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| 1 | SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade显示文摘Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy. | Mingxia Zhao Wenjie Guo Yuanyuan Wu Chenxi Yang Liang Zhong Guoliang Deng Yuyu Zhu Wen Liu Yanhong Gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 18 |
| 2 | Phylogenetic diversity and specificity of bacteria associated with Microcystis aeruginosa and other cyanobacteria显示文摘Interactions between bacteria and cyanobacteria have been suggested to have a potential to influence harmful algal bloom dynamics; however, little information on these interactions has been reported. In this study, the bacterial communities associated with five strains of Microcystis aeruginosa, three species of other Microcystis spp., and four representative species of non-Microcystis cyanobacteria were compared. Bacterial 16S rDNA fragments were amplified and separated by denaturing gradient gel electrophoresis (DGGE) followed by DNA sequence analysis. The similarities among bacterial communities associated with these cyanobacteria were compared to the digitized DGGE profiles using the cluster analyses. The bacterial community structure of all cyanobacterial cultures differed. Cluster analysis showed that the similarity values among M. aeruginosa cultures were higher than those of other cyanobacterial cultures. Sequence analysis of DGGE fragments indicated the presence of bacteria including, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Bacteroidetes and Actinobacteria in the cyanobacterial cultures. Members of the Sphingomonadales were the prevalent group among the Microcystis-associated bacteria. The results provided further evidence for species-specific associations between cyanoabcteria and heterotrophic bacteria, which are useful for understanding interactions between Microcystis and their associated bacteria. | SHI Limei CAI Yuanfeng YANG Hualin XING Peng LI Pengfu KONG Lingdong KONG Fanxiang | 2009 | Journal of Environmental Sciences2009，21，11： | 11 |
| 3 | Individual particle analysis of aerosols collected at Lhasa City in the Tibetan Plateau显示文摘To understand the composition and major sources of aerosol particles in Lhasa City on the Tibetan Plateau(TP), individual particles were collected from 2 February to 8 March, 2013 in Tibet University. The mean concentrations of both PM2.5and PM10 during the sampling were25.7 ± 21.7 and 57.2 ± 46.7 μg/m3, respectively, much lower than those of other cities in East and South Asia, but higher than those in the remote region in TP like Nam Co, indicating minor urban pollution. Combining the observations with the meteorological parameters and back trajectory analysis, it was concluded that local sources controlled the pollution during the sampling. Transmission electron microscopy(TEM) combined with energydispersive X-ray spectra(EDS) was used to study 408 particles sampled on four days. Based on the EDS analysis, a total of 8 different particle categories were classified for all 408 particles, including Si-rich, Ca-rich, soot, K-rich, Fe-rich, Pb-rich, Al-rich and other particles.The dominant elements were Si, Al and Ca, which were mainly attributed to mineral dust in the earth's crust such as feldspar and clay. Fe-, Pb-, K-, Al-rich particles and soot mainly originated from anthropogenic sources like firework combustion and biomass burning during the sampling. During the sampling, the pollution mainly came from mineral dust,while the celebration ceremony and religious ritual produced a large quantity of anthropogenic metal-bearing particles on 9 and 25 February 2013. Cement particles also had a minor influence. The data obtained in this study can be useful for developing pollution control strategies. | Bu Duo Yunchen Zhang Lingdong Kong Hongbo Fu Yunjie Hu Jianmin Chen Lin Li A.Qiong | 2015 | Journal of Environmental Sciences2015，27，3： | 4 |
| 4 | New opportunities and challenges of natural products research:When target identification meets single-cell multiomics显示文摘Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization. | Yuyu Zhu Zijun Ouyang Haojie Du Meijing Wang Jiaojiao Wang Haiyan Sun Lingdong Kong Qiang Xu Hongyue Ma Yang Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，11： | 3 |
| 5 | Neuron stem cell NLRP6 sustains hippocampal neurogenesis to resist stress-induced depression显示文摘Neurogenesis decline in hippocampal dentate gyrus(DG)participates in stress-induced depressive-like behaviors,but the underlying mechanism remains poorly understood.Here,we observed low-expression of NOD-like receptor family pyrin domain containing 6(NLRP6)in hippocampus of stress-stimulated mice,being consistent with high corticosterone level.NLRP6 was found to be abundantly expressed in neural stem cells(NSCs)of DG.Both Nlrp6 knockout(Nlrp6^(-/-))and NSCconditional Nlrp6 knockout(Nlrp6CKO)mice were susceptible to stress,being more likely to develop depressive-like behaviors.Interestingly,NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up.Nlrp6 deficiency promoted esophageal cancer-related gene 4(ECRG4)expression and caused mitochondrial dysfunction.Corticosterone as a stress factor significantly down-regulated NLRP6 expression,damaged mitochondrial function and suppressed cell proliferation in NSCs,which were blocked by Nlrp6 overexpression.ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders.Pioglitazone,a well-known clinical drug,up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction.In conclusion,this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs,and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression. | Chuanfeng Tang Qiaona Wang Jingyan Shen Congying Wang Hong Ding Shiyu Wen Fan Yang Ruiqing Jiao Xingxin Wu Jianmei Li Lingdong Kong | 2023 | Acta Pharmaceutica Sinica B2023，13，5： | 3 |
| 6 | Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis显示文摘Impairment of glucose(Glu)uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases.Heterogeneous nuclear ribonucleoprotein A1(hnRNP Al)is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions.The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis.Our results showed that conditional deletion of hnRNP Al in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet(HFD).Conditional knockout mice fed a HFD showed exacerbated obesity,insulin resistance,and hepatic steatosis.In vitro interference of hnRNP Al in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake,whereas hnRNP Al overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin.The expression and stability of glycogen synthase(gysl)mRNA were also decreased in the absence of hnRNP A l.Mechanistically,hnRNP Al interacted with gys l and stabilized its mRNA,thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue.Taken together,our findings are the first to show that reduced expression of hnRNP Al in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis. | Mingxia Zhao Lihong Shen Zijun Ouyang Manru Li Guoliang Deng Chenxi Yang Wei Zheng Lingdong Kong Xuefeng Wu Xudong Wu Wenjie Guo Ye Yin Qiang Xu Yang Sun | 2020 | Journal of Molecular Cell Biology2020，12，4： | 2 |
| 7 | Insights into summertime haze pollution events over Shanghai based on online water-soluble ionic composition of aerosols显示文摘 | Huanhuan Du Lingdong Kong Tiantao Cheng Jianmin Chen Jianfei Du Ling Li Xiangao Xia Chunpeng Leng Guanghan Huang | 2011 | Atmospheric Environment2011，，29： | 2 |
| 8 | Consecutive transport of anthropogenic air masses and dust storm plume: Two case events at Shanghai, China显示文摘 | Lin Wang Huanhuan Du Jianmin Chen Min Zhang Xiaoying Huang Haobo Tan Lingdong Kong Fuhai Geng | 2013 | Atmospheric Research2013，，： | 1 |
| 9 | Consecutive transport of anthropogenic air masses and dust storm plume: Two case events at Shanghai, China显示文摘 | Lin Wang Huanhuan Du Jianmin Chen Min Zhang Xiaoying Huang Haobo Tan Lingdong Kong Fuhai Geng | 2013 | Atmospheric Research2013，，： | 1 |
| 10 | Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: impli- cations for the treatment of affeetive disorders显示文摘 | KONG Lingdong TAN Renxiang WOO A Y | 2001 | Pharmacology & Toxicology2001，88，2： | 1 |
| 11 | A Chinese herbalmedicine Ermiao wan reduces serum uric acid level and inhibitsliver xanthine dehydrogenase and xanthine oxidase in mice显示文摘 | KONG Lingdong YANG Chen GE Fei | 2004 | JEthnopharmacol2004，93，23： | 1 |
| 12 | Administrationof procyanidins from grape seeds reduces serum uric acid levelsand decreases hepatic xanthine dehydrogenase /oxidase activities inoxonate-treated mice显示文摘 | WANG Ying ZHU Jixiao KONG Lingdong | 2004 | Basic Clin Pharmacol Toxicol2004，94，5： | 1 |
| 13 | Effects of Biotaorientalis extract and its flavonoid constituents, quercetin and rutinon serum uric acid levels in oxonate-induced mice and xanthinedehydrogenase and xanthine oxidase activities in mouse liver显示文摘 | ZHU Jixiao WANG Ying KONG Lingdong | 2004 | JEthnopharmacol2004，93，1： | 1 |
| 14 | NSI into ammonium particle-to-gas conversion based on chemical coupling between non-sulfate ammonium and nitrate or nitrate plus chloride显示文摘 | Du Huanhuan Kong Lingdong Cheng Tiantao | 2010 | Aerosol and Air Qual- ity Research2010，10，6： | 1 |
| 15 | Insights into summertime haze pollution events over Shanghai based on online water-soluble ionic composition of aerosols 显示文摘 | DU Huanhuan KONG Lingdong CHENG Tiantao | 2011 | AtmosEnviron2011，45，： | 1 |
| 16 | Insights into summer time haze pollution events over Shanghai based on online water-soluble ionic composition of aerosols 显示文摘 | Huanhuan Du Lingdong Kong Tiantao Cheng | 2011 | Atmospheric Environment2011，，45： | 1 |
| 17 | Colorimetric-assisted photoelectrochemical sensing for dual-model detection of sialic acid via oxidation-power mediator integration显示文摘Development of sensitive and accurate methods for sialic acid(SA) determination is of great significance in early cancer diagnosis.Here,a colorimetric-assisted Photoelectrochemical(PEC) sensor was constructed for SA detection based on the two pairs of cis-diol groups in SA molecule.With the specific recognition of SA via the two pairs of cis-diol groups,the prepared gold-modified Bi_(2)S_(3)(AuNPs@Bi_(2)S_(3)) and metal organic framework(Au@PCN-224) were introduced to the electrode and formed a sandwich structure.Based on the properties of inert electroconductivity and nanozyme of the PCN-224,dual-readout of photocurrent and visualization was achieved with the presence of 3',3',5',5'-tetramethylbenzidine(TMB).Moreover,to intensify the visualization signal,Ce^(3+) was employed as the mediator to boost the catalysis capability by transferring energy from PCN-224 surface to the whole system.With the unique SA recognition and the mediation of Ce^(3+),both the photocurrent and the visualization signals sensitively responded with the SA concentration linearly.The present method showed greatly high sensitivity,selectivity and accuracy for SA detection with a limit of detection of 1.44μmol/L and a wide linear range of 5-1000μmol/L.This method provided a new promising platform for SA detection and a potential strategy for design of novel biosensors with dual-model readout. | Yuanyuan Cheng Rong-Mei Kong Wenao Hu Xiaoxia Tian Lingdong Zhang Lian Xia Fengli Qu | 2023 | Chinese Chemical Letters2023，34，3： | 0 |
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