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A proteomic landscape of pharmacologic perturbations for functional relevance

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Journal of Pharmaceutical Analysis 2024年第1期14卷 128-139页

作者： Zhiwei Liu Shangwen Jiang Bingbing Hao Shuyu Xie Yingluo Liu Yuqi Huang Heng Xu Cheng Luo Min Huang Minjia Tan Jun-Yu Xu State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing210023China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdong528400China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing210023China

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

关键词： Proteomics Drug Perturbation Drug target Drug combination

The shear strength of the interface between artificial rock and printed concrete at super-early ages

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Frontiers of Structural and Civil Engineering 2024年第1期18卷 51-65页

作者： Yong Yuan Xiaoyun Wang Jiao-Long Zhang Yaxin Tao Kim Van Tittelboom Luc Taerwe Geert De Schutter College of Civil Engineering Tongji UniversityShanghai 200092China State Key Laboratory of Disaster Reduction in Civil Engineering Tongji UniversityShanghai 200092China Belgium-china Joint Laboratory for Industrialized Construction Tongji UniversityShanghai 200092China Magnel-Vandepitte Laboratory for Structural Engineering and Building Materials Ghent UniversityGhent 9052Belgium

3D concrete printing has the potential to replace shotcrete for construction of linings of tunnels in hard *** shear strength of the interface between rock and printed concrete is vital,especially at super-early ***,traditional methods for testing the shear strength of the interface,e.g.,the direct shear test,are time-consuming and result in a high variability for fast-hardening printed *** this paper,a new fast bond shear test is *** test can be completed in 1 min,with another 2 min for preparing the next *** influence of the matrix composition,the age of the printed matrices,and the interface roughness of the artificial rock substrate on the shear strength of the interface was experimentally *** tests were conducted at the age of the matrices at the 1st,the 4th,the 8th,the 16th,the 32nd,and the 64th min after its final setting.A dimensionless formula was established to calculate the shear strength,accounting for the age of the printed matrices,the interface roughness,and the shear failure *** was validated by comparing the calculated results and the experimental results of one group of samples.

关键词： rock tunnel printed concrete interface fast bond shear test shear strength

Harnessing exosomes for targeted therapy:strategy and application

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Biomaterials Translational 2024年第1期5卷 46-58页

作者： Xiaoxiang Ren Ruixue Xu Chenjie Xu Jiacan Su Organoid Research Center Institute of Translational MedicineShanghai UniversityShanghaiChina Department of Microbial Pathogenesis Yale University School of MedicineNew HavenCTUSA Department of Biomedical Engineering City University of Hong KongHong Kong Special Administrative RegionChina Department of Orthopedic Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina National Center for Translational Medicine(shanghai)SHU Branch Shanghai UniversityShanghaiChina

Exosomes,nanoscopic extracellular vesicles produced by cells,are pivotal in mediating intracellular communication by transporting nucleic acids,proteins,lipids,and other bioactive molecules,thereby influencing physiological and pathological *** endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic *** their potential,the clinical utility of exosomes is hampered by challenges such as limited storage stability,yield,purity,and targeting *** review focuses on exosomes as targeted therapeutic agents,examining their biogenesis,classification,isolation,and characterisation,while also addressing the current limitations in yield,purity,and *** delve into the literature to propose optimisation strategies that can enhance their therapeutic efficacy and accelerate the translation of exosome-based therapies into clinical practice.

关键词： biomedical engineering exosomes modification nanotechnology targeted therapy

Analgesic nanomedicines for the treatment of chronic pain

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BMEMat(BioMedical Engineering Materials) 2024年第1期2卷 76-87页

作者： Hao Liu Hongjun Zhuang Ya Wang Yuen Yee Cheng Feixiang Chen Jian Chen Xinglei Song Run Zhang Yanyan Liu Wenbo Bu State Key Laboratory of Molecular Engineering of Polymers Department of Materials ScienceFudan UniversityShanghaiChina Department of Rehabilitation Zhongshan HospitalFudan UniversityShanghaiChina Central Laboratory The First Affiliated Hospital of Xiamen UniversityXiamenChina Institute for Biomedical Materials&Devices(IBMD) Faculty of ScienceThe University of Technology SydneySydneyNew South WalesAustralia Department of Anatomy and Physiology Shanghai Jiao Tong University School of MedicineShanghaiChina Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQueenslandAustralia

Chronic pain is a major cause of suffering that often accompanies diseases and therapies,affecting approximately 20%of individuals at some point in their ***,current treatment modalities,such as anesthetic and antipyretic analgesics,have limitations in terms of efficacy and side *** technology offers a promising avenue to overcome these challenges and introduce new therapeutic *** article reviews the recent research on nanomedicine analgesics,integrating analyses of neuroplasticity changes in neurons and pathways related to the transition from acute to chronic ***,it explores potential future strategies using nanomaterials,aiming to provide a roadmap for new analgesic development and improved clinical pain *** leveraging nanotechnology,these approaches hold the potential to revolutionize pain treatment by delivering targeted and effective relief while minimizing side effects.

关键词： analgesics chronic pain local anesthetics nanomedicine neuroplasticity

Insights into therapeutic peptides in the cancerimmunity cycle:Update and challenges

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3818-3833页

作者： Xiaokun Zhang Ye Wu Jiayi Lin Shengxin Lu Xinchen Lu Aoyu Cheng Hongzhuan Chen Weidong Zhang Xin Luan shanghai Frontiers Science Center for Chinese Medicine Chemical Biology Institute of Interdisciplinary Integrative Medicine Research and Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Medicinal Plant Development Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100193China School of Pharmacy Second Military Medical UniversityShanghai 200433China Department of Pharmacology School of PharmacyFudan UniversityShanghai 201203China

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer *** vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target *** review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint *** attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical ***,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

关键词： Cancer-immunity cycle Oncolytic peptide Peptide neoantigen vaccine Peptide mimotope Immune checkpoint blockade Cancer immunotherapy Synthetic long peptide vaccine Peptide-major histocompatibility complex

Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma

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iLIVER 2024年第1期3卷 38-44页

作者： Ming-Da Wang Yong-Kang Diao Lan-Qing Yao Zhong-Qi Fan Ke-Chun Wang Han Wu Li-Hui Gu Jia-Hao Xu Chao Li Guo-Yue Lv Tian Yang Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University(Navy Medical University)Shanghai 200438China Department of Hepatobiliary and Pancreatic Surgery General Surgery CenterFirst Hospital of Jilin UniversityChangchun 130021China

Hepatocellular carcinoma(HCC)is a prevalent malignancy worldwide,ranking as the sixth most common malignancy and the third leading cause of cancer-related *** diagnosis,limited management options,and its complex etiology contribute to the poor prognosis and high mortality *** advances in understanding the molecular mechanisms of HCC and innovations in high-throughput sequencing technologies have led to the development of molecular diagnostics and personalized therapies for this challenging *** review provides a comprehensive overview of research on the molecular diagnosis and individualized treatment for *** highlight key advances and potential future directions and discuss the application of next-generation sequencing technologies to identify and characterize genetic and epigenetic alterations in HCC *** technologies may aid in the selection of targeted therapies,prediction of treatment response,and monitoring disease ***,we explore the role of liquid biopsy in HCC diagnosis,prognosis prediction,and treatment monitoring,focusing on circulating tumor cells,circulating tumor DNA,and extracellular *** also explore the evolving landscape of personalized therapy for HCC,including targeted therapies against key oncogenic signaling pathways,immune checkpoint inhibitors,tumor-agnostic therapies,and innovative cellbased *** discuss the challenges and opportunities that lie ahead in the quest to improve HCC patient outcomes through the integration of molecular diagnostics and individualized precision *** emphasize the need for multi-interdisciplinary collaboration,refinement of predictive and prognostic biomarkers,and the development of more effective combination strategies for HCC management in the new area of precision medicine.

关键词： Hepatocellular carcinoma Liquid biopsy Diagnosis Immune checkpoint inhibitors Targeted therapy

Through-polymer,via technology-enabled,flexible,lightweight,and integrated devices for implantable neural probes

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Microsystems & Nanoengineering 2024年第2期10卷 279-291页

作者： Cunkai Zhou Ye Tian Gen Li Yifei Ye Lusha Gao Jiazhi Li Ziwei Liu Haoyang Su Yunxiao Lu Meng Li Zhitao Zhou Xiaoling Wei Lunming Qin Tiger H.Tao Liuyang Sun College of Electronics and Information Engineering Shanghai University of Electric PowerShanghaiChina 2020 X-Lab Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghaiChina School of Graduate Study University of Chinese Academy of SciencesBeijingChina State Key Laboratory of Transducer Technology Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghaiChina Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijingChina School of Physical Science and Technology ShanghaiTech UniversityShanghaiChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina Neuroxess Co. Ltd.(Jiangxi)NanchangJiangxiChina Guangdong Institute of Intelligence Science and Technology HengqinZhuhaiGuangdongChina Tianqiao and Chrissy Chen Institute for Translational Research ShanghaiChina

In implantable electrophysiological recording systems,the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal *** advancements in MEMS and CMOS technology have significantly improved these components,their interconnection still relies on conventional printed circuit boards and sophisticated *** conventional approach adds considerable weight and volume to the package,especially for high channel count *** address this issue,we developed a through-polymer via(TPV)method inspired by the through-silicon via(TSV)technique in advanced three-dimensional *** innovation enables the vertical integration of flexible probes,amplifier chips,and PCBs,realizing a flexible,lightweight,and integrated device(FLID).The total weight of the FLIDis only 25%that of its conventional counterparts relying on adapters,which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without ***,by incorporating a platinum-iridium alloy as the top layer material for electrical contact,the FLID realizes exceptional electrical performance,enabling in vivo measurements of both local field potentials and individual neuron action *** findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

关键词： alloy neural recording

面向高性能柔性电子的强韧、可修复和优异抗穿刺的氟化弹性体

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Science Bulletin 2024年第12期69卷 1875-1886页

作者：贾宇杰管清宝储成臻张璐之 Rasoul Esmaeely Neisiany 顾士甲孙俊芬游正伟 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Institute of Functional MaterialsCollege of Materials Science and EngineeringResearch Base of Textile Materials for Flexible Electronics and Biomedical Applications(China Textile Engineering Society)Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative MedicineDonghua UniversityShanghai 201620China Biotechnology Centre Silesian University of TechnologyGliwice 44-100Poland Department of Polymer Engineering Hakim Sabzevari UniversitySabzevar ***Iran

There is usually a trade-off between high mechanical strength and dynamic self-healing because the mechanisms of these properties are mutually ***,we design and fabricate a fluorinated phenolic polyurethane(FPPU)elastomer based on octafluoro-4,4'-biphenol to overcome this *** fluorine-based motif not only tunes interchain interactions throughπ-πstacking between aromatic rings and free-volume among polymer chains but also improves the reversibility of phenol-carbamate bonds via electron-withdrawing effect of fluorine *** developed FPPU elastomer shows the highest recorded puncture energy(648.0 m J),high tensile strength(27.0 MPa),as well as excellent selfhealing efficiency(92.3%),along with low surface energy(50.9 MJ m^(-2)),notch-insensitivity,and reprocessability compared with non-fluorinated counterpart biphenolic polyurethane(BPPU)*** advantage of the above-mentioned merits of FPPU elastomer,we prepare an anti-fouling triboelectric nanogenerator(TENG)with a self-healable,and reprocessable elastic *** from stronger electron affinity of fluorine atoms than hydrogen atoms,this electronic device exhibits ultrahigh peak open-circuit voltage of 302.3 V compared to the TENG fabricated from BPPU ***,a healable and stretchable conductive composite is *** research provides a distinct and general pathway toward constructing high-performance elastomers and will enable a series of new applications.

关键词： Fluorinated elastomer Polyurethane Phenol-carbamate bonds Self-healing Reprocessable

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline:A Community‑Based Cohort Study

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Phenomics 2024年第1期4卷 51-55页

作者： Jialin Li Qingxia Huang Yingzhe Wang Mei Cui Kelin Xu Chen Suo Zhenqiu Liu Yanpeng An Li Jin Huiru Tang Xingdong Chen Yanfeng Jiang State Key Laboratory of Genetic Engineering Human Phenome InstituteZhangjiang Fudan International Innovation Centerand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan University2005 Songhu RdShanghai 200438China Fudan University Taizhou Institute of Health Sciences Taizhou 225326China State Key Laboratory of Genetic Engineering School of Life SciencesMetabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular PhenomicsHuman Phenome InstituteZhongshan HospitalFudan University2005 Songhu RdShanghai 200438China Department of Neurology Huashan HospitalFudan UniversityShanghai 200040China Ministry of Education Key Laboratory of Public Health Safety Department of BiostatisticsSchool of Public HealthFudan UniversityShanghai 200032China Ministry of Education Key Laboratory of Public Health Safety Department of EpidemiologySchool of Public HealthFudan UniversityShanghai 200032China shanghai Institute of Infectious Disease and Biosecurity Shanghai 200032China Yiwu Research Institute of Fudan University Yiwu 322000ZhejiangChina International Human Phenome Institute(shanghai) Shanghai 201203China Greater Bay Area Institute of Precision Medicine(Guangzhou) Fudan UniversityGuangzhou 511462China

Cardiovascular health metrics are now widely recognized as modifable risk factors for cognitive decline and *** perturbations might play roles in the linkage of cardiovascular diseases and *** metabolites profling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive *** a prospective community-based cohort in china(n=725),312 serum metabolic phenotypes were quantifed,and cardiovascular health score was calculated including smoking,exercise,sleep,diet,body mass index,blood pressure,and blood *** function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline.A better cardiovascular health was signifcantly associated with lower risk of concentration decline and orientation decline(hazard ratio(HR):0.84–0.90;p<0.05).Apolipoprotein-A1,high-density lipoprotein(HDL)cholesterol,cholesterol ester,and phospholipid concentrations were signifcantly associated with a lower risk of longitudinal memory and orientation decline(p<0.05 and adjusted-p<0.20).Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and-3(proportion of mediation:7.68–8.21%,both p<0.05).Cardiovascular risk factors were associated with greater risks of cognitive decline,which were found to be mediated by circulating lipoproteins,particularly the medium-size HDL *** fndings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

关键词： Cardiovascular risk factors Lipoproteins Lipids Cognition Cognitive decline