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Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

Journal of Molecular Cell biology 2024年第3期16卷 9-23页

作者： Ilaria Frasson Linda Diamante Manuela Zangrossi Elena Carbognin Anna Dalla Pietà Alessandro Penna Antonio Rosato Ranieri Verin Filippo Torrigiani Cristiano Salata Marìa Paula Dizanzo Lorenzo Vaccaro Davide Cacchiarelli Sara N.Richter Marco Montagner Graziano Martello Department of Molecular Medicine University of PaduaPadua 35121Italy Department of biology Armenise/Harvard Pluripotent Stem Cell Biology LaboratoryUniversity of PaduaPadua 35131Italy Department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35128Italy Veneto Institute of Oncology IOV-IRCCS Padua 35128Italy Department of Comparative Biomedicine and Food Science University of PaduaPadua 35020Italy Telethon Institute of Genetics and Medicine(TIGEM) Armenise/Harvard Laboratory of Integrative GenomicsPozzuoli 80078Italy Department of Translational Medicine University of Naples Federico IINaples 80138Italy School for Advanced Studies Genomics and Experimental Medicine ProgramUniversity of Naples Federico IINaples 80138Italy microbiology and Virology Unit Padua University HospitalPadua 35128Italy

The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral *** host dependency factors,*** proteins required for viral replication,would help prevent the development of ***,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host *** this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and *** regularly interspaced short palindromic repeats screening identified host genes required for each variant during *** of the genes were shared by multiple *** validated our hits with small molecules and repurposed the US Food and Drug Administration-approved *** the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral *** such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse *** study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.

关键词： SARS-CoV-2 variants of concern host dependency factors antivirals N-acetyl cysteine

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地表城市热岛时空演变——对夏季热浪时期的关注

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Journal of Geographical Sciences 2024年第6期34卷 1065-1082页

作者：任嘉义杨俊于文博丛楠肖向明夏建红李雪铭 School of Humanities and Law Northeastern UniversityShenyang 110169China Human Settlements Research center Liaoning Normal UniversityDalian 116029LiaoningChina Jangho Architecture College Northeastern UniversityShenyang 110169China Lhasa Plateau Ecosystem Research Station Institute of Geographic Sciences and Natural Resources ResearchCASBeijing 100101China Department of microbiology and Plant biology Center for Earth Observation and ModelingUniversity of OklahomaNormanOK 73019USA School of Earth and Planetary Sciences(EPS) Curtin UniversityPerth 65630Australia

Many cities face heat wave(HW) events, combined with the existent surface urban heat island(SUHI) effects. This places pressure on human settlements and sustainable development. However, few studies have investigated the SUHI effects from the perspective of HWs. In this study, the summer HWs in Beijing from 2001 to 2021 were calculated, and the evolution of HWs and SUHIs was quantitatively analyzed based on the dynamic nature of the urban-rural boundary. Beijing experienced 27 HWs in the 21 years, including 10 instances in June, four in July, and 13 in August. The SUHI varied during HWs, between 2–3℃ in most years. The highest SUHI occurred in 2019, reaching 3.99℃ and covering the largest area(10,887 km^(2)). The fluctuation in HWs and SUHIs generally displayed the same spatiotemporal pattern, and HWs amplified the SUHIs to a certain extent, with the highest correlation coefficient being 0.44. Additionally, impervious surfaces and cropland contributed most to SUHIs,and night light enhanced SUHIs. Observing the co-evolution of HWs and SUHIs will be helpful for ecological maintenance and urban infrastructure optimization and provide theoretical support for reducing heat risk and improving the human settlement environment.

关键词： heat wave surface urban heat island interactive Self-organization algorithm centroid migration Beijing

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The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China(Life Sciences) 2024年第9期67卷 1867-1880页

作者： Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen Xing-Jie Liang Yu Han Dandan Liu Jinchao Zhang State Key Laboratory of New Pharmaceutical Preparations and Excipients/Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education/College of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei ProvinceHebei UniversityBaoding 071002China CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Cancer stem cells(CSCs)play an important role in metastasis development,tumor recurrence,and treatment resistance,and are essential for the eradication of ***,therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape,which leads to enhanced aggressive behaviors compared with CSCs that have never been ***,the underlying mechanisms regulating the therapeutic escape remain *** this end,we established a model to isolate the therapeutic escaped CSCs(TSCSCs)from breast CSCs and performed the transcription profile to reveal the ***,we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway,resulting in TSCSCs exhibiting enhanced motility and ***,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo,which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and *** obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

关键词： therapeutic escape breast cancer stem cells motility p38/MAPK signaling pathway molecular mechanism

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Enterococcus faecalis provides protection during scavenging in carrion crow (Corvus corone)

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Zoological Research 2024年第3期45卷 451-463页

作者： Bin Hu Jia-Min Wang Qing-Xun Zhang Jing Xu Ya-Nan Xing Bo Wang Shu-Yi Han Hong-Xuan He CAS Key Laboratory of Animal Ecology and Conservation biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Beijing Milu Ecological Research center Beijing 102600China Beijing Capital International Airport Co. Ltd.Beijing 101300China

The gut microbiota significantly influences host physiology and provides essential ecosystem *** diet can affect the composition of the gut microbiota,the gut microbiota can also help the host adapt to specific dietary *** carrion crow(Corvus corone),an urban facultative scavenger bird,hosts an abundance of pathogens due to its scavenging *** this,carrion crows infrequently exhibit illness,a phenomenon related to their unique physiological *** present,however,the role of the gut microbiota remains incompletely *** this study,we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing,*** findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria(75.51%)and Firmicutes(22.37%).Significant differences were observed in the relative abundance of Enterococcus faecalis among groups,highlighting its potential as a biomarker of facultative scavenging behavior in carrion ***,*** isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica *** showed that *** down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha(TNF-α),interferon gamma(IFN-γ),and interleukin 6(IL-6),prevented *** colonization,and regulated the composition of gut microbiota in mice,thereby modulating the host’s immune regulatory ***,*** exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior,offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

关键词： Carrion crow Facultative scavenger Gut microbiota Enterococcus faecalis 16S rRNA sequencing

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Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo Stem Cell biology and Therapy Laboratory The Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Pediatric Surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their *** differentiation is associated with an increase in mitochondrial content and *** metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate ***-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell *** found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and *** of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic *** also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro *** LETM1 was knocked down in vivo,there was reduced tumor formation and lung *** data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma Stemness

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Dengue outbreaks in northern Nigeria: Evaluating the recommended Takeda vaccine and future prevention strategies

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World Journal of Virology 2024年第3期13卷 41-48页

作者： Ismail Rabiu Hafsat Abubakar Musa Zephaniah Isaiah Mujahid Hussaini Muhammad Muhsin Umar Suleiman Mustapha Jaafaru Isah Abdullahi Aminu Shehu Mariya Abdullahi Sani College of Life Science Department of Biomedical Science and Environmental BiologyKaohsiung Medical UniversityKaohsiung 80708TaiwanChina Department of microbiology Faculty of Life ScienceBayero University KanoKano 700006Kano StateNigeria Department of microbiology Umaru Musa Yar’adua UniversityKatsina 820102Katsina StateNigeria Department of microbiology Faculty of ScienceKaduna State UniversityTafawa Balewa Way 800283Kaduna StateNigeria National Reference Laboratory Nigeria Center for Disease ControlGaduwa 900231AbujaNigeria Department of microbiology and Biotechnology Federal UniversityDutse 720223Jigawa StateNigeria Monitoring and Evaluation Unit(Jigawa State Office) World Health OrganizationDutse 720223Jigawa StateNigeria

Dengue fever,caused by the dengue virus(DENV),poses a significant public health challenge globally,with Nigeria experiencing sporadic outbreaks.A clear understanding of the dengue burden has not been achieved in Nigeria,just as in other African *** the epidemiology and burden of dengue fever is essential for effective prevention and control *** paper examines the recent dengue outbreaks in northern Nigeria,particularly in Sokoto state,and evaluates the recommended Takeda dengue vaccine(TDV)along with future prevention *** limited surveillance and underreporting,dengue fever is endemic in Nigeria(with over 5 million cases and 5000 dengue-related deaths in 2023),with recent outbreaks indicating a growing *** TDV,a live attenuated tetravalent vaccine,has shown promise in preventing dengue fever,but challenges such as vaccine acceptance and access-ibility need to be *** urbanization contributes to the disease's spread,which is influenced by factors such as population density,cultural beliefs,water storage practices,hygiene,and water supply *** prevention strategies must focus on government intervention,community practices,and innovative vector control measures to mitigate the spread of DENV in *** study will serve as a valuable reference for policy-makers,researchers,and clinicians in the management and control of DENV in Nigeria and Africa as a whole.

关键词： Dengue outbreaks Northern Nigeria Takeda dengue vaccine Vaccine acceptance Epidemiology

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Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine

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Cancer biology & Medicine 2024年第9期21卷 754-768页

作者： Lina Hu Xuanye Zhang Shengbing Zang Sun Yat-sen University Cancer center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Department of Pathology Sun Yat-sen University Cancer Center Department of Medical Oncology Sun Yat-sen University Cancer Center

Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA) among various cancers with unique aberrant profiles and pathogenic effects, especially in peripheral T-cell lymphoma(PTCL). The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type, thereby leading to different functional and biological properties, which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors. However, the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated. Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways. The promising potential of targeting RHOA as a therapeutic modality is also outlined. This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.

关键词： Drug target Ras homolog family member A mutation pathogenesis peripheral T-cell lymphoma personalized medicine

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Plasma proteome profiling reveals biomarkers of chemotherapy resistance in patients with advanced colorectal cancer

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Quantitative biology 2024年第2期12卷 215-224页

作者： Jingxin Yang Jin Chen Luobin Zhang Fangming Zhou Xiaozhen Cui Ruijun Tian Ruilian Xu Medical Genetic center Affiliated Shenzhen Maternity and Child Healthcare HospitalSouthern Medical UniversityShenzhenChina Clinical center for Molecular Diagnosis and Therapy The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina Department of Chemistry and Research center for Chemical biology and Omics Analysis School of ScienceSouthern University of Science and TechnologyShenzhenChina Department of Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenChina

Colorectal cancer(CRC)is one of the most common *** with advanced CRC can only rely on chemotherapy to improve ***,primary drug resistance frequently occurs and is difficult to *** in plasma protein composition have shown potential in clinical ***,it is urgent to identify potential protein biomarkers for primary resistance to chemotherapy for patients with *** sample preparation and high-throughput analysis were used to explore potential plasma protein *** susceptibility testing of circulating tumor cells(CTCs)has been investigated,and the relationship between their values and protein expressions has been *** addition,the differential proteins in different chemotherapy outcomes have been ***,the potential biomarkers have been detected via enzyme-linked immunosorbent assay(ELISA).Plasma proteome of 60 CRC patients were *** correlation between plasma protein levels and the results of drug susceptibility testing of CTCs was performed,and 85 proteins showed a significant positive or negative correlation with chemotherapy ***-four CRC patients were then divided into three groups according to their chemotherapy outcomes(objective response,stable disease,and progressive disease),and 37 differential proteins were found to be related to chemotherapy *** overlapping proteins were further investigated in an additional group of 79 patients using *** levels of F5 and PROZ significantly increased in the progressive disease group compared to other outcome *** study indicated that F5 and PROZ proteins could represent potential biomarkers of resistance to chemotherapy in advanced CRC patients.

关键词： biomarker chemotherapy resistance colorectal cancer plasma proteome

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Inhibition of p53 inhibitors:progress,challenges and perspectives

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Journal of Molecular Cell biology 2019年第7期11卷 586-599页

作者： Gema Sanz Madhurendra Singh Sylvain Peuget Galina Selivanova Department of microbiology Tumor and Cell BiologyBiomedicum 8CKarolinska InstituteSE17165Sweden

p53 is the major tumor suppressor and the most frequently inactivated gene in cancer.p53 could be disabled either by mutations or by upstream negative regulators,including,but not limited to MDM2 and MDMX.p53 activity is required for the prevention as well as for the eradication of *** of p53 activity in mouse models leads to the suppression of established tumors of different *** findings provide a strong support to the anti-cancer strategy aimed for p53 *** this review,we summarize recent progress in the development of small molecules,which restore the tumor suppressor function of wild-type p53 and discuss their clinical *** discuss different aspects of p53-mediated response,which contribute to suppression of tumors,including non-canonical p53 activities,such as regulation of immune *** targeting p53 inhibitors is a very promising approach,there are certain limitations and concerns that the intensive research and clinical evaluation of compounds will hopefully help to overcome.

关键词： p53 tumor suppression anti-cancer therapy targeted drugs transcription factor immune response

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Detection of Progesterone Receptor as a Method of Diagnosing Mammary Cancer in Female Dogs

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Open Journal of Veterinary Medicine 2024年第8期14卷 217-227页

作者： José de Jesús Vázquez Pérez Angel Ramses Figueroa Hernandez Jorge Peregrina Sandoval Guillermo Nolasco Rodríguez Manuel Rosales Cortés Department of Veterinary Medicine University Center of Biological and Agricultural Sciences University of Guadalajara Zapopan Mexico Department of Cellular and Molecular biology University Center for Biological and Agricultural Sciences University of Guadalajara Zapopan Mexico

Introduction: Canine mammary gland tumor is the most common type of neoplasia in non-ovariectomized bitches. Approximately 50% of tumors are malignant. Neoplasms originating from the mammary gland represent the most common neoplastic disease in canines in Veterinary Medicine. Aim: Relate the expression of the receptor to progesterone (PR) with the tumor stage of canine mammary carcinoma. Material and Methods: Analytical-cross-sectional study, samples of paraffinized tumor tissue obtained from 30 canine patients with breast cancer were used. The expression of PR was performed by immunohistochemical labeling, using murine anti-PR (anti-PR Biocare brand). A descriptive analysis was carried out with the results using the SPSS program. Results: The predominant histological subtype of breast cancer was tubular carcinoma with 12 patients, followed by papillary cystic carcinoma with 6 patients, solid carcinoma 5, carcinosarcoma 4 and comedocarcinoma 3. There was a significant trend between breast cancer subtypes, histological grade G1. Among the histopathological findings, the degree of invasion is related to the presence of tumor cells in adjacent lymph nodes, which is why it is a prognostic indicator. The expression of PR in the tumor tissue samples it was 42.8% positive versus 57.14% negative, of which 75% correspond to G1, 8.3% to G2 and 16.6% to G3. With respect to the relationship of the expression of PR vs type of tumor, it was found that 50% correspond to tubular carcinoma, 33.3% to papillary cystic carcinoma, 8.3% to solid carcinoma and 8.3% to comedocarcinoma. Conclusion: The hormone receptor was negative in more than half of the patients and histological grade is significantly associated with tumor subtypes, this study emphasizes the need to introduce receptor testing into our routine clinical practice to offer the best treatment for breast cancer.

关键词： Cancer Mammary Gland Progesterone Immunohistochemistry Progesterone Membrane Receptor Component 1 (PGRMC 1)

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