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Role of FK506-binding protein in Ca^(2+) spark regulation

Science Bulletin 2017年第19期62卷 1295-1303页

作者： Yan-Ting Zhao Yun-Bo Guo Xue-Xin Fan Hua-Qian Yang Peng Zhou Zheng Chen Qi Yuan Haihong ye Guang-ju Ji shi-Qiang Wang State Key Laboratory of Membrane Biology College of Life SciencesPeking University National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of Sciences School of Basic Medical Sciences Beijing Institute for Brain Disorders Center of SchizophreniaCapital Medical University

The elementary Ca^2＋ release events, Ca2＋ sparks, has been found for a quarter of century. However, the molecular regulation of the spark generator, the ryanodine receptor （RyR） on the sarcoplasmic reticulum, remains obscure. Although each subunit of the RyR homotetramer has a site for FKS06-binding protein （FKBP）, the role of FKBPs in modifying RyR Ca^2＋ sparks has been debated for long. One of the reasons behind the controversy is that most previous studies detect spontaneous sparks, where the mixture with out-of-focus events and local wavelets prevents an accurate characterization of Ca^2＋ sparks. In the pre- sent study, we detected Ca^2＋ sparks triggered by single L-type Ca^2＋ channels （LCCs） under loose-seal patch clamp conditions in FKS06-treated or FKBPI2.6 knockout cardiomyocytes. We found that FKBP dissociation both by FKS06 and by rapamycin decreased the Ca^2＋ spark amplitude in ventricular cardiomyocytes. This change was neither due to decreased releasable Ca^2＋ in the sarcoplasmic reticulum, nor explained by changed RyR sensitivity. Actually FKS06 increased the LCC-RyR coupling probability and curtailed the latency for an LCC to trigger a RyR Ca^2＋ spark. FKBP12.6 knockout had similar effects as FKS06/rapamycin treatment, indicating that the decreased spark amplitude was attributable to the dissociation of FKBP12.6 rather than FKBP12. We also explained how decreased amplitude of spontaneous sparks after FKBP dissociation sometimes appears to be increased or unchanged due to inappropriate data processing. Our results provided firm evidence that without the inter-RyR coordination by functional FKBP12.6, the RyR recruitment during a Ca^2＋ spark would be compromised despite the sensitization of individual RyRs.

关键词： Ca^2+ sparkFKSO6-binding protein Ryanodine receptorlntracellular calcium Excitation-contraction coupling

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Mechanistic study on the regioselectivity of Co-catalyzed hydroacylation of 1,3-dienes

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Chinese Chemical Letters 2015年第1期26卷 58-62页

作者： Yuan-ye Jiang Hai-Zhu Yu Jing shi Department of Chemistry University of Science and Technology of China Department of Polymer Science and Engineering University of Science and Technology Beijing

Density functional theory（DFT） method was used to explore the origin of the regioselectivity of Cocatalyzed hydroacylation of 1,*** reaction of 2-methyl-1,3-butadiene and benzaldehyde with1,3-bis（diphenylphosphino）propane ligand was chosen as the model *** energies of the intermediates and transition states in the stages of oxidative cyclization,β-H elimination and C-H reductive elimination were *** results show that β-H elimination is the ratedetermining step for the whole catalytic cycle.C1-Selective oxidative cyclization is favored over C4-selective oxidative ***.C4-selective oxidative cyclization is kinetically disfavored than all the steps in C1-hydroacylation mechanisms,consistent with the experimentally obtained C1-selective hydroacylation *** the reason for such observation,we suggest that both electronic and steric effects contribute to the *** the electronic aspect,C1 is more electron rich than C4 due to the methyl group on C2,which makes the electrophilic attack of aldehyde carbon on C1 more *** the steric aspect,the methyl group locates farther from the ligands in the transition state of C1-selective oxidative cyclization than in that of C4-selective oxidative cyclization.

关键词： Density functional theory Cobalt Regioselectivity Hydroacylation

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Long non-coding RNA NONMMUG014387 promotes Schwann cell proliferation after peripheral nerve injury

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Neural Regeneration Research 2017年第12期12卷 2084-2091页

作者： Bin Pan Zhong-ju shi Jia-yin Yan Jia-he Li shi-qing Feng Department of Orthopedics Tianjin Medical University General Hospital Tianjin China

Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1（Cthrc1）. Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid p HBAd-MCMV-GFP-NONMMUG014387 and p HBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups： control（Schwann cells without intervention）, Ad-GFP（Schwann cells with GFP overexpression）, and Ad-NONMMUGO148387（Schwann cells with GFP and NONMMUGO148387 overexpression）. Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lnc RNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, m RNA and protein levels of Cthrc1, Wnt5 a, ROR2, Rho A, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.

关键词： nerve regeneration peripheral nerve injury Schwann cells long non-coding RNAs proliferation Wnt/PCP pathway Cell CountingKit-8 assay adenovirus overexpression sciatic nerve Cthrcl neural regeneration

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Construction of the Skeleton of Phthalascidin, Mechanism of the Formation of the Key Tricyclic Lactam Intermediate

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Chinese Chemical Letters 2002年第8期13卷 701-704页

作者： Zhan Zhu LIU ye WANG shi Zhi CHEN Institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050

The mechanism of the formation of a key tricyclic lactam intermediate 3 was studied. It was found that the E-form compound 3 was transformed from the Z-form compound 4. The formation of 4 was a kinetically controlled process while the formation of 3 was a thermodynamically favorable one. A possible mechanism was given in this paper.

关键词： Lactam phthalascidin mechanism Et-743.

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Stapled SC34EK fusion inhibitors with high potency against HIV-1and improved protease resistance

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Chinese Chemical Letters 2018年第7期29卷 1167-1170页

作者： ye Guo Lili Fu Xiaowen Fan Xuanling shi School of Pharmacy Baotou Medical College Comprehensive AIDS Research Center School of Medicine Tsinghua University

HIV fusion inhibitors are promising therapeutic agents for AIDS treatment. One fusion inhibitor has been approved as anti-HIV drug, while more of them are in preclinical studies or clinical trials. Highly active fusion inhibitors with excellent pharmacokinetic properties are still needed for development of anti-HIV drugs. We found that all-hydrocarbon staples inserted in SC34 EK could not only enhance the inhibitory activity of inhibitors against HIV-1, but also improve protease resistance. Further study revealed that SC34 EK-1 containing a staple was a potent fusion inhibitor with IC;value of 0.04-6.4 nmol/L towards diverse HIV-1 subtypes and half-life value of 112 min against protease hydrolysis. X-ray crystallography studies indicated that introduction of a hydrocarbon staple in SC34 EK could make the amino acid at the interaction surface form perfect conformation to promote inhibitor peptide interacting with target.

关键词： Fusion inhibitor HIV-1 Stapled peptide SC34EK

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Distribution characteristics of wave energy in the Zhe-Min coastal area

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Acta Oceanologica Sinica 2022年第5期41卷 163-172页

作者： Qin ye Zhongliang Yang Min Bao Weiyong shi Hongyuan shi Zaijin You Wenyan Zhang Second Institute of Oceanography Ministry of Natural ResourcesHangzhou310012China State Key Laboratory of Satellite Ocean Environment Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou310012China Ludong University Yantai264025China Dalian Maritime University Dalian116026China Institute of Coastal System Helmholtz-Zentrum HereonGeesthacht21502Germany

A 10-year(2003–2012)hindcast was conducted to study the wave field in the Zhe-Min coastal area(Key Area OE-W2)located off Zhejiang and Fujian provinces of *** by the wind field from a weather research and forecasting model(WRF),high-resolution wave modelling using the SWAN was carried out in the study *** simulated wave fields show a good agreement with *** the simulation results,we conducted statistical analysis of wave power density in terms of spatial distribution and temporal *** effective duration of wave energy in the sea area was discussed,and the stability of wave energy was evaluated using the coefficient of variation of wave power *** indicate that the wave energy resource in the study area was about 4.11×10^(6) *** distribution of wave energy tends to increase from the north(off Zhejiang coast)to the south(off Fujian coast),and from near-shore area to the open *** sea areas with wave power density greater than 2 kW/m are mostly distributed seaward of the 10-m isobath,and the contours of the wave power density are almost parallel to the *** sea areas around the islands that are far from the mainland are rich in wave energy,usually more than 6 kW/m,and therefore are of obvious advantages in planning wave energy development and *** effective duration of wave energy in the offshore area shows an increasing trend from north(off Zhejiang coast)to south(off Fujian coast),with values of∼3500 h in the north and∼4450 h in the *** coefficient of variation of wave energy in this region is mostly in the range of 1.5–3.0,and gradually decreases from the north to the south,suggesting that the wave energy in the south is more stable than that in the north.

关键词： SWAN model wave energy wave power density effective duration Zhe-Min coastal area

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A New Method for Resource Allocation Optimization in Disaster Reduction and Risk Governance

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International Journal of Disaster Risk Science 2016年第2期7卷 138-150页

作者： Xiao-Bing Hu Ming Wang Tao ye Peijun shi State Key Laboratory of Earth Surface Processes and Resource Ecology Beijing Normal University Academy of Disaster Reduction and Emergence Management Beijing Normal University

How to allocate and use resources play a crucial role in disaster reduction and risk governance(DRRG).The challenge comes largely from two aspects: the resources available for allocation are usually limited in quantity; and the multiple stakeholders involved in DRRG often have conflicting interests in the allocation of these limited resources. Therefore resource allocation in DRRG can be formulated as a constrained multiobjective optimization problem(MOOP). The Pareto front is a key concept in resolving a MOOP, and it is associated with the complete set of optimal solutions. However, most existing methods for solving a MOOPs only calculate a part or an approximation of the Pareto front, and thus can hardly provide the most effective or accurate support to decisionmakers in DRRG. This article introduces a new method whose goal is to find the complete Pareto front that resolves the resource allocation optimization problem in *** theoretical conditions needed to guarantee finding a complete Pareto front are given and a practicable, ripplespreading algorithm is developed to calculate the complete Pareto front. A resource allocation problem of risk governance in agriculture is then used as a case study to test the applicability and reliability of the proposed method. The results demonstrate the advantages of the proposed method in terms of both solution quality and computational efficiency when compared with traditional methods.

关键词： Disaster reduction Multiobjective optimization Pareto front Resource allocation Risk governance Ripple-spreading algorithm

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A Trust Region Algorithm for Solving Bilevel Programming Problems

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Acta Mathematicae Applicatae Sinica 2013年第3期29卷 491-498页

作者： Guo-shan LIU shi-qin XU Ji-ye HAN School of Business Renmin University of China Academy of Mathematics and Systems Science Chinese Academy of Sciences

In this paper, we present a new trust region algorithm for a nonlinear bilevel programming problem by solving a series of its linear or quadratic approximation subproblems. For the nonlinear bilevel programming problem in which the lower level programming problem is a strongly convex programming problem with linear constraints, we show that each accumulation point of the iterative sequence produced by this algorithm is a stationary point of the bilevel programming problem.

关键词： Bilevel programming problem trust region algorithm global convergence mathematical program with equilibrium constraints stationary point

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Local Preserving Graphs Using Intra-Class Competitive Representation for Dimensionality Reduction of Hyperspectral Image

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Journal of Beijing Institute of Technology 2021年第2期30卷 139-158页

作者： Zhen ye shihao shi Tao Sun Lin Bai School of Electronics and Control Engineering Chang’an UniversityXi’an 710064China

As a key technique in hyperspectral image pre-processing,dimensionality reduction has received a lot of ***,most of the graph-based dimensionality reduction methods only consider a single structure in the data and ignore the interfusion of multiple *** this paper,we propose two methods for combining intra-class competition for locally preserved graphs by constructing a new dictionary containing neighbourhood *** two methods explore local information into the collaborative graph through competing constraints,thus effectively improving the overcrowded distribution of intra-class coefficients in the collaborative graph and enhancing the discriminative power of the *** classifying four benchmark hyperspectral data,the proposed methods are proved to be superior to several advanced algorithms,even under small-sample-size conditions.

关键词： intra-class competition graph construction hyperspectral image dimensionality reduction

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Energy Consumption and Its Influencing Factors of Iron and Steel Enterprise

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Journal of Iron and Steel Research International 2013年第8期20卷 8-13页

作者： DU Tao shi Tian LIU Yong ye Jian-bo State Environmental Protection Key Laboratory of Eco-Industry Northeastern University

Based on the theory of system energy-saving, a multilevel input-output computational model ot the iron and steel enterprise was established. And one example was calculated using this model to analyze the product energy value, the process of energy consumption and energy consumption per ton of steel of an iron and steel enterprise. The influences of factory layout, steel ratio and production structure are calculated and analyzed. The calculation example indicates that reasonable factory layout is helpful to reduce its transportation energy consumption, decrease loss of heat, improve product rate and reduce environmental contamination; ore to steel ratio and iron to steel ratio decrease at the same degree; the influence of ore to steel ratio on energy intensity per ton is less than that of iron to steel ratio. The lord process product structure has a certain effect on comprehensive energy consumption per ton of steel.

关键词： energy consumption product energy value input-output model influencing factor

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