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‘C-type’ closed state and gating mechanisms of K2P channels revealed by conformational changes of the TREK-1 channel

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journal of Molecular Cell Biology 2022年第1期14卷 47-55页

作者： Qiansen Zhang jie Fu shaoying Zhang Peipei Guo shĳie Liu juwen shen jiangtao Guo Huaiyu Yang shanghai Key Laboratory of Regulatory Biology Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Biophysics and Department of Pathology of Sir Run Run shaw Hospital Zhejiang University School of MedicineHangzhou 310058China

Two-pore domain potassium (K2P) channels gate primarily within the selectivity filter, termed ‘C-type’ gating. Due to the lack of structural insights into the nonconductive (closed) state, ‘C-type’ gating mechanisms remain elusive. Here, molecular dynamics (MD) simulations on TREK-1, a K2P channel, revealed that M4 helix movements induce filter closing in a novel ‘deeper-down’ structure that represents a ‘C-type’ closed state. The ‘down’ structure does not represent the closed state as previously proposed and instead acts as an intermediate state in gating. The study identified the allosteric ‘seesaw’ mechanism of M4 helix movements in modulating filter closing. Finally, guided by this recognition of K2P gating mechanisms, MD simulations revealed that gain-of-function mutations and small-molecule activators activate TREK-1 by perturbing state transitions from open to closed states. Together, we reveal a ‘C-type’ closed state and provide mechanical insights into gating procedures and allosteric regulations for K2P channels.

关键词： K2P state selectivity filter C-type gating

An investigation of the L-shell x-ray conversion efficiency for laser-irradiated tin foils

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Plasma Science and Technology 2020年第4期22卷 48-54页

作者： David BAILIE Cormac HYLAND raj L SINGH Steven WHITE Gianluca SARRI Francis P KEENAN David RILEY Steven j ROSE Edward G HILL Feilu WANG Dawei YUAN Gang ZHAO Huigang WEI Bo HAN Baoqiang ZHU jianqiang ZHU Pengqian YANG Centre for Plasma Physics School of Mathematics and PhysicsQueen's University BelfastBelfastBT7 INNUnited Kingdom Astrophysics Research Centre School of Mathematics and PhysicsQueen's University BelfastBelfastBT7 INNUnited Kingdom Plasma Physics Group Blackett LaboratoryPrince Consort RoadLondonSW72AZUnited Kingdom Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100012People's Republic of China Department of Astronomy Beijing Normal UniversityBeijing 100875People's Republic of China shanghai Institute of Optics and Fine Mechanics Chinese Academy of Sciences.Shanghai 201800People's Republic of China

We have used the shenguangⅡlaser in third harmonic(351 nm)to investigate the emission of L-shell radiation in the 3.3–4.4 ke V range generated using thin foils of Sn coated onto a parylene substrate with irradiation of order 1015 W cm-2 and nanosecond pulse *** our experiment,we have concentrated on assessing the emission on the non-laser irradiated side as this allows an experimental geometry relevant to experiments on photo-ionised plasmas where a secondary target must be placed close to the source,to achieve x-ray fluxes appropriate to astrophysical *** L-shell conversion efficiencies are estimated to be of order 1%,with little dependence on Sn thickness between 400 and 800 nm.

关键词： conversion efficiency laser plasma x-ray sources laboratory astrophysics

Oseltamevir Helps Cure COVID 19, Corona Pandemic Carried by Global Abortion/Contraception, Global Blood/Necrotic Tissue Environmental Pollution;Guaranteed Corona Elimination by Implementing Many Childbirth per Family [Earth Bus Fare/Ticket];Contraception Reversal;Abolition of Global Contraception [One Child Policy, Small Family Norms], Abortion [jumping off Cliff to Fly-Marred Science]<br/>—Retrospective Analysis

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Open journal of Preventive Medicine 2021年第8期11卷 347-367页

作者： Elizabeth j. S. Veerakesari Celestine raj Manohar Darmalingam Zumu Akash Karpagam Faculty of Medical Sciences and Research Tamil Nadu India

Over the past one year and three months, 150 out patients with COVID 19 have been treated with early initiation of Oseltamevir 75 mg × 2 [150 mg] twice daily, with azithromycin, cephalosporin [to give atypical bacterial cover, gram positive bacterial cover, respectively] enabling cure. Corona virus pandemic was enabled by global contraception/abortion [non evidence based non medical practice] with its blood/necrotic tissue environmental pollution-documented by rising environmental oestrogen/alpha feto protein/beta human chorionic gonadotropin. Global contraception abortion with its blood, necrotic tissue environmental pollution provides a rich environmental media for Corona virus-a fastidious organism to become pandemic, with recurrent mutations. Guaranteed elimination of this fastidious organism-corona virus [and other microbes like Ebola, Nipah…] by implementing many childbirths per mother [earth bus fare/ticket] as God ordained abolition of global contraception, abortion, one child policy/small family norms [jumping off cliff to fly-marred science] with its blood/necrotic tissue pollution, mandatory reversal of contraception. Steroids are deleterious in any viral infection, being immunosuppressants-secondary mucormycosis, other fungal [less virulent] infections can follow;corona virus itself can mutate, gain virulence, drug resistance;but prior contraception-destroying germ cells, prior abortion [destruction of tissue] in the victim host result in auto-immunity of corresponding gradations including fatal HLH [Hemophagocytic lymphohistiocytosis], cytokine storm, requiring immunomodulation with plasmapheresis, steroids, hydroxychloroquine without much avail. Vaccine is live attenuated virus administered to our tissue, to elicit antibody response to the future viral invasion;inhaled virus elicits autoimmunity of varied gradations, [including fatal HLH] in the victim host, secondary to prior abortions/contraception [varied destruction of tissue, germ cells in the vic

关键词： Oseltamevir Elimination of Corona Virus Steroids Blood/Necrotic Tissue Pollution

Effect of pancreatic endotherapy on quality of life in chronic pancreatitis patients:A systematic review

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World journal of Gastrointestinal Endoscopy 2021年第8期13卷 336-344页

作者： Samuel Y Han Georgios I Papachristou raj j shah Darwin L Conwell Division of Gastroenterology Hepatology and NutritionThe Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of Gastroenterology and Hepatology University of Colorado Anschutz Medical CampusAuroraCO 80045United States

BACKGROUND Pancreatic endotherapy provides treatment options for the management of chronic pancreatitis-related structural complications such as pancreatic duct stones,strictures,and pancreatic fluid *** studies detailing endotherapy,however,have focused on technical success outcomes such as stone clearance or stricture *** To review the effect of pancreatic endotherapy on patient-centered *** Systematic review of studies examining pancreatic *** A total of 13 studies including 3 randomized clinical trials were *** majority of studies found an improvement in quality of life with pancreatic *** While pancreatic endotherapy does appear to improve quality of life,there are clear gaps in knowledge regarding many pancreatic endotherapy ***,qualitative analysis is lacking in these studies and further work is needed to elucidate the patient experience with pancreatic endotherapy.

关键词： Chronic pancreatitis Pancreatic endotherapy Endoscopic retrograde cholangiopancreatography Quality of life

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese journal of Integrative Medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying Thomas j.Sferra LIU Hui-xin LI Li PENG jun shEN A-ling Clinical Research Institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of Integrative Medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) *** polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in *** treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

Composition and Regeneration of Trees in the Community Forests of Lamjung District,Nepal

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journal of Resources and Ecology 2021年第5期12卷 658-668页

作者： Tilak Babu CHAPAGAI Dipak KHADKA Dinesh raj BHUjU Narendra raj KHANAL shI shi CUI Dafang Central Department of Environmental Science Tribhuvan UniversityKirtipur 44618Nepal Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm College of Forestry and Landscape ArchitectureSouth China Agricultural UniversityGuangzhou 510642China Golden Gate International College Tribhuvan UniversityKathmandu 4059Nepal Environment Protection and Study Center Kathmandu 44600Nepal Nepal Academy of Science and Technology Lalitpur 3323Nepal Central Department of Geography Tribhuvan UniversityKirtipur 44618Nepal

The community forest program in Nepal is one of the successful conservation *** species in a forest ecosystem have a fundamental role in maintaining the vegetation structure,complexity,and *** study analyzes the composition and regeneration of tree species in five community forests(CFs)of the sub-tropical region,Lamjung district,Nepal for preparing baseline data for long-term research projects and helps the community to manage their CFs *** species data were generated by stratified random sampling using 35 quadrate plots(size:20 m x 20 m).The density of adult trees in the forests ranged from 575 Ind ha^(-1)(Tilahar CF)to 1196 Ind/ha(Deurali Thadopakha CF).The sapling ranged from 2533 Ind ha^(-1)(Tilahar CF)to 4000 Ind ha^(-1)(Thuliban CF)and seedling from 19583 Ind ha^(-1)(Tilahar CF)to 37500 Ind ha^(-1)(Thuliban CF).Similarly,the adult tree basal area varied from 28.34 m^(2) ha^(-1)(Tilahar CF)to 49 m^(2) ha^(-1)(Deurali CF).The adult tree diversity index(shannon-Weiner’s H)also ranged from 1.08(Thuliban CF)to 1.88(Tilahar CF).The tree species such as Sapium insigne,Ficus benghalensis,Lagerstroemia parviflore,Albizia *** Pinus roxburghii were weak *** general,the forests have good regeneration status except for Tilahar Community Forest,but based on the DBH size class distribution diagram,there is no sustainable *** the five community forests the DBH size of adults was significantly different,and the DBH of Deurali Thadopakha was the *** only few species have good regeneration and most of the species have weak,poor to no *** dominancy of fewer species like shorea robusta,Castanopsis indica,and Schima wallichii accordingly maintain the overall regeneration of tree of CFs,so further plantation needs to be done inside the CF by triage accordingly those species whose regeneration has poor.

关键词： community forest composition regeneration species tree

Isolation of Cell Lines for HPV Life Cycle Studies

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Isolation of Cell Lines for HPV Life Cycle Studies

An authentication and plausibility model for big data analytic under LOS and NLOS conditions in 5G-VANET

24th International Papillomavirus Conference and Clinical Workshop

作者： Erin Isaacson Deborah j jackson Ken raj john Doorbar Division of Virology National Institute for Medical ResearchMill Hill.LondonUnited Kingdom Division of Virology National Institute for Medical ResearchMill Hill.LondonUnited Kingdom Division of Virology National Institute for Medical ResearchMill Hill.LondonUnited Kingdom Division of Virology National Institute for Medical ResearchMill Hill.LondonUnited Kingdom

＜正＞The HPV productive cycle requires the maintenance of viral episomes in cells of the basal layer,and the initiation of viral genome amplification and the assembly of infectious virions in the upper epithelial *** events can be recreated in the laboratory using raft culture techniques,using keratinocytes transfected with viral episomes,or keratinocyte cell lines derived from low-grade cervical *** two such lines are in common use for the analysis of HPV life-cycle events,the W12 line,

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Science China(Information Sciences) 2020年第12期63卷 67-83页

作者： S.A.SOLEYMANI M.H.ANISI A.Hanan ABDULLAH M.Asri NGADI sh.GOUDARZI M.Khurram KHAN M.Nazri KAMA School of Computing Faculty of Engineering Universiti Teknologi Malaysia (UTM) School of Computer Science and Electronic Engineering University of Essex Centre of Artificial Intelligence National University of Malaysia (UKM) Center of Excellence in Information Assurance (CoEIA) King Saud University Advanced Informatics School Menara Razak Universiti Teknologi Malaysia (UTM)

The exchange of correct and reliable data among legitimate nodes is one of the most important challenges in vehicular ad hoc networks(VANETs). Malicious nodes and obstacles, by generating inaccurate information, have a negative impact on the security of 5G-VANET. The big data generated in the vehicular network is also an issue in the security of VANET. To this end, a security model based on authentication and plausibility is proposed to improve the safety of network named ‘AFPM’. In the first layer, an authentication mechanism using edge nodes along with 5G is proposed to deal with the illegitimate nodes who enter the network and broadcast wrong information. In the authentication mechanism, because of the growth of the connected vehicles to the edge nodes that lead to generating big data and hence the inappropriateness of the traditional data structures, cuckoo filter, as a space-efficient probabilistic data structure, is used. In the second layer, a plausibility model by performing fuzzy logic is presented to cope with inaccurate information. The plausibility model is based on detection of inconsistent data involved in the event message. The plausibility model not only tackles with inaccurate, incomplete, and inaccuracy data but also deals with misbehaviour nodes under both line-of-sight(LOS) and non-line-of-sight(NLOS) conditions. All obtained results are validated through well-known evaluation measures such as F-measure and communication overhead. The results presented in this paper demonstrate that the proposed security model possesses a better performance in comparison with the existing studies.

关键词： authentication plausibility fuzzy logic cuckoo filter 5G-VANET big data

Antibacterial activity of selected marine macro algae against vancomycin resistant Enterococcus faecalis

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journal of Coastal Life Medicine 2014年第12期 940-946页

作者： Manivachagam Chandrasekaran Venugopalan Venkatesalu Gnanaprakasam Adaikala raj Department of Botany Annamalai UniversityAnnamalainagar-608002Tamil NaduIndia Botany Wing-DDE Annamalai UniversityAnnamalainagar-608002Tamil NaduIndia

Objective:To evaluate the antibacterial activity of different extracts of Caulerpa chemnitzia(Epser)***,Caulerpa racemosa(Frosk.)Weber-van-Bosse(***),Caulerpa scalpelliformis(***.)Weber-van-Bosse,Ulva lactuca Lin,Ulva fasciata Dellie,Ulva reticulata Forsk,Stoechospermum marginatum(Ag.)Kutz(***),Sargassum wightii Grev,Gracilaria verrucosa(Huds.)Papenfuss and Gracilaria edulis(***)*** against Enterococcus faecalis(MTCC 439)(***)and one clinical isolate of vancomycin resistant ***:The selected marine macro algae were extracted with different solvents viz.,hexane,chloroform,ethyl acetate,acetone and *** assay was carried out by using disc diffusion method,determination of minimum inhibitory concentration and minimum bactericidal ***:The maximum antibacterial activity was recorded in the ethyl acetate extracts of *** and *** than the other *** mean zone of inhibition produced by the extracts in agar diffusion assays against the tested bacterial strains ranged from 7.1 to 14.5 *** minimum inhibitory concentration was between 250 and 500μg/mL,while the minimum bactericidal concentration was from 500 to 1000μg/*** ethyl acetate extracts of the seaweeds showed the presence of strong terpenoids,tannins and phenolic compounds compared with the other solvent ***:These findings suggest that ethyl acetate extracts of *** and *** can be used as an antibacterial substance for the treatment of infection caused by ***.

关键词： Marine macro algae Antibacterial activity Vancomycin resistant Enterococcus faecalis strains