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Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy

Chinese Chemical Letters 2024年第4期35卷 316-320页

作者： Ling-Ling Wu Xiangchuan Meng Qingyang Zhang Xiaowan Han feiya yang Qinghua Wang Hai-Yu Hu Nianzeng Xing Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China

Photoacoustic agents combining photodynamic therapy(PDT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared(NIR)-absorption and maximizing non-radiative energy transfer are essential for effective photoacoustic imaging(PAI) and therapy applications. In addition, such molecules with high specificity and affinity to cancer cells are urgently needed, which would further decrease the side effect during treatments. In this study, we applied a heavy-atom engineering strategy and introduced p-aminophenol,-thio, and-seleno moieties into NIR heptamethine cyanine(Cy7) skeleton(Cy7-X-NH_(2), X = O, S, Se) to significantly increase photothermal conversion efficiency for PTT and promote intersystem crossing for PDT.Additionally, we designed a series of nitroreductase(NTR)-activated photoacoustic probes(Cy7-X-NO_(2),X = O, S, Se), and target hypoxic tumors with NTR overexpression. Our prostate cancer targeting probe,Cy7-Se-NO_(2)-KUE, exhibited specific tumor photoacoustic signals and effective tumor killing through outstanding synergistic PTT/PDT in vivo. These findings highlighted a versatile strategy for cancer photoacoustic diagnosis and enhanced phototherapy.

关键词： Heavy-atom effect Phototherapy Photoacoustic imaging Hypoxia-responsive Prostate cancer

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Membrane dual-targeting probes:A promising strategy for fluorescence-guided prostate cancer surgery and lymph node metastases detection

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1204-1215页

作者： Ling-Ling Wu Qinxin Zhao Qinghua Wang Qingyang Zhang feiya yang Bo Zheng Hai-Yu Hu Nianzeng Xing State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Urology Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013China Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

关键词： Activated probe Small molecule nanoparticle Self-assembly Dual-targeting Near-infrared Prostate cancer Fluorescence-guided surgery Metastases

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A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

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Chinese Medical Journal 2024年第6期137卷 676-682页

作者： Linfeng Xi Han Kang Mei Deng Wenqing Xu feiya Xu Qian Gao Wanmu Xie Rongguo Zhang Min Liu Zhenguo Zhai Chen Wang Capital Medical University Beijing 100069China National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Advanced Research Infervision Medical Technology Co.Ltd.Beijing 100025China Department of Radiology China-Japan Friendship HospitalBeijing 100029China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730China Department of Radiology Peking University China-Japan Friendship School of Clinical MedicineBeijing 100191China

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise diagnosis.In population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying biomarkers.This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods:This is a single-center retrospective study.Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose APE.Thereafter,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years algorithm.Eventually,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)analysis.Results:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart failure.Among eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment strategy.The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.Conclusions:Based on RF algorithm,a novel prediction model was finally constructed for APE diagnosis.When compared to the current clinica

关键词： Acute pulmonary embolism Machine learning Wells score Revised Geneva score Years algorithm

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The establishment of polypeptide PSMA-targeted chimericantigen receptor-engineered natural killer cells forcastration-resistant prostate cancer and the induction of ferroptosis-related cell death

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Cancer Communications 2022年第8期42卷 768-783页

作者： Liyuan Wu Fei Liu Le Yin Fangming Wang Hui Shi Qinxin Zhao feiya yang Dong Chen Xiying Dong Yuchun Gu Nianzeng Xing State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Molecular Pharmacology Laboratory Institute of Molecular MedicinePeking UniversityBeijing 100871P.R.China Translation Medicine Research Group Aston Medical SchoolAston UniversityBirminghamB47ETUnited Kingdom Research and Development Department Allife Medicine Inc.Beijing 100176P.R.China Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730P.R.China Department of Urology Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanShanxi 030013P.R.China

Background:The mortality of castration-resistant prostate cancer(CRPC)is high due to lack of an effective treatment.Chimeric antigen receptor(CAR)-based therapy is a promising immunotherapeutic strategy.Here,we aimed to design a novel CAR-natural killer(NK)cells with a clinically significant tumoricidal effect on CRPC.Methods:We constructed novel CAR-NK92MI cells with a CD244-based recombinant lentiviral vector.Different intracellular segments(CD244,NKG2D,or CD3ζ)were screened to identify the best candidate according to cell lysis assay and CD107a expression levels.To enhance the affinity of the CAR to the tumor antigen,we compared an antibody specific for prostate-specific membrane antigen(anti-PSMA)with PSMA-targeted polypeptide(p-PSMA),which was screened by phage display combinatorial library.Then,CAR-NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were generated.In addition,we verified their tumor-killing effect in vitro and in vivo.The release of cytokine by NK92MI cells was compared with that by CAR-NK92MI cells through flow cytometry and enzyme-linked immunosorbent assay.Moreover,ferroptosis-related cell death was explored as a possible underlying mechanism.Results:Three different CAR intracellular regions CAR1(CD244),CAR2(CD244,NKG2D)and CAR3(CD244,NKG2D,and CD3ζ)were constructed.CAR2 was chosen to confer a stronger tumoricidal ability on CAR-NK92MI cells.Compared with anti-PSMA,p-PSMA exhibited enhanced affinity for the tumor antigen.Thus,p-PSMA-CAR-NK92MI cells,which expressed CAR with a polypeptide-based antigen-binding region,an intracellular CD244 and a NKG2D costimulatory domain,were generated.They could selectively and successfully kill PSMA+target cells and exhibited specific lysis rate of 73.19%for PSMA-positive C4-2 cells and 33.04%for PSMA-negative PC3 cells.Additionally,p-PSMA-CAR-NK92MI cells had significantly higher concentrations of IFN-γ,TNF-αand granzyme B than NK92MI cells.In a CRPC cancer xenograft model,p-PSMA-CAR-NK92MI cells significantly inhibited

关键词： CAR-NK92MI chimeric antigen receptors immunotherapy prostate-specific membrane antigen ferroptosis

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Selective nano-buckling improves the performance of graphene logic transistors

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National Science Review 2024年第2期11卷 95-96页

作者： Tong yang Ming yang Department of Applied Physics The Hong Kong Polytechnic University Research Centre for Nanoscience and Nanotechnology The Hong Kong Polytechnic University

The massive integration of silicon-based transistors into modern electronic devices greatly increases power consumption and heat generation/dissipation[1]. In this concern, transistors based on atomically-thin graphene that exhibit high electric and thermoelectric conductivities with negligible contact resistance,

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Deep Insight of Design,Mechanism,and Cancer Theranostic Strategy of Nanozymes

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Nano-Micro Letters 2024年第2期16卷 165-217页

作者： Lu yang Shuming Dong Shili Gai Dan yang He Ding Lili Feng Guixin yang Ziaur Rehman Piaoping yang Key Laboratory of Superlight Materials and Surface Technology Ministry of EducationCollege of Materials Science and Chemical EngineeringHarbin Engineering UniversityHarbin 150001People’s Republic of China Yantai Research Institute Harbin Engineering UniversityYantai 264000People’s Republic of China Key Laboratory of Green Chemical Engineering and Technology of Heilongjiang Province College of Material Science and Chemical EngineeringHarbin University of Science and TechnologyHarbin 150040People’s Republic of China Department of Chemistry Quaid-i-Azam UniversityIslamabad 45320Pakistan

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007,nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity,low cost,mild reaction conditions,good stability,and suitable for large-scale production.Recently,with the cross fusion of nanomedicine and nanocatalysis,nanozyme-based theranostic strategies attract great attention,since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects.Thus,various nanozymes have been developed and used for tumor therapy.In this review,more than 270 research articles are discussed systematically to present progress in the past five years.First,the discovery and development of nanozymes are summarized.Second,classification and catalytic mechanism of nanozymes are discussed.Third,activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory,machine learning,biomimetic and chemical design.Then,synergistic theranostic strategy of nanozymes are introduced.Finally,current challenges and future prospects of nanozymes used for tumor theranostic are outlined,including selectivity,biosafety,repeatability and stability,in-depth catalytic mechanism,predicting and evaluating activities.

关键词： Nanozymes Classification Prediction and design Catalytic mechanism Tumor theranostics

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Fresh-Keeping Decision and Coordination of Fresh Agricultural Product Supply Chain Considering Carbon Cap-and-Trade under Different Dominance

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Journal of Systems Science and Systems Engineering 2024年第1期33卷 30-51页

作者： yang yang Guanxin Yao China Institute for Agricultural Equipment Industrial Development Jiangsu UniversityZhenjiang212013China Jiangsu Modern Logistics Research Base Yangzhou UniversityYangzhou225009China

In the context of low carbon,this paper discussed the impact of the carbon cap-and-trade policy on the fresh-keeping decision-making of two-echelon fresh agricultural product supply chains under different dominance,and designed cost-sharing contracts to coordinate the supply chain of fresh agricultural products dominated by suppliers and retailers respectively.The results showed that:dominance has no effect on the fresh-keeping decision and total revenue of fresh agricultural product supply chain,but it affects the internal income distribution,and dominance does not always bring more benefits;the implementation of carbon cap-and-trade reduces the fresh-keeping decision-making of fresh agricultural products supply chain and reduces the free-rider income of followers;the role of higher carbon trading price is twofold,which not only brings about the speculation of leading enterprises,but also promotes the application of low-carbon technologies;consumers’high preference for freshness,low-cost and high-efficiency low-carbon technology are all conducive to improving the fresh-keeping efforts and benefits of the supply chain;cost-sharing contracts can coordinate the supply chain of fresh agricultural products.

关键词： Dominant power carbon cap-and-trade policy fresh agricultural product supply chain fresh-keeping decision-making

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Overview of radar detection methods for low altitude targets in marine environments

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Journal of Systems Engineering and Electronics 2024年第1期35卷 1-13页

作者： yang Yong yang Boyu School of Electronic Science National University of Defense TechnologyChangsha 410073China

In this paper,a comprehensive overview of radar detection methods for low-altitude targets in maritime environments is presented,focusing on the challenges posed by sea clutter and multipath scattering.The performance of the radar detection methods under sea clutter,multipath,and combined conditions is categorized and summarized,and future research directions are outlined to enhance radar detection performance for low-altitude targets in maritime environments.

关键词： radar sea clutter multipath scattering detection low altitude target

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Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： yang Li Shu-ting yang Shuying yang Department of Basic&Translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopaedic Surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA Center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn Center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic tissue.In recent decades,AML patients are significantly increased.In 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to AML.What’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 months.Notwithstanding great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality rates.More importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for AML.Thus,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

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The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

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Neural Regeneration Research 2024年第2期19卷 282-288页

作者： Zhuoyang Yu Yan Teng Jing yang Lu yang Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Laboratory of Aging Research School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

关键词： adult neurogenesis Alzheimer’s disease amyotrophic lateral sclerosis exosome Huntington’s disease neurodegenerative disease neurogenic niches Parkinson’s disease

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