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Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang Jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang Yuanyu Huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National clinical research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key laboratory of Tropical Disease research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key laboratory of Antiviral Drug research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health *** light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently ***,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 *** aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,*** protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion

Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key laboratory of experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

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International Journal of Oral Science 2024年第2期16卷 265-279页

作者： Alfredo Torres M.Angélica Michea Ákos Végvári Marion Arce Valentina Pérez Marcela Alcota Alicia Morales Rolando Vernal Mauricio Budini Roman A.Zubarev Fermín E.González laboratory of experimental Immunology&Cancer Faculty of DentistryUniversity of ChileSantiagoChile Department of Conservative Dentistry Faculty of DentistryUniversity of ChileSantiagoChile Division of Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden Periodontal Biology laboratory Faculty of DentistryUniversidad de ChileSantiagoChile laboratory of Cellular and Molecular Pathology Institute for Research in Dental SciencesFaculty of DentistryUniversity of ChileSantiagoChile

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains *** investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed *** progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further *** metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with *** western blot analyses validated key ***,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis *** progression was identified as occurring at a faster rate than traditionally *** samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic *** addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of ***,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of ***,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to *** analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal *** findings may le

关键词： finding progression faster

Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 1-3页

作者： Kazuaki Shimada Kenichi Nakamura Noboru Yamamoto Department of Hepatobiliary and Pancreatic Surgery National Cancer Center HospitalTokyo 104-0045Japan clinical research Support Offce National Cancer Center HospitalTokyo 104-0045Japan Department of experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan

Precision medicine is a growing field *** its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical *** main obstacles are associated... 详细信息

关键词： clinical Cancer overcome

Acceptor-engineering tailored type-Ⅰ photosensitizer with aggregation-induced NIR-II emission for cancer multimodal phototheranostics

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Science China Chemistry 2024年第8期67卷 2647-2660页

作者： Jiangao Li Niu Niu Deliang Wang Xue Liu Yi Qin Lei Wang Ben Zhong Tang Dong Wang Center for AIE research Shenzhen Key Laboratory of Polymer Science and TechnologyGuangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China Guangzhou Municipal and Guangdong Provincial Key laboratory of Molecular Target Clinical Pharmacologythe State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)Shenzhen 518172China

Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline(ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared(NIR-II) emission. experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole(BBTD) and 6,7-diphenylthiadiazoloquinoxaline(DPTQ), ITQ-based photosensitizer(TITQ) showed superior aggregation-induced emission(AIE) characteristics, much stronger type-I reactive oxygen species(ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.

关键词： phototheranostics aggregation-induced emission NIR-Ⅱfluorescence acceptor engineering photodynamic-photothermal therapy

Unlocking epigenetics for precision treatment of Ewing’s sarcoma

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Chinese Journal of Cancer research 2024年第3期36卷 322-340页

作者： Zhehao Fan Shuangshuang Dong Ning Wang Muhammad Babar Khawar Jingcheng Wang Haibo Sun Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Jiangsu Key laboratory of experimental&Translational Non-Coding RNA research Yangzhou 225001China Department of Pathology Northern Jiangsu People’s Hospital Affiliated to Yangzhou University/Clinical Medical CollegeYangzhou UniversityYangzhou 225001China Department of Orthopedics Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhou 225001China

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young *** the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains ***,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS *** regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating *** studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug *** review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

关键词： Ewing’s sarcoma epigenetic targets drug resistance drug development

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

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Neural Regeneration research 2024年第12期19卷 2626-2636页

作者： Blanca Molins Andrea Rodríguez Víctor Llorenç Alfredo Adán Group of Ocular Inflammation:clinical and experimental Studies Institut d’Investigacions Biomèdiques AgustíPi I Sunyer(IDIBAPS)BarcelonaSpain Institut Clínic d’Oftalmologia(ICOF) Hospital Clínic BarcelonaSpain

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the ***,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular *** in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying *** Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie *** the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of *** review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic ***,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

关键词： age-related macular degeneration Bruch's membrane decellularization retinal pigment epithelium scaffold

SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice

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research 2024年第3期2023卷 369-389页

作者： Xiujuan Du Yuhua Yan Juehua Yu Tailin Zhu Chu-Chung Huang Lingli Zhang Xingyue Shan Ren Li Yuan Dai Hui LV Xiao-Yong Zhang Jianfeng Feng Wei-Guang Li Qiang Luo Fei Li Developmental and Behavioral Pediatric Department Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children's Environmental HealthXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Developmental and Behavioral Pediatric Department Shanghai Xinhua Children's HospitalShanghai 200092China National clinical research Center for Aging and Medicine at Huashan Hospital Institute of Science and Technology for Brain-lnspired IntelligenceMinistry of Education-Key Laboratory of Computational Neuroscience and Brain-lnspired IntelligenceFudan UniversityShanghai 200433China State Key laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science Institutes of Brain Science and Human Phenom InstituteFudan UniversityShanghai 200032China Shanghai Key laboratory of Brain Functional Genomics(Ministry of Education) School of Life SciencesEast China Normal UniversityShanghai 200062China Department of Rehabilitation Medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Center for experimental Studies and research The First Affliated Hospital of Kunming Medical UniversityKunming 650032China Shanghai research Center for Brain Science and Brain-lnspired Intelligence Shanghai201210China Institute of Cognitive Neuroscience School of Psychology and Cognitive ScienceEast China Normal UniversityShanghai 200062China.

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

关键词： metabolism impaired reversed

Distinct but correct: generating diversified and entity-revised medical response

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Science China(Information Sciences) 2024年第3期67卷 94-113页

作者： Bin LI Bin SUN Shutao LI Encheng CHEN Hongru LIU Yixuan WENG Yongping BAI Meiling HU College of Electrical and Information Engineering Hunan University School of Mathematics Sun Yat-sen University JD Technology National laboratory of Pattern Recognition Institute of AutomationChinese Academy of Sciences Xiangya Hospital of Central South University Teaching and research Section of clinical Nursing Xiangya Hospital of Central South University

Medical dialogue generation(MDG) is applied for building medical dialogue systems for intelligent consultation. Such systems can communicate with patients in real time, thereby improving the efficiency of clinical diagnosis. However, predicting correct entities and correctly generating distinct responses remain a great challenge. Inspired by actual doctors’ responses to patients, we consider MDG a two-stage task: entity prediction and dialogue generation. For entity prediction, we design an ent-mac post pre-training strategy by leveraging external medical entity knowledge to enhance the pre-trained model. For dialogue generation, we propose an entity-aware fusion MDG method in which predicted entities are integrated into the dialogue generation model through different encoding fusion mechanisms, using information from different sources. Because the diverse beam search algorithm can produce responses with entities that deviate from the predicted entities, an entity-revised diverse beam search is proposed to correct the entities entailed in the generated responses and make the generated responses more distinct. The experimental results on the China Conference on Knowledge Graph and Semantic Computing 2021(A/B tests) and the International Conference on Learning Representations 2021(online test) datasets show that the proposed method outperforms several state-of-the-art methods, which demonstrates its practicability and effectiveness.

关键词： medical entity prediction ent-mac post pre-training strategy entity-aware fusion medical dialogue generation encoding fusion mechanism entity-revised diverse beam search