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Identification of endothelial protein C receptor as a novel druggable agonistic target for reendothelialization promotion and thrombosis prevention of eluting stent

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Bioactive Materials 2024年第11期41卷 485-498页

作者： Jing Chen Changyi Zhou weilun Fang Jiasheng Yin Jian Shi Junbo Ge Li Shen Shi-Ming Liu Shao-Jun Liu Guangzhou Institute of Cardiovascular Disease Guangdong Key Laboratory of Vascular DiseasesThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong510260PR China Department of Cardiology The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong510260PR China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai200032PR China Research Unit of Cardiovascular Techniques and Devices Chinese Academy of Medical SciencesFudan UniversityShanghai200433PR China Department of Cardiology The First Affliated HospitalGuangzhou University of Chinese MedicineGuangzhouGuangdong510000PR China

The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.

关键词： EPCR Reendothelialization Agonistic target Eluting stent Stent thrombosis

Regulation of cytokinin biosynthesis using PtRD26pro-IPT module improves drought tolerance through PtARR10-PtYUC4/5-mediated reactive oxygen species removal in Populus

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Journal of Integrative Plant Biology 2022年第3期64卷 771-786页

作者： Hou-Ling Wang Qi Yang Shuya Tan Ting Wang Yi Zhang Yanli Yang weilun Yin Xinli Xia Hongwei Guo Zhonghai Li National Engineering Laboratory for Tree Breeding College of Biological Sciences and TechnologyBeijing Forestry UniversityBeijing100083 China Department of Biology Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education InstitutesSouthern University of Science and Technology(SUSTech)Shenzhen518055 China

Drought is a critical environmental factor which constrains plant survival and *** engineering provides a credible strategy to improve drought tolerance of ***,we generated transgenic poplar lines expressing the isopentenyl transferase gene(IPT)under the driver of Pt RD26 promoter(PtRD26 pro-IPT).Pt RD26 is a senescence and drought-inducible NAC transcription *** RD26 pro-IPT plants displayed multiple phenotypes,including improved growth and drought *** analysis revealed that auxin biosynthesis pathway was activated in the PtRD26 pro-IPT plants,leading to an increase in auxin *** analysis revealed that ARABIDOPSIS RESPONSE REGULATOR10(PtARR10),one of the type-B ARR transcription factors in the cytokinin pathway,was induced in PtRD26 pro-IPT plants and directly regulated the transcripts of YUCCA4(Pt YUC4)and YUCCA5(PtYUC5),two enzymes in the auxin biosynthesis *** of PtYUC4 enhanced drought tolerance,while simultaneous silencing of PtYUC4/5 evidently attenuated the drought tolerance of Pt RD26 pro-IPT ***,Pt YUC4/5 displayed a conserved thioredoxin reductase activity that is required for drought tolerance by deterring reactive oxygen species *** work reveals the molecular basis of cytokinin and auxin interactions in response to environmental stresses,and shed light on the improvement of drought tolerance without a growth penalty in trees by molecular breeding.

关键词： auxin cytokinin drought tolerance leaf senescence PtARR PtYUC ROS

Numerical characteristics of the full operator hybrid simulation method

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Earthquake Engineering and Engineering Vibration 2011年第3期10卷 453-463页

作者： Chung-Chan hung Yong-Song Chen Department of Civil Engineering Central University （NCU） Chinese Taipei Department of Mechanical Engineering Chung Cheng University （NCCU） Chinese Taipei

The full operator method （FOM） has been proposed to overcome some of the shortcomings of the commonly used operator splitting method （OSM）. In particular, the FOM is improved by increasing the accuracy of both the predictor and corrector using the estimated tangent stiffness of the tested structure. The numerical characteristics of the FOM, including stability and accuracy, are investigated in this study. It is shown that FOM is conditionally stable. The stability and accuracy characteristics are dependent on the accuracy of the estimated tangent stiffness and the parameters associated with the acceleration variation in the time-stepping integration method. Mass-spring systems with different types of nonlinearity, including hardening, stiffening, and softening behavior, are used to evaluate the performance of the FOM. It is found that the FOM can capture these types of nonlinearity with satisfactory accuracy. Using a prototype 12-story composite coupled wall system, the influences of the strong nonlinearity of the system as well as the displacement control errors from hydraulic actuators on the performance of the FOM are explored. The results show that the FOM is capable of generating reasonably accurate results despite the presence of strong structural nonlinearity and displacement control errors.

关键词： hybrid simulation tangent stiffness numerical characteristic composite coupled wall system collapse behavior nonlinear behavior

Exploratory analysis of grocery product networks

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Journal of Management Analytics 2022年第2期9卷 169-184页

作者： Ping-hung Hsieh College of Business Oregon State UniversityCorvallisOR 97331USA

Finding meaningful sets of co-purchased products allows retailers to manageinventory better and develop market strategies. Analyzing the baskets ofproducts, known as market basket analysis, is typically carried out usingassociation rule mining or community detection approach. This article usesboth methods to investigate a transaction dataset collected from a brick-andmortargrocery store. The findings reveal interesting purchasing patterns oflocal residents and prompt us to consider dynamic modeling of the productnetwork in the future.

关键词： market basket analysis association rules community detection graph theory social networks transaction data

Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis

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Journal of Pharmaceutical Analysis 2024年第8期14卷 1140-1157页

作者： weilun Cheng Wanqi Mi ShiyuanWang Xinran Wang Hui Jiang Jing Chen Kaiyue Yang Wenqi Jiang Jun Ye Baoliang Guo Yunpeng Zhang Department of General Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin150001China College of Bioinformatics Science and Technology Harbin Medical UniversityHarbin150081China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

Breast cancer remains a leading cause of mortality in women ***-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic *** the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable *** the scope of our study,high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue ***,TNBC exhibited significant specificity regarding cell proliferation,differentiation,and disease *** associations between tumor grade,prognosis,and TNBC oncogenes were established via pseudotime trajectory ***,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in ***,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor *** genes in these three cluster cells could therefore serve as potential therapeutic targets for *** collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as *** further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse ***,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

关键词： Triple-negative breast cancer Single-cell RNA sequencing Epithelial-mesenchymal transition Macrophage polarization Therapeutic drugs Bioinformatics

Enhanced Intrusion Detection System for an EH IoT Architecture Using a Cooperative UAV Relay and Friendly UAV Jammer

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IEEE/CAA Journal of Automatica Sinica 2021年第11期8卷 1786-1799页

作者： Van Nhan Vo hung Tran Chakchai So-In Institute of Research and Development Duy Tan UniversityDa Nang 550000Vietnam Faculty of Information Technology Duy Tan UniversityDa Nang 550000Vietnam Applied Network Technology Laboratory Department of Computer ScienceFaculty of ScienceKhon Kaen UniversityKhon Kaen 40002Thailand Faculty of Computer Science Phenikaa UniversityHanoi 100000Vietnam

In this paper,the detection capabilities and system performance of an energy harvesting(EH)Internet of Things(Io T)architecture in the presence of an unmanned aerial vehicle(UAV)eavesdropper(UE)are *** communication protocol is divided into two *** the first phase,a UAV relay(UR)cooperates with a friendly UAV jammer(UJ)to detect the UE,and the UR and UJ harvest energy from a power beacon(PB).In the second phase,a ground base station(GBS)sends a confidential signal to the UR using non-orthogonal multiple access(NOMA);the UR then uses its harvested energy to forward this confidential signal to IoT destinations(IDs)using the decode-and-forward(DF)***,the UJ uses its harvested energy to emit an artificial signal to combat the detected UE.A closed-form expression for the probability of detecting the UE(the detection probability,DP)is derived to analyze the detection ***,the intercept probability(IP)and throughput of the considered IoT architecture are ***,we identify the optimal altitudes for the UR and UJ to enhance the system and secrecy *** Carlo simulations are employed to verify our approach.

关键词： Detection probability(DP) energy harvesting(EH) friendly UAV jammer Internet of Things(IoT) system performance UAV detection

Second-order phase correction of NMR spectra acquired using linear frequency-sweeps

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Magnetic Resonance Letters 2022年第1期2卷 1-8,I0002页

作者： Zhehong Gan Ivan hung National High Magnetic Field Laboratory 1800 East Paul Dirac DriveTallahasseeFL32310USA

NMR spectra acquired with experiments using frequency-sweeps such as the wide-band uniform-rate smooth truncation(WURST)spin-echo and Carr-Purcell-Meiboom-Gill(CPMG)sequences cannot be absorptively phased by using only conventional zerothand first-order phase *** of phase correction up to the secondorder is described for obtaining absorptive spectra,which have more desirable line shapes and noise properties than magnitude *** relationship of the second-order phase to the parameters of frequency sweeps is *** second-order phasing in the frequency-domain is equivalent to a point spread in the time-domain *** application of second-order phase correction is demonstrated with a wideline 35Cl CPMG spikelet spectrum.

关键词： Second-order phase Noise Line shape Absorptive Dispersive Frequency sweep CHIRP WURST Adiabatic Broadband CPMG Spin-echo Wideline ^(35)Cl

Classification of brain arteriovenous malformations located in motor-related areas based on location and anterior choroidal artery feeding

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Stroke & Vascular Neurology 2021年第3期6卷 441-448,I0073-I0075页

作者： Yuming Jiao Hao Li weilun Fu Jiancong Weng Ran Huo Yinyan Wang Shuo Wang Tao Jiang Yong Cao Ji Zong Zhao Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Center of Stroke Beijing Institute for Brain DisordersBeijingChina Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease BeijingChina Beijing Neurosurgical Institute Capital Medical UniversityBeijingChina

Objective Surgical management of arteriovenous malformations(AVMs)involving motor cortex or fibre tracts(M-AVMs)is *** study aimed to construct a classification system based on nidus locations and anterior choroidal artery(AChA)feeding to pre-surgically evaluate motor-related and seizure-related outcomes in patients undergoing resection of *** and materials A total of 125 patients who underwent microsurgical resection of M-AVMs were retrospectively *** subtypes were identified based on nidus location:(I)nidus involving the premotor area and/or supplementary motor areas;(II)nidus involving the precentral gyrus;(III)nidus involving the corticospinal tract(CST)and superior to the posterior limb of the internal capsule;(IV)nidus involving the CST at or inferior to the level of posterior limb of the internal *** addition,we divided type IV into type IVa and type IVb according to the AChA ***-related motor deficit(MD)evaluations were performed 1 week(short-term)and 6 months(long-term)after *** The type I patients exhibited the highest incidence(62.0%)of pre-surgical epilepsy among the four *** analysis showed that motor-related area subtypes(p=0.004)and diffuse nidus(p=0.014)were significantly associated with long-term ***-term MDs were significantly less frequent in type I than in the other *** IV patients acquired the highest proportion(four patients,25.0%)of long-term poor outcomes(mRS>2).Type IVb patients showed a significantly higher incidence of post-surgical MDs than type IVa patients(p=0.041).The MDs of type III or IV patients required more recovery *** the 62 patients who had pre-surgical seizures,90.3%(56/62)controlled their seizures well and reached Engel class I after *** Combining the consideration of location and AChA feeding,the classification for M-AVMs is a useful approach for predicting post-surgical motor function and decision-making.

关键词： capsule epilepsy Surgical

On Huppert＇s Conjecture for Alternating Groups of Low Degrees

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Algebra Colloquium 2015年第2期22卷 293-308页

作者： hung Ngoc Nguyen hung P. Tong-Viet Thomas P. Wakefield Department of Mathematics The University of Akron Akron Ohio 44325 USA School of Mathematical Sciences. North-West University (Mafikeng Campus) Mmabatho 2735 South Africa Department of Mathematics and Statistics Youngstown State University One University Plaza Youngstown Ohio 44555 USA

Bertram Huppert conjectured in the late 1990s that the nonabelian simple groups are determined up to an abelian direct factor by the set of their character degrees. Although the conjecture has been established for various simple groups of Lie type and simple sporadic groups, it is expected to be difficult for alternating groups. In [5], Hup- pert verified the conjecture for the simple alternating groups AN of degree up to 11. In this paper, we continue his work and verify the conjecture for the alternating groups of degrees 12 and 13.

关键词： alternating groups character degrees