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JMCB Symposium 2019:The legend of p53 ***

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Journal of Molecular Cell Biology 2019年第7期11卷 628-629页

作者： Ping Zhang Suzanne P.Christen Gareth l.Bond ludwig Institute for Cancer Research Nuffield Department of MedicineUniversity of OxfordOxford 0X3 7DQUK The Simons Center for Systems Biology Institute for Advanced StudyPrincetonNJ 08540USA

The exciting symposium hosted by Journal of Molecular Cell Biology (JMCB),with the theme 'The legend of p53 ***',took place in Hangzhou,China on May 10-12,*** symposium provided the opportunity for delegates in the fields of p53 biology,epigenetics,and cancer research to share scientific updates and to bridge the gap between basic scienee and translational *** delegates also enjoyed celebrations ofthe 40th anniversary ofthe discovery of p53,as well as the 50th anniversary ofthe discovery of RNA polymerases.

关键词： symposium JMCB polymerases

Dying by fire: noncanonical functions of autophagy proteins in neuroinflammation and neurodegeneration

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Neural Regeneration Research 2022年第2期17卷 246-250页

作者： Alexis D.Rickman Addison Hilyard Bradlee l.Heckmann Department of Cell Biology Microbiology&Molecular Biology University of South FloridaTampaFLUSA USF Health Byrd Alzheimer’s Center and Neuroscience Institute Morsani College of MedicineTampaFLUSA Department of Molecular Medicine Morsani College of MedicineTampaFLUSA

Neuroinflammation and neurodegeneration are key components in the establishment and progression of neurodegenerative diseases including Alzheimer's Disease(AD). Over the past decade increasing evidence is emerging for the use of components of the canonical autophagy machinery in pathways that are characterized by lC3 lipidation yet are distinct from traditional macro-autophagy. One such pathway that utilizes components of the autophagy machinery to target lC3 to endosomes, a process termed lC3-associated endocytosis(lANDO), has recently been identified and regulates neuroinflammation. Abrogation of lANDO in microglia cells results in a propensity for elevated neuroinflammatory cytokine production. Using the well-established 5 xFAD model of AD to interrogate neuroinflammatory regulation, impairment of lANDO through deletion of a key upstream regulator Rubicon or other downstream autophagy components, exacerbated disease onset and severity, while deletion of microglial autophagy alone had no measurable effect. Mice presented with robust deposition of the neurotoxic AD protein β-amyloid(Aβ), microglial activation and inflammatory cytokine production, tau phosphorylation, and aggressive neurodegeneration culminating in severe memory impairment. lANDO-deficiency impaired recycling of receptors that recognize Aβ, including TlR4 and TREM2. lANDO-deficiency alone through deletion of the WD-domain of the autophagy protein ATG16 l, revealed a role for lANDO in the spontaneous establishment of age-associated AD. lANDO-deficient mice aged to 2 years presented with advanced ADlike disease and pathology correlative to that observed in human AD patients. Together, these studies illustrate an important role for microglial lANDO in regulating CNS immune activation and protection against neurodegeneration. New evidence is emerging that demonstrates a putative linkage between pathways such as lANDO and cell death regulation via apoptosis and possibly necroptosis. Herein, we provide a

关键词： aging Alzheimer's disease autophagy inflammation lC3-associated endocytosis microglia neurodegeneration neuroinflammation

Penny Arcade冒险——在黑暗的雨滑悬崖上，首部曲

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程序员（游戏创造） 2008年第9期 42-47页

作者： Hothead joel De Young 李丹（译） Hothead游戏公司的COO 中国软件与技术服务股份有限公司

《Penny Arcade冒险-在黑暗的雨滑悬崖上，首部曲》是根据美国当下脍炙人口的讽刺幽默漫画《Penny Arcade》改编的一款科技与超现实主义风格相结合的游戏，Mike是漫画的原作者，而Jerry则是漫画剧本的作者，漫画讲述的是美国宅男的风趣... 详细信息

《Penny Arcade冒险-在黑暗的雨滑悬崖上，首部曲》是根据美国当下脍炙人口的讽刺幽默漫画《Penny Arcade》改编的一款科技与超现实主义风格相结合的游戏，Mike是漫画的原作者，而Jerry则是漫画剧本的作者，漫画讲述的是美国宅男的风趣生活。此次Hothead公司购买了《Penny Arcade》的版权，并与漫画的原作者们展开了一次愉快的合作。本文为制作影视动漫改编游戏的项目提供了宝贵的经验，让我们一起来回顾他们离奇的项目制作旅程。

关键词：悬崖冒险超现实主义 Mike ad公司漫画作者美国

Using our mini-brains: cerebral organoids as an improved cellular model for human prion disease

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Neural Regeneration Research 2020年第6期15卷 1019-1020页

作者： Bradley R.Groveman Ryan walters Cathryn l.Haigh laboratory of Persistent Viral Diseases National Institute of Allergy and Infectious Diseases Division of Intramural ResearchRocky Mountain Laboratories National Institutes of Health

Neurodegenerative diseases are an ever-increasing burden in an aging *** no cure is available for any of these diseases and treatment is based on managing *** many candidate therapeutics demonstrating promise in animal models,none has yet shown efficacy in human *** is self-evident that humans are different from the animals used to model our diseases,especially models that have been highly manipulated to generate a disease in an animal that does not naturally have such a *** differences are likely the reason for the failures of drug candidates in human trials but,until recently,human models of neurodegenerative diseases were *** development of the human cerebral organoid model,by differentiating three-dimensional human neuronal tissue from pluripotent stem cells,represents a significant advance in studying human brain *** organoids have been used to model Alzheimer’s disease,Parkinson’s disease,Down’s syndrome dementia and we have now shown they can be infected with human prions creating a new model of human prion diseases.

关键词： cerebral likely spite

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棘球蚴病的内科治疗进展

中国普外基础与临床杂志 2024年第10期31卷 1188-1192页

作者：何达吴建利吕晓菊四川大学华西医院感染性疾病中心成都610041 成都市双流区第一人民医院-四川大学华西空港医院心血管病区成都610200

棘球蚴病(也称“包虫病”)是严重威胁人类健康的一种人畜共患疾病。该病在我国分布范围广,在西藏自治区、青海省、新疆维吾尔自治区、四川省等地都有分布,增加了我国社会经济负担。人类主要感染泡型和囊型棘球蚴病,主要累及肝、肺、脑... 详细信息

棘球蚴病(也称“包虫病”)是严重威胁人类健康的一种人畜共患疾病。该病在我国分布范围广,在西藏自治区、青海省、新疆维吾尔自治区、四川省等地都有分布,增加了我国社会经济负担。人类主要感染泡型和囊型棘球蚴病,主要累及肝、肺、脑、骨等器官组织。首选外科手术切除,内科药物治疗也是重要治疗方式,当前经典的药物主要是阿苯达唑及吡喹酮单独或联合应用,现也已有一些包括广谱抗感染药物如硝唑尼特等、抑制细胞增殖药物如硼替佐米等、代谢药物如二甲双胍等或传统医药如青蒿素等尝试用于治疗棘球蚴病。还提出了对棘球蚴病建议采用癌症管理模式,并且经抗虫治疗后的囊型棘球蚴病影像学随访时间至少需超过3年、泡型棘球蚴病至少需超过10年,更重要的是采取宣教、疫苗接种等措施,积极预防和控制棘球蚴病,以有效降低棘球蚴病的发生率与减少传播。

关键词：棘球蚴病包虫病囊型棘球蚴病泡型棘球蚴病阿苯达唑吡喹酮抗虫化疗

Testosterone,cardiomyopathies,and heart failure:a narrative review

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Asian Journal of Andrology 2021年第4期23卷 348-356页

作者： Rodica Diaconu Ionuţ Donoiu Oana Mirea Tudor Adrian Bălşeanu Department of Cardiology University of Medicine and PharmacyCraiova 200349Romania Department of Physiology University of Medicine and PharmacyCraiova 200349Romania

Testosterone exerts an important regulation of cardiovascular function through genomic and nongenomic pathways. It produces several changes in cardiomyocytes, the main actor of cardiomyopathies, which are characterized by pathological remodeling, eventually leading to heart failure. Testosterone is involved in contractility, in the energy metabolism of myocardial cells, apoptosis, and the remodeling process. In myocarditis, testosterone directly promotes the type of inflammation that leads to fibrosis, and influences viremia with virus localization. At the same time, testosterone exerts cardioprotective effects that have been observed in different studies. There is increasing evidence that low endogenous levels of testosterone have a negative impact in some cardiomyopathies and a protective impact in others. This review focuses on the interrelationships between testosterone and cardiomyopathies and heart failure.

关键词： androgens cardiomyocytes heart disease myocardial prognosis

Common genetic variants in the TP53 pathway and their impact on cancer

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Journal of Molecular Cell Biology 2019年第7期11卷 578-585页

作者： Thibaut Barnoud Joshua l.D.Parris Maureen E.Murphy Program in Molecular and Cellular Oncogenesis The Wistar InstitutePhiladelphiaPA 19104USA Cell and Molecular Biology Program Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaPA 19104USA

The TP53 gene is well known to be the most frequently mutated gene in human *** addition to mutations,there are > 20 different coding region single-nucleotide polymorphisms (SNPs) in the TP53 gene,as well as SNPs in MDM2,the negative regulator of *** of these SNPs are known to alter p53 pathway *** makes p53 rather unique among cancer-critical genes,*** coding regions of other cancer-critical genes like Ha-Ras,RB,and PI3KCA do not have non-synonymous coding region SNPs that alter their function in *** next frontier in p53 biology will consist of probing which of these coding region SNPs are moderately or strongly pathogenic and whether they influence cancer risk and the efficacy of cancer *** challenge after that will consist of determining whether we can tailor chemotherapy to correct the defects for each ofthese *** we review the SNPs in TP53 and MDM2 that show the most significant impact on cancer and other *** also propose avenues for how this information can be used to better inform personalized medicine approaches to cancer and other diseases.

关键词： p53 Pro47Ser Pro72Arg PAS MDM2 SNP309

PANoptosis:new insights in regulated cell death in ischemia/reperfusion models

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Neural Regeneration Research 2023年第2期18卷 342-343页

作者： Paloma González-Rodríguez Arsenio Fernández-lópez Área de Biología Celular Instituto de BiomedicinaUniversidad de LeónSpain

See related article,pp 357-363The first study describing the cell death and destruction of tissues,organs,and organ systems as programmed events during the development of multicellular organisms was performed by JW Saunders Jr in *** term apoptosis was introduced by Kerr,Wyllie,and Currie in 1972 to describe a programmed phenomenon opposite to mitosis in the regulation of animal cell ***,a description of ectodermal cell lineages as programmed cell death in the worm Caenorhabditis elegans was publishedby JE Sulston and HR Horvitz in 1976.

关键词： organs insight opposite

Oral purgative and simethicone before small bowel capsule endoscopy

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World Journal of Gastrointestinal Endoscopy 2013年第2期5卷 67-73页

作者： Bruno joel Ferreira Rosa Mara Barbosa Joana Magalhes Ana Rebelo Maria Joo Moreira José Cotter Gastroenterology Department Alto Ave Hospital Center-Guimar es4835-044 Guimar esPortugal

AIM:To evaluate small bowel cleansing quality,diagnostic yield and transit time,comparing three cleansing protocols prior to capsule ***:Sixty patients were prospectively enrolled and randomized to one of the following cleansing protocols:patients in Group A underwent a 24 h liquid diet and overnight fasting;patients in Group B followed protocol A and subsequently were administered 2 l of polyethylene glycol(PEG) the evening before the procedure;patients in Group C followed protocol B and were additionally administered 100 mg of simethicone 30 min prior to capsule *** bowel cleansing was independently assessed by two experienced endoscopists and classified as poor,fair,good or excellent according to the proportion of small bowel mucosa under perfect conditions for *** there was no agreement between the two endoscopists,the images were reviewed and discussed until a consensus was *** preparation was considered acceptable if > 50% or adequate if > 75% of the mucosa was in perfect cleansing *** amount of bubbles was assessed independently and it was considered significant if it prevented a correct interpretation of the *** endoscopic findings,gastric emptying time(GET) and small bowel transit time(SBTT) were recorded for each ***:There was a trend favoring Group B in achieving an acceptable(including fair,good or excellent) level of cleansing(Group A:65%;Group B:83.3%;Group C:68.4%) [P = not significant(NS)] and favoring Group C in attaining an excellent level of cleansing(Group A:10%;Group B:16.7%;Group C:21.1%)(P = NS).The number of patients with an adequate cleansing of the small bowel,corresponding to an excellent or good classification,was 5(25%) in Group A,5(27.8%) in Group B and 4(21.1%) in Group C(P = 0.892).Conversely,7 patients(35%) in Group A,3 patients(16.7%) in Group B and 6 patients(31.6%) in Group C were considered to have poor small bowel cleansing(P = 0.417),with sig

关键词： Small bowel capsule endoscopy Bowel preparation Polyethylene glycol Simethicone