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Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy

Science Bulletin 2024年第17期69卷 2745-2755页

作者： Changlun Wang Mengxin Xu Zihang Zhang Senhai Zeng Siyong Shen Zexuan Ding Junyi Chen xi-yang cui Zhibo Liu Beijing National Laboratory for Molecular Sciences Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental ScienceKey Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Peking University-Tsinghua University Center for Life Sciences Peking UniversityBeijing 100871China Changping Laboratory Beijing 102206China Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education Key Laboratory for Research and Evaluation of Radiopharmaceuticals of National Medical Products AdministrationDepartment of Nuclear MedicinePeking University Cancer HospitalBeijing 100142China

Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumorselective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [^(18)F]FDG(2-[^(18)F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note,an OxaliPt(IV) linker is designed to construct an [^(18)F]FDG-activated antibody-drug conjugate(Pt-ADC).Sequential injection of Pt-ADC and [^(18)F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation,and we find that [^(18)F]FDG is capable of deprotecting various radiotherapy-removable protecting groups(RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.

关键词： Prodrugactivation Radiopharmaceutical Radiochemistry [^(18)F]FDG Platinum(IV)prodrug

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Covalent targeted radioligands potentiate radionuclide therapy

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四川生理科学杂志 2024年第5期46卷 1155-1155页

作者： xi-yang cui 不详

Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue,which remains a major challenge5,6.A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal *** we installed a sulfur(VI)fluoride exchange(SuFEx)chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour *** the engineered radiopharmaceutical binds to the tumour-specific protein,the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the'click'SuFEx reaction.

关键词： targeted fluoride readily

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Raindrop Size Distributions in the Zhengzhou Extreme Rainfall Event on 20 July 2021:Temporal-Spatial Variability and Implications for Radar QPE

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Journal of Meteorological Research 2024年第3期38卷 489-503页

作者： Liman cui Haoran LI Aifang SU yang ZHANG xiaona LYU Le xi Yuanmeng ZHANG Henan Key Laboratory of Agrometeorological Support and Applied Technique China Meteorological AdministrationZhengzhou450003China State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing100081China Henan Meteorological Observatory Zhengzhou450003China

In this study,a regional Parsivel OTT disdrometer network covering urban Zhengzhou and adjacent areas is employed to investigate the temporal-spatial variability of raindrop size distributions(DSDs)in the Zhengzhou extreme rainfall event on 20 July *** rain rates observed by disdrometers and rain gauges from six operational sites are in good agreement,despite significant site-to-site variations of 24-h accumulated rainfall ranging from 198.3 to 624.1 *** Parsivel OTT observations show prominent temporal-spatial variations of DSDs,and the most drastic change was registered at Zhengzhou Station where the record-breaking hourly rainfall of 201.9 mm over 1500-1600 LST(local standard time)was *** hourly rainfall is characterized by fairly high concentrations of large raindrops,and the mass-weighted raindrop diameter generally increases with the rain rate before reaching the equilibrium state of DSDs with the rain rate of about 50 mm h^(−1).Besides,polarimetric radar observations show the highest differential phase shift(K_(dp))and differential reflectivity(Z_(dr))near surface over Zhengzhou Station from 1500 to 1600 *** light of the remarkable temporal-spatial variability of DSDs,a reflectivity-grouped fitting approach is proposed to optimize the reflectivity-rain rate(Z-R)parameterization for radar quantitative precipitation estimation(QPE),and the rain gauge measurements are used for *** results show an increase of mean bias ratio from 0.57 to 0.79 and a decrease of root-mean-square error from 23.69 to 18.36 for the rainfall intensity above 20.0 mm h^(−1),as compared with the fixed Z-R *** study reveals the drastic temporal-spatial variations of rain microphysics during the Zhengzhou extreme rainfall event and warrants the promise of using reflectivity-grouped fitting Z-R relationships for radar QPE of such events.

关键词： extreme rainfall raindrop size distribution radar quantitative precipitation estimation(QPE)

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Single transition-metal atoms anchored on a novel Diracdispersiveπ-πconjugated holey graphitic carbon nitride substrate:computational screening toward efficient bifunctional OER/ORR electrocatalysts

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Rare Metals 2024年第8期43卷 3819-3832页

作者： Chun-Yao Fang xi-Hang Zhang Qiang Zhang Di Liu xiao-Meng cui Jing-Cheng Xu Cheng-Long Shi Meng-Yu yang College of Science University of Shanghai for Science and TechnologyShanghai 200093China School of Materials and Chemistry University of Shanghai for Science and TechnologyShanghai 200093China

Nonprecious-metal-group single-metal-atom catalysts with bifunctional catalytic capabilities toward the oxygen evolution reaction(OER)and oxygen reduction reaction(ORR)are highly sought after in energy-conversion and storage ***,producing renewable and sustainable energy sources remains ***,single-transition metal atoms anchored onπ-πconjugated two-dimensional(2D)graphitic carbon nitride substrates formπ-d conjugated conductive channels that enhance the overall electrocatalytic ***,firstprinciples calculations were carried out to design and demonstrate a novel macropore graphitic carbon nitride(gC_(10)N_(3))as a promising 2D electrocatalyst substrate to support single-transition metal(TM,from Sc to Au).The"donation-acceptance"charge interaction in the TM-N_(2)moiety effectively balances the adsorption strength of oxygenated intermediates in Ni@g-C_(10)N_(3)and Rh@gC_(10)N_3,making them effective bifunctional OER/ORR electrocatalysts with IrO_(2)/Pt-beyond overpotentials being as low as 0.39/0.38 V and 0.54/0.44 V,***,they possess high stability and conductivity and are less susceptible to oxidation and corrosion under working *** guarantees high activity under ambient ***,the origin of the OER/ORR activity of TM@g-C_(10)N_(3) is explained using multilevel descriptors:intrinsic(p,Bader charge,integral crystal orbital Hamilton population(ICOHP),bond length,and d-band center(εd).In particular,for optimal Ni@g-C_(10)N_(3),the clear hybridization between the Ni-d orbital and surface O-p orbital causes the paired electrons to occupy the bonding *** enables OH~*to be adsorbed on the Ni@g-C_(10)N_(3),thereby achieving the highest catalytic performance.

关键词： First-principles calculation Oxygen evolution reaction Oxygen reduction reaction Bifunctional electrocatalysts Single-metal-atom electrocatalysts

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In-situ TEM study of the effect of hydrogen-helium ratio on defect characteristics in Fe9Cr1.5W0.4Si F/M steel during H_(2)^(+)&He^(+)simultaneous irradiation

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Journal of Materials Science & Technology 2024年第6期173卷 192-201页

作者： Dewang cui Ziqi Cao Kun He Yuanming Li xi Qiu Guang Ran College of Energy Xiamen UniversityXiamen 361102China Fujian Provincial Nuclear Energy Engineering Technology Research Center Xiamen 361102China Science and Technology on Reactor Fuel and Materials Laboratory Chengdu 610041China Nuclear Power Institute of China Chengdu 610041China Science and Technology on Reactor System Design Technology Laboratory Chengdu 610041China

The effect of hydrogen and helium interaction,especially H-He ratio,on the irradiation behavior of nuclear materials has not yet been ***,this is an important basis for evaluating the irradiation properties of nuclear materials and developing high irradiation resistant ***,30 keV H_(2)^(+)and He^(+)dual beams with four H-He ratios of 0:10,3:10,15:10,and 30:10 were used to irradiate the newly developed Fe9Cr1.5W0.4Si F/M steel in TEM to in-situ study the interaction and ratio effect of hydrogen and *** addition of H atoms significantly promoted the nucleation of dislocation loops and *** the early stage of irradiation,the average size and density of dislocation loops increased with the increase of H-He ***,the larger the H-He ratio,the easier it was to form a complex dislocation ***,the final saturation size of bubbles increased with the increase of H-He *** was first found that the swelling was affected by H concentrations,with high H concentrations slowing down the increase in *** a certain irradiation dose,a specific H-He ratio would lead to a swelling peak of Fe9Cr1.5W0.4Si F/M *** super-sized bubbles at grain boundaries(GBs)were found after H addition,resulting in a bigger swelling of GBs than the *** the swelling of the GBs and the matrix show a dependence on the H-He *** current work is of great significance for understanding the interaction between hydrogen and helium in nuclear materials.

关键词： Dose ratio effect Ferritic-martensitic steel Hydrogen&helium synergetic irradiation In-situ TEM

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Insights into postural orthostatic tachycardia syndrome after COVID-19 in pediatric patients

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World Journal of Pediatrics 2024年第3期20卷 201-207页

作者： Ya-xi cui Jun-Bao Du Hong-Fang Jin Department of Pediatrics Peking University First HospitalNo.1 Xi-an Men StreetWest DistrictBeijing 100034China State Key Laboratory of Vascular Homeostasis and Remodeling Peking UniversityBeijing 100191China

The pandemic caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)profoundly threatened human health globally and greatly impacted the world economy[1].While most patients recovered,some suff... 详细信息

关键词： acute patients tachycardia

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Highly-chlorinated inert and robust interphase without mineralization of oxide enhancing high-rate Li metal batteries

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Chinese Chemical Letters 2024年第6期35卷 239-243页

作者： Long Li Kang yang Chenpeng xi Mengchao Li Borong Li Gui Xu Yuanbin xiao xiancai cui Zhiliang Liu Lingyun Li Yan Yu Chengkai yang Key Laboratory of Advanced Materials Technologies International(HongKong Macao and Taiwan)Joint Laboratory on Advanced Materials TechnologiesSchool of Materials Science and EngineeringFuzhou UniversityFuzhou 350108China College of Material Sciences and Chemical Engineering Harbin Engineering UniversityHarbin 150001China

Side reactions and dendrite growth triggered by the unstable interface and inhomogeneous deposition have become the biggest obstacle to the commercialization for lithium metal *** this study,a highly-chlorinated organic-inorganic hybrid interfacial protective layer is developed by rationally tuning the interfacial passivation and robustness to achieve the convenient and efficient Li metal *** polyvinyl chloride(PVC)can effectively resist water and oxygen,which is confirmed by density functional *** organic-dominant solid electrolyte interphases(SEI)with lithium chloride are investigated by the X-ray photoelectron spectroscopy(XPS)with little mineralization of oxide,such as Li_(2)O and Li_(2)CO_(3).With such artificial SEI,a uniform and dense lithium deposition morphology are formed and an ultra-long stable cycle of over 500 h are achieved even at an ultra-high current density of 10 m A/cm^(2).Moreover,the simple and convenient protected anode also exhibits excellent battery stability when paired with the LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)and LiFePO_(4)(LFP)cathode,showing great potential for the commercial application of lithium metal batteries.

关键词： Highly-chlorinated Water/oxygen resistance Stable interphase Dendrite-free lithium metal batteries High-rate

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Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress

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Chinese Journal of Integrative Medicine 2024年第5期30卷 398-407页

作者： JI xiao-di yang Ding cui xi-yuan LOU Li-xia NIE Bo ZHAO Jiu-li ZHAO Ming-jing WU Ai-ming Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Key Laboratory of Chinese Internal Medicine of Ministry of Education and BeijingBeijing 100700China Department of Traditional Chinese Medicine Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China

Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)***:A left coronary artery ligation-induced HF after myocardial infarction model was used in this *** were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of *** function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and *** and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial *** m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by *** protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western *** T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of ***:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(P<0.05,P<0.01).HE staining showed that QLQX ameliorated cardiac pathologic damage to some *** staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleave

关键词： heart failure Qili Qiangxin Capsule miR133a endoplasmic reticulum stress apoptosis

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A Brief Overview of the Development and Significance of Modern Scientific Medicine in China:Take Chinese Academy of Medical Science and Peking Union Medical College as an Example

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Chinese Medical Sciences Journal 2024年第2期39卷 140-143页

作者： Pu-An cui Zhe-xi Gong Zhong He School of Humanities and Social Sciences Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China

Since the early 20th century,China has gradually established a clinical,educational,and research system centered around modern scientific medicine,which has now become the dominant force in China's medical and health system and services,with the construction and development of the Chinese Academy of Medical Sciences and Peking Union Medical College as the most prominent *** scientific medicine in the new era requires close cooperation across multiple disciplines and fields to build a high-quality and efficient medical and health service *** also involves combining the excellent traditional Chinese culture with Western medicine to explore a unique path of modern scientific medicine with Chinese characteristics.

关键词： modern scientific medicine cultural confidence multiple view

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Phosphotungstic acid immobilized on amino-functionalized TS-1 zeolite as a solid acid catalyst for the synthesis of tributyl citrate

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Chinese Journal of Chemical Engineering 2024年第6期70卷 199-210页

作者： Pei Li Bianfang Shi Junyao Shen Ran cui Wenze Guo Ling Zhao Zhenhao xi State Key Laboratory of Chemical Engineering East China University of Science and TechnologyShanghai 200237China Key Laboratory of Smart Manufacturing in Energy Chemical Process Ministry of EducationEast China University of Science and TechnologyShanghai 200237China

The amino-functionalization of TS-1 zeolite followed by immobilization of phosphotungstic acid(HPW)was presented to prepare a strong solid acid catalyst for the synthesis of bio-based tributyl citrate from the esterification of citric acid and n-butanol.γ-Aminopropyltriethoxysilane(APTES)was first grafted on the TS-1 zeolite via the condensation reactions with surface hydroxyl groups,and subsequently the HPW was immobilized via the reaction between the amino groups and the protons from HPW-forming strong ionic *** Keggin structure of HPW and MFI topology of TS-1 zeolite were well maintained after the *** amino-functionalization generated abundant uniformly distributed active sites on TS-1 for HPW immobilization,which promoted the dispersity,abundance,as well as the stability of the acid *** tetrahedrally coordinated framework titanium and non-framework titania behaved as weak Lewis acid sites,and the protons from the immobilized HPW acted as the moderate or strong Brønsted acid *** optimized TBC yield of 96.2%(mol)with a conversion of-COOH of 98.1%(mol)was achieved at 150℃for 6 h over the HPW immobilized on amino-functionalized *** catalyst exhibited good stability after four consecutive reaction runs,where the activity leveled off at still a relatively high level after somewhat deactivation possibly caused by the leaching of a small portion of weakly anchored APTES or HPW.

关键词： Amino-functionalization Phosphotungstic acid TS-1 zeolite Esterification Tributyl citrate

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