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Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer *** remains elusive how CTCs evade immune surveillance and elimination by immune *** this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer ***,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in ***,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune ***,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

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儿童常见实体肿瘤分子学进展

临床与实验病理学杂志 2024年第7期40卷 673-679页

作者：殷敏智 kenneth Tou En Chang 上海交通大学医学院附属上海儿童医学中心病理科 200127 Department of Pathology and Laboratory Medicine KK Women’s and Children’s HospitalSingapore 229899 Duke-NUS Medical School Singapore 169857

儿童肿瘤包含一大类罕见肿瘤,虽然只占全年龄段肿瘤患者的极小比例,但却是儿童患者致死的主要原因。成人恶性肿瘤主要起源于上皮,儿童肿瘤通常来源于中胚层或神经外胚层,在肿瘤的发生、发展、治疗和预后等均与成人肿瘤明显不同,WHO(2023... 详细信息

儿童肿瘤包含一大类罕见肿瘤,虽然只占全年龄段肿瘤患者的极小比例,但却是儿童患者致死的主要原因。成人恶性肿瘤主要起源于上皮,儿童肿瘤通常来源于中胚层或神经外胚层,在肿瘤的发生、发展、治疗和预后等均与成人肿瘤明显不同,WHO(2023)肿瘤分类中首次将儿童肿瘤进行独立归类。研究者认为肿瘤的本质是一种基因病,2018年有文献从基因层面指出儿童肿瘤和成人肿瘤有诸多不同[1-2]:成人由于后天环境等因素的影响,使细胞长期连续遭遇“打击”(大部分为基因突变),最终发展为肿瘤。

关键词：肿瘤儿童分子学

UV-Based Advanced Oxidation Processes for Antibiotic Resistance Control: Efficiency, Influencing Factors, and Energy Consumption

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Engineering 2024年第6期37卷 27-39页

作者： Jiarui Han Wanxin Li Yun Yang Xuanwei Zhang Siyu Bao Xiangru Zhang Tong Zhang kenneth Mei Yee Leung Department of Civil and Environment Engineering The Hong Kong University of Science and TechnologyHong Kong 999077China Department of Civil Engineering The University of Hong KongHong Kong 999077China State Key Laboratory of Marine Pollution and Department of Chemistry City University of Hong KongHong Kong 999077China

Antibiotic resistant bacteria(ARB)with antibiotic resistance genes(ARGs)can reduce or eliminate the effectiveness of antibiotics and thus threaten human *** United Nations Environment Programme considers antibiotic resistance the first of six emerging issues of *** oxidation processes(AOPs)that combine ultraviolet(UV)irradiation and chemical oxidation(primarily chlorine,hydrogen peroxide,and persulfate)have attracted increasing interest as advanced water and wastewater treatment *** integrated technologies have been reported to significantly elevate the efficiencies of ARB inactivation and ARG degradation compared with direct UV irradiation or chemical oxidation alone due to the generation of multiple reactive *** this study,the performance and underlying mechanisms of UV/chlorine,UV/hydrogen peroxide,and UV/persulfate processes for controlling ARB and ARGs were reviewed based on recent *** affecting the process-specific efficiency in controlling ARB and ARGs were discussed,including biotic factors,oxidant dose,UV fluence,pH,and water matrix *** addition,the cost-effectiveness of the UV-based AOPs was evaluated using the concept of electrical energy per *** UV/chlorine process exhibited a higher efficiency with lower energy consumption than other UV-based AOPs in the wastewater matrix,indicating its potential for ARB inactivation and ARG degradation in wastewater *** studies are required to address the trade-off between toxic byproduct formation and the energy efficiency of the UV/chlorine process in real wastewater to facilitate its optimization and application in the control of ARB and ARGs.

关键词： Advanced oxidation processes Ultraviolet/chlorine Ultraviolet/hydrogen peroxide Ultraviolet/persulfate Antibiotic resistant bacteria Antibiotic resistance genes

Challenges in Diagnosing and Managing Dieulafoy’s Lesions: A Case Report Highlighting the Importance of Clinical Suspicion and Multidisciplinary Approach in Obscure Gastrointestinal Bleeding

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Open Journal of Gastroenterology 2024年第3期14卷 80-86页

作者： Feruza Abraamyan Neeladri Misra kenneth Tran Khalid Mahmood Benjamin Coombs Shilpa Lingala Sutter Roseville Medical Center Roseville USA

Upper gastrointestinal bleeding remains a significant cause of hospital admissions. Even though the incidence of peptic ulcer disease and gastritis is decreasing, the incidence rates in neoplasm, Dieulafoy’s lesions, angiodysplasia, and esophagitis are trending up, which necessities physicians to be aware of those pathologies and their specifics. Here, we represent a case of a 62-year-old male on dual antiplatelet therapy who was transferred to our hospital due to severe melena with suspicion of upper gastrointestinal bleeding. Due to hemodynamic instability, the patient was intubated and started on vasopressors. However, several repeated EGDs and CTs of the abdomen with GI bleeding protocol did not reveal the location of active bleeding to stop it. At the same time, clinically, the patient was hemodynamically unstable with continued melena. On the last EGD, a small area of concern resembling gastric varix was clipped for identification purposes, and the patient underwent a selective angiogram with further diagnosis of Dieulafoy’s lesion, which was successfully embolized. Our case demonstrates that Dieulafoy’s lesions can present as severe life-threatening hemorrhage, hard to diagnose with traditional methods such as EGD or CTs, in which case it is recommended to proceed with an angiogram sooner rather than later for further diagnosis and treatment if needed.

关键词： Upper Gastrointestinal Bleeding Dieulafoy’s Lesion Angiodysplasia Melena Hematochezia EGD Angiogram Embolization

Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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野树林

疯狂英语（新悦读） 2024年第2期 40-42,75,76页

作者： kenneth Grahame 不详

《柳林风声》(The Wind in the Willows)是以动物为主角的童话,文笔典雅,描写细致,富含哲理。书中塑造了几个可爱的动物形象:胆小怕事但又生性喜欢冒险的鼹鼠,热情好客、充满浪漫情趣的水鼠,侠义十足、具有领袖风范的老獾,喜欢吹牛、喜... 详细信息

《柳林风声》(The Wind in the Willows)是以动物为主角的童话,文笔典雅,描写细致,富含哲理。书中塑造了几个可爱的动物形象:胆小怕事但又生性喜欢冒险的鼹鼠,热情好客、充满浪漫情趣的水鼠,侠义十足、具有领袖风范的老獾,喜欢吹牛、喜欢炫耀、追求时髦的蛤蟆,敦厚老实的水獭。他们生活在河岸或大森林里,经历了一系列的冒险。

关键词：动物形象领袖风范冒险

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为什么写作比口语更难？

中学生英语 2024年第33期 4-5页

作者： kenneth Beare 苗淑华

对许多英语学习者来说，学会流利地用英语写作比学会流利地说英语要困难得多。即使对于高水平的学习者来说，掌握用英语写也比说慢得多。这有许多原因：写作更正式英语写作比英语口语更需要遵循语法规则。例如，如果有人说“请借来我你...

对许多英语学习者来说，学会流利地用英语写作比学会流利地说英语要困难得多。即使对于高水平的学习者来说，掌握用英语写也比说慢得多。这有许多原因：写作更正式英语写作比英语口语更需要遵循语法规则。例如，如果有人说“请借来我你的钢笔”，很明显说话者想说“请把你的钢笔借给我”。在写作中，文字更为重要，因为它们没有视觉语境。当你说话时，你可以微笑，给人留下好印象。在写作时，你能利用的就只有文字。

关键词：

腹腔内伴EWSR1/FUS-CREM重排恶性上皮样肿瘤1例

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中华病理学杂志 2024年第3期53卷 299-302页

作者：吴佳慧许淑霞徐曼沈萍陈洁枫金晓婷 Chik Hong Kuick kenneth Tou En Chang 殷敏智上海交通大学医学院附属上海儿童医学中心病理科上海200127 福建省儿童医院(上海儿童医学中心福建医院)病理科福州350011 重庆医科大学附属儿童医院病理科重庆400000 Department of Pathology and Laboratory Medicine KK Women′s and Children′s HospitalSingapore 229899Singapore

腹腔内伴EWSR1/FUS-CREM重排恶性上皮样肿瘤是新近发现、分化不明的恶性肿瘤,形态学及免疫表型显示上皮分化,具有恶性潜能及转移倾向。本文报道1例多次复发伴肺转移的病例。镜下肿瘤界限尚清,有纤维性假包膜,肿瘤周边及细胞巢间隔见较... 详细信息

腹腔内伴EWSR1/FUS-CREM重排恶性上皮样肿瘤是新近发现、分化不明的恶性肿瘤,形态学及免疫表型显示上皮分化,具有恶性潜能及转移倾向。本文报道1例多次复发伴肺转移的病例。镜下肿瘤界限尚清,有纤维性假包膜,肿瘤周边及细胞巢间隔见较多炎性细胞浸润,肿瘤细胞呈上皮样、多边形,胞质丰富,呈嗜酸性,核呈圆形或卵圆形,可见小核仁。肿瘤细胞上皮细胞膜抗原弥漫强阳性,广谱细胞角蛋白局灶强阳性,波形蛋白、WT1、突触素、Calretinin等阴性。分子检测示EWSR1-ATF1融合。

关键词：腹腔内转移倾向假包膜免疫表型波形蛋白肺转移纤维性恶性肿瘤

Why ecosystem characteristics predicted from remotely sensed data are unbiased and biased at the same time-and how this affects applications

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Forest Ecosystems 2024年第1期11卷 24-31页

作者： Goran Ståhl Terje Gobakken Svetlana Saarela Henrik J.Persson Magnus Ekstrom Sean P.Healey Zhiqiang Yang Johan Holmgren Eva Lindberg kenneth Nystrom Emanuele Papucci Patrik Ulvdal Hans OleØrka Erik Næsset Zhengyang Hou Håkan Olsson Ronald E.McRoberts Department of Forest Resource Management Swedish University of Agricultural Sciences90183UmeåSweden Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life SciencesÅsNorway USDA Forest Service Rocky Mountain Research StationOgdenUTUSA The Key Laboratory for Silviculture and Conservation of Ministry of Education Beijing Forestry UniversityBeijing100083China Department of Forest Resources University of MinnesotaSt.PaulMNUSA

Remotely sensed data are frequently used for predicting and mapping ecosystem characteristics,and spatially explicit wall-to-wall information is sometimes proposed as the best possible source of information for ***,wall-to-wall information typically relies on model-based prediction,and several features of model-based prediction should be understood before extensively relying on this type of *** such feature is that model-based predictors can be considered both unbiased and biased at the same time,which has important implications in several areas of *** this discussion paper,we first describe the conventional model-unbiasedness paradigm that underpins most prediction techniques using remotely sensed(or other)auxiliary *** this point of view,model-based predictors are typically ***,we show that for specific domains,identified based on their true values,the same model-based predictors can be considered biased,and sometimes severely *** suggest distinguishing between conventional model-bias,defined in the statistical literature as the difference between the expected value of a predictor and the expected value of the quantity being predicted,and design-bias of model-based estimators,defined as the difference between the expected value of a model-based estimator and the true value of the quantity being *** show that model-based estimators(or predictors)are typically design-biased,and that there is a trend in the design-bias from overestimating small true values to underestimating large true ***,we give examples of applications where this is important to acknowledge and to potentially make adjustments to correct for the design-bias *** argue that relying entirely on conventional model-unbiasedness may lead to mistakes in several areas of application that use predictions from remotely sensed data.

关键词： Bias Model-based inference Design-based inference