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| 1 | LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase显示文摘Limb and CNS expressed 1 like(LIX1L) is over-expressed in several types of tumors.However,the function of LIX1L in glucose metabolism and hepatocellular carcinoma(HCC) progression remains elusive.Here we report that LIX1L is over-expressed in human HCC tissues,which predicts unfavorable prognosis.LIX1L deficiency in vivo significantly attenuated liver cancer initiation in mice.Functional studies indicated that LIX1L overexpression elevated proliferation,migratory,invasive capacities of HCC cells in vitro,and promoted liver cancer growth and metastasis in vivo.LIX1L knockdown up-regulated fructose-1,6-bisphosphatase(FBP1) expression to reduce glucose consumption as well as lactate production.Mechanistically,LIX1L increased miR-21-3p expression,which targeted and suppressed FBP1,thereby promoting HCC growth and metastasis.MiR-21-3p inhibitor could abrogate LIX1L induced enhancement of cell migration,invasion,and glucose metabolism.Inhibition of miR-21-3p suppressed tumor growth in an orthotopic tumor model.Our results establish LIX1L as a critical driver of hepatocarcinogenesis and HCC progression,with implications for prognosis and treatment. | Jie Zou Xiaoyun Zhu Dejuan Xiang Yanqiu Zhang Jie Li Zhigui Su Lingyi Kong Hao Zhang | 2021 | Acta Pharmaceutica Sinica B2021，11，6： | 4 |
| 2 | Spirolindemers A and B,Lindenane Sesquiterpenoid Oligomers Equipped with Oxaspiro[4.5]decane from Chloranthus henryi显示文摘Spirolindemers A and B,unprecedented lindenane sesquiterpenoid dimer(1)and trimer(2)equipped with oxaspiro[4.5]decane unit,were discovered from the medicinal plant Chloranthus henryi.Their structures including absolute configurations were achieved by HRMS,NMR,ECD,X-ray diffraction analyses,and quantum chemical calculations.Biogenetically,hetero-and homo-Diels-Alder additions may dominate the formation of oxaspiro[4.5]decane and spiro[4.5]decane skeletons,respectively.Compound 1 showed anti-inflammatory activity by inhibiting the expression of iNOS and COX-2. | Jixin Li Jun Chi Pengfei Tang Yunpeng Sun Weijia Lu Wenjun Xu Yongyue Wang Jun Luo Lingyi Kong | 2022 | Chinese Journal of Chemistry2022，40，5： | 4 |
| 3 | Identification of a novel PHGDH covalent inhibitor by chemical proteomics and phenotypic profiling显示文摘The first rate-limiting enzyme of the serine synthesis pathway(SSP), phosphoglycerate dehydrogenase(PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A(WA), a natural small molecule,as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue(Cys295)of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain(SBD)of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species(ROS) were elevated, leading to the inhibition of tumor proliferation.This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH. | Chen Chen Tianyu Zhu Xiaoqin Liu Dongrong Zhu Yi Zhang Sifang Wu Chao Han Hao Zhang Jianguang Luo Lingyi Kong | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 2 |
| 4 | Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation: A new platform for synergistic oncology therapy显示文摘Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors,it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels,tissues,and cell barriers to thereafter demonstrate excellent antitumor effects.To further overcome these inherent obstacles,we designed and prepared mycoplasma membrane(MM)-fused liposomes(LPs)with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles.We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod(LPsR848).Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848.The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors.Facilitated by the formation of neutrophil extracellular traps(NETs),podophyllotoxin(POD)-loaded MM-fused LPs(MM-LPs-POD)were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation.MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model.Overall,such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy. | Xiaobei Cheng Pei Yu Xiang Zhou Jiale Zhu Yubao Han Chao Zhang Lingyi Kong | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 2 |
| 5 | Correlation and interaction between temperature and freeze-thaw in representative regions of Antarctica显示文摘As the most sensitive and direct indicator of global climate change,the freezing and thawing of the Antarctic ice sheet is of great significance for research on surface mass and energy balance.In this study,four representative regions in Antarctica were selected and correlation analysis,Granger causality testing,and cluster analysis were applied to comprehensively analyze the correlation and response of spatiotemporal variation in freeze-thaw and temperature.The conclusions are as follows.(1)In the Antarctic Peninsula,a phenomenon was demonstrated that the summer shifts rearward.Hotter December and colder March temperatures were observed in the Amery Ice Shelf and Queen Maud Land.(2)The Antarctic Peninsula featured the most severe degree of melting among the four regions,with the largest melt area in the past 30 years appearing during the 2015/2016 season.However,the number of melt days in most areas of the Antarctic Peninsula was observed to have decreased.(3)There is a strong correlation between the freeze-thaw state of the Antarctic ice sheet and temperature,as well as spatial differences among regions,but the data were clustered at different time scales. | Dong Liang Huadong Guo Qing Cheng Lu Zhang Lingyi Kong | 2022 | International Journal of Digital Earth2022，15，1： | 1 |
| 6 | Steroidal saponins from roots of Asparagus officinalis显示文摘 | HUANG Xuefeng KONG Lingyi | 2006 | Steroids2006，71，： | 1 |
| 7 | A new steroidal saponin from the dried stems of Asparagus offlclnalis L显示文摘 | Zhouxuan Sun Xuefeng Huang Lingyi Kong | 2010 | Fitoterapia2010，，81： | 1 |
| 8 | Rapid identification of C21 steriodal saponins in Cynanehum versicolor Bunge by electrospray ionization multi-stage tandem mass spectrometry and liquid chromatography tandem mass spectrometry 显示文摘 | Zheng Zhaoguang Zheng Weidong Kong Lingyi | 2007 | Rapid Commun Mass Spectrum2007，21，： | 1 |
| 9 | Chemical constituents from Alpinia tonkinensis显示文摘 | Zhang Jian Kong Lingyi | 2004 | J Asian Nat Prod Res2004，6，3： | 1 |
| 10 | Preparative isolation and purification of psoralen and isopsoralen from Psoralea corylifolia by high-speed counter-current chromatography显示文摘 | Renmin Liu Aifeng Li Ailing Sun Lingyi Kong | 2004 | Journal of Chromatography A2004，，1： | 1 |
| 11 | Sarcaglarols A-D, Lindenane-Monoterpene Heterodimers from Sarcandra glabra Based on Molecular Networks显示文摘Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells. | Yongyue Wang Zhirong Cui Jun Chi Pengfei Tang Meihui Zhang Jixin Li Yongyi Li Hao Zhang Jun Luo Lingyi Kong | 2021 | Chinese Journal of Chemistry2021，39，1： | 1 |
| 12 | Studies on the chemical constituents of Desmodium styracifoliun, (Osbeck) Merr显示文摘 | Lin Yuying Kong Lingyi | 2006 | Asian J Trad Med2006，1，1： | 1 |
| 13 | Diverse Ring-seco Limonoids from Munronia unifoliolata and Their Biological Activities显示文摘Twenty-two new limonoids,mufolinoids A—V(1—22),including six rings A,B-seco limonoids(1—6),twelve ring A-seco limonoids(7—18),four ring-intact limonoids(19—22),together with thirteen known compounds(23—35)were isolated from Munronia unifoliolata.Their structures including absolute configurations were elucidated by combination of NMR,HR-MS,single-crystal X-ray diffraction and calculations of ECD and NMR technologies.Compounds 24,25,33,34 could be significantly reversed the multidrug resistance of MCF-7/doxorubicin(DOX)cells,and the reversal fold(RF)was much higher than that of positive drug Verapamil.Compounds 24,28,and 29 exhibited significant anti-inflammatory activity with the IC50 values in the range of 17.7—39.4μmol/L.Furthermore,compound 29 could markedly inhibit the release of IL-1βby inhibiting the initiation and assembly of NLRP3 inflammasome,which demonstrates the great potential of limonoids as an anti-inflammatory agent. | Yunpeng Sun Qiurong Li Letian Cui Pengfei Tang Yongyi Li Lingyi Kong Jun Luo | 2022 | Chinese Journal of Chemistry2022，40，1： | 1 |
| 14 | Studies on the chemical constituents of Desmodium styracifolium (Osbeck) Merr 显示文摘 | Lin Yuying Kong Lingyi | 2006 | Asian J Trad Med2006，1，1： | 1 |
| 15 | Studies on the chemical constituents of Desmodium styracifolium (Osbeck) Merr显示文摘 | LIN Yuying KONG Lingyi | 2006 | Asian Journal of Traditional Medicines2006，1，1： | 1 |
| 16 | Automatic authenti- cation and distinction of Epimedium koreanum and Epimedium wusha- nense with HPLC fingerprint analysis assisted by pattern recognition tech- niques显示文摘 | WANG Lingbo WANG Xiaobing KONG Lingyi | 2012 | Biochemical Systematics and Ecology2012，40，： | 1 |
| 17 | Steroidal saponins from roots of Asparagus officinalis显示文摘 | Xuefeng Huang Lingyi Kong | 2006 | Steroids2006，71，： | 1 |
| 18 | Steroidal alka-loid saponins and steroidal saponins from Solanum surat-tense显示文摘 | Yuanyuan Lu Jianguang Luo Lingyi Kong | 2011 | Phytochemistry2011，72，7： | 1 |
| 19 | Studies on the chemical constituents of Desmodium styracifolium (Osbeck) Merr显示文摘 | Lin Yuying Kong Lingyi | 2006 | Asian J Trad Med2006，1，1： | 1 |
| 20 | Pharmacokinetic study and metabolite identification of the bidesmosidic triterpenoid saponin BTS-1 in rat plasma显示文摘Assays based on high-performance liquid chromatography(HPLC)and liquid chromatography tandem mass spectrometry(LC–MSn)have been developed and validated for the determination and metabolite identification of the bidesmosidic triterpenoid saponin,BTS-1(3-O-β-D-galactopyranosyl-(1-2)-[β-D-xylopyranosyl-(1-3)]-β-D-glucuronopyranosyl gypsogenin 28-O-α-L-arabinopyranosyl-(1-3)-βD-xylopyranosyl-(1-4)-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside),in rat plasma.The assay was successfully applied to a pharmacokinetic study in rats given a single oral dose of BTS-1(400 mg/kg).The results indicated that the compound was rapidly absorbed(Tmax=1.2870.29 h,Cmax=37.475.6 mg/mL)and slowly eliminated(t1/2=13.276.6 h).In addition,secondary glycosides and aglycones of BTS-1 were detected and identified.Since these metabolites are known to be activeα-glucosidase inhibitors,they probably play an important role in mediating the pharmacological effects of the saponin. | Jianguang Luo Chan Zhou Wei Zhang Lingyi Kong | 2013 | Acta Pharmaceutica Sinica B2013，3，3： | 1 |
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