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| 1 | Enhanced secondary pollution offset reduction of primary emissions during COVID-19 lockdown in China显示文摘To control the spread of the 2019 novel coronavirus(COVID-19),China imposed nationwide restrictions on the movement of its population(lockdown)after the Chinese New Year of 2020,leading to large reductions in economic activities and associated emissions.Despite such large decreases in primary pollution,there were nonetheless several periods of heavy haze pollution in eastern China,raising questions about the well-established relationship between human activities and air quality.Here,using comprehensive measurements and modeling,we show that the haze during the COVID lockdown was driven by enhancements of secondary pollution.In particular,large decreases in NOx emissions from transportation increased ozone and nighttime NO_(3)radical formation,and these increases in atmospheric oxidizing capacity in turn facilitated the formation of secondary particulate matter.Our results,afforded by the tragic natural experiment of the COVID-19 pandemic,indicate that haze mitigation depends upon a coordinated and balanced strategy for controlling multiple pollutants. | Xin Huang Aijun Ding Jian Gao Bo Zheng Derong Zhou Ximeng Qi Rong Tang Jiaping Wang Chuanhua Ren Wei Nie Xuguang Chi Zheng Xu Liangduo Chen Yuanyuan Li Fei Che Nini Pang Haikun Wang Dan Tong Wei Qin Wei Cheng Weijing Liu Qingyan Fu Baoxian Liu Fahe Chai Steven JDavis Qiang Zhang Kebin He | 2021 | National Science Review2021，8，2： | 47 |
| 2 | Breeding high-yield superior quality hybrid super rice by rational design显示文摘The challenge of meeting the increasing demand for worldwide rice production has driven a sustained quest for advances in rice breeding for yield. Two breakthroughs that led to quantum leaps in productivity last century were the introduction of semidwarf varieties and of hybrid rice. Subsequent gains in yield have been incremental. The next major leap in rice breeding is now upon us through the application of rational design to create defined ideotypes. The exploitation of wide-cross compatibility and intersubspecific heterosis,combined with rapid genome sequencing and the molecular identification of genes for major yield and quality traits have now unlocked the potential for rational design. | Qian Qian Longbiao Guo Steven M.Smith Jiayang Li | 2016 | National Science Review2016，3，3： | 48 |
| 3 | PM_(2.5)-bound polycyclic aromatic hydrocarbons(PAHs) in Beijing:Seasonal variations,sources,and risk assessment显示文摘Polycyclic aromatic hydrocarbons(PAHs) have been of health concern due to its carcinogenesis and mutagenesis. In this study, we aimed to assess the variations, sources, and lifetime excessive cancer risk(ECR) attributable to PAHs bound to ambient particulate matters with aerodynamic diameter less than 2.5 μm(PM_(2.5)) in metropolitan Beijing, China. We collected24-hour integrated PM_(2.5) samples on daily basis between November 2014 and June 2015 across both central heating(cold months) and non-heating(warm months) seasons, and further analyzed the PAH components in these daily PM_(2.5) samples. Our results showed that total concentrations of PM_(2.5)-bound PAHs varied between(88.6 ± 75.4) ng/m^3 in the cold months and(11.0 ± 5.9) ng/m^3 in the warm months. Benzo[a]pyrene(Ba P), the carcinogenic marker of PAHs,averaged at 5.7 and 0.4 ng/m^3 in the cold and warm months, respectively. Source apportionment analyses illustrated that gasoline, biomass burning, diesel, coal combustion and cooking were the major contributors, accounting for 12.9%, 17.8%, 24.7%, 24.3% and 6.4% of PM_(2.5)-bound PAHs, respectively. The BaP equivalent lifetime ECR from inhalation of PM_(2.5)-bound PAHs was 16.2 cases per million habitants. Our results suggested that ambient particulate reduction from energy reconstruction and adaption of clean fuels would result in reductions PM_(2.5)-bound PAHs and its associated cancer risks. However, as only particulate phased PAHs was analyzed in the present study, the concentration of ambient PAHs could be underestimated. | Baihuan Feng Lijuan Li Hongbing Xu Tong Wang Rongshan Wu Jie Chen Yi Zhang Shuo Liu Steven Sai Hang Ho Junji Cao Wei Huang | 2019 | Journal of Environmental Sciences2019，31，3： | 17 |
| 4 | Chinese Tuina Downregulates the Elevated Levels of Tissue Plasminogen Activator in Sciatic Nerve Injured Sprague-Dawley Rats显示文摘Objective:To elucidate the mechanism of Chinese tuina in treating sciatic nerve crush injury,and to detect the levels of tissue plasminogen activator(t PA)and plasminogen activator inhibitor-1(PAI-1),which is thought to play an important role in nerve regeneration.Methods:Thirty-two adult male Sprague-Dawley rats were subjected to sciatic nerve crush injury and 16 rats(sham-operated group)went through a sham operation.Control group was given no treatment while tuina group received tuina therapy since day 7 post-surgery.Tuina treatment was performed once a day and lasted for 20 days.The sciatic functional index was examined every 5days during the treatment session.The rats'gastrocnemius muscles were evaluated for changes in mass and immunohistochemistry techniques were performed to detect the levels of tP A and PAI-1.Results:Tuina therapy improved the motor function of sciatic nerve injured rats(P<0.05),however,it did not increase muscle volume(P<0.05).Tuina downregulated the levels of t PA and PAI-1(P<0.05).Conclusions:The present study implies that tuina treatment could accelerate rehabilitation of peripheral nerve injury. | PAN Fan YU Tian-yuan Steven Wong XIAN Si-tong LU Meng-qian WU Jian-cong GAO Yu-feng LI Xiao-qin GENG Nan YAO Bin-bin | 2017 | Chinese Journal of Integrative Medicine2017，23，8： | 16 |
| 5 | ζ-Carotene Isomerase Suppresses Tillering in Rice through the Coordinated Biosynthesis of Strigolactone and Abscisic Acid显示文摘Rice tillering is an important agronomic trait affecting grain yield.Here,we identified a high-tillering mutant tillering20(t20),which could be restored to the wild type by treatment with the strigolactone(SL)analog rac-GR24.T20 encodes a chloroplast ζ-carotene isomerase(Z-ISO),which is involved in the biosynthesis of ca-rotenoids and their metabolites,SL and abscisic acid(ABA).The t20 mutant has reduced SL and ABA,raising the question of how SL and ABA biosynthesis is coordinated,and whether they have overlapping functions in tillering.We discovered that rac-GR24 stimulated T20 expression and enhanced all-trans-p-carotene biosynthesis.Importantly,rac-GR24 also stimulated expression of Oryza sativa 9-CIS-EPOXY-CAROTENOID DIOXYGENASE 1(OsNCED1)through induction of Oryza sativa HOMEOBOX12(0sHOX12),promoting ABA biosynthesis in shoot base.On the other hand,ABA treatment significantly repressed SL biosynthesis and the ABA biosynthetic mutants displayed elevated SL biosynthesis.ABA treatment reduced the number of basal tillers in both t20 and wild-type plants.Furthermore,while ABA-deficient mu-tants aba1 and aba2 had the same number of basal tillers as wild type,they had more unproductive upper tillers at maturity.This work demonstrates complex interactions in the biosynthesis of carotenoid,SLs and ABA,and reveals a role for ABA in the regulation of rice tillering. | Xue Liu Qingliang Hu Jijun Yan Kai Sun Yan Liang Meiru Jia Xiangbing Meng Shuang Fang Yiqin Wang Yanhui Jing Guifu Liu Dianxing Wu Chengcai Chu Steven M.Smith Jinfang Chu Yonghong Wang Jiayang Li Bing Wang | 2020 | Molecular Plant2020，13，12： | 11 |
| 6 | Molecular Cytogenetic Characterization and Stem Rust Resistance of Five Wheat-Thinopyrum ponticum Partial Amphiploids显示文摘Partial amphiploids created by crossing common wheat(Triticum aestivum L.) and Thinopyrum ponticum(Podp.) Barkworth & D.R.Dewey are important intermediates in wheat breeding because of their resistance to major wheat diseases.In this study,we examined the chromosome compositions of five Xiaoyan-series wheat-Th.ponticum partial amphiploids(Xiaoyan 68.Xiaoyan 693,Xiaoyan 784,Xiaoyan 7430,and Xiaoyan 7631) using GISH,multicolor-GISH.and multicolor-FISH.We found several chromosome changes in these lines.For example,wheat chromosomes 1B and 2B were added in Xiaoyan 68 and Xiaoyan 7430,respectively,while wheat chromosome6 B was eliminated from Xiaoyan 693 and Xiaoyan 7631.Chromosome rearrangements were also detected in these amphiploids.including an interspecific translocation involving chromosome 4D and some inlergenomic translocations,such as A-B and A-D translocations,among wheat genomes.Analysis of the Th.ponticum chromosomes in the amphiploids showed that some lines shared the same alien chromosomes.We also evaluated these partial amphiploids for resistance to nine races of stem rust,including TTKSK(commonly known as Ug99).Three lines,Xiaoyan 68,Xiaoyan 784,and Xiaoyan 7430,exhibited excellent resistance to ail nine races,and could therefore be valuable sources of stem rust resistance in wheat breeding. | Qi Zheng Zhenling Lv Zhixia Niu Bin Li Hongwei Li Steven S.Xu Fangpu Han Zhensheng Li | 2014 | Journal of Genetics and Genomics2014，41，11： | 9 |
| 7 | 不同木柴在两种条件下燃烧生成的颗粒物中多环芳烃的排放特性研究显示文摘将马尾松、赤桉、甜叶桉树和锦熟黄杨四种木柴,使用普通家用木柴燃烧加热炉在两种条件下进行燃烧,采集燃烧所排放的颗粒物样品并分析,获得了颗粒物中多环芳烃(Polycyclic Aromatic Hydrocarbons简写为PAHs)的排放因子及单个多环芳烃化合物的分布规律。结果显示:在颗粒物中检测出的多环芳烃化合物主要是分子量较大并被称为基因致毒性类的多环芳烃化合物,实验还发现:在四种木柴中,马尾松具有最高的多环芳烃化合物的排放因子,其次是赤桉和锦熟黄杨,最低的是甜叶桉树。两种不同的燃烧条件相比,慢燃烧比快燃烧所产生的总多环芳烃化合物和基因致毒性多环芳烃化合物的量都要高。 | 张卫东 LINDA Y.ZOU YUNGCAN LI STEVEN ATKISTON | 2003 | 中国环境监测2003，19，5： | 7 |
| 8 | Spin probes for electron paramagnetic resonance imaging显示文摘Electron paramagnetic resonance imaging (EPRI) is a relatively recent imaging technique, which provides potentially multidimensional imaging of the spatial distribution of paramagnetic species. Thanks to the use of stable spin probes, low frequency EPR imaging has recently allowed the use of large tissue samples or whole animals in vivo in the field of biology and medicine. It is normally necessary to introduce prior intravenous or intramuscular infusion of stable or slowly metabolizable non-toxic water-soluble paramagnetic materials, or stable implantable particulate materials as spin probes into the system. The classification and research progress of spin probes at present were described briefly. Three important potential approaches in water-soluble paramagnetic materials design including deuterated, site-specific and macromolecular conjugated nitroxides were also investigated. | YAN GuoPing PENG Lei JIAN ShuangQuan LI Liang BOTTLE Steven Eric | 2008 | Chinese Science Bulletin2008，53，24： | 7 |
| 9 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 10 | Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma显示文摘Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs. | Liang Wang Steven Mo Xin Li Yingzhi He Jing Yang | 2020 | Cancer Biology & Medicine2020，17，3： | 5 |
| 11 | LPS对BALB/C小鼠肾小管上皮细胞TLR4和TNFα、IL-6表达的影响显示文摘目的探讨TLR4在BALB/C小鼠肾小管上皮细胞(TEC)的表达和内毒素/脂多糖(LPS)刺激后TLR4的变化,以及对产生肿瘤坏死因子α(TNFα)、白细胞介素-6(IL-6)的影响。方法通过RT-PCR方法检测TLR4 mRNA、TNFαm RNA和IL-6 mRNA在TEC的表达;流式细胞术检测TEC的TLR4膜蛋白水平;ELISA检测培养的TEC上清中TNFα、IL-6的含量。结果正常TEC有TLR4 mRNA表达,但TNFα mRNA、IL-6 mRNA表达甚弱。经LPS刺激后,TEC中的TLR4 mRNA、TNFα mRNA和IL-6 mRNA表达均显著增强,TLR4膜蛋白以及培养上清中的TNFα、IL-6水平亦相应增加。结论TLR4在LPS激活的TEC中表达显著增强,同时TEC分泌的炎症因子TNFα、IL-6的水平也相应上调。 | 朱晓玲 Li Ke 王永钧 杨亚珍 Wuding Zhou Steven Sacks | 2008 | 医学研究杂志2008，37，1： | 5 |
| 12 | Location patterns of urban industry in Shanghai and implications for sustainability显示文摘瓷器经济经历了快速的转变并且工业重构。术语城市的工业在中国城市经历重构以内描述工业的一种特别类型。给也从城市中心关门了或重定位到城市的穗并且在以外的工业公司的高百分比,突现的全球城市象上海那样,为本地经济、城市的开发正在实现策略,它在城市中心和城市的穗包含城市的工业升级的众多的公司。这研究试图用 2008 微地理的数据在上海城市的区域以内分析七个城市的工业扇区的地点模式。为了避免统一问题(MAUP ) 问题,包括最近的邻居分析的四项基于距离的措施,核密度评价, K 功能和合作地点的可修改的 Areal,商广泛地被使用了分析并且比较在七个部门之间的集中和合作地点。结果揭示也与距离和有趣的合作地点变化的迥异的模式。结果如下:城市中心和城市的穗从城市中心与 20-30 km 有城市的工业公司,而是地区的最高的紧张是为大多数范畴的一个分水岭;集中的度与距离变化,在更短的距离更弱,增加直到 30 km 的最大的距离然后减少直到 50 km;为所有城市的工业,有模式的三种类型,在距离的一个改变的范围的聚类的、随机、分散的分发的混合。因而,这份报纸主张城市的工业的地点模式思考阶段特定的工业重构和空间转变,由可持续性目的调节了。 | CAO Weidong LI Yingying CHENG Jianquan Steven MILLINGTON | 2017 | Journal of Geographical Sciences2017，27，7： | 5 |
| 13 | A refutation of reported Levallois technology from Guanyindong Cave in south China显示文摘As one of the most complex forms of lithic technology known for the Paleolithic,research on the Levallois stoneknapping method is critically relevant to our understanding of the cognitive abilities and depth of planning capabilities of archaic hominins;as well as the diffusion of knowledge and social learning in Pleistocene societies.For decades,Levallois technology was thought to be absent from East Asia for much of the Pleistocene,appearing only quite late(ca.50-40 ka BP)[1,2].In a recent paper,H u et al.claim that Levallois technology was present at the Guanyindong(GYD)site in Qianxi County,Guizhou,Province,South China by at least 170 ka BP[3].This report claims that the GYD site is an exceptional case,preserving evidence of Levallois technology earlier than 50 ka BP. | Feng Li Yinghua Li Xing Gao Steven L.Kuhn Eric Boёda John W.Olsen | 2019 | National Science Review2019，6，6： | 4 |
| 14 | Preparation and Surfactant Properties of Amino Acid-based Surfactants显示文摘1-O-aminoacyl-3-O-alkyl acyl glycerols were synthesized by lipases in good yields andtheir surfactant properties were explored. | Qian CHEN Steven F. CHEN Zu Yi LI(1 Shanghai Institute of Organic Chemistry. Chinese Academy of Sciences. 354 Fenglin Lu.Shanghai 2000322 Depaftment of Botany. The University of Hong Kong) | 1999 | Chinese Chemical Letters1999，10，9： | 4 |
| 15 | Cyber Attack Protection and Control of Microgrids显示文摘Recently, the smart grid has been considered as a next-generation power system to modernize the traditional grid to improve its security, connectivity, efficiency and sustainability.Unfortunately, the smart grid is susceptible to malicious cyber attacks, which can create serious technical, economical, social and control problems in power network operations. In contrast to the traditional cyber attack minimization techniques, this paper proposes a recursive systematic convolutional(RSC) code and Kalman filter(KF) based method in the context of smart grids.Specifically, the proposed RSC code is used to add redundancy in the microgrid states, and the log maximum a-posterior is used to recover the state information, which is affected by random noises and cyber attacks. Once the estimated states are obtained by KF algorithm, a semidefinite programming based optimal feedback controller is proposed to regulate the system states, so that the power system can operate properly. Test results show that the proposed approach can accurately mitigate the cyber attacks and properly estimate and control the system states. | Md Masud Rana Li Li Steven W.Su | 2018 | IEEE/CAA Journal of Automatica Sinica2018，5，2： | 4 |
| 16 | FIH-1-modulated HIF-1α C-TAD promotes acute kidney injury to chronic kidney disease progression via regulating KLF5 signaling显示文摘Incomplete recovery from episodes of acute kidney injury(AKI)can predispose patients to develop chronic kidney disease(CKD).Although hypoxia-inducible factor-1α(HIF-1α)is a master regulator of the response to hypoxia/ischemia,the role of HIF-1α in CKD progression following incomplete recovery from AKI is poorly understood.Here,we investigated this issue using moderate and severe ischemia/reperfusion injury(I/RI)mouse models.We found that the outcomes of AKI were highly associated with the time course of tubular HIF-1α expression.Sustained activation of HIF-1α,accompanied by the development of renal fibrotic lesions,was found in kidneys with severe AKI.The AKI to CKD progression was markedly ameliorated when PX-478(a specific HIF-1α inhibitor,5 mg·kg^(−1)·d^(−1),i.p.)was administered starting on day 5 after severe I/RI for 10 consecutive days.Furthermore,we demonstrated that HIF-1α C-terminal transcriptional activation domain(C-TAD)transcriptionally stimulated KLF5,which promoted progression of CKD following severe AKI.The effect of HIF-1α C-TAD activation on promoting AKI to CKD progression was also confirmed in in vivo and in vitro studies.Moreover,we revealed that activation of HIF-1αC-TAD resulted in the loss of FIH-1,which was the key factor governing HIF-1α-driven AKI to CKD progression.Overexpression of FIH-1 inhibited HIF-1α C-TAD and prevented AKI to CKD progression.Thus,FIH-1-modulated HIF-1α C-TAD activation was the key mechanism of AKI to CKD progression by transcriptionally regulating KLF5 pathway.Our results provide new insights into the role of HIF-1α in AKI to CKD progression and also the potential therapeutic strategy for the prevention of renal diseases progression. | Zuo-lin Li Bin Wang Lin-li Lv Tao-tao Tang Yi Wen Jing-yuan Cao Xiao-xiao Zhu Song-tao Feng Steven DCrowley Bi-cheng Liu | 2021 | Acta Pharmacologica Sinica2021，42，12： | 3 |
| 17 | Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia显示文摘Venetoclax,an FDA-approved Bcl-2 selective inhibitor for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia(AML),is tolerated well in elderly patients with AML and has good overall response rates;however,resistance remains a concern.In this study,we show that targeting CDK9 with voruciclib in combination with venetoclax results in synergistic antileukemic activity against AML cell lines and primary patient samples.CDK9 inhibition enhances venetoclax activity through downregulation of Mcl-1 and c-Myc.However,downregulation of Mcl-1 is transient,which necessitates an intermittent treatment schedule to allow for repeated downregulation of Mcl-1.Accordingly,an every other day schedule of the CDK9 inhibitor is effective in vitro and in vivo in enhancing the efficacy of venetoclax.Our preclinical data provide a rationale for an intermittent drug administration schedule for the clinical evaluation of the combination treatment for AML. | Daniel A.Luedtke Yongwei Su Jun Ma Xinyu Li Steven ABuck Holly Edwards Lisa Polin Juiwanna Kushner Sijana HDzinic Kathryn White Hai Lin Jeffrey WTaub Yubin Ge | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 18 | Parenchymal Volume Preservation and Ischemia During Partial Nephrectomy: Functional and Volumetric Analysis显示文摘 | Maria C. Mir Rebecca A. Campbell Nidhi Sharma Erick M. Remer Jianbo Li Sevag Demirjian Jihad Kaouk Steven C. Campbell | 2013 | Urology2013，，： | 3 |
| 19 | Epigenetic states and expression of imprinted genes in human embryonic stem cells显示文摘AIM: To investigate the epigenetic states and expres- sion of imprinted genes in five human embryonic stem cell (hESC) lines derived in Taiwan. METHODS: The heterozygous alleles of single nucleo- tide polymorphisms (SNPs) at imprinted genes were analyzed by sequencing genomic DNAs of hESC lines and the monoallelic expression of the imprinted genes were confirmed by sequencing the cDNAs. The expres- sion profiles of 32 known imprinted genes of five hESC lines were determined using Affymetrix human genome U133 plus 2.0 DNA microarray. RESULTS: The heterozygous alleles of SNPs at seven imprinted genes, IPW , PEG10 , NESP55 , KCNQ1 , ATP10A ,TCEB3C and IGF2 , were identified and the monoallelic expression of these imprinted genes except IGF2 were confirmed. The IGF2 gene was found to be imprinted in hESC line T2 but partially imprinted in line T3 and not imprinted in line T4 embryoid bodies. Ten imprinted genes, namely GRB10 , PEG10 , SGCE, MEST , SDHD , SN- RPN , SNURF , NDN , IPW and NESP55 , were found to be highly expressed in the undifferentiated hESC lines and down-regulated in differentiated derivatives. The UBE3A gene abundantly expressed in undifferentiated hESC lines and further up-regulated in differentiated tissues. The expression levels of other 21 imprinted genes were relatively low in undifferentiated hESC lines and five of these genes (TP73 , COPG2 , OSBPL5 , IGF2 and ATP10A ) were found to be up-regulated in differentiated tissues. CONCLUSION: The epigenetic states and expression of imprinted genes in hESC lines should be thoroughly studied after extended culture and upon differentiation in order to understand epigenetic stability in hESC lines before their clinical applications. | Steven Shoei-Lung Li Sung-Liang Yu Sher Singh | 2010 | World Journal of Stem Cells2010，2，4： | 3 |
| 20 | Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors显示文摘Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors. | Yan Chen Xingguo Hou Dapeng Li Jin Ding Jiayue Liu Zilei Wang Fei Teng Hongjun Li Fan Zhang Yi Gu Steven Yu Xueming Qian Zhi Yang Hua Zhu | 2023 | Journal of Pharmaceutical Analysis2023，13，4： | 2 |
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