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Engineered stem cells by emerging biomedical stratagems

Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao Department of Vascular Surgery.nanjing Drum Tower Hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary Surgery and Transplantation Surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China shenzhen research institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

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In Vivo Voltammetric Imaging of Metal Nanoparticle-Catalyzed Single-Cell Electron Transfer by Fermi Level-Responsive Graphene

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research 2024年第1期2023卷 271-280页

作者： Qing Xia Rui Liu Xueqin Chen Zixuan Chen Jun-Jie Zhu State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023P.R.China shenzhen research institute of nanjing university Shenzhen 518000P.R.China

Metal nanomaterials can facilitate microbial extracellular electron transfer(EET)in the electrochemically active biofilm.However,the role of nanomaterials/bacteria interaction in this process is still unclear.Here,we reported the single-cell voltammetric imaging of Shewanella oneidensis MR-1 at the single-cell level to elucidate the metal-enhanced EET mechanism in vivo by the Fermi level-responsive graphene electrode.Quantified oxidation currents of~20 fA were observed from single native cells and gold nanoparticle(AuNP)-coated cells in linear sweep voltammetry analysis.On the contrary,the oxidation potential was reduced by up to 100 mV after AuNP modification.It revealed the mechanism of AuNP-catalyzed direct EET decreasing the oxidation barrier between the outer membrane cytochromes and the electrode.Our method offered a promising strategy to understand the nanomaterials/bacteria interaction and guide the rational construction of EET-related microbial fuel cells.

关键词： Fermi voltammetry Electron

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Intelligent diagnosis of retinal vein occlusion based on color fundus photographs

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 1-6页

作者： Yu-Ke Ji Rong-Rong Hua Sha Liu Cui-Juan Xie Shao-Chong Zhang Wei-Hua Yang Eye Hospital Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina College of Electronic Information Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210000Jiangsu ProvinceChina shenzhen Eye institute Shenzhen Eye HospitalJinan UniversityShenzhen 518000Guangdong ProvinceChina

AIM:To develop an artificial intelligence(AI)diagnosis model based on deep learning(DL)algorithm to diagnose different types of retinal vein occlusion(RVO)by recognizing color fundus photographs(CFPs).METHODS:Totally 914 CFPs of healthy people and patients with RVO were collected as experimental data sets,and used to train,verify and test the diagnostic model of RVO.All the images were divided into four categories[normal,central retinal vein occlusion(CRVO),branch retinal vein occlusion(BRVO),and macular retinal vein occlusion(MRVO)]by three fundus disease experts.Swin Transformer was used to build the RVO diagnosis model,and different types of RVO diagnosis experiments were conducted.The model’s performance was compared to that of the experts.RESULTS:The accuracy of the model in the diagnosis of normal,CRVO,BRVO,and MRVO reached 1.000,0.978,0.957,and 0.978;the specificity reached 1.000,0.986,0.982,and 0.976;the sensitivity reached 1.000,0.955,0.917,and 1.000;the F1-Sore reached 1.000,0.9550.943,and 0.887 respectively.In addition,the area under curve of normal,CRVO,BRVO,and MRVO diagnosed by the diagnostic model were 1.000,0.900,0.959 and 0.970,respectively.The diagnostic results were highly consistent with those of fundus disease experts,and the diagnostic performance was superior.CONCLUSION:The diagnostic model developed in this study can well diagnose different types of RVO,effectively relieve the work pressure of clinicians,and provide help for the follow-up clinical diagnosis and treatment of RVO patients.

关键词： deep learning artificial intelligence Swin Transformer diagnostic model retinal vein occlusion color fundus photographs

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Dual-channel mechano-phosphorescence:a combined locking effect with twisted molecular structures and robust interactions

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Light(Science & Applications) 2024年第4期13卷 738-746页

作者： Zongliang Xie Zhu Mao Hailan Wang Yuxin Xiao Xiayu Zhang Tao Yu Zhongfu An Wei Huang Frontiers Science Center for Flexible Electronics Xi’an Institute of Flexible Electronics&Xi’an Institute of Biomedical Materials and EngineeringNorthwestern Polytechnical University127 West Youyi RoadXi’an 710072China. research&Development institute of Northwestern Polytechnical university in shenzhen Shenzhen 518100China. shenzhen institutes of Advanced Electronic Materials Shenzhen 518100China. Key Laboratory of Flexible Electronics&institute of Advanced Materials Nanjing Tech University30 South Puzhu RoadNanjing 211816China

Organic mechanoluminescence materials,featuring dual emission and ultralong phosphorescence characteristics,exhibit significant potential for applications in real-time stress sensing,pressure-sensitive lighting,advanced security marking techniques,and material breakage monitoring.However,due to immature molecular design strategies and unclear luminescence mechanisms,these materials remain rarely reported.In this study,we propose a valuable molecular design strategy to achieve dual-channel mechano-phosphorescence.By introducing the arylphosphine oxide group into a highly twisted molecular framework,enhanced intra-and intermolecular interactions could be achieved within rigid structures,leading to dual-channel mechanoluminescence with greatly promoted ultralong phosphorescence.Further investigations reveal the substantial boosting effect of intra-and intermolecular interactions on mechanoluminescence and ultralong phosphorescence properties by locking the highly twisted molecular skeleton.This work provides a concise and guiding route to develop novel smart responsive luminescence materials for widespread applications in material science.

关键词： channel luminescence locking

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HCSP-Net:A Novel Model of Age-Related Macular Degeneration Classification Based on Color Fundus Photography

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Computers, Materials & Continua 2024年第4期79卷 391-407页

作者： Cheng Wan Jiani Zhao Xiangqian Hong Weihua Yang Shaochong Zhang College of Electronic and Information Engineering/College of Integrated Circuits Nanjing University of Aeronautics and AstronauticsNanjing211106China shenzhen Eye institute Shenzhen Eye HospitalJinan UniversityShenzhen518040China

Age-related macular degeneration(AMD)ranks third among the most common causes of blindness.As the most conventional and direct method for identifying AMD,color fundus photography has become prominent owing to its consistency,ease of use,and good quality in extensive clinical practice.In this study,a convolutional neural network(CSPDarknet53)was combined with a transformer to construct a new hybrid model,HCSP-Net.This hybrid model was employed to tri-classify color fundus photography into the normal macula(NM),dry macular degeneration(DMD),and wet macular degeneration(WMD)based on clinical classification manifestations,thus identifying and resolving AMD as early as possible with color fundus photography.To further enhance the performance of this model,grouped convolution was introduced in this study without significantly increasing the number of parameters.HCSP-Net was validated using an independent test set.The average precision of HCSPNet in the diagnosis of AMD was 99.2%,the recall rate was 98.2%,the F1-Score was 98.7%,the PPV(positive predictive value)was 99.2%,and the NPV(negative predictive value)was 99.6%.Moreover,a knowledge distillation approach was also adopted to develop a lightweight student network(SCSP-Net).The experimental results revealed a noteworthy enhancement in the accuracy of SCSP-Net,rising from 94%to 97%,while remarkably reducing the parameter count to a quarter of HCSP-Net.This attribute positions SCSP-Net as a highly suitable candidate for the deployment of resource-constrained devices,which may provide ophthalmologists with an efficient tool for diagnosing AMD.

关键词： Computer-aided diagnosis deep learning age-related macular degeneration transformer

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Reversible Optical Isolators and Quasi-Circulators Using a Magneto-Optical Fabry-Pérot Cavity

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Chinese Physics Letters 2024年第4期41卷 59-68页

作者：张天天周文鹏李志向唐宇涛许帆吴浩东张涵唐江山阮亚平夏可宇 College of Engineering and Applied Sciences National Laboratory of Solid State Microstructuresand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China shenzhen Shaanxi Coal Hi-tech research institute Co. LtdShenzhen 518083China School of Physics Nanjing UniversityNanjing 210023China Jiangsu Key Laboratory of Artificial Functional Materials Nanjing UniversityNanjing 210023China

Nonreciprocal optical devices are essential for laser protection,modern optical communication and quantum information processing by enforcing one-way light propagation.The conventional Faraday magneto-optical nonreciprocal devices rely on a strong magnetic field,which is provided by a permanent magnet.As a result,the isolation direction of such devices is fixed and severely restricts their applications in quantum networks.In this work,we experimentally demonstrate the simultaneous one-way transmission and unidirectional reflection by using a magneto-optical Fabry-Pérot cavity and a magnetic field strength of 50 mT.An optical isolator and a three-port quasi-circulator are realized based on this nonreciprocal cavity system.The isolator achieves an isolation ratio of up to 22 dB and an averaged insertion loss down to 0.97 dB.The quasi-circulator is realized with a fidelity exceeding 99% and an overall survival probability of 89.9%,corresponding to an insertion loss of~0.46 dB.The magnetic field is provided by an electromagnetic coil,thereby allowing for reversing the light circulating path.The reversible quasi-circulator paves the way for building reconfigurable quantum networks.

关键词： quantum reciprocal insertion

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Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

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Genes & Diseases 2024年第2期11卷 1009-1021页

作者： Gaojia Zhang Ling Li Yan Kong Dandan Xu Yu Bao Zhiting Zhang Zhixiang Liao Jiao Jiao Dandan Fan Xiaojing Long Ji Dai Chunming Xie Zhiqiang Meng Zhijun Zhang Department of Neurology Affiliated Zhongda HospitalResearch Institution of NeuropsychiatrySchool of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China shenzhen Key Laboratory of Drug Addiction Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)ShenzhenGuangdong 518000China CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute (BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Lauterbur research Center for Biomedical Imaging Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China shenzhen-Hong Kong institute of Brain Sciences-shenzhen Fundamental research Institutions ShenzhenGuangdong 518000China Brain Cognition and Brain Disease institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

关键词： Biomarker Cerebrospinal fluid Major depressive disorder Microglia derived extracellular vesicles Vitamin-D binding protein

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Functional Optical Fiber Sensors Detecting Imperceptible Physical/Chemical Changes for Smart Batteries

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Nano-Micro Letters 2024年第8期16卷 268-308页

作者： Yiding Li Li Wang Youzhi Song Wenwei Wang Cheng Lin Xiangming He institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing 100084People’s Republic of China National Engineering research Center of Electric Vehicles Beijing Institute of Technology(BIT)Beijing 100081People’s Republic of China shenzhen Automotive research institute of BIT(shenzhen research institute of National Engineering research Center of Electric Vehicles) Shenzhen 518118People’s Republic of China

The battery technology progress has been a contradictory process in which performance improvement and hidden risks coexist.Now the battery is still a“black box”,thus requiring a deep understanding of its internal state.The battery should“sense its internal physical/chemical conditions”,which puts strict requirements on embedded sensing parts.This paper summarizes the application of advanced optical fiber sensors in lithium-ion batteries and energy storage technologies that may be mass deployed,focuses on the insights of advanced optical fiber sensors into the processes of one-dimensional nano-micro-level battery material structural phase transition,electrolyte degradation,electrode-electrolyte interface dynamics to three-dimensional macro-safety evolution.The paper contributes to understanding how to use optical fiber sensors to achieve“real”and“embedded”monitoring.Through the inherent advantages of the advanced optical fiber sensor,it helps clarify the battery internal state and reaction mechanism,aiding in the establishment of more detailed models.These advancements can promote the development of smart batteries,with significant importance lying in essentially promoting the improvement of system consistency.Furthermore,with the help of smart batteries in the future,the importance of consistency can be weakened or even eliminated.The application of advanced optical fiber sensors helps comprehensively improve the battery quality,reliability,and life.

关键词： Smart battery Advanced embedded optical fiber sensor Battery internal physical/chemical state Quality-reliability-life characteristic

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Recent progress about transmission electron microscopy characterizations on lithium-ion batteries

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Journal of Energy Chemistry 2024年第8期95卷 39-56页

作者： Yihang Liu Qiuyun Li Ziqiang Wang institute of Materials research Shenzhen International Graduate School Tsinghua University

With the rapid development of portable electronics, new energy vehicles, and smart grids, ion batteries are becoming one of the most widely used energy storage devices, while the safety concern of ion batteries has always been an urgent problem to be solved. To develop a safety-guaranteed battery, the characterization of the internal structure is indispensable, where electron microscopy plays a crucial role. Based on this, this paper summarizes the application of transmission electron microscopy(TEM) in battery safety, further concludes and analyzes the aspects of dendrite growth and solid electrolyte interface(SEI) formation that affect the safety of ion batteries, and emphasizes the importance of electron microscopy in battery safety research and the potential of these techniques to promote the future development of this field. These advanced electron microscopy techniques and their prospects are also discussed.

关键词： Dendrites Electron microscopy characterizations Lithium-ion batteries SEI

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Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

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Acta Pharmaceutica Sinica B 2024年第1期14卷 319-334页

作者： Ying Qin Dekang Li Chunting Qi Huaijiang Xiang Huyan Meng Jingli Liu Shaoqing Zhou Xinyu Gong Ying Li Guifang Xu Rui Zu Hang Xie Yechun Xu Gang Xu Zheng Zhang Shi Chen Lifeng Pan Ying Li Li Tan Interdisciplinary research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China university of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Chemical Biology Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Drug research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China institute of Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518112China Department of Burn and Plastic Surgery Shenzhen Institute of Translational MedicineShenzhen University Medical SchoolShenzhen Second People’s Hospitalthe First Affiliated Hospital of Shenzhen UniversityShenzhen 518035China

Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical evaluation.Recently,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.Here,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i.We also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62,which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases.Collectively,62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

关键词： RIPK1 Necroptosis Type-II kinase inhibitors Rational design Lead optimization Structure‒activity relationship Anti-inflammation Preclinical drug discovery

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