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Crosstalk between the b7/CD28 and EGFR pathways:Mechanisms and therapeutic opportunities

Genes & Diseases 2022年第5期9卷 1181-1193页

作者： Xiaoxin Ren Yixian Li christopher Nishimura Xingxing Zang Department of Microbiology and Immunology Albert Einstein College of MedicineNew YorkNY 10461USA Division of Pediatric Hematology/Oncology/Transplant and Cellular Therapy Children's Hospital at MontefioreBronxNY 10467USA Department of Medicine Albert Einstein College of MedicineNew YorkNY 10461USA Department of Urology Albert Einstein College of MedicineNew YorkNY 10461USA

Somatic activating mutations in the epidermal growth factor receptor(EGFR)are one of the most common oncogenic drivers in cancers such as non-small-cell lung cancer(NSCLC),metastatic colorectal cancer,glioblastoma,head and neck cancer,pancreatic cancer,and breast ***-targeted agents against EGFR signaling pathways have shown robust clinical efficacy,but patients inevitably experience acquired *** immune checkpoint inhibitors(ICIs)targeting PD-1/PD-L1 have exhibited durable anti-tumor responses in a subset of patients across multiple cancer types,their efficacy is limited in cancers harboring activating gene alterations of *** studies have demonstrated that upregulation of new b7/CD28 family members such as b7-H3,b7x and HHLA2,is associated with EGFR signaling and may contribute to resistance to EGFR-targeted therapies by creating an immunosuppressive tumor microenvironment(TME).In this review,we discuss the regulatory effect of EGFR signaling on the PD-1/PD-L1 pathway and new b7/CD28 family member *** these interactions may inform combination therapeutic strategies and potentially overcome the current challenge of resistance to EGFR-targeted *** also summarize clinical data of anti-PD-1/PD-L1 therapies in EGFR-mutated cancers,as well as ongoing clinical trials of combination of EGFR-targeted therapies and anti-PD-1/PD-L1 immunotherapies.

关键词： Combination therapies EGFR Immune checkpoint blockade New b7/CD28 members PD-1/PD-L1 pathway

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Hepatitis D infection:from initial discovery to current investigational therapies

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Gastroenterology Report 2019年第4期7卷 231-245,I0001页

作者： ben L.Da Theo Heller christopher Koh Digestive Diseases branch National Institute of Diabetes&Digestive&Kidney DiseasesNational Institutes of HealthBethesdaMDUSA Liver Diseases branch National Institute of Diabetes&Digestive&Kidney DiseasesNational Institutes of HealthBethesdaMDUSA

Hepatitis D is the most severe form of viral hepatitis associated with a more rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma and mortality compared with hepatitis b *** once thought of as a disappearing disease,hepatitis D is now becoming recognized as a serious worldwide issue due to improvement in diagnostic testing and immigration from endemic *** these concerns,there is currently only one accepted medical therapy(pegylated-interferon-a)for the treatment of hepatitis D with less than desirable efficacy and significant side *** to these reasons,many patients never undergo ***,increasing knowledge about the virus and its life cycle has led to the clinical development of multiple promising new therapies that hope to alter the natural history of this disease and improve patient *** this article,we will review the literature from discovery to the current investigational therapies.

关键词： Hepatitis D hepatitis b epidemiology natural history outcome treatment novel therapies

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Male fertility following childhood cancer: current conceptsand future therapies

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Asian Journal of Andrology 2003年第4期5卷 325-337页

作者： Mark F. H. brougham christopher J. H.Kelnar Richard M.Sharpe W.Hamish b.Wallace Royal Hospital for Sick Children Edinburgh United KingdomRoyal Hospital for Sick Children Edinburgh United KingdomMRC Human Reproductive Sciences Unit Centre for Reproductive Biology University of Edinburgh United KingdomRoyal Hospital for Sick Children Edinburgh United Kingdom

Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeu tic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for H... 详细信息

bstract>Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeu tic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for Hodgkin's disease, are particularly associated with subsequent infertility. Radiotherapy may also cause gonadal damage, most notably following direct testicular irradiation or total body irradiation. because of the varied nature of the cytotoxic insult, it can be difficult to predict the likelihood of infertility in later life. Currently it is not possible to detect gonadal damage early due to the lack of a sensitive marker of gonadal function in the prepubertal age *** cryopreservation is currently the only method of preserving fertility in patients receiving gonadotoxic therapy. This is only applicable to postpubertal patients and can be problematic in the adolescent age group. At present there is no provision for the prepubertal boy, although there are a number of experimental methods currently being investigated. by harvesting testicular tissue prior to gonadotoxic therapy, restoration of fertility could be achieved following treatment, either by germ cell transplantation or by in vitro maturation of the germ cells harvested. Alternatively, rendering the testes quiescent during cytotoxic treatment may protect the germ cells from subsequent damage. In addition to the many scientific and technical issues to be overcome prior to clinical application of these techniques, a number of ethical and legal issues must also be addressed to ensure a safe and realistic prospect for future fertility in these patients.

关键词： infertility childhood cancer semen cryopreservation germ cell transplantation In vitro germ cell maturation assisted reproductive techniques

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Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第7期19卷 1407-1408页

作者： Naomi Hartopp Andrea Markovinovic christopher CJ Miller Patricia Gomez-Suaga Sheffield Institute for Translational Neuroscience University of SheffieldSheffieldUK Department of basic and Clinical Neuroscience Institute of PsychiatryPsychology and NeuroscienceLondonUK Universidad de Extremadura.Departamento de bioquímica y biología Molecular y Genética Facultad de Enfermería y Terapia OcupacionalCáceresSpain Centro de Investigación biomédica en Red en Enfermedades Neurodegenerativas-Instituto de Salud Carlos Ⅲ(CIbER-CIbERNED-ISCⅢ) MadridSpain Instituto Universitario de Investigación biosanitaria de Extremadura(INUbE) CáceresSpain

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron *** is currently no cure and approximately 90% of cases are *** shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile *** and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

关键词： senile sclerosis

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Extracellular matrices, artificial neural scaffolds and the promise of neural regeneration

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Neural Regeneration Research 2014年第17期9卷 1573-1577页

作者： Christian b.Ricks Samuel S.Shin christopher becker Ramesh Grandhi Department of Neurological Surgery University of Pittsburgh Medical CenterPittsburghPAUSA University of Pittsburgh School of Medicine PittsburghPAUSA

Over last 20 years, extracellular matrices have been shown to be useful in promoting tissue regeneration. Recently, they have been used and have had success in achieving neurogenesis. Recent developments in extracellular matrix design have allowed their successful in vivo incorporation to engender an environment favorable for neural regeneration in animal models. Promising treatments under investigation include manipulation of the intrinsic extracellular matrix and incorporation of engineered naometer-sized scaffolds through which inhibition of molecules serving as barriers to neuroregeneration and delivery of neurotrophic factors and/or cells for successful tissue regeneration can be achieved. Further understanding of the changes incurred within the extracellular matrix following central nervous system injury will undoubtedly help design a clinically efficacious extracellular matrix scaffold that can mitigate or reverse neural degeneration in the clinical setting.

关键词： extraceUular matrix neurogenesis scaffolds neural stem cells

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Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants

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Plant Communications 2024年第6期5卷 246-262页

作者： George Heslop-Harrison Kazumi Nakabayashi Ana Espinosa-Ruiz Francesca Robertson Robert baines christopher R.L.Thompson Katrin Hermann David Alabadí Gerhard Leubner-Metzger Robin S.b.Williams Centre for biomedical Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Centre for Plant Molecular Sciences Department of Biological SciencesRoyal Holloway University of LondonEgham TW200EXUK Instituto de biología Molecular y Celular de Plantas(CSIC-UPV) 46022 ValenciaSpain Centre for Life’s Origins and Evolution Department of GeneticsEvolution and EnvironmentUniversity College LondonLondonUK Syngenta Crop Protection AGSteinSwitzerland

Allelochemicals represent a class of natural products released by plants as root,leaf,and fruit exudates that interfere with the growth and survival of neighboring *** how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant *** such allelochemical,Myrigalone A(MyA)produced by Myrica gale,inhibits seed germination and seedling growth through an unknown ***,we investigate MyA using the tractable modelDictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylenesynthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase(ACO).Furthermore,in silico modeling predicts the direct binding of MyA to ACO within the catalytic *** ***,ablation of ACO mimics the MyA-dependent developmental delay,which is partially restored by exogenous ethylene,and MyA reduces ethylene *** Arabidopsis thaliana,MyA treatment delays seed germination,and this effect is rescued by exogenous *** also mimics the effect of established ACO inhibitors on root and hypocotyl extension,blocks ethylenedependent root hair production,and reduces ethylene ***,in silico binding analyses identify a rangeof highlypotentethylene inhibitorsthatblock ethylene-dependent responseand reduce ethyleneproduction in ***,we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.

关键词： 1-aminocyclopropane-1-carboxylic acid ACC ACC oxidase ACO allelochemicals ethylene synthesis inhibitors structure-activity relationship

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Effect of Ni particle size on the production of renewable methane from CO_(2) over Ni/CeO_(2) catalyst

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Journal of Energy Chemistry 2021年第10期30卷 602-611,I0015页

作者： Lili Lin Clifford A.Gerlak Chang Liu Jordi Llorca Siyu Yao Ning Rui Feng Zhang Zongyuan Liu Sen Zhang Kaixi Deng christopher b.Murray José A.Rodriguez Sanjaya D.Senanayake Chemistry Division Brookhaven National LaboratoryUptonNY 11973USA Institute of Industrial Catalysis State Key Laboratory of Green Chemistry Synthesis TechnologyCollege of Chemical EngineeringZhejiang University of TechnologyHangzhou 310014ZhejiangChina Department of Chemistry University of VirginiaCharlottesvilleVA 22904USA Institute of Energy Technologies Department of Chemical Engineering and Barcelona Research Center in Multiscale Science and EngineeringUniversitat Politècnica de CatalunyaEEBEEduard Maristany 10-1408019 BarcelonaSpain Zhejiang University Key Laboratory of biomass Chemical Engineering of Ministry of Education College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027ZhejiangChina Chemistry Department State University of New YorkStony BrookNYUSA Departments of Chemistry and Materials Science&Engineering University of Pennsylvania231 South 34th Street394PhiladelphiaPA 19104USA

Production of’renewable Methane’has attracted renewed research interest as a fundamental probe reaction and process for CO_(2)utilization through potential use in Cl fuel production and even for future space exploration ***_(2)methanation is a structure sensitive reaction on Ni/CeO_(2)*** precisely elucidate the size effect of the Ni metal center on the CO_(2)methanation performance,we prepared2%Ni/CeO_(2)catalysts with pre-synthesized uniform Ni particles(2,4 and 8 nm)on a high surface area CeO_(2)*** electron microscopy(TEM)and ambient pressure X-ray photo spectroscopy(AP-XPS)characterization have confirmed that the catalyst structure and chemical state was uniform and stable under reaction *** 8 nm sized catalyst showed superior methanation selectivity over the 4 and 2 nm counterparts,and the methanation activity in term of TOF is 10 times and 70 times higher than for the 4 and 2 nm counterparts,*** DRIFTS studies revealed that the larger Ni(8 nm particles)over CeO_(2)efficiently facilitated the hydrogenation of the surface formate intermediates,which is proposed as the rate determining step accounting for the excellent CO_(2)methanation performance.

关键词： CO_(2)methanation Particle size effect Ni/CeO_(2) In situ DRIFTS Mechanism investigation

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Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim böttrich Pascal bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer Robert Ringseis Klaus Eder Karsten Krüger christopher Weyh Department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

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Laparoendoscopic single site,laparoscopic or open surgery for adrenal tumors:Selecting the optimal approach

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World Journal of Clinical Urology 2014年第2期3卷 54-65页

作者： christopher b Riedinger Conrad M Tobert brian R Lane Michigan State University College of Human Medicine Grand RapidsMI 49503United States Urology Division Spectrum Health Hospital SystemGrand RapidsMI 49503United States

Numerous surgical modalities are available to treat adrenal lesions. Minimally-invasive approaches for adrenalectomy are indicated in most circumstances, and new evidence continues to be accumulated. In this context, current indications for open surgical adrenalectomy(OS-A), minimally-invasive adrenalectomy(MI-A), and laparoendoscopic single-site adrenalectomy(LESS-A) remain unclear. A comprehensive Englishlanguage literature review was performed using MEDLINE/Pub MED to identify articles and guidelines pertinent to the surgical management of adrenal tumors. A comprehensive chart review was performed for three illustrative cases. Clinical recommendations were generated based on relevant literature and the expertise of the investigator group. MI-A offers advantages over OS-A in properly selected patients, who experience fewer complications, lower blood loss, and shorter hospital stays. Robot-assisted laparoscopic and retroperitoneoscopic adrenalectomy may offer advantages over transperitoneal surgery, and LESS-A may be an even less-invasive option that will require further evaluation. MI-A remains the surgical treatment of choice for most adrenal lesions. Tumor size and stage are the primary indications for selecting alternative treatment modalities. OS-A remains the gold standard for large tumors(> 10 cm) and suspected or known advanced stage malignancy. LESS-A appears to be an appropriate initial approach for small tumors(< 4-5 cm), including pheochromocytoma and isolated adrenal metastases.

关键词： Adrenal masses Surgical approach Indications Open adrenalectomy Laparoscopic adrenalectomy Laparoendoscopic single-site adrenalectomy

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A high-throughput screening assay for eukaryotic elongation factor 2 kinase inhibitors

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Acta Pharmaceutica Sinica b 2016年第6期6卷 557-563页

作者： Ting Xiao Rui Liu christopher G.Proud Ming-Wei Wang The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Department of Pharmacy Medical College of Nanchang University Center for biological Sciences Life Sciences Building University of Southampton South Australian Health and Medical Research Institute

Eukaryotic elongation factor 2 kinase (eEF2K) inhibitors may aid in the development of new therapeutic agents to combat cancer. Purified human eEF2K was obtained from an Escherichia coli expression system and a luminescence-based high-throughput screening (HTS) assay was developed using MH-1 peptide as the substrate. The luminescent readouts correlated with the amount of adenosine triphosphate remaining in the kinase reaction. This method was applied to a large-scale screening campaign against a diverse compound library and subsequent confirmation studies. Nine initial hits showing inhibitory activities on eEF2K were identified from 56,000 synthetic compounds during the HTS campaign, of which, five were chosen to test their effects in cancer cell lines. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier b.V. This is an open access article under the CC bY-NC-ND

关键词： eEF2K Inhibito High-throughput screening Luminescenc MH-1 peptide

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