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The two sides of chromosomal instability:drivers and brakes in cancer

Signal Transduction and Targeted Therapy 2024年第4期9卷 1595-1624页

作者： Rendy Hosea sharon Hillary Sumera Naqvi Shourong Wu Vivi Kasim Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400045China The 111 Project Laboratory of Biomechanics and Tissue Repair College of BioengineeringChongqing UniversityChongqing 400044China Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing UniversityChongqing 400030China

Chromosomal instability(CIN)is a hallmark of cancer and is associated with tumor cell *** triggers a chain reaction in cells leading to chromosomal abnormalities,including deviations from the normal chromosome number or structural changes in *** arises from errors in DNA replication and chromosome segregation during cell division,leading to the formation of cells with abnormal number and/or structure of *** in DNA replication result from abnormal replication licensing as well as replication stress,such as double-strand breaks and stalled replication forks;meanwhile,errors in chromosome segregation stem from defects in chromosome segregation machinery,including centrosome amplification,erroneous microtubule-kinetochore attachments,spindle assembly checkpoint,or defective sister chromatids *** normal cells,CiN is deleterious and is associated with DNA damage,proteotoxic stress,metabolic alteration,cell cycle arrest,and ***,despite these negative consequences,CiN is one of the hallmarks of cancer found in over 90%of solid tumors and in blood ***,CiN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity,thereby facilitating adaptive resistance to therapies;however,excessive CiN could induce tumor cells death,leading to the"just-right"model for CIN in *** the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor *** review provides an overview of causes and consequences of CIN,as well as the paradox of CIN,a phenomenon that continues to perplex ***,this review explores the potential of CIN-based anti-tumor therapy.

关键词： chromosomal consequences thereby

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CTLA4 protects against maladaptive cytotoxicity during the differentiation of effector and follicular CD4^(+)T cells

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Cellular & Molecular Immunology 2023年第7期20卷 777-793页

作者： Yuwei Hao Bahar Miraghazadeh Rochna Chand Ainsley R.Davies Chelisa Cardinez Kristy Kwong Morgan B.Downes Rebecca A.Sweet Pablo F.Cañete Lloyd J.D’Orsogna David A.Fulcher sharon choo Desmond Yip Geoffrey Peters Sonia Yip Matthew J.Witney Maxim Nekrasov Zhi-Ping Feng David C.Tscharke Carola G.Vinuesa Matthew C.Cook Centre for Personalised Immunology John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia Translational Research Unit The Canberra HospitalCanberraACTAustralia Division of Immunology and Infectious Diseases John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia Department of Immunology Fiona Stanley HospitalPerthWAAustralia Department of Immunology The Royal Children’s HospitalMelbourneVICAustralia Department of Medical Oncology The Canberra HospitalCanberraACTAustralia ANU Medical School The Australian National UniversityCanberraACTAustralia NHMRC Clinical Trials Unit The University of SydneySydneyNSWAustralia The ACRF Biomolecular Resource Facility John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia ANU Bioinformatics Consultancy John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia Francis Crick Institute 1 Midland RdLondon NW11ATUK Cambridge Institute of Therapeutic Immunology and Infectious Disease University of CambridgeCambridgeUnited Kingdom.

As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency(PAD),analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene ***57 marks dysfunctional T cells that have differentiated after antigenic ***,while circulating CD57^(+)CD4^(+)T cells are normally rare,we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or *** performed single-cell RNA-seq analysis of matched CD57^(+)CD4^(+)T cells from blood and tonsil *** CD57^(+)CD4^(+)T cells(CD4cyt)exhibited a cytotoxic transcriptome similar to that of CD8^(+)effector cells,could kill B cells,and inhibited B-cell ***4 restrained the formation of *** CD57 also marked an abundant subset of follicular helper T cells,which is consistent with their antigen-driven differentiation,this subset had a preexhaustion transcriptomic signature marked by TCF7,TOX,and ID3 expression and constitutive expression of CTLA4 and did not become cytotoxic even after CTLA4 ***,CD57^(+)CD4^(+)T-cell cytotoxicity and exhaustion phenotypes are compartmentalised between blood and germinal ***4 is a key modifier of CD4^(+)T-cell cytotoxicity,and the pathological CD4cyt phenotype is accentuated by infection.

关键词： CTLA4 Immunodeficiency Cell exhaustion Terminal differentiation Cytotoxic CD4^(+)T cells CD57

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Translating bacteriophage-derived depolymerases into antibacterial therapeutics:Challenges and prospects

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Acta Pharmaceutica Sinica B 2024年第1期14卷 155-169页

作者： Honglan Wang Yannan Liu Changqing Bai sharon Shui Yee Leung School of Pharmacy the Chinese University of Hong KongHong Kong SARChina Emergency Medicine Clinical Research Center Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Respiratory Shenzhen University General HospitalShenzhen University Clinical Medical AcademyGuangdong 518055China

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and *** depolymerases are enzymes responsible for degrading diverse bacterial surface *** are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic *** depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection ***,some formulation approaches have been developed for improved stability and activity of ***,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and *** development must address these obstacles for clinical ***,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant ***,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

关键词： Phage-derived polysaccharide depolymerases Bacteriophage proteins Bacterial capsules Polysaccharide capsules Antibiotic resistance Biofilms Antibacterial therapy Antimicrobial adjuvants Combination treatment

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Propagation and Pinning of Travelling Wave for Nagumo Type Equation

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Journal of Applied Mathematics and Physics 2024年第3期12卷 861-869页

作者： sharon-Yasotha Veerayah-Mcgregor Valipuram Manoranjan Department of Mathematics Washington State University Pullman Washington USA

In this paper, we study the propagation and its failure to propagate (pinning) of a travelling wave in a Nagumo type equation, an equation that describes impulse propagation in nerve axons that also models population growth with Allee effect. An analytical solution is derived for the traveling wave and the work is extended to a discrete formulation with a piecewise linear reaction function. We propose an operator splitting numerical scheme to solve the equation and demonstrate that the wave either propagates or gets pinned based on how the spatial mesh is chosen.

关键词： Operator Splitting Travelling Wave Piecewise Reaction Nagumo Equation Pinning Finite Differences

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Grafts in Peyronie’s surgery without the use of prostheses:a systematic review and meta-analysis

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Asian Journal of Andrology 2024年第3期26卷 250-259页

作者： Anastasios Natsos Vasileios Tatanis Stavros Kontogiannis sharon Waisbrod Kristiana Gkeka Mohamed Obaidad Angelis Peteinaris Konstantinos Pagonis Costas Papadopoulos Panagiotis Kallidonis Evangelos Liatsikos Petros Drettas Department of Urology University of PatrasPatras 26500Greece Uroclinic Pfaeffikon 8808Switzerland Department of Medical Physics University of PatrasPatras26500Greece Department of Urology Medical University of ViennaVienna 1090Austria

Peyronie’s disease(PD)is characterized by abnormal penile curvature,and various surgical methods have been developed usingdifferent graft ***,there is currently no universal agreement on which type of graft is the *** objective of thisreview was to evaluate the available literature and identify the most effective graft material for penile curvature correction in PD.A literature search was conducted using electronic databases,including PubMed,Scopus,and the Cochrane *** patients,intervention,comparison,and outcome(PICO)approach was used to define the eligibility of *** authors independentlyselected studies,evaluated them,and extracted ***-effect models using the DerSimonian–Laird method were *** were single-arm studies and had a high risk of *** mucosa grafts(BMG)were found to result in the highest penilestraightening rates and were associated with the least de novo erectile *** grafts demonstrated a high successrate in straightening despite a higher mean preoperative curvature,while Tutoplast grafts had a higher incidence of postoperativeerectile *** had the highest percentage of postoperative penile ***,the TachoSil graft showed thebest performance when preoperative curvature is taken into *** on the available literature,BMG appear to be the mosteffective for penile curvature correction in PD,but this is offset by the requirement for low preoperative *** TachoSilgraft shows the best overall performance when preoperative curvature is *** randomized clinical trials arestill needed to determine graft superiority.

关键词： erectile function penile curvature penile grafts Peyronie’s disease

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Acceptability of Caesarean Section among Pregnant Women Seeking Antenatal Care at Women and Newborn Hospital-University Teaching Hospitals, Lusaka Zambia

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Open Journal of Obstetrics and Gynecology 2024年第5期14卷 721-743页

作者： Huhenya sharon Chongo Maureen Masumo Namayipo Nankamba Lusaka College of Nursing and Midwifery University Teaching Hospital Lusaka Zambia Department of Midwifery Women and Child Health School of Nursing Sciences University of Zambia Lusaka Zambia

Caesarean section remains one of the most common obstetric and major operations performed on women during pregnancy and has contributed to improving maternal and foetal health. Consequently, significant mortality and morbidity from pregnancy and labour-related causes can be eliminated by a timely caesarean section. The acceptance of the life-saving procedure remains unsatisfactory in most sub-Saharan nations. The study aimed to assess the acceptability of caesarean section and associated factors among pregnant women seeking antenatal care at Women and Newborn Hospital-University Teaching Hospitals in Lusaka Zambia. The study utilised a quantitative cross-sectional analytical study design involving 420 pregnant women selected using systematic random sampling at Women and Newborn Hospital-University Teaching Hospitals Lusaka Zambia. Data was obtained using an Interview schedule and analysed using R software version 4.3.2. Chi-square, Fisher’s exact test, Wilcoxon rank sum test and binary logistic regression for statistical analysis at a 5% level of significance. The study found that the acceptability of Caesarean section as a mode of delivery was low (29%) among respondents at Women and Newborn Hospital-University Teaching Hospitals. This was influenced by marital status (P = 0.002), socioeconomic status (P = 0.050), parity (P = 0.004), gestation age (P = 0.008), previous history of caesarean section (P = 0.003), knowledge (P < 0.001), attitude (P < 0.001), and sociocultural beliefs (P = 0.045). Low acceptability of Caesarean section delivery is common among women at Women and Newborn Hospital-University Teaching Hospitals, despite its potential benefits for maternal and neonatal health. Socio-demographic and maternal characteristics, knowledge, attitude, perception, and socio-cultural beliefs play a major role in determining acceptability. Therefore, efforts to enhance acceptability should focus on improving knowledge, enhancing positive perceptions and attitudes, an

关键词： Caesareans Section Acceptability Knowledge Attitude Perception

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Ischemic stroke with concomitant clear cell carcinoma of the ovary:A case report and review of literature

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World Journal of Clinical Cases 2024年第20期12卷 4397-4404页

作者： Wing Yu sharon Siu Dah-Ching Ding Department of Obstetrics and Gynecology Hualien Tzu Chi HospitalHualien 970Taiwan Department of Obstetrics and Gynecology Hualien Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationTzu Chi UniversityHualien 970Taiwan Institute of Medical Sciences Tzu Chi UniversityHualien 970Taiwan

BACKGROUND Ischemic stroke is a rare event associated with an elevated risk of blood clot formation owing to an underlying ***,we present a case of ovarian carcinoma that led to cerebral *** SUMMARY A 43-year-old woman experienced sudden onset right-sided paralysis and difficulty speaking two days after discovery of a large ovarian tumor measuring approximately 14 cm,which was suspected to be *** examination revealed left middle cerebral artery *** patient had a history of hypertension and *** stabilization with heparin treatment and vital signs management,the patient underwent debulking surgery,including total hysterectomy,bilateral salpingo-oophorectomy,omentectomy,and bilateral pelvic and para-aortic lymph node *** final diagnosis was clear cell carcinoma of the right ovary(stage IA).Subsequently,the patient completed six rounds of adjuvant chemotherapy while simultaneously undergoing ***,the patient is able to walk independently,although she still experiences *** Prompt medical intervention and interdisciplinary care are crucial in the setting of incidental findings such as a large ovarian tumor.

关键词： Ovarian cancer Ischemic stroke Coagulation Infarction Case report

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： sharon J.Brown Rafael J.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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有压差下全接触刷式密封迟滞特性数值研究

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兵器装备工程学报 2024年第1期45卷 180-187,222页

作者：刘美红汤俊锋康宇驰许嘉辉李川 sharon Kao-Walter 昆明理工大学机电工程学院昆明650000 布莱金厄理工学院数学和自然科学系瑞典卡尔斯克鲁纳SE-37179

刷式密封迟滞特性引起的泄漏问题、摩擦磨损问题及流动换热问题较为突出。刷式密封迟滞特性数值模型呈现接触对多、刷丝大变形的特点,存在非线性程度较高、收敛性较差的问题。提出了基于有限元软件ABAQUS的刷式密封迟滞特性求解模型,考... 详细信息

刷式密封迟滞特性引起的泄漏问题、摩擦磨损问题及流动换热问题较为突出。刷式密封迟滞特性数值模型呈现接触对多、刷丝大变形的特点,存在非线性程度较高、收敛性较差的问题。提出了基于有限元软件ABAQUS的刷式密封迟滞特性求解模型,考虑刷丝之间接触、刷丝与背板接触、刷丝与转子之间接触,引入阻尼提高模型收敛性。在数值计算与实验结果、理论计算对比验证的基础上,研究了刷丝自由端长度、刷丝直径、刷丝倾斜角度以及上下游压差对迟滞特性和接触力最大值的影响程度。研究结果表明:随着上下游压差、直径的增大,刷式密封迟滞特性呈现增加的趋势,而刷丝倾角的增加导致迟滞特性呈现递减的趋势,刷丝自由端长度的改变对迟滞特性的影响较小;刷丝直径是影响刷丝与转子之间接触力最大值的主要因素,刷丝倾斜角度对接触力最大值有一定程度影响。上述研究为分析刷式密封迟滞特性提供了理论依据,为降低迟滞特性提供了参考。

关键词：刷式密封迟滞特性几何参数迟滞能接触力

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