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Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

Journal of Biomedical research 2024年第4期38卷 358-368页

作者： Yifei Cheng Rongjie Shi Shuai ben Silu Chen Shuwei Li Junyi Xin Meilin Wang Gong Cheng department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China department of Urology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China Jiangsu cancer Hospital Jiangsu Institute of Cancer Researchthe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the *** first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc *** then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA *** the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell ***,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting *** conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

关键词： genetic variants prostate cancer circRNA RNA-binding protein RNA splicing sing-cell RNA sequencing

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Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong Zhong Wei Zhao Bing Yao Lin Ding Huangxian Ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China department of Reproductive Medical Center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation Center(ChemBIC) Nanjing UniversityNanjing 210023China Center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

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Conserved RB functions in development and tumor suppression

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Protein & Cell 2011年第11期2卷 864-878页

作者： Gabriel M.Gordon Wei Du ben may department for cancer research University of ChicagoChicagoIL 60637USA

The variety of human cancers in which the retinoblastoma protein pRb is inactivated reflects both its broad importance for tumor suppression and its multitude of cellular *** evidence indicates that pRb contributes to a diversity of cellular functions,including cell proliferation,differentiation,cell death,and genome *** performs these diverse functions through the formation of large complexes that include E2F transcription factors and chromatin *** this review we will discuss some of the recent advances made in understanding the structure and function of pRb as they relate to tumor suppression,and highlight research using Drosophila melanogaster that reveals important,evolutionarily conserved functions of the RB family.

关键词： RB E2F Drosophila Rbf cell cycle chromatin modification

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Glutathione depletion based Pt(Ⅳ) hybrid mesoporous organosilica delivery system to conquer cisplatin chemoresistance: A “one stone three birds” strategy

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Chinese Chemical Letters 2024年第10期35卷 278-285页

作者： Linjie Ju Zhongxi Huang Qian Shen Chan Fu Shuanghe Li Wenjie Duan Chenfeng Xu Weizhen An Zhiqiang Zhai Jifu Wei Changmin Yu Guoren Zhou department of Pharmacy Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjing210009China Key Laboratory of Flexible Electronics(KLOFE) School of Flexible Electronics(Future Technologies)&Institute of Advanced Materials(IAM)Nanjing Tech University(NanjingTech)Nanjing211816China department of Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjing 210009China Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization College of Resources and Environmental SciencesNanjing AgriculturalUniversityNanjing210095China

The occurrence of acquired resistance to cisplatin(DDP)that induces the toxic drug effects has always been a huge challenge and urgently needs to be resolved in the cancer *** combination of anticancer drugs with different mechanisms can remarkably improve the chemotherapeutic *** that glutathione(GSH)plays as the driving factors in the resistance of DDP,here we have firstly proposed a“three birds,one stone”based nanoplatform to achieve triple synergetic effects simultaneously addressing DDP resistance in non-small cell lung cancer(NSCLC).Specifically,we initially designed and synthesized a DDP prodrug[Pt(Ⅳ)]bridged silsesquioxane precursor(Pt-Si).Then Pt-Si and bis[3-(triethoxysilyl)propyl]diselenide(BTESe PD)were integrated into the framework of mesoporous organosilica nanoparticles(MONs)to obtain a nanocarrier MONPt/*** loading with norcantharidin(NCTD)and modifying with the aptamer AS1411 based G-quadruplex(Apt),the Apt@NCTD@MONPt/Seexhibit impressive tumor homing *** being endocytosed,(Ⅰ)the diselenide and-O-Pt(Ⅳ)-O-rich scaffold can be reduced by the excessive GSH,followed by(Ⅱ)breaking the redox homeostasis via GSH depletion and precise release of the ***,the encapsulated NCTD is also released along with the degradation of the nanocarriers thereby(Ⅲ)achieving the GSH depletion and synergistic anti-tumor effect of NCTD and *** together,we believe this“one stone,three birds”strategy may be a promising paradigm to conquer drug resistance for clinical care.

关键词： MON_(ptse) NSCLC Glutathione depletion Responsive biodegradation Traditional Chinese medicines Synergistictherapy

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Spatial relationship of tertiary lymphoid structures and tumor-associated neutrophils in bladder cancer and prognostic potential for anti-PD-L1 immunotherapy

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cancer Communications 2024年第4期44卷 499-503页

作者： Xuechun Wang Anna Juncker-Jensen Gang Huang Mate Levente Nagy Xuemin Lu Liang Cheng Xin Lu department of Biological Sciences Boler-Parseghian Center for Rare and Neglected DiseasesHarper Cancer Research InstituteUniversity of Notre DameNotre DameINUSA NeoGenomics Laboratories Inc.Aliso ViejoCAUSA department of Pathology and Laboratory Medicine Brown University Warren Alpert Medical SchoolLifespan Academic Medical CenterLegorreta Cancer Center at Brown UniversityProvidenceRIUSA Tumor Microenvironment and Metastasis Program Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolisINUSA

Dear Editor,Tertiary lymphoid structures(TLSs)are organized clus-ters of immune cells found in non-lymphoid tissues of chronic inflammation,including solid tumors[1].High endothelial venules(HEVs)positive for peripheral node addressin(PNAd)are present in TLSs and may pro-vide highway entry for ***-residing TLSs may be formed by the concerted actions of cytokines and chemokines,a finding supported by the relation between a 12-chemokine signature and TLSs[2].

关键词： bladder lymphoid inflammation

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Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

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cancer Advances 2024年第3期7卷 1-7页

作者： Ning Zhao Dong-Mei Han Cai-Hong Wu Hao Jin National Clinical research Center for cancer Tianjin Cancer Hospital Airport HospitalTianjin 300308China Center for Precision cancer Medicine&Translational research Tianjin Cancer Hospital Airport HospitalTianjin 300308China Oncology department Tianjin Cancer Hospital Airport HospitalTianjin 300308China.

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and ***:A total of 50 healthy peoples and 60 cervical cancer patients were *** patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after *** on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical ***:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral *** for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK ***:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical *** study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

关键词： CD8 positive T lymphocytes flow cytometry natural killer cells radiotherapy uterine cervical neoplasms

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Engineered exosome hybrid copper nanoscale antibiotics facilitate simultaneous self-assembly imaging and elimination of intracellular multidrug-resistant superbugs

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Chinese Chemical Letters 2024年第7期35卷 319-324页

作者： Zengchao Guo Weiwei Liu Tengfei Liu Jinpeng Wang Hui Jiang Xiaohui Liu Yossi Weizmann Xuemei Wang State Key Laboratory of Digital Medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China department of Chemistry Ben-Gurion University of the NegevBeer-Sheva 8410501Israel

With the increasing emergence of bacterial infections,especially multidrug-resistant(MDR)bacteria,poses an urgent *** study demonstrated a novel multifunctional nanotheranostics platform developed by the strategic integration of both in-situ bio-assembly imaging and target bacteria *** the introduction of copper ions into bacteria,the Cu^(2+)could spontaneously bio-selfassembled into a multifunctional copper nanoclusters(NCs)which efficiently enhanced epigallocatechin gallate(EGCG)uptake into *** visualizing the bacteria,the developed theranostic nanoplatform exhibited highly efficient disinfection activities with negligible side effects as reflected by higher cell viability and insignificant hemolytic ***,the exosomal formulation of EGCG integrated with Cu^(2+)showed an increased intracellular antibacterial activity,which could eliminate most of the methicillin-resistant Staphylococcus aureus(MRSA)phagocytosed by macrophages,guide macrophages toward M2-like phenotype polarization and alleviate inflammation,without exhibiting obvious cytotoxicity on host *** regimen could be viewed as an effective strategy for the sterilization of intractable bacterial infections.

关键词： In situ self-assembled Exosome Antibacterial agents Bioimaging Intracellular infection

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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

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Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu Jie Chen Ping He Yan Cheng Kunrui Zhu Dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

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Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

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World Journal of Gastroenterology 2024年第8期30卷 806-810页

作者： Jian-Hong Zhong department of Hepatobiliary Surgery Guangxi Medical University Cancer HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or *** a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free *** therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue *** and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of *** questions need to be addressed by clinicians and researchers.

关键词： Adjuvant therapy Hepatocellular carcinoma Tumor recurrence Unanswered questions

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Exploring groundwater quality in semi-arid areas of Algeria:Impacts on potable water supply and agricultural sustainability

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Journal of Arid Land 2024年第2期16卷 147-167页

作者： Noua ALLAOUA Hinda HAFID Haroun CHENCHOUNI Laboratory of Natural Resources and Management of Sensitive Environments Larbi Ben M'hidi UniversityOum-El-Bouaghi 04000Algeria department of Nature and Life Sciences Faculty of Exact Sciences and Nature and Life SciencesLarbi Ben M'hidi UniversityOum-El-Bouaghi 04000Algeria Laboratory of Algerian Forests and Climate Change Higher National School of ForestsKhenchela 40000Algeria

Groundwater quality assessment is important to assure safe and durable water *** semi-arid areas of Algeria,groundwater represents the main water resource for drinking water supply of the rural population as well as for irrigation of agricultural *** samples from wells and springs were collected from the Gargaat Tarf and Annk Djemel sub-watersheds of the Oum El Bouaghi,Algeria,and were analyzed and compared with the World Health Organization(WHO)*** showed that most of the measured physical and chemical parameters exceeded the quality limits according to the WHO *** had a slightly alkaline water pH(7.00-7.79),electrical conductivity>1500μS/cm,chloride>500 mg/L,calcium>250 mg/L,and magnesium>155 mg/*** quality index(WQI)results showed that 68%of the area had excellent water quality,24%of the samples fell into good category,and only 8%were of poor quality and unsuitable for human *** wells in the area showed bacterial *** coliforms(453.9(±180.3)CFU(colony-forming units)/100 mL),fecal coliforms(243.2(±99.2)CFU/100 mL),and fecal streptococci(77.9(±32.0)CFU/100 mL)loads were above the standard limits set by the *** results confirmed that water resources in the study area were strongly influenced by anthropogenic activities and were not recommended for consumption as drinking water.

关键词： bacteriological indicator groundwater watershed physical-chemical parameter water quality index

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