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mechanism-driven strategies for prevention of rheumatoid arthritis

Rheumatology & Autoimmunity 2022年第3期2卷 109-119页

作者： V.michael Holers Kristine A.Kuhn m.Kristen Demoruelle Jill m.Norris Gary S.Firestein Eddie A.James William H.Robinson jane H.Buckner Kevin D.Deane Division of Rheumatology University of Colorado School of MedicineAuroraColoradoUSA Department of Epidemiology Colorado School of Public HealthAuroraColoradoUSA Division of Rheumatology Allergy and ImmunologyUniversity of California San DiegoLa JollaCaliforniaUSA Benaroya Research Institute SeattleWashingtonUSA Division of Immunology and Rheumatology Stanford UniversityStanfordCaliforniaUSA Department of medicine Division of RheumatologyVA Palo Alto Health Care SystemPalo AltoCaliforniaUSA

In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid *** period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical *** the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk *** these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint *** model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA *** we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical ***,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.

关键词： autoimmune disease inflammation mucosa prevention rheumatoid arthritis

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Cotton GhBAK1 mediates Verticillium Wilt Resistance and Cell Death

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Journal of Integrative Plant Biology 2013年第7期55卷 586-596页

作者： Xiquan Gao Fangjun Li maoying Li Ali S.Kianinejad jane K.Dever Terry A.Wheeler Zhaohu Li Ping He Libo Shan Department of Plant Pathology and microbiology and Institute for Plant Genomics and BiotechnologyTexas A&M UniversityCollege Station College of Agriculture Nanjing Agricultural University College of Agronomy and Biotechnology China Agricultural University Department of Biochemistry and Biophysics and Institute for Plant Genomics and Biotechnology Texas A&M UniversityCollege Station University of Texas at Brownsville Texas A&m AgriLife Research and Extension Center

Virus-induced gene silencing （VIGS） offers a powerful approach for functional analysis of individual genes by knocking down their expression. We have adopted this approach to dissect gene functions in cotton resistant to Verticfllium wilt, one of the most devastating diseases worldwide. We showed here that highly efficient VIGS was obtained in a cotton breeding line （CA4002） with partial resistance to Verticillium wilt, and GhmKK2 and Gh Ve I are required for its resistance to Verticillium wilt. Arabidopsis AtBAK1/SERK3, a central regulator in plant disease resistance, belongs to a subfamily of somatic embryogenesis receptor kinases （SERKs） with five members, AtSERK1 to AtSERK5. Two BAK1 orthologs and one SERK1 ortholog were identified in the cotton genome. Importantly, GhBAK1 is required for CA4002 resistance to Verticillium wilt. Surprisingly, silencing of GhBAK1 is sufficient to trigger cell death accompanied with production of reactive oxygen species in cotton. This result is distinct from Arabidopsis in which AtBAK1 and AtSERK4 play redundant functions in cell death control. Apparently, cotton has only evolved SERK1 and BAK1 whereas AtSERK4/5 are newly evolved genes in Arabidopsis. Our studies indicate the functional importance of BAK1 in Verticillium wilt resistance and suggest the dynamic evolution of SERK family members in different plant species.

关键词： Cell death: Gossvoium hirsutum: Verticillium dahliae: virus-induced qene silence.

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Roles of Arabidopsis Patatin-Related Phospholipases A in Root Development Are Related to Auxin Responses and Phosphate Deficiency

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molecular Plant 2010年第3期3卷 524-538页

作者： Steffen Rietz Georgi Dermendjiev Esther Oppermann Fikadu Getah Tafesse Yunus Effendi Andre Holk jane E. Parker markus Teige Gunther F.E. Scherer max Planck Institute for Plant Breeding Research Department of Plant Microbe Interactions Carl von Linne Weg 10 D-50829 Cologne Germany Leibniz University Hannover Molecular Developmental Physiology Herrenhauser Str. 2 D-30419 Hannover Germany University of Vienna MFPL Department of Biochemistry Dr. Bohrgasse 9 A-1030 Wien Austria Present address: University of Utrecht Department of Membrane Enzymology Inst. Biomembranes Padualaan 8 NL 3584 CH Utrecht. The Netherlands

Phospholipase A enzymes cleave phospho- and galactolipids to generate free fatty acids and lysolipids that function in animal and plant hormone signaling. Here, we describe three Arabidopsis patatin-related phospholipase A （pPLA） genes AtPLAIVA, AtPLAIVB, and AtPLAIVC and their corresponding proteins. Loss-of-function mutants reveal roles for these pPLAs in roots during normal development and under phosphate deprivation. AtPLAIVA is expressed strongly and exclusively in roots and AtplalVA-null mutants have reduced lateral root development, characteristic of an impaired auxin response. By contrast, AtPLAIVB is expressed weakly in roots, cotyledons, and leaves but is transcriptionally induced by auxin, although AtplalVB mutants develop normally. AtPLAIVC is expressed in the floral gynaecium and is induced by abscisic acid （ABA） or phosphate deficiency in roots. While an AtplalVC-1 loss-of-function mutant displays ABA respon- siveness, it exhibits an impaired response to phosphate deficiency during root development. Recombinant AtPLA proteins hydrolyze preferentially galactolipids and, less efficiently, phospholipids, although these enzymes are not localized in chloroplasts. We find that AtPLAIVA and AtPLAIVB are phosphorylated by calcium-dependent protein kinases in vitro and this enhances their activities on phosphatidylcholine but not on phosphatidylglycerol. Taken together, the data reveal novel functions of pPLAs in root development with individual roles at the interface between phosphate deficiency and auxin signaling.

关键词： Abiotic/environmental stress hormonal regulation protein phosphorylation/dephosphorylation signaltransduction gene regulation Arabidopsis.

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Gastroesophageal reflux disease after diagnostic endoscopy in the clinical setting

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World Journal of Gastroenterology 2013年第16期19卷 2514-2520页

作者： Nora B Zschau jane m Andrews Richard H Holloway mark N Schoeman Kylie Lange William CE Tam Gerald J Holtmann Department of Gastroenterology and Hepatology Royal Adelaide Hospital Faculty of Health Sciences University of AdelaideAdelaide Department of Gastroenterology and Hepatology Lyell McEwin Hospital Department of Gastroenterology and Hepatology University of Queensland School of Medicine Princess Alexandra Hospital

AIm: To investigate the outcome of patients with symptoms of gastroesophageal reflux disease (GERD) referred for endoscopy at 2 and 6 mo post endoscopy. mETHODS: Consecutive patients referred for upper endoscopy for assessment of GERD symptoms at two large metropolitan hospitals were invited to participate in a 6-mo non-interventional (observational) *** two institutions are situated in geographically and socially disparate areas. Data collection was by selfcompletion of questionnaires including the patient assessment of upper gastrointestinal disorders symptoms severity and from hospital records. Endoscopic finding using the Los-Angeles classification, symptom severity and it's clinically relevant improvement as change of at least 25%, therapy and socio-demographic factors were assessed. RESULTS: Baseline data were available for 266 patients and 2-mo and 6-mo follow-up data for 128 and 108 patients respectively. At baseline, 128 patients had erosive and 138 non-erosive reflux disease. Allmost all patient had proton pump inhibitor (PPI) therapy in the past. Overall, patients with non-erosive GERD at the index endoscopy had significantly more severe symptoms as compared to patients with erosive or even complicated GERD while there was no difference with regard to medication. After 2 and 6 mo there was a small, but statistically significant improvement in symptom severity (7.02 ± 5.5 vs 5.9 ± 5.4 and 5.5 ± 5.4 respectively); however, the majority of patients continued to have symptoms (i.e. , after 6 mo 81% with GERD symptoms). Advantaged socioeconomic status as well as being unemployed was associated with greater improvement. CONCLUSION: The majority of GORD patients receive PPI therapy before being referred for endoscopy even though many have symptoms that do not sufficiently respond to PPI therapy.

关键词： Gastroesophageal reflux disease Epidemiology Proton pump inhibitor Acid suppressive therapy Endoscopy Barrett’s esophagus Functional gastrointestinal disorders

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moldable and transferrable conductive nanocomposites for epidermal electronics

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npj Flexible Electronics 2022年第1期6卷 363-371页

作者： myeong Namkoong Heng Guo md Saifur Rahman Daniel Wang Cassandra jane Pfeil Sophia Hager Limei Tian Department of Biomedical Engineering and Center for Remote Health Technologies and SystemsTexas A&M UniversityCollege StationTX 77843USA

Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring,human-machine interface,and the Internet of ***-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic ***,realizing conductive nanocomposites with high conductivity,electromechanical stability,and low modulus over a large area at sub-100μm resolution remains ***,we report a moldable,transferrable,high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate).The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual *** patterned the nanocomposite via a simple,low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft,skin-interfaced electrophysiological *** signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel *** nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.

关键词： conductive transfer interface

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Cell-type-specific transcriptomics reveals that root hairs and endodermal barriers play important roles in beneficial plant-rhizobacterium interactions

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molecular Plant 2023年第7期16卷 1160-1177页

作者： Eline H.Verbon Louisa m.Liberman Jiayu Zhou Jie Yin Corném.J.Pieterse Philip N.Benfey loannis A.Stringlis Ronnie de Jonge Plant-microbe Interactions Department of BiologyScience4LifeUtrecht UniversityP.0.Box 800.563508 TB Utrechtthe Netherlands Howard Hughes medical Institute Duke UniversityDurhamNC 27708USA Department of Biology Duke UniversityDurhamNC 27708USA Laboratory of Plant Pathology Agricultural University of Athens75 lera Odos str11855 AthensGreece

Growth-and health-promoting bacteria can boost crop productivity in a sustainable *** simiae WCS417is sucha bacterium that efficiently colonizes roots,modifiesthe architecture of the root systemto increase its size,and induces systemic resistance to make plants more resistant to pests and *** previous work suggested that WCS417-induced phenotypes are controlled by root cell-type-specific ***,it remains unclear how WCS417 affects these *** this study,we transcriptionally profiled five Arabidopsis thaliana root cell types following WCS417 *** found that the cortex and endodermis have the most differentially expressed genes,even though they are not in direct contact with this epiphytic *** of these genes are associated with reduced cell wall biogenesis,and mutant analysis suggests that this downregulation facilitates WCS417-driven root architectural ***,we observed elevated expression of suberin biosynthesis genes and increased deposition of suberin in the endodermis of WCS417-colonized *** an endodermal barrier mutant,we showed the importance of endodermal barrier integrity for optimal plant-beneficial bacterium *** of the transcriptome profiles in the two epidermal cell types that are in direct contact with WcS417-trichoblasts that form root hairs and atrichoblasts that do not-implies a difference in potential for defense gene *** both cell types respond to WCS417,trichoblasts displayed both higher basal and WCS417-dependent activation of defense-related genes compared with *** suggests that root hairs may activate root immunity,a hypothesis that is supported by differential immune responses in root hair *** together,these results highlight the strength of cell-type-specific transcriptional profiling to uncover"masked"biological mechanisms underlying beneficial plant-microbe associations.

关键词： FACs cell-type-specific transcriptomics root immunity beneficial rhizobacteria suberin root hair

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Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery

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Asian Journal of Pharmaceutical Sciences 2018年第6期13卷 592-599页

作者： Anna Slita Anna Egorova Eudald Casals Anton Kiselev Jessica m.Rosenholm Pharmaceutical Sciences Laboratory Faculty of Science and EngineeringAbo Akademi University D.O.Ott Research Institute of Obstetrics Gynaecology and Reproductology

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles(mSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of mSNs with surface-hyperbranching polymerized poly(ethyleneimine)(hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered si RNA/mSNs, mDA-mB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated si RNA/mSN complexes provide more effective delivery of si RNAs compared to unmodified mSNs. Thus, it can be concluded that appropriately surface-modified mSNs can be considered as prospective vectors for therapeutic siRNA delivery.

关键词： Gene therapy Nanocarriers siRNA delivery mesoporous silica nanoparticles

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澳大利亚初级保健诊所新发腰背痛患者的预后：起始队列研究

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英国医学杂志中文版 2008年第6期11卷 339-342页

作者： Nicholas Henschke Christopher G maher Kathryn m Refshauge Robert D Herbert Robert G Cumming jane Bleasel John York Anurina Das James H mcAuley 蓝恭涛(译) musculoskeletal Division The George Institute for International Health Sydney Australia Back Pain Research Group Faculty of Health Sciences University of Sydney School of Public Health University of Sydney Department of Rheumatology Royal Prince Alfred Hospital Sydney 不详

目的估计初级保健诊所内新发腰背痛患者的1年预后，并确定其预后因素。设计1年随访队列研究。地点澳大利亚悉尼的初级保健诊所。参试者初级保健诊所接诊的973例非特异性腰背痛连续患者（平均年龄43.3岁，男性54.8％）。该起始队列患者... 详细信息

目的估计初级保健诊所内新发腰背痛患者的1年预后，并确定其预后因素。设计1年随访队列研究。地点澳大利亚悉尼的初级保健诊所。参试者初级保健诊所接诊的973例非特异性腰背痛连续患者（平均年龄43.3岁，男性54.8％）。该起始队列患者腰背痛时间不足两周，征集自170名全科医生、理疗师或按摩师诊所。主要评估指标参试者完成基线调查问卷后，分别于初次就诊后6周、3个月和21个月时复查评估。评估内容包括：工作恢复情况、功能恢复情况和疼痛消失情况。潜在预后因素与恢复所需时间的关联性用Cox回归建模分析。结果12个月随访率〉97％。基线时工作能力下降的患者半数在14天内恢复了以前的工作状态（95％可信区间11-17天），83％在3个月内恢复。残疾（中位恢复时间31天，25-37天）和疼痛（中位58天，52-63天）则需要较长的时间才能恢复。只有72％的受试者于基线访问后12个月获得完全康复。高龄、赔偿诉讼、疼痛较重、就诊前腰背痛时间较长、就诊前因疼痛活动减少天数较多、抑郁情绪以及预期危险持续与所需恢复时问较长相关。结论在这个急性腰背痛初级保健患者队列，患者的预后并不像临床指南声称的那样乐观。多数患者的恢复缓慢。近三分之一的患者在腰背痛发作后1年尚未恢复。

关键词：腰背痛患者初级保健预后因素队列研究澳大利亚诊所新发评估指标

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Convergence of normal stem cell and cancer stem cell developmental stage:Implication for differential therapies

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World Journal of Stem Cells 2011年第9期3卷 83-88页

作者： Shengwen Calvin Li Katherine L Lee jane Luo Jiang F Zhong William G Loudon Neuro-Oncology Research Laboratory Center for Neuroscience and Stem Cell ResearchChildren's Hospital of Orange CountyUniversity of California Irvine455 South Main StreetOrangeCA 92868United States Beckman Coulter Inc.250 South Kraemer BoulevardBreaCA 92821United States Department of Pathology Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033United States Department of Neurological Surgery University of California IrvineOrangeCA 92862United States

Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental *** postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and *** can be the key to the elaboration of anti-cancer-based *** this article,we focus on a controversial new theme relating to *** may have a critical stage characterized as a "therapeutic window",which can be identified by asso-ciation of molecular,biochemical and biological *** such a stage can allow the production of more effective therapies (*** stem cells) to treat several *** importantly,confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against *** conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem ***,there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of *** on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of *** crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (*** stem cells,CSC and embryonic stem cells).The differential studies of the convergence may result in novel therapies for treating cancers.

关键词： Neural stem cell Cancer stem cell Convergence Therapeutic

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Small P values may not yield robust findings:an example using REST-meta-PD

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Science Bulletin 2021年第21期66卷 2148-2152,M0003页

作者： Xi-Ze Jia Na Zhao Hao-ming Dong Jia-Wei Sun marek Barton Roxana Burciu Nicolas Carrière Antonio Cerasa Bo-Yu Chen Jun Chen Stephen Coombes Luc Defebvre Christine Delmaire Kathy Dujardin Fabrizio Esposito Guo-Guang Fan Federica Di Nardo Yi-Xuan Feng Brett W.Fling Saurabh Garg moran Gilat martin Gorges Shu-Leong Ho Fay BHorak Xiao Hu Xiao-Fei Hu Biao Huang Pei-Yu Huang Ze-Juan Jia Christina Jones Jan Kassubek Lenka Krajcovicova Ajay Kurani Jing Li Qing Li Ai-Ping Liu Bo Liu Hu Liu Wei-Guo Liu Renaud Lopes Yu-Ting Lou Wei Luo Tara madhyastha Ni-Ni mao Grainne mcAlonan martin J.mcKeown Shirley Pang Andrea Quattrone Irena Rektorova Alessia Sarica Hui-Fang Shang James m.Shine Priyank Shukla Tomas Slavicek Xiao-Peng Song Gioacchino Tedeschi Alessandro Tessitore David Vaillancourt Jian Wang Jue Wang Z.jane Wang Lu-Qing Wei Xia Wu Xiao-Jun Xu Lei Yan Jing Yang Wan-Qun Yang Nai-Lin Yao De-Long Zhang Jiu-Quan Zhang min-ming Zhang Yan-Ling Zhang Cai-Hong Zhou Chao-Gan Yan Xi-Nian Zuo mark Hallett Tao Wu Yu-Feng Zang Center for Cognition and Brain Disorders the Affiliated HospitalHangzhou Normal UniversityHangzhou 310015China Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments Hangzhou 311121China National Basic Science Data Center Beijing 100190China State Key Laboratory of Cognitive Neuroscience and Learning&mcGovern Institute for Brain Research Beijing Normal UniversityBeijing 100875China School of Information and Electronics Technology Jiamusi UniversityJiamusi 154007China Neuroscience Program Central European Institute of TechnologyCEITECMasaryk UniversityBrno 62500Czech Republic Department of Applied Physiology and Kinesiology University of FloridaGainesville FL 32611USA Univ.Lille InsermCHU LilleU1172-LilNCog-Lille Neuroscience&CognitionLille F-59000France The Institute for Biomedical Research and Innovation National Research CouncilMangone CS 87050Italy Department of Radiology The First Affiliated Hospital of China Medical UniversityShenyang 110001China Department of Radiology Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Department of medicine Surgery and DentistryScuola Medica SalernitanaUniversity of SalernoFiscianoSA 132-84084Italy Department of Advanced medical and Surgery Sciences University of Campania“Luigi Vanvitelli”Caserta 81100Italy Eye Center of the 2nd Affiliated Hospital Medical College of Zhejiang UniversityHangzhou 310020China Zhejiang Provincial Key Lab of Ophthalmology Hangzhou 310020China Department of Health and Exercise Science Colorado State UniversityFort Collins CO 80523USA Pacific Parkinson’s Research Centre University of British ColumbiaVancouver BC V6E 2M6Canada Department of medicine(Neurology)University of British Columbia Vancouver BC V6T 1B7Canada Brain and mind Center The University of SydneySydney NSW 2006Australia Department of Neurology Ulm UniversityUlm 89081Germany Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong Kong 999077China Department of

Thousands of resting state functional magnetic resonance imaging(RS-f mRI)articles have been published on brain *** precise localization of abnormal brain activity,a voxel-level comparison is *** of the large number of voxels in the brain,multiple comparison correction(mCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent mCC)is widely recommended[1].

关键词：帕金森病 precise correction

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