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| 1 | Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagy显示文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC. | Ting Zhang Xinrui Yang Wanping Xu Jing Wang Dawei Wu Zhixian Hong Shengxian Yuan Zhen Zeng Xiaodong Jia Shanshan Lu Rifaat Safadi Sen Han Zhihong Yang Leonard M.Neckers Suthat Liangpunsakul Weiping Zhou Yinying Lu | 2021 | Cancer Biology & Medicine2021，18，3： | 7 |
| 2 | Land-use changes in the small watershed of the Loess Plateau,hilly-gully region, China显示文摘As more and more farmland is converted to forestry, the need for effective decision support regarding the use of land in the fragile ecological environment of the Loess Plateau hilly-gully area. The Luoyugou watershed was chosen as the study area to calculate the single dynamic degree, integrated dynamic degree, and change indexes of land use, as well as the land-use type transition matrix. This was done by interpreting the TM and SPOT images of the Luoyugou watershed in 1986, 1995, and2004 and making statistical analysis. The results of ou statistical analysis show that the conversion of slope farm land to terrace and forest land plays a dominant role in land-use changes in the Luoyugou watershed from 1986 to2004. The land-use changes are mainly driven by popula tion growth, socio-economic development, consume spending, and investment in forest ecology. | Yini Han Jianzhi Niu Feizhou Wu | 2015 | Journal of Forestry Research2015，26，1： | 2 |
| 3 | Tailored Therapy Versus Empiric Chosen Treatment for Helicobacter pylori Eradication: A Meta-Analysis显示文摘 | Han Chen Yini Dang Xiaoying Zhou Bingtuan Liu Shiyu Liu Guoxin Zhang | 2016 | Medicine2016，，7： | 1 |
| 4 | Enhanced chemoselectivity of a plant cytochrome P450 through protein engineering of surface and catalytic residues显示文摘Cytochrome P450s(P450s)are the most versatile catalysts utilized by plants to produce structurally and functionally diverse metabolites.Given the high degree of gene redundancy and challenge to functionally characterize plant P450s,protein engineering is used as a complementarystrategy to study the mechanisms of P450-mediated reactions,or to alter their functions.We previously proposed an approach of engineering plant P450s based on combining high accuracy homology models generated by Rosetta combined with data-driven design using evoluti onary information of these enzymes.With this strategy,we repurposed a multi-functional P450(CYP87D20)into a monooxygenase after red esigning its active site.Since most plant P450s are membrane-anchored proteins that are adapted to the micro-environments of plant cells,expressing them in heterologous hosts usually results in problems of expression or activity.Here,we applied compu-tational design to tackle these issues by simultaneous optimization of the protein surface and active site.After screening 17 variants,effective su bstitutions of surface residues were observed to improve both expression and activity of CYP87D20.In addition,the identified substitutions were additive and by com-bining them a highly eficient C11 hydroxylase of cucurbitadienol was created to participate in the mogrol biosynthesis.This study shows the importance of considering the interplay between surface and active site residues for P450 engineering.Our integrated strategy also opens an avenue to create more tai loring enzymes with desired functions for the metabolic engineering of high-valued compounds like mogrol,the precursor of natural sweetener mogrosides. | Xiaopeng Zhang Wei Luo Yinying Yao Xuming Luo Chao Han Yang Zhong Bo Zhang Dawei Li Lida Han Sanwen Huang Per Greisen Yi Shang | 2021 | aBIOTECH2021，2，3： | 1 |
| 5 | Starvation-Sensitized and Oxygenation-Promoted Tumor Sonodynamic Therapy by a Cascade Enzymatic Approach显示文摘The therapeutic outcomes of noninvasive sonodynamic therapy(SDT)are always compromised by tumor hypoxia,as well as inherent protective mechanisms of tumor.Herein,we report a simple cascade enzymatic approach of the concurrent glucose depletion and intratumoral oxygenation for starvation-sensitized and oxygenation-amplified sonodynamic therapy using a dual enzyme and sonosensitizer-loaded nanomedicine designated as GOD/CAT@ZPF-Lips.In particular,glucose oxidase-(GOD-)catalyzed glycolysis would cut off glucose supply within the tumor,resulting in the production of tumor hydrogen peroxide(H_(2)O_(2))while causing tumor cells starvation.The generated H_(2)O_(2)could subsequently be decomposed by catalase(CAT)to generate oxygen,which acts as reactants for the abundant singlet oxygen(^(1 O_(2))production by loaded sonosensitizer hematoporphyrin monomethyl ether(HMME)upon the US irradiation,performing largely elevated therapeutic outcomes of SDT.In the meantime,the severe energy deprivation enabled by GOD-catalyzed glucose depletion would prevent tumor cells from executing protective mechanisms to defend themselves and make the tumor cells sensitized and succumbed to the cytotoxicity of^(1 O_(2)).Eventually,GOD/CAT@ZPF-Lips demonstrate the excellent tumoral therapeutic effect of SDT in vivo without significant side effect through the cascade enzymatic starvation and oxygenation,and encouragingly,the tumor xenografts have been found completely eradicated in around 4 days by the intravenous injection of the nanomedicine without reoccurrence for as long as 20 days. | Wencheng Wu Yinying Pu Han Lin Heliang Yao Jianlin Shi | 2021 | Research2021，，1： | 1 |
| 6 | From liver fibrosis to hepatocarcinogenesis: Role of excessive liver H_(2)O_(2) and targeting nanotherapeutics显示文摘Liver fibrosis and hepatocellular carcinoma(HCC)have been worldwide threats nowadays.Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage.In pathological liver,excessive H_(2)O_(2) is generated and accumulated,which impacts the functionality of hepatocytes,Kupffer cells(KCs)and hepatic stellate cells(HSCs),leading to genesis of fibrosis and HCC.H_(2)O_(2) accumulation is associated with overproduction of superoxide anion(O_(2)^(·-))and abolished antioxidant enzyme systems.Plenty of therapeutics focused on H_(2)O_(2) have shown satisfactory effects against liver fibrosis or HCC in different ways.This review summarized the reasons of liver H_(2)O_(2) accumulation,and the role of H_(2)O_(2) in genesis of liver fibrosis and HCC.Additionally,nanotherapeutics targeting H_(2)O_(2) were summarized for further consideration of antifibrotic or antitumor therapy. | Meiyu Shao Yifan Wang Hongyan Dong Lu Wang Xiaoqing Zhang Xin Han Xianan Sang Yini Bao Mengyun Peng Gang Cao | 2023 | Bioactive Materials2023，，5： | 0 |
| 7 | Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas显示文摘Adenosquamous carcinoma of the pancreas(ASCP)is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate.However,little is known about its genomic landscape and prognostic biomarkers.A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma(PDAC)tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers.The homozygous deletion of the 9p21.3 region(including CDKN2A,CDKN2B,and MTAP)(9p21 loss)occurred in both ASCP and PDAC,and a higher frequency of 9p21 loss was observed in ASCP(12.5%vs 2.0%,P=0.022).Notably,9p21 loss was significantly associated with poor disease-free survival(DFS)in ASCP patients(mDFS(Median DFS)=4.17 vs 7.33 months,HR(Hazard Ratio)=3.70,P=0.009).The most common gene alterations in patients with ASCP were KRAS(96%),TP53(81%),CDKN2A(42%),SMAD4(21%),CDKN2B(13%),and FAT3(13%).The mutation rates of ACVR2A(6.25%vs 0%),FANCA(6.25%vs 0%),RBM10(6.25%vs 0%),and SPTA1(8.33%vs 1.02%)were significantly higher in ASCP than in PDAC.In conclusion,we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP,which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP. | Yina Jiang Yinying Wu Liwen Zhang Yan Wang Guiping Xu Yuan Deng Liang Han Enxiao Li Qingyong Ma Mian Xu Zheng Wu Zheng Wang | 2023 | Precision Clinical Medicine2023，6，4： | 0 |
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