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| 1 | Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins显示文摘The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic,leading to millions of infections and hundreds of thousands of human deaths.The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses,although the viral proteins responsible for this immune evasion are not clear.In this study,we identified SARS-CoV-2 structural proteins,accessory proteins,and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways.In particular,the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways.Viral accessory protein 0RF3a had the unique ability to inhibit STING,but not the RLR response.On the other hand,structural protein N was a unique RLR inhibitor.0RF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-KB signaling.3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling.Diverse vertebrate STINGs,including those from humans,mice,and chickens,could be inhibited by 0RF3a and 3CL of SARS-CoV-2.The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo.Since evasion of host innate immune responses is essential for the survival of all viruses,our study provides insights into the design of therapeutic agents against SARS-CoV-2. | Yajuan Rui Jiaming Su Si Shen Ying Hu Dingbo Huang Wenwen Zheng Meng Lou Yifei Shi Meng Wang Shiqi Chen Na Zhao Qi Dong Yong Cai Rongzhen Xu Shu Zheng Xiao-Fang Yu | 2021 | Signal Transduction and Targeted Therapy2021，6，4： | 1 |
| 2 | A topological polymer network with Cu(Ⅱ)-coordinated reversible imidazole-urea locked unit constructs an ultra-strong self-healing elastomer显示文摘It is exceedingly desired, but difficult to construct self-healing materials with both excellent mechanical properties and healing efficiency, which are usually realized by using mutually exclusive methods. Here, we reconcile this contradiction by utilizing copper-bis-(imidazole-2-yl)-methane-urea(Cu-BIMU) locked units based on novel designed dynamic imidazole-urea bonds with coupled multiple noncovalent bonds(coordination bonds, π-π stacking bonds, and hydrogen bonds). The coordination of Cu(II) greatly reduces the electron-cloud density of imidazole, which lowers the free energy barrier of imidazole-urea bonds and promotes their reversible dissociation, as demonstrated by the density functional theory and small-molecule model reaction. The topological design of Cu-BIMU polyurethane(Cu-BIMU-PU), which concentrates multiple crosslinking-in-one locked unit to avoid the formation of excessive crosslinking sites to ensure high chain mobility, facilitates self-healing. Accumulative extensive intermolecular interactions endowed excellent mechanical properties to the resulting Cu-BIMU-PU elastomer with a tensile strength of 65.3 MPa, among the highest ever-reported value. This work provides a novel molecular design principle for fabricating high-performance dynamic polymers. | Lei Yang Zenghe Liu Rasoul Esmaeely Neisiany Jiaming Lou Yifan Guo Luzhi Zhang Huijie Liu Shuo Chen Shijia Gu Zhengwei You | 2023 | Science China Chemistry2023，66，3： | 0 |
| 3 | Peptide-Conjugated AggregationInduced Emission Fluorogen:Precise and Firm Cell Membrane Labeling by Multiple Weak Interactions显示文摘The cell membrane is a vital barrier that protects the cell from external damage and is involved in many biochemical processes.Thus,it is of great significance to label the cell membrane to explore its function.However,due to its complex and dynamic nature,precise and firm cell membrane labeling simultaneously is still a challenge.Herein,we report the fabrication of a peptide-conjugated aggregationinduced emission fluorogen(AIEgen),RTP,consisting of three main components:(1)An integrin-targeting peptide(RGD,R),which could bind specifically to integrinαvβ3 on cell membranes through ligand–receptor interaction.(2)An AIE-active tetraphenylethene derivative(T-MY,T)for fluorescent imaging.(3)Palmitic acid-modified peptide(Pal-RRRR,P),in which Pal isinserted into the lipid on the cellmembrane by hydrophobic interaction,and RRRR interacted with the negatively charged cell membrane components(proteins and lipids)through electrostatic forces.RTP could precisely label tumor cells with high integrinαvβ3 expression andfirmly trace the cellmembrane for up to 4 h;it also has a strong resistance to photobleaching.Moreover,RTP achieved in vivo tumor-specific imaging via cell membrane labeling.Thereby,utilizing multiple weak interactions between the fluorescent probe and the cell membrane provided a new strategy for precise and firm imaging of the cell membrane simultaneously. | Juliang Yang Jing-Jing Hu Jiaming Wei Jun Dai Rui Liu Fan Xia Xiaoding Lou | 2022 | CCS Chemistry2022，4，2： | 0 |
| 4 | TRAF3 activates STING-mediated suppression of EV-A71 and target of viral evasion显示文摘Innate immunity represents one of the main host responses to viral infection.1,2,3 STING(Stimulator of interferon genes),a crucial immune adapter functioning in host cells,mediates cGAS(Cyclic GMP-AMP Synthase)sensing of exogenous and endogenous DNA fragments and generates innate immune responses.4 Whether STING activation was involved in infection and replication of enterovirus remains largely unknown.In the present study,we discovered that human enterovirus A71(EV-A71)infection triggered STING activation in a cGAS dependent manner.EV-A71 infection caused mitochondrial damage and the discharge of mitochondrial DNA into the cytosol of infected cells.However,during EV-A71 infection,cGAS-STING activation was attenuated.EV-A71 ^(pro)teins were screened and the viral ^(pro)tease 2A^(pro) had the greatest capacity to inhibit cGAS-STING activation.We identified TRAF3 as an important factor during STING activation and as a target of 2A^(pro).Supplement of TRAF3 rescued cGAS-STING activation suppression by 2A^(pro).TRAF3 supported STING activation mediated TBK1 phosphorylation.Moreover,we found that 2A^(pro) ^(pro)tease activity was essential for inhibiting STING activation.Furthermore,EV-D68 and CV-A16 infection also triggered STING activation.The viral ^(pro)tease 2A^(pro) from EV-D68 and CV-A16 also had the ability to inhibit STING activation.As STING activation prior to EV-A71 infection generated cellular resistance to EV-A71 replication,blocking EV-A71-mediated STING suppression represents a new anti-viral target. | Wenwen Zheng Zhenbang Zhou Yajuan Rui Runxin Ye Fengyan Xia Fei Guo Xiaoman Liu Jiaming Su Meng Lou Xiao-Fang Yu | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 0 |
| 5 | Vulnerability Assessment of Distributed Load Shedding Algorithm for Active Distribution Power System Under Denial of Service Attack显示文摘In order to deal with frequency deviation andsupply-demand imbalance in active distribution power system, inthis paper a distributed under frequency load shedding (UFLS)strategy is proposed. Different from conventional centralizedUFLS schemes, no centralized master station gathering all thebuses’ information is required. Instead, each bus decides itsown load shedding amount by only relying on limited peer-topeer communication. However, such UFLS strategy may sufferfrom some unexpected cyber-attacks such as integrity attacksand denial of service (DoS) attack. The latter DoS attack aimsto degrade the system performance by jamming or breakingthe communication, which is of high probability to happen inpractical power system. To assess the vulnerability of proposeddistributed UFLS algorithm, the effect of DoS attack on distributed average consensus algorithm is theoretically derived,which indicates that the final consensus value can be estimatedby a given attack probability. It is also investigated that such DoSattack does harm to the load shedding amount and finally affectsthe system frequency performance in the active distributionpower system. Several case studies implemented on an IEEE33-bus active distribution power system are conducted to verifythe effectiveness of the theoretical findings and investigate thevulnerability of the considered power system. | Weiwei Xu Jiaming Weng Boliang Lou Xiaoming Huang Hongyang Huang Jun Wu Dan Zhou | 2023 | CSEE Journal of Power and Energy Systems2023，9，6： | 0 |
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