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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 | Regulation of the cellular uptake of nanopartides by the orientation of helical polypeptides显示文摘Controlling the cellular interactio n and internal izatio n of polymer-modified nan oparticles (NPs) is of central importa nee to the developme nt of promisi ng nano medici nes. Here, we describe the use of synthetic polypeptides for NP surface coati ng and regulati on of their cellular uptake behaviors by simply switching the conformation and anchoring orientation. Our results show that gold NPs (AuNPs) coated with a helical poly(Y-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)esteryl「glutamate)(L-P(EG3Glu)5o) from the C-terminus ((L-C)-AuNPs) exhibit greater zeta potential and more cellular uptake (2.0-5.5 fold higher) than those coated with the same polypeptide but anchored from the N-terminus ((L-N)-AuNPs), or from both the C- and N-terminus at a 1/1 molar ratio ((L-C/L-N)-AuNPs). A similar orientation-regulated cellular internalization pattern is observed in D-P(EG3Glu)50 but not the unstructured DL-P(EG3Glu)5o-rnodified AuNPs, suggesting an important and universal role of the helix-derived macrodipole in cellular uptake. Moreover, this orientation-governed internalization is successfully reproduced in P(EG3Glu)50-coated gold nano rods (AuNRs), and applied to the desig n of doxorubici reloaded polypeptide micelles. Simulation study offers time-resolved in sights regarding the NP-membrane in teracti ons and membrane remodeling. Thus, our study provides a delicate way of regulating the surface chemistry of NPs and the subsequent NP-cell interactions. Moreover, the results highlight the uniqueness of polypeptides in NP surface engineering, and urge a more careful consideration on the polymer orientation effect. | Chong Zhang Jianhua Lu Falin Tian Lindong Li Yingqin Hou Yaoyi Wang Lingdong Sun Xinghua Shi Hua Lu | 2019 | Nano Research2019，12，4： | 4 |
| 3 | 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 |
| 4 | 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 |
| 5 | Functional-template directed self-assembly(FTDSA) of mesostructured organic-inorganic hybrid materials显示文摘Since the discovery of a surfactant directed self-assembly approach for the fabrication of mesoporous silica in 1992,increasing attention has been focused on the design and synthesis of mesostructured functional materials.Organic functionalization is becoming a major topic in this research field,since highly ordered mesostructured organic-inorganic hybrids offer novel functionalities and enhanced performance over their individual components.We begin with a brief overview of the three fundamental methods(post-synthetic grafting technique,co-condensation method,and preparation of periodic mesoporous organosilicas) for the preparation of organically functionalized mesostructured silica,and focus on one of the most promising approaches,which herein was named as functional-template directed self-assembly(FTDSA) approach,and in the eyes of the authors it has a special position in the preparation of this class of hybrid materials.A comprehensive overview of the state of research in the area of FTDSA and its potential applications will be given. | LI LeLe SUN LingDong ZHANG YaWen m YAN ChunHua | 2009 | Science China Chemistry2009，52，11： | 2 |
| 6 | Luminescence resonance energy transfer based on β-NaYF_4:Yb,Er nanoparticles and TRITC dye显示文摘β-NaYF4:Yb,Er nanoparticles (NPs) are one of the most efficient upconversion materials, which can convert near-infrared light to higher-energy light through multiple photon absorptions or energy transfer. In addition, they may be attractive alternative donors for luminescence resonance energy transfer (LRET) studies, because of their sharp absorption and emission profiles, high quantum yields, large anti-stokes shifts, long lifetime, low toxicity, and superior photo-stability. In principle, many problems of fluorescence resonance energy transfer (FRET), such as excitation of acceptors, emission overlaps between donors and acceptors, high background noise, potential toxicity, and instability, can be overcome using β-NaYF4:Yb,Er NPs as energy donors. Because the organic coating induced separation can significantly reduce the energy transfer efficiency and aqueous FRET system is difficult to be applied in devices, we demonstrate a novel NP-dye LRET system in solid state. The emission of the β-NaYF4:Yb,Er NPs at 539 nm overlaps with the absorption of the tetrametrylrhodarnine isothiocyante (TRITC), satisfying the requirement of LRET process. Since TRITC molecules are adsorbed on the β-NaYF4:Yb,Er NPs by an electrostatic interaction, the interaction distance is suitable for LRET without any further modulation. The resultant solid LRET system is ready for the further applications for devices. | SUN LingDong, GU JianQin, ZHANG ShuZhuo, ZHANG YaWen & YAN ChunHua Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Materials Chemistry and Applications & PKU-HKU Joint Lab in Rare Earth Materials and Bioinorganic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China | 2009 | Science China Chemistry2009，52，10： | 2 |
| 7 | Controlled synthesis and assembly of ceriabased nanomaterials 显示文摘 | Yuan Quan Duan Haohong Li Lele Sun Lingdong Zhang Yawen Yan Chunhua | 2009 | Journal of Colloid and Interface Science2009，335，2： | 1 |
| 8 | Luminescent properties of Li+ doped nanosized Y203:Eu3+ 显示文摘 | SUN Lingdong QIAN Cheng LIAO Chunsheng | 2001 | Solid State Commun2001，119，6： | 1 |
| 9 | Size control and photoluminescence enhancement of CdS nanoparticles prepared via reverse micelle method 显示文摘 | Zhang Jun Sun Lingdong Liao Chunsheng | 2002 | Solid State Communications2002，124，12： | 1 |
| 10 | Corre- lationbetween Size-Dependent Luminescent Properties and LocalStructure around Eu^3+ Ions in YBO3: Eu Nanocrystals: an XAFS Study 显示文摘 | Wei Zhenggui Sun Lingdong Jiang Xiaocheng | 2003 | Chemistry of Materials2003，15，15： | 1 |
| 11 | Synthesis and size dependent luminescent properties of hexagonal(Y, Gd)BO3: Eu nanocrystals 显示文摘 | Wei Zhenggui Sun Lingdong Liao Chunsheng | 2002 | Journal of Materials Chemistry2002，12，12： | 1 |
| 12 | Size- Dependent Chromaticityin YBO3: Eu Nanocrystals: Correlation with Microstructure and Site Symmetry 显示文摘 | Wei Zhenggui Sun Lingdong Liao Chunsheng | 2002 | Journal of Physical Chemistry B2002，106，10： | 1 |
| 13 | Fluore- scence intensity and color purity improvement in nanosized YBO3: Eu 显示文摘 | Wei Zhenggui Sun Lingdong Liao Chunsheng | 2002 | Applied Physics Letters2002，80，8： | 1 |
| 14 | 显示文摘 | Jiang Xiaocheng Sun Lingdong Feng Wei Yan Chunhua | 2004 | Crystal Growth Des2004，4，3： | 1 |
| 15 | Size-depen- dent chromaticity in YBOs : Eu nanocrystals: correlation withmicrostrueture and site symmetry显示文摘 | Wei Zhenggui Sun Lingdong Liao Chunsheng | 2002 | The Journal of Physical Chemistry B2002，106，10： | 1 |
| 16 | Fluoresc- ence intensity and color purity improvement in nanosized YBO3 Eu显示文摘 | Wei Zhenggui Sun Lingdong Liao Chunsheng | 2002 | AIP Publishing2002，80，8： | 1 |
| 17 | Synthesis and assembly of rare earth nanostructures directed by the principle of coordination chemistry in solution-based process显示文摘 | FENG Wei SUN Lingdong ZHANG Yawen | 2010 | Coordination Chemistry Reviews2010，254，910： | 1 |
| 18 | Synthesis and optical properties of ZnS:Cu(II) nanoparticles 显示文摘 | Wang Mingwen Sun Lingdong Fu Xuefeng | 2000 | Solid State Communications2000，115，： | 1 |
| 19 | ZnO nanowires fabricated by a convenient route显示文摘 | ZhangJ un Sun Lingdong Pan Huayong | 2002 | NewJ Chem2002，26，1： | 1 |
| 20 | Fabrication of size controllable YVO 4 nanoparticles via microemulsion-mediated synthetic process显示文摘 | Lingdong Sun Yingxin Zhang Jun Zhang Chunhua Yan Chunsheng Liao Yiqiang Lu | 2002 | Solid State Communications2002，，： | 1 |
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