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| 1 | Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids显示文摘The re-emergence of Zika virus(ZIKV)in the Western Hemisphere has resulted in global public health crisis since 2015.ZIKV preferentially infects and targets human neural progenitor cells(hNPCs)and causes fetal microcephaly upon maternal infection.hNPCs not only play critical roles during fetal brain development,but also persist in adult brain throughout life.Yet the mechanism of innate antiviral immunity in hNPCs remains largely unknown.Here,we show that ZIKV infection triggers the abundant production of virus-derived small interfering RNAs in hNPCs,but not in the more differentiated progenies or somatic cells.Ablation of key RNAi machinery components significantly enhances ZIKV replication in hNPCs.Furthermore,enoxacin,a broad-spectrum antibiotic that is known as an RNAi enhancer,exerts potent anti-ZIKV activity in hNPCs and other RNAi-competent cells.Strikingly,enoxacin treatment completely prevents ZIKV infection and circumvents ZIKV-induced microcephalic phenotypes in brain organoid models that recapitulate human fetal brain development.Our findings highlight the physiological importance of RNAi-mediated antiviral immunity during the early stage of human brain development,uncovering a novel strategy to combat human congenital viral infections through enhancing RNAi. | Yan-Peng Xu Yang Qiu Boya Zhang Guilai Chen Qi Chen Miao Wang Fan Mo Jiuyue Xu Jin Wu Rong-Rong Zhang Meng-Li Cheng Na-Na Zhang Bao Lyu Wen-Liang Zhu Meng-Hua Wu Qing Ye Da Zhang Jiang-Hong Man Xiao-Feng Li Jie Cui Zhiheng Xu Baoyang Hu Xi Zhou Cheng-Feng Qin | 2019 | Cell Research2019，29，4： | 8 |
| 2 | The combination of PD-1 blockade with interferon-αhas a synergistic effect on hepatocellular carcinoma显示文摘Background The efficacy of immune checkpoint inhibitors(ICIs),such as programmed cell death protein-1(PD-1)or its ligand 1(PD-L1)antibody,in hepatocellular carcinoma(HCC)is limited,and it is recommended that they be combined with other therapies.We evaluated the combination of pegylated interferon-α(Peg-IFNα)with PD-1 blockade in HCC mouse models.Methods We analyzed the effects of Peg-IFNαon tumor-infiltrating immune cells and PD-1 expression in the HCC immune microenvironment and examined the underlying mechanism of its unique effect on the PD-1 pathway.The in vivo efficacy of anti-PD-1 and Peg-IFNαwas evaluated in both subcutaneous and orthotopic mouse models of HCC.Results The combination of Peg-IFNαwith PD-1 blockade dramatically enhanced T-cell infiltration,improved the efficacy of PD-1 antibody and prolonged mouse survival compared with PD-1 antibody monotherapy.Mechanistically,Peg-IFNαcould recruit cytotoxic CD8+T cells to infiltrate the HCC microenvironment by inducing tumor cells to secrete the chemokine CCL4.Nevertheless,the HCC microenvironment quickly overcame the immune responses by upregulating PD-1 expression in CD8+T cells via the IFNα-IFNAR1-JAK1-STAT3 signaling pathway.The combination of PD-1 blockade with Peg-IFNαcould restore the cytotoxic capacity of CD8+T cells and exerted a significant synergistic effect on HCC.Conclusion These results indicate that in addition to initiating the antitumor immune response itself,Peg-IFNαcan also generate a microenvironment favoring PD-1 blockade.Thus,the combination of Peg-IFNαand PD-1 blockade can be a promising strategy for HCC. | Ying Zhu Mo Chen Da Xu Tian-En Li Ze Zhang Jian-Hua Li Xiang-Yu Wang Xin Yang Lu Lu Hu-Liang Jia Qiong-Zhu Dong Lun-Xiu Qin | 2022 | Cellular & Molecular Immunology2022，19，6： | 6 |
| 3 | Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization显示文摘 | Jin‐Kyu Kang Mi‐Sook Kim Chul Koo Cho Kwang Mo Yang Hyung Jun Yoo Jin Ho Kim Sun Hyun Bae Da Hoon Jung Kum Bae Kim Dong Han Lee Chul Ju Han Jin Kim Su Cheol Park Young Han Kim | 2012 | Cancer2012，，21： | 3 |
| 4 | Overexpression of wild- type androgen receptor in muscle recapitulates polyglutamine disease显示文摘 | Monks DA Johansen JA Mo K | 2007 | Proc Natl Acad Sci U S A2007，104，18： | 1 |
| 5 | Polycystic ovary syndrome: etiology, pathogenesis and diagnosis 显示文摘 | Goodarzi MO Dumesic DA Chazenhalk G | 2011 | Nat Rev Endocrinol2011，7，4： | 1 |
| 6 | Efficient generation of retinal progenitor cells from human embryonic stem cells 显示文摘 | Lamba DA Karl MO Ware CB Reh TA | 2005 | Proc Natl Acad Sci USA2005，103，12： | 1 |
| 7 | Palycystic ovary syndrome: an ancient disorder? 显示文摘 | Azziz R Dumesic DA Goodarzi MO | 2011 | Fertil Steril2011，95，5： | 1 |
| 8 | Urethral injuries in female subjects following pelvic fractures显示文摘 | Perry MO Husmann DA | 1992 | J Urol1992，147，： | 1 |
| 9 | Polycystic ovary syndrome: etiology, pathogenesis and diagnosis 显示文摘 | Goodarzi MO Dumesic DA Chazenbalk G | 2011 | Endocrinol2011，7，4： | 1 |
| 10 | Efficient generation of retinal progenitor cells from human embryonic stem cells 显示文摘 | Lamba DA Karl MO Ware CB | 2006 | Nat Acad Sci USA2006，103，12： | 1 |
| 11 | Incidence and risk factors for agranulocytosis in Latin American countries—the Latin Study显示文摘 | Nelson Hamerschlak Eliane Maluf Alexandre Biasi Cavalcanti álvaro Avezum Júnior José Eluf-Neto Roberto Passeto Falc?o Irene Gyongyvér Heidemarie Lorand-Metze Daniel Goldenberg Cézar Leite Santana Daniela de Oliveira Werneck Rodrigues Leny Nascimento da Mo | 2008 | European Journal of Clinical Pharmacology2008，，9： | 1 |
| 12 | Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis显示文摘 | Natália P. Mo?o Laura F. Martin Ana Carolina Pereira Jossimara Polettini José C. Pera?oli Kunie I.R. Coelho Márcia G. da Silva | 2013 | European Journal of Obstetrics and Gynecology2013，，： | 1 |
| 13 | Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy显示文摘 | Monks DA Rao P Mo K | 2008 | Horm Behav2008，53，5： | 1 |
| 14 | Major renal lacerations with a devitalized fragment following blunt abdominal trauma:a comparison between nonoperative (expectant) versus surgical management显示文摘 | Husmann DA Giling PJ Perry MO | 1993 | J Urol1993，150，230： | 1 |
| 15 | Polycystic ovary syndrome:etiology,pathogenesis and diagnosis显示文摘 | Goodarzi MO Dumesic DA Chazenbalk G | | 0，，04： | 1 |
| 16 | Prognostic utility of heart - type fatty acid binding protein in patients with acute coronary syndromes 显示文摘 | Donoghue MO Lemos JA Morrow DA | 2006 | Circulation2006，114，6： | 1 |
| 17 | Polycys- tic ovary syndrome: etiology, pathogenesis and diagnosis 显示文摘 | Goodarzi MO Dumesic DA Chazenbalk G | 2011 | Nat Rev Endocrinol2011，7，4： | 1 |
| 18 | Polycystic ovary syndrome:etiology,pathoenesis and diagnosis显示文摘 | Coodarzi MO Dumesic DA Chazenbalk G | 2011 | Nat Rev Endocrinol2011，7，： | 1 |
| 19 | Polycys- tic ovary syndrome: etiology, pathogenesis and diagnosis 显示文摘 | Goodarzi MO Dumesie DA Chazenbalk G | 2011 | Nat Rev Endocrinol2011，7，4： | 1 |
| 20 | Polycystic ovary syndrome:etiology,pathogenesis and diagnosis显示文摘 | Goodarzi MO Dumesic DA Chazenbalk G | 2011 | Nat Rev Endocrinol2011，7，4： | 1 |
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