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| 1 | A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy显示文摘The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy. | Xiaoge Zhang Lili Cheng Yao Lu Junjie Tang Qijun Lv Xiaomei Chen You Chen Jie Liu | 2022 | Nano-Micro Letters2022，14，2： | 1 |
| 2 | Dihydroartemisinin beneficially regulates splenic immune cell heterogeneity through the SOD3-JNK-AP-1 axis显示文摘The immunomodulatory potential of dihydroartemisinin(DHA) has recently been highlighted;however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular and biochemical approaches to elucidate the immunomodulatory mechanisms of DHA. In this study, we found that DHA induced both spleen enlargement and rearrangement of splenic immune cell subsets in mice. It was revealed that DHA promoted the reversible expansion of effective regulatory T cells and interferon-γ^(+)cytotoxic CD8^(+)T cells in the spleen via induction of superoxide dismutase 3(SOD3) expression and increased phosphorylation of c-Jun N-terminal kinases(JNK) and its downstream activator protein 1(AP-1) transcription factors. Further, SOD3 knockout mice were resistant to the regulatory effect of DHA. Thus, DHA,through the activation of the SOD3-JNK-AP-1 axis, beneficially regulated immune cell heterogeneity and splenic immune cell homeostasis to treat autoimmune diseases. | Yiwei Zhang Qilong Li Ning Jiang Ziwei Su Quan Yuan Lei Lv Xiaoyu Sang Ran Chen Ying Feng Qijun Chen | 2022 | Science China(Life Sciences)2022，65，8： | 1 |
| 3 | Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation显示文摘Artemisinin(ART)and dihydroartemisinin(DHA),apart from their profound anti-malaria effect,can also beneficially modulate the host immune system;however,the underlying molecular mechanisms remain unclear.Here,we report that DHA selectively induced T-cell activation,with an increased proportion of Ki67^(+)CD4^(+)T cells,CD25^(+)CD4^(+)T cells,interferon(IFN)-γ-producing CD8^(+)T cells,Brdu^(+)CD8^(+)T cells and neutrophils,which was found to enhance cellular immunity to experimental malaria and overcome immunosuppression in mice.We further revealed that DHA upregulated the expression of cell proliferation-associated proteins by promoting the phosphorylation of mitogen-activated protein kinase(MAPK),cyclin-dependent kinases(CDKs),and activator protein 1 in the spleen.This study is the first to provide robust evidence that DHA selectively induced the expansion of subsets of splenic T cells through phosphorylated CDKs and MAPK to enhance cellular immune responses under non-pathological or pathological conditions.The data significantly deepened our knowledge in the mechanism underlying DHA-mediated immunomodulation. | Qilong Li Quan Yuan Ning Jiang Yiwei Zhang Ziwei Su Lei Lv Xiaoyu Sang Ran Chen Ying Feng Qijun Chen | 2022 | Signal Transduction and Targeted Therapy2022，7，8： | 0 |
| 4 | A cell wall invertase modulates resistance to fusarium crown rot and sharp eyespot in common wheat显示文摘Fusarium crown rot(FCR) and sharp eyespot(SE)are serious soil-borne diseases in wheat and its relatives that have been reported to cause wheat yield losses in many areas. In this study, the expression of a cell wall invertase gene, TaCWI-B1,was identified to be associated with FCR resistance through a combination of bulk segregant RNA sequencing and genome resequencing in a recombinant inbred line population. Two biparental populations were developed to further verify TaCWI-B1 association with FCR resistance.Overexpression lines and ethyl methanesulfonate(EMS) mutants revealed TaCWI-B1 positively regulating FCR resistance. Determination of cell wall thickness and components showed that the TaCWI-B1-overexpression lines exhibited considerably increased thickness and pectin and cellulose contents. Furthermore, we found that TaCWI-B1 directly interacted with an alphagalactosidase(TaGAL). EMS mutants showed that TaGAL negatively modulated FCR resistance. The expression of TaGAL is negatively correlated with TaCWI-B1 levels, thus may reduce mannan degradation in the cell wall, consequently leading to thickening of the cell wall. Additionally, TaCWI-B1-overexpression lines and TaGAL mutants showed higher resistance to SE;however, TaCWI-B1 mutants were more susceptible to SE than controls.This study provides insights into a FCR and SE resistance gene to combat soil-borne diseases in common wheat. | Guoguo Lv Yixiao Zhang Lin Ma Xiangning Yan Mingjie Yuan Jianhui Chen Yongzhen Cheng Xi Yang Qi Qiao Leilei Zhang Mohsin Niaz Xiaonan Sun Qijun Zhang Shaobin Zhong Feng Chen | 2023 | Journal of Integrative Plant Biology2023，65，7： | 0 |
| 5 | Bilayer hydrogel dressing with lysozymeenhanced photothermal therapy for biofilm eradication and accelerated chronic wound repair显示文摘Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds.Photothermal therapy(PTT)emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat.However,the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues.Besides,the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation.Herein,we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds.Gelatin was used as inner layer hydrogel to reserve lysozyme(LZM)loaded mesoporous polydopamine(MPDA)(MPDA-LZM)nanoparticles,which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles.MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability,could deeply penetrate and destroy biofilms.In addition,the outer layer hydrogel consisted of gelatin methacryloyl(GelMA)and epidermal growth factor(EGF)promoted wound healing and tissue regeneration.It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo.Overall,the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds. | Yizhen Wang Qijun Lv You Chen Langtao Xu Miao Feng Zhiyong Xiong Jiajun Li Jie Ren Jie Liu Bo Liu | 2023 | Acta Pharmaceutica Sinica B2023，13，1： | 0 |
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