provide inertial support and accurate SOC balancing.The stability is also proved using root locus analysis.Finally,simulations under different conditions are carried out to verify the effectiveness of the proposed method.

关键词： VSG Cascaded h-bridge converters Battery energy storage system Renewable energy integration

Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro

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Journal of Integrative Medicine 2022年第4期20卷 365-375页

作者： cai-lian Fan Wan-jun cai Meng-nan Ye Miao Chen Yi Dai Department of Cardiology the First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou 510632Guangdong ProvinceChina College of Pharmacy Jinan UniversityGuangzhou 510632Guangdong ProvinceChina

Objective: Qili Qiangxin(QLQX), a compound herbal medicine formula, is used effectively to treat congestive heart failure in China. however, the molecular mechanisms of the cardioprotective effect are still unclear. This study explores the cardioprotective effect and mechanism of QLQX using the hypoxiareoxygenation(h/R)-induced myocardial injury model.Methods: The main chemical constituents of QLQX were analyzed using high-performance liquid chromatography-evaporative light-scattering detection. The model of h/R-induced myocardial injury in h9c2 cells was developed to simulate myocardial ischemia–reperfusion injury. Apoptosis, autophagy,and generation of reactive oxygen species(ROS) were measured to assess the protective effect of QLQX. Proteins related to autophagy, apoptosis and signalling pathways were detected using Western blotting.Results: Apoptosis, autophagy and the excessive production of ROS induced by h/R were significantly reduced after treating the h9c2 cells with QLQX. QLQX treatment at concentrations of 50 and 250 μg/mL caused significant reduction in the levels of LC3Ⅱ and p62 degradation(P he AMPK/mTOR signalling pathway. Furthermore, the AMPK inhibitor Compound C(at 0.5 μmol/L),and QLQX(250 μg/mL) significantly inhibited h/R-induced autophagy and apoptosis(P hile AICAR(an AMPK activator, at 0.5 mmol/L) increased cardiomyocyte apoptosis and autophagy and abolished the anti-apoptotic effect of QLQX. Similar phenomena were also observed on the expressions of apoptotic and autophagic proteins, demonstrating that QLQX reduced the apoptosis and autophagy in the h/R-induced injury model via inhibiting the AMPK/mTOR pathway. Moreover, ROS scavenger,N-Acetyl-L-cysteine(NAC, at 2.5 mmol/L), significantly reduced h/R-triggered cell apoptosis and autophagy(P hile, NAC treatment down-regulated the ratio of phosphorylation of AMPK/AMPK(P hich showed a similar effect to QLQX.Conclusion: QLQX plays a cardioprotective role by alleviating apoptotic a

关键词： herbal medicine Qili Qiangxin formula hypoxia–reoxygenation Reactive oxygen species Autophagy Apoptosis AMPK/mTOR pathway

Supported Pt-Ni bimetallic nanoparticles catalyzed hydrodeoxygenation of dibenzofuran with high selectivity to bicyclohexane

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Chinese Chemical Letters 2022年第1期33卷 234-238页

作者： Pengyu Wu Chun cai Chemical Engineering College Nanjing University of Science and TechnologyNanjing 210094China

Catalytic hydrodeoxygenation(hDO)is one of the most effective methods to upgrade the oxygen-containing compounds derived from coal tar to valuable hydrocarbons.herein,an efficient bimetallic catalyst Pt_(1)Ni_(4)/MgO was prepared and applied in the hDO of dibenzofuran(DBF).high yield(95%)of the desired product bicyclohexane(BCh)was achieved at 240℃and 1.2 MPa of h_(2).Superior catalytic performance could be ascribed to the"relay catalysis"of Pt sites and Ni sites,and the reaction pathway is proposed as well.Scale-up experiment and recyclability test were also performed,which demonstrated the recyclability and promising potential application of Pt_(1)Ni_(4)/MgO.

关键词： hydrodeoxygenation Dibenzofuran Bicyclohexane Bimetallic catalyst Relay catalysis

Research and application advances in rehabilitation assessment of stroke

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第8期23卷 625-641页

作者： Kezhou LIU Mengjie YIN Zhengting cai Department of Biomedical Engineering School of Automation(Artificial Iintlligence)Hangzhou Dianzi UniversityHangzhou 310018China

Stroke has a high incidence and disability rate, and rehabilitation is an effective means to reduce the disability rate of patients. To systematize rehabilitation assessment, which is the foundation for rehabilitation therapy, we summarize the assessment methods commonly used in research and clinical applications, including the various types of stroke rehabilitation scales and their applicability, and related biomedical detection technologies, including surface electromyography(sEMG),motion analysis systems, transcranial magnetic stimulation(TMS), magnetic resonance imaging(MRI), and combinations of different techniques. We also introduce some assessment techniques that are still in the experimental phase, such as the prospective application of artificial intelligence(AI) with optical correlation tomography(OCT) in stroke rehabilitation. This review provides a useful bibliography for the assessment of not only the severity of stroke injury, but also the therapeutic effects of stroke rehabilitation, and establishes a solid base for the future development of stroke rehabilitation skills.

关键词： Stroke Rehabilitation assessment Stroke assessment scales Detection technology Artificial intelligence

Exosomes: a novel therapeutic target for Alzheimer's disease?

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Neural Regeneration Research 2018年第5期13卷 930-935页

作者： Zhi-You cai Ming Xiao Sohel h.Quazi Zun-Yu Ke Department of Neurology Chongqing General Hospital Department of Anatomy Nanjing Medical University Department of Biological and health Sciences Texas A & M University-Kingsville Department of Neurology Renmin Hospital Hubei University of Medicine

Extracellular exosomes are formed inside the cytoplasm of cells in compartments known as multivesicular bodies. Thus, exosomes contain cytoplasmic content. Multivesicular bodies fuse with the plasma membrane and release exosomes into the extracellular environment. Comprehensive research suggests that exosomes act as both inflammatory intermediaries and critical inducers of oxidative stress to drive progression of Alzheimer＇s disease. An important role of exosomes in Alzheimer＇s disease includes the formation of neurofibrillary tangles and beta-amyloid production, clearance, and accumulation. In addition, exosomes are involved in neuroinflammation and oxidative stress, which both act as triggers for beta-amyloid pathogenesis and tau hyperphosphorylation. Further, it has been shown that exosomes are strongly associated with beta-amyloid clearance. Thus, effective measures for regulating exosome metabolism may be novel drug targets for Alzheimer＇s disease.

关键词： nerve regeneration microvesicle beta-amyloid tau neuroinflammation oxidative stress therapeutic target neurodegeneration dementia neural regeneration

Scavenging and release of REE and hFSE by Na-metasomatism in magmatic-hydrothermal systems

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Fundamental Research 2024年第2期4卷 315-323页

作者： Wu-Bin Yang he-cai Niu Ning-Bo Li Pete hollings Shannon Zurevinski Roger h.Mitchell Key Laboratory of Mineralogy and Metallogeny/Guangdong Provincial Key Laboratory of Mineral Physics and Materials Guangzhou Institute of GeochemistryChinese Academy of SciencesGuangzhou 510640China CAS Center for Excellence in Deep Earth Science Guangzhou 510640China Department of Geology Lakehead UniversityThunder BayON P7B 5E1Canada

Exploitable or potentially exploitable deposits of critical metals,such as rare-earth(REE)and high-field-strength elements(hFSE),are commonly associated with alkaline or peralkaline igneous rocks.however,the origin,transport and concentration of these metals in peralkaline systems remains poorly understood.This study presents the results of a mineralogical and geochemical investigation of the Na-metasomatism of alkali amphiboles and clinopyroxenes from a barren peralkaline granite pluton in NE China,to assess the remobilization and redistribution of REE and hFSE during magmatic-hydrothermal evolution.Alkali amphiboles and aegirine-augites from the peralkaline granites show evolutionary trends from sodic-calcic to sodic compositions,with increasing REE and hFSE concentrations as a function of increasing Na-index[Na^(#),defined as molar Na/(Na+Ca)ratios].The Na-amphiboles(i.e.,arfvedsonite)and aegirine-augites can be subsequently altered,or breakdown,to form hydrothermal aegirine during late-or post-magmatic alteration.Representative compositions analyzed by insitu LA-ICPMS show that the primary aegirine-augites have high and variable REE(2194-3627 ppm)and hFSE(4194-16,862 ppm)contents,suggesting that these critical metals can be scavenged by alkali amphiboles and aegirine-augites.Compared to the primary aegirine-augites,the presentative early replacement aegirine(Aeg-I,Na^(#)=0.91-0.94)has notably lower REE(1484-1972)and hFSE(4351-5621)contents.In contrast,the late hydrothermal aegirine(Aeg-II,Na^(#)=0.92-0.96)has significantly lower REE(317-456 ppm)and hFSE(6.44-72.2 ppm)contents.Given that the increasing Na^(#)from aegirine-augites to hydrothermal aegirines likely resulted from Na-metasomatism,a scavenging-release model can explain the remobilization of REE and hFSE in peralkaline granitic systems.The scavenging and release of REE and hFSE by Na-metasomatism provides key insights into the genesis of globally significant REE and hFSE deposits.The high Na-index of the hydrothermal aegirine might be useful as a geo

关键词： Critical metals Alkali amphiboles Na-metasomatism REE and hFSE Na-index(Na^(#))

Preparation and reaction mechanism of novel Ce_(x)Co_(y)Cuz oxide composite catalysts towards oxidation of o-xylene

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Journal of Rare Earths 2022年第10期40卷 1573-1583页

作者： Mengge Zhao Weijian cai Jiwu Li School of Environmental Science and Engineering Zhejiang Gongshang UniversityHangzhou 310018China Department of Chemistry School of Food Science and BiotechnologyZhejiang Gongshang UniversityHangzhou 310018China

Ce_(x)Co_(y)Cuzoxide composite catalysts were prepared by using polyethylene glycol, citrate sol-gel method combined with PMMA template for the oxidation of o-xylene. The catalysts were characterized by the Xray diffraction(XRD), h2-temperature programmed reduction(h2-TPR), X-ray photoelectron spectroscopy(XPS) and Fourier transform infrared spectroscopy(FT-IR), etc. The catalytic activity for o-xylene was investigated. The catalytic degradation pathway and mechanism of o-xylene were inferred. The results show that Ce O_(2)is mainly present on the surface of all catalysts. The surface area of Ce_(2)Co1Cu1is up to 77.2 m^(2)/g, and the average pore size is 10.62 nm. It exhibits redox and sufficient Ce^(4+)and Ce^(^(3+)), and reactive oxygen species, and has maximum O-h and C=O in the five catalyst samples. The catalytic activity of Ce2Co1Cu1is the best at low temperature, with the T50and T90values of 235 and 258°C at a space velocity of 32000 h-1, respectively. The o-xylene is oxidized to o-methyl benzaldehyde, and then further oxidized to o-methylbenzoic acid, and finally CO_(2)and h2O are formed.

关键词： Ce_(x)Co_(y)Cuz composite oxide catalyst Polyethylene glycol Citrate sol-gel method Catalytic activity o-xylene Rare earths