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| 1 | Tumor-expressed B7-H3 mediates the inhibition of antitumor T-cell functions in ovarian cancer insensitive to PD-1 blockade therapy显示文摘Although PD-L1/PD-1 blockade therapy has been approved to treat many types of cancers,the majority of patients with solid tumors do not respond well,but the underlying reason remains unclear.Here,we studied ovarian cancer(OvCa),a tumor type generally resistant to current immunotherapies,to investigate PD-1-independent immunosuppression.We found that PD-L1 was not highly expressed in the tumor microenvironment(TME)of human OvCa.Instead,B7-H3,another checkpoint molecule,was highly expressed by both tumor cells and tumor-infiltrating antigen-presenting cells(APCs),which correlated with T-cell exhaustion in patients.Using ID8 OvCa mouse models,we found that B7-H3 expressed on tumor cells,but not host cells,had a dominant role in suppressing antitumor immunity.Therapeutically,B7-H3 blockade,but not PD-1 blockade,prolonged the survival of ID8 tumorbearing mice.Collectively,our results demonstrate that tumor-expressed B7-H3 inhibits the function of CD8^(+)T cells and suggest that B7-H3 may be a target in patients who are not responsive to PD-L1/PD-1 inhibition,particularly OvCa patients. | Dongli Cai Jiaming Li Dingfeng Liu Shanjuan Hong Qin Qiao Qinli Sun Pingping Li Nanan Lyu Tiantian Sun Shan Xie Li Guo Ling Ni Liping Jin Chen Dong | 2020 | Cellular & Molecular Immunology2020，17，3： | 8 |
| 2 | Ferroptosis as a novel form of regulated cell death:Implications in the pathogenesis,oncometabolism and treatment of human cancer显示文摘The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy.Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells.Anti-tumor drugs were developed to induce apoptosis,but some patient’s show apoptosis escape and chemotherapy resistance.Therefore,other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment.Ferroptosis is a newly discovered iron-dependent,non-apoptotic type of cell death that is highly negatively correlated with cancer development.Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis.This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment. | Feifei Pu Fengxia Chen Zhicai Zhang Deyao Shi Binlong Zhong Xiao Lv Andrew Blake Tucker Jiaming Fan Alexander J.Li Kevin Qin Daniel Hu Connie Chen Hao Wang Fang He Na Ni Linjuan Huang Qing Liu William Wagstaff Hue H.Luu Rex C.Haydon Le Shen Tong-Chuan He Jianxiang Liu Zengwu Shao | 2022 | Genes & Diseases2022，9，2： | 6 |
| 3 | Effect of Al content on the reaction between Fe-10Mn-xAl(x=0.035wt%,0.5wt%,1wt%,and 2wt%)steel and CaO-SiO_(2)-Al_(2)O_(3)-MgO slag显示文摘The effect of Al content(0.035 wt%,0.5 wt%,1 wt%,and 2 wt%)on the composition change of steel and slag as well as inclusion transformation of high manganese steel after it has equilibrated with Ca O-Si O_(2)-Al_(2)O_(3)-Mg O slag was studied using the method of slag/steel reaction.The experimental results showed that as the initial content of Al increased from 0.035 wt%to 2 wt%,Al gradually replaced Mn to react with Si O_(2)in slag to avoid the loss of Mn due to the reaction;this process caused both Al_(2)O_(3)in slag and Si in steel to increase while Si O_(2)and Mn O in slag to reduce.In addition,the type of inclusions also evolved as the initial Al content increased.The evolution route of inclusions was Mn O→Mn O-Al_(2)O_(3)-Mg O→Mg O→Mn O-Ca O-Al_(2)O_(3)-Mg O and Mn O-Ca O-Mg O.The shape of inclusions evolved from spherical to irregular,became faceted,and finally transformed to spherical.The average size of inclusions presented a trend that was increasing first and then decreasing.The transformation mechanism of inclusions was explored.As the initial content of Al increased,Mg and Ca were reduced from top slag into molten steel in sequence,which consequently caused the transformation of inclusions. | Huixiang Yu Dexin Yang Jiaming Zhang Guangyuan Qiu Ni Zhang | 2022 | International Journal of Minerals,Metallurgy and Materials2022，29，2： | 4 |
| 4 | Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration显示文摘Low back pain,mainly caused by intervertebral disc degeneration(IVDD),is a common health problem;however,current surgical treatments are less than satisfactory.Thus,it is essential to develop novel non-invasive surgical methods for IVDD treatment.Here,we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage(ECM-Gels)that are loaded with cartilage endplate stem cells(CESCs).After loaded with CESCs overexpressing Sphk2(Lenti-Sphk2-CESCs)and injected near the cartilage endplate(CEP)of rats in vivo,ECM-Gels produced Sphk2-engineered exosomes(Lenti-Sphk2-Exos).These exosomes penetrated the annulus fibrosus(AF)and transported Sphk2 into the nucleus pulposus cells(NPCs).Sphk2 activated the phosphatidylinositol 3-kinase(PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs,ultimately ameliorating IVDD.This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes. | Liwen Luo Junfeng Gong Zhouguang Wang Yao Liu Jiaming Cao Jinghao Qin Rui Zuo Hongyu Zhang Shuai Wang Ping Zhao Di Yang Mengjie Zhang Yanqiu Wang Junfeng Zhang Yue Zhou Changqing Li Bing Ni Zhiqiang Tian MingHan Liu | 2022 | Bioactive Materials2022，7，9： | 1 |
| 5 | Argonaute(AGO)proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells(MSCs)显示文摘As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs.However,the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood.Emerging evidence indicates that noncoding RNAs,especially microRNAs,may play important roles in regulating MSC differentiation and bone formation.As highly conserved RNA binding proteins,Argonaute(AGO)proteins are essential components of the multi-protein RNA-induced silencing complexes(RISCs),which are critical for small RNA biogenesis.Here,we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs.We first found that BMP9 upregulated the expression of Ago1,Ago2 and Ago3 in MSCs.By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes,we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase(ALP)activity in MSCs.Furthermore,we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization,and ectopic bone formation.Collectively,our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs. | Yukun Mao Na Ni Linjuan Huang Jiaming Fan Hao Wang Fang He Qing Liu Deyao Shi Kai Fu Mikhail Pakvasa William Wagstaff Andrew Blake Tucker Connie Chen Russell R.Reid Rex C.Haydon Sherwin H.Ho Michael J.Lee Tong-Chuan He Jian Yang Le Shen Lin Cai Hue H.Luu | 2021 | Genes & Diseases2021，8，6： | 1 |
| 6 | SiRNA-mediated ankyrin-G silence modulates the expression of voltage-gated Na channels in murine hippocampal HT22 cells显示文摘Background:Voltage-gated sodium channels are the targets of many commonly used antiepileptic drugs.NaV1.6,encoded by Scn8a,increased in chronic mesial temporal epilepsy animal models and co-localized with Ankyrin-G,encoded by Ank3.We hypothesized that inhibition of Ank3 transcription by siRNA decrease the expression of NaV1.6.Results:We characterized expression of the target genes in hippocampal neuron HT22 cells by Real time-PCR.The melt peak in the resolution curve of Scn1a,Scn8a and Ank3 were all unique.Ank3 transcription was interfered and the relative Ank3 mRNA levels of the three interfered groups compared to GAPDH were 0.89±0.13,0.52±0.07 and 0.26±0.05 while that of the negative control group was 1.01±0.08(P<0.05).When Ank3 transcription was inhibited by siRNA,the relative mRNA levels of Scn8a decreased in the three groups(0.91±0.09,0.33±0.06 and 0.25±0.05),compared to the negative control group(1.10±0.09).Tested by Western blotting,protein levels of ankyrinG and Nav1.6 decreased after ank3-siRNA.Ankyrin-G in negative control group,group1,group2 and group1+2 were 0.813±0.051,0.744±0.041,0.477±0.055 and 0.351±0.190 respectively(P<0.01)while Nav1.6 were 0.934±0.036,0.867±0.078,0.498±0.070 and 0.586±0.180(P<0.01).The quantity analysis of immunofluorescence showed significant decrease of ankyrin-G and Nav1.6(Student’s test,P=0.046 and 0.016 respectively).Conclusion:We therefore concluded that in HT22 cells the expression of Nav1.6 was down-regulated by Ank3 RNA interference. | Guanzhong Ni Xiaoting Hao Xiaodong Cai Jiaming Qin Liemin Zhou Patrick Kwan Ziyi Chen | 2019 | Acta Epileptologica2019，1，1： | 0 |
| 7 | Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering显示文摘Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration. | Jiamin Zhong Hao Wang Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi Connie Chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo Guillermo A.Ameer Le Shen Tong-Chuan He Jiaming Fan | 2022 | Bioactive Materials2022，7，3： | 0 |
| 8 | Microstructure and Property Analysis of AerMet100 Steel Manufactured by In-situ Rolling Mixed Wire Arc Additive Manufacturing显示文摘Aer Met100 steel thick wall is fabricated by in-situ rolling composite wire arc additive manufacturing(WAAM).The microstructure and mechanical properties of Aer Met100 steel after heat treatment are studied.The results show that after the introduction of in-situ rolling force,the grain of Aer Met100 steel is broken,the anisotropy is eliminated,and the microstructure is refined obviously.The microstructure of Aer Met100 steel after heat treatment is mainly lath martensite and reverse austenite.There are 40 nm-68.6 nm alloy carbides precipitated in the martensitic matrix,and the hardening mechanism is mainly Orowan bypass strengthening.The film-like reverse austenite with the thickness ranging from 2 nm to 5 nm exists between the martensitic lath,which improves the toughness of the maraging steel.Good combination of strength and toughness can be achieved through proper heat treatment process. | NI Jiaming LEI Lei LI Baohui LIU Siyu CHENG Peng ZHANG Haiou | 2022 | 上海航天(中英文)2022，39，1： | 0 |
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