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Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1441-1456页

作者： Xin zhuo Yue Wu Xiujuan Fu Jianbin Li Yuxin xiang Xiaoyu Liang Canquan Mao Yuhong Jiang Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue *** is an urgent need to explore potential drug strategies for mitigating lung ***-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal ***,it has been rarely reported about the role of PAR2 in lung *** study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in ***,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of *** also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS ***,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

关键词： Protease-activated receptor 2(PAR2) CRISPR-Cas9 Gene editing Inflammation Acute lung inflammation NLRP3 Nanoparticles Drug delivery

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Phase diagram and transport properties of Sb-doped Ca0.88La0.12Fe2As2 single crystals

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Frontiers of physics 2017年第4期12卷 167-172页

作者： xiang-zhuo Xing Wei Zhou Chun-Qiang Xu Nan Zhou Fei-Fei Yuan Yu-Feng Zhang Xiao-Feng Xu Zhi-xiang Shi department of Physics and Key Laboratory of MEMS of the Ministry of Education Southeast University Nanjing 211189 China department of Physics and Hangzhou Key Laboratory of Quantum Matters Hangzhou Normal University Hangzhou 310036 China

The effects of isovalent Sb substitution on the superconducting properties of the Ca0.88La0.12Fe2（As1-ySby）2 system have been studied through electrical resistivity measure- ments. It is seen that the antiferromagnetic or structural transition is suppressed with Sb content, and a high-To superconducting phase, accompanied by a low-Tc phase, emerges at 0.02 ≤y ≤ 0.06. In this intermediate-doping regime, normal-state transport shows non-Fermi-liquid-like behaviors with nearly T-linear resistivity above the high-Tc phase. With further Sb doping, this high-Tc phase abruptly vanishes for y 〉 0.06 and the conventional Fermi liquid is restored, while the low-T,, phase remains robust against Sb inlpurities. The coincidence of the high-Tc phase and non-Fermi liquid transport behaviors in the intermediate Sb-doping regime suggests that AFM fluctuations play an important role in the observed non-Fermi liquid behaviors, which may be intimately related to the unusual nonbulk high-Tc phase in this system.

关键词： Sb doped Ca0.88La0.12Fe2As2 superconductors electrical resistivity measurement phase diagram

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A Potential Model for detecting Crowding-induced Epithelial Cell and Cancer Cell Extrusion

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Current Medical Science 2019年第3期39卷 391-395页

作者： Ping HAN Dong-xiao LI Yu LEI Jing-mei LIU xiang-ming DING Han WANG zhuo-ying LIN Wei YAN de-an TIAN department of Gastroenterology Tongji HospitalTongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Overcrowding and cell deformation lead to the shedding of apoptotic and live cells to maintain homeostasis in the epithelium. Recent studies have attempted to explain the effect of extrusion on epithelial homeostasis and tumor metastasis, but lack the requisite quantitative models for testing extrusion. Here, we designed a petri dish inversion model to detect the extrusion ability of both normal epithelial cells and epithelial cancer cells. Firstly, we found cell extrusion was observed in both normal epithelial cells (LO2 cells) and cancer cells;in confluent LO2 cell culture, certain cells were surrounded by their neighbors, suffered "collective attack", and were then made round in shape. Green fluorescent protein (GFP)-labeled cancer cells were also found to be squeezed by normal LO2 cells. Using the petri dish inversion model, we quantified the number of extrusion cells, and demonstrated that the ability of cancer cell extrusion was related to the metastatic potential of cancer cell lines. Our findings provide a novel model to detect crowdinginduced epithelial cell and cancer cell extrusion. This novel model provides a quantitative method for research into apoptotic and cancer cell extrusion, particularly in human hepatocellular carcinoma.

关键词： hepatocellular carcinoma metastasis epithelial homeostasis crowding extrusion

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Interspecies Phylogenetic Analysis of Clonorchis sinensis in High-incidence Areas of Hunan Province, China

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Biomedical and Environmental Sciences 2021年第11期34卷 881-890页

作者： LONG Xiao Lei WANG Shi Ping ZHOU Shuai Feng LI Zheng xiang ZHUANG Shi Feng HE zhuo department of Medical Parasitology Xiangya School of MedicineCentral South UniversityChangsha 410028HunanChina Hunan Provincial Center for Disease Control and prevention Changsha 410005HunanChina

Objective This study aims to investigate the infection of Clonorchis sinensis(***)in highincidence areas of Hunan Province,*** phylogenetic analysis of the *** species in the highly infected areas was carried *** Infection of the definitive human host and intermediate fish host by *** was investigated,and the mitochondrial genes cox1 and Nad1 were used as genetic markers for phylogenetic *** In 2016–2020,the average population infection rate of Hunan was 1.38%,while in Tongdao County the rate was up to 26.90%,and the highest fish infection rate was detected in Qiyang County(99.44%in the dorsal fin of crucian carp).High genetic sequence similarity was observed in the samples from Qiyang and Lengshuitan which exhibited high homology with those from Guangdong and Gansu,whereas the parasitic species from Tongdao was highly homologous with those located in high-latitude ***,no significant difference was found in the gene sequence of the parasitic species in definitive hosts dogs and *** The systematically study of *** infection in the high-incidence areas will contribute greatly to the prevention and effectively controlling the spread of Clonorchis sinensis in Hunan Province The endemic of *** infection in Hunan Province is the result of co-action of local and foreign parasite species.

关键词： Clonorchis sinensis Mitochondrial genes Coxl Nodi Phytogeny

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Laparoscopic segmental colectomy for colonic lymphangiomas: A definitive, minimally invasive surgical option

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World Journal of Gastroenterology 2014年第26期20卷 8745-8750页

作者： Chang-Hua zhuo de-Bing Shi Min-Gang Ying Yu-Fan Cheng Yu-Wei Wang Wen-Ming Zhang San-Jun Cai Xin-xiang Li department of Oncology Shanghai Medical CollegeFudan University department of Colorectal Surgery Fudan University Shanghai Cancer Center department of Surgical Oncology Fujian Provincial Cancer HospitalTeaching Hospital of Fujian Medical University department of Pathology Fudan University Shanghai Cancer Center department of Endoscopy Fudan University Shanghai Cancer Center

Colonic lymphangioma is an unusual benign *** herein describe two cases.A 36-year-old woman was admitted with one year of intermittent abdominal pain;colonoscopy,abdominopelvic computed tomography and endoscopic ultrasonography(EUS)revealed enlarged cystic masses at the ascending *** another 40-year-old man,colonoscopy and EUS revealed an asymptomatic lobulated cystic mass with four small sessile polyps at the sigmoid *** patients underwent laparoscopic segmental *** masses were histologically confirmed as cystic lymphangiomas,and the patients were discharged without *** management of colonic lymphangioma depends on the individual situation;close surveillance or endoscopic therapy may be appropriate for asymptomatic lesions smaller than 2.5 cm in *** intervention can be considered for larger lesions or in patients who develop complication *** segmental colon resection may be recommended to excise relatively large submucosal lesions because it is a definitive,minimally invasive intervention with a fast postoperative recovery.

关键词： Cystic lymphangioma Colon neoplasm Laparoscopic surgery Colectomy Segmental resection

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Antiferromagnetic insulating state in quasi-one-dimensional K_(2)Cr_(3)As_(3)H

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Science China(Physics,Mechanics & Astronomy) 2023年第3期66卷 139-146页

作者： Bai-zhuo Li Si-Qi Wu Jin-Jin xiang Qin-Qing Zhu Yi Liu Chao Cao Guang-Han Cao School of Physics Zhejiang UniversityHangzhou 310030China School of Science Westlake Institute for Advanced StudyWestlake UniversityHangzhou 310064China department of Applied Physics Zhejiang University of TechnologyHangzhou 310023China Center for Correlated Matter Zhejiang UniversityHangzhou 310030China Zhejiang Province Key Laboratory of Quantum Technology and devices Interdisciplinary Center for Quantum InformationState Key Lab of Silicon MaterialsZhejiang UniversityHangzhou 310030China

Quasi-one-dimensional(Q1D) Cr-based pnictide K_(2)Cr_(3)As_(3)exhibits superconductivity probably with spin-triplet pairing. It is of fundamental importance to explore the parent compound from which superconductivity emerges. Here we report the synthesis,crystal structure, physical properties, and density functional theory(DFT) calculations of(nearly) fully hydrogenized K_(2)Cr_(3)As_(3)*** is found that the intercalation of hydrogen in K_(2)Cr_(3)As_(3)leads to absence of metallicity as well as superconductivity. An antiferromagnetic transition nearby room temperature is evidenced from the measurements of magnetic susceptibility and heat *** antiferromagnetic insulating state can be reproduced by the DFT calculations, which show a novel non-collinear co-planar magnetic order. Our result sheds light on the mechanism of unconventional superconductivity in Q1D Cr-based superconductors.

关键词： quasi-one-dimensional Cr-based superconductor antiferromagnetism DFT calculations

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Insights on the mechanism of Na-ion storage in expanded graphite anode

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Journal of Energy Chemistry 2021年第2期30卷 56-62,I0003页

作者： Xiaodan Li Zhibin Liu Jinliang Li Hang Lei Wenchen zhuo Wei Qin xiang Cai Kwun Nam Hui Likun Pan Wenjie Mai Siyuan Laboratory Guangdong Provincial Engineering Technology Research Center of Vacuum Coating Technologies and New Energy MaterialsDepartment of PhysicsJinan UniversityGuangzhou 510632GuangdongChina Shanghai Key Laboratory of Magnetic Resonance School of Physics and Electronic ScienceEast China Normal UniversityShanghai 200062China department of Chemistry Jinan UniversityGuangzhou 510632GuangdongChina College of Materials Science and Engineering Changsha University of Science and TechnologyChangsha 410114HunanChina department of Light Chemical Engineering Guangdong PolytechnicFoshan 528041GuangdongChina Institute of Applied Physics and Materials Engineering University of MacaoAvenida da UniversidadeTaipaMacao 999078China

Currently,Na-ion battery(NIB) has become one of the most potential alternatives for Li-ion batteries due to the safety and low *** a promising anode for Na-ion storage,expanded graphite has attracted considerable ***,the sodiation-desodiation process is still *** our work,we obtain expanded graphite through slight modified Hummer's method and subsequent thermal treatment,which exhibits excellent cycling *** at a high current density of 1 A g^(-1),our expanded graphite still remains a high reversible capacity of 100 mA h g^(-1) after 2600 ***,we also investigate the electrochemical mechanism of our expanded graphite for Na-ion storage by operando Raman technique,which illuminate the electrochemical reaction during different sodiation-desodiation processes.

关键词： Expanded graphite Sodiation-desodiation process Operando Raman spectroscopies Na-ion batteries

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Primary human hepatocyte transplantation in the therapy of hepatic failure:2 cases report

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Asian Pacific Journal of Tropical Medicine 2012年第2期5卷 165-168页

作者： zhuo-Ri Li Xian-Hai Mao Xiao-Xuan Hu Sheng-Dan Nie Yong-Zhong Shi Hua xiang Jian-Hui Yang Ou-de Cao department of Hepatobiliary Surgery Hainan Provincial People's Hospital department of Hepatobiliary Surgery Hunan Provincial People's Hospital department of Internal Medicine of Hepathopathy Hunan Provincial People's Hospital Clinical Research Institute Hunan Provincial People's Hospital Minimally Invasive and Interventional Center Hunan Provincial People's Hospital

Liver failure is the end stage of hepatopathy with unfavorable *** two patients with liver failure,viable primary human hepatocytes,obtained from resected liver tissue of patients with *** transplanted into the spleen by interventional therapy through femoral arterial *** transplantation,the patients’ clinical symptoms and liver function were significantly ***,their bilirubin increased within six days following *** suffered from hepatic coma and give up treatment and the other patient died forteen days after *** is technically safe to treat liver failure by intrasplenic transplantation of adult hepatocytes and the clinical efficacy has been *** to make transplanted hepatic cells proliferate and functionally survive is the key point to maintain continuous improvement of the recipient’s hepatic function.

关键词： Cell transplantation Hepatocyte Liver failure

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Anticoagulant rodenticide intoxication in east China:a three-year analysis

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Forensic Sciences Research 2016年第1期1卷 22-27页

作者： Hui Yan Lin Zhu Xianyi zhuo Min Shen Ping xiang department of Forensic Toxicology Shanghai Key Laboratory of Forensic MedicineShanghai Forensic Service PlatformInstitute of Forensic ScienceMinistry of JusticePRCShanghaiChina

The study was designed to analyze the incidence and pattern of anticoagulant rodenticide intoxication in east China and to discuss strategies of diagnosis based on laboratory analysis experience.A total of 117 patients with anticoagulant rodenticide poisoning confirmed by toxicological analysis in east China were included in this study from 2011 to *** mean concentration of anticoagulant rodenticide,age,and gender of these patients,as well as the mode and type of poisoning,were *** age ranged from less than 1 to 80 years with the feeble preponderance of males(M D 53.0%,F D 47.0%).The 0–9 age group covered the largest ratio of these anticoagulant rodenticide poisoning *** or voluntary ingestion seems to be the most common cause of intoxication,with still the poisoning cause being unknown for a large number of positive *** was the most commonly observed anticoagulant rodenticide found in the biological samples,followed by *** concentrations of bromadiolone and brodifacoum that were detected in the first collected whole blood from each patient ranged from 1 to 878 ng/mL(mean 97.9 ng/mL)and from 0.5 to 1566 ng/mL(mean 225.1 ng/mL),*** data analysis shows a high incidence of anticoagulant rodenticide poisoning without awareness of the poisoned subjects,clearly emphasizing the need for toxicological analysis in patients with vitamin K-dependent coagulation disorder and restriction on availability of anticoagulant rodenticide.

关键词： Forensic science forensic toxicology anticoagulant rodenticides intoxication bromadiolone brodifacoum poisoning

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Two Crystal Phases of C3N4 Found in Carbon Nitride Films Prepared by Ion Implantation

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Chinese Physics Letters 1996年第10期13卷 782-785页

作者： GU You-song PAN Li-qing ZHAO Min-xue CHANG xiang-rong TIAN Zhong-zhuo XIAO Ji-mei department of Material Physics and State Key Laboratory of New Metal MaterialsBeijing University of Sciences and TechnologyBeijing 100083

CNx films prepared by high dose ion implantation and post-annealing were studied by Auger electron spectroscopy,x-ray photoelectron spectroscopy and x-ray diffraction.A nearly uniform CNx layer was *** and nitrogen were found covalently bonded in the films.X-ray diffraction results showed that two crystal phases of C_(3)N_(4),β-C_(3)N_(4) and p-C_(3)N_(4),have been formed in the matrix of carbon.

关键词： diffraction. implantation spectroscopy

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