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哲学抑或思想史?——试论沃格林历史哲学的限度与中国“效应”

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湖北大学学报（哲学社会科学版） 2024年第2期51卷 87-95,178页

作者：庄振华陕西师范大学马克思主义学部陕西西安710650

沃格林的历史哲学对各种文明表现出西方学者中罕见的宽容与深度,成为中国思想建构的一个有益镜鉴,然而这种哲学在思想性质、秩序观、历史观等方面的限度也不可不察。在思想性质方面,它在根本上乃是一种思想史的乃至社会科学的考察,即从... 详细信息

沃格林的历史哲学对各种文明表现出西方学者中罕见的宽容与深度,成为中国思想建构的一个有益镜鉴,然而这种哲学在思想性质、秩序观、历史观等方面的限度也不可不察。在思想性质方面,它在根本上乃是一种思想史的乃至社会科学的考察,即从过往思想中总结历史规律,并以某种本身貌似自明的模型来评判历史,而没有达到哲学对这种考察方式之效力应有的更深刻反思。在秩序观方面,沃格林忽视了他心目中的一些灵知主义“典型”在现代性的边缘之处通达宇宙秩序的可能性。在历史观方面,沃格林虽然反对人的解释受到历史的主导,主张“历史的秩序来自秩序的历史”,却由于致思方式的局限,仅仅看到“历史中的哲学”,没有真正达到“哲学观照的历史”,尤其是忽略了黑格尔历史哲学与谢林肯定哲学“究天人之际”的旨趣。鉴于这些限度,加之中国文明在根本上并未遵从西方以形式感主导的构成方式,我们在沃格林之后“接着说”时不应以沃格林的论述框架为“底本”,而只应将其作为我们重新发掘中国文明“道中庸”的不同方式时的外部参照物。

关键词：沃格林历史哲学思想史中国文明

Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2392-2407页

作者： Sihui Cai Chenqiu Zhang zhen zhuang Shengnan Zhang Ling Ma Shuai Yang Tao Zhou Zheyu Wang Weihong Xie Shouheng Jin Jincun Zhao Xiangdong Guan Jianfeng Wu Jun Cui Yaoxing Wu Guangdong Province Key Laboratory of Pharmaceutical Functional Genes The First Affiliated Hospital of Sun Yat-sen UniversitySchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Critical Care Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Currently,the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide.COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon(IFN-I)signal,along with limited activation of antiviral immune responses as well as enhanced viral infectivity.Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways.However,it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection.In the current study,we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA(mtDNA),which in turn triggers cGAS to activate IFN-I signaling.As countermeasures,SARS-CoV-2 nucleocapsid(N)protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling.Mechanically,N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation(LLPS),subsequently impairs the double-strand DNA(dsDNA)detection ability of cGAS.Taken together,our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.

关键词： interferon separated cGAS

P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-CoV-2 entry and ACE2 autophagic degradation

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5353-5367页

作者： Ming Liu Bingtai Lu Yue Li Shuofeng Yuan zhen zhuang Guangyu Li Dong Wang Liuheyi Ma Jianheng Zhu Jinglu Zhao Chris Chung-Sing Chan Vincent Kwok-Man Poon Kenn Ka-Heng Chik Zhiyao Zhao Huifang Xian Jingxian Zhao Jincun Zhao Jasper Fuk-Woo Chan Yuxia Zhang Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical University510623 GuangzhouGuangdongChina Medical Research Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangdongChina State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedineThe University of Hong KongPokfulamHong KongChina Department of Clinical Microbiology and Infection Control The University of Hong Kong Shenzhen HospitalShenzhenGuangdongChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong KongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affliated Hospital of Guangzhou Medical UniversityGuangzhouChina The Third Afliated Hospital of zhengzhou University 450052 ZhengzhouChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina Chongqing International Institute for Immunology ChongqingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has had a significant impact on healthcare systems and economies worldwide.The continuous emergence of new viral strains presents a major challenge in the development of effective antiviral agents.Strategies that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 infection.ACE2,an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system,is the receptor for SARS-CoV-2.ACE2 interacts with the spike protein and facilitates viral attachment and entry into host cells.Yet,SARS-CoV-2 infection also promotes ACE2 degradation.Whether restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be determined.Here,we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement.In contrast,free cellular spike protein is selectively cleaved into S1 and s2 subunits in a lysosomal-dependent manner.Importantly,we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 strains.FRAX-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated hamsters.In summary,our findings have identified novel pathways regulating viral entry,as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.

关键词： ACE2 inflammation rearrangement

RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-kB hyper-activation and inflammation

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1601-1613页

作者： Yaoxing Wu Ling Ma Sihui Cai zhen zhuang Zhiyao Zhaou Shouheng Jin Weihong Xie Lingli Zhou Lei Zhang Jincun Zhao Jun Cui MOE Key Laboratory of Gene Funrtion and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina

The ongoing 2019 novel coronavirus disease(COVID-19)caused by SARS-CoV-2 has posed a worldwide pandemic and a major global public health threat.The severity and mortality of COVID-19 are associated with virus-induced dysfunctional inflammatory responses and cytokine storms.However,the interplay between host inflammatory responses and SARS-CoV-2 infection remains largely unknown.Here,we demonstrate that SARS-CoV-2 nucleocapsid(N)protein,the major structural protein of the virion,promotes the virus-triggered activation of NF-kB signaling.After binding to viral RNA,N protein robustly undergoes liquid-liquid phase separation(LLPS),which recruits TAK1 and IKK complex,the key kinases of NF-kB signaling,to enhance NF-kB activation.Moreover,1,6-hexanediol,the inhibitor of LLPS,can attenuate the phase separation of N protein and restrict its regulatory functions in NF-kB activation.These results suggest that LLPS of N protein provides a platform to Induce NF-kB hyper-activation,which could be a potential therapeutic target against COVID-19 severe pneumonia.

关键词： inflammation separation activation

Main protease of SARS-CoV-2 serves as a bifunctional molecule in restricting type I interferon antiviral signaling

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Signal Transduction and Targeted Therapy 2020年第1期5卷 646-648页

作者： Yaoxing Wu Ling Ma zhen zhuang Sihui Cai Zhiyao Zhao Lingli Zhou Jing Zhang Pei-Hui Wang Jincun Zhao Jun Cui MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen University510275 GuangzhouGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical University510182 GuangzhouGuangdongChina Advanced Medical Research Institute Cheeloo College of MedicineShandong University250012 JinanShandongChina

Dear Editor,At present,the world is suffering from an ongoing pandemic of 2019 novel coronavirus(COVID-19)which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2/2019-nCoV).To date,>20 million cases were confirmed with a death toll at>700,000.Although there are no clinically specific and effective antiviral treatments toward SARS-CoV-2 infection so far,the pathological study of SARS-CoV-2 infection and the development of SARS-CoV-2-specific vaccines are progressing rapidly within these several months.1 However,few reports mentioned the mechanism employed by SARS-CoV-2 for evading from surveillance of immune system.

关键词： acute respiratory death

Therapeutic potential of C1632 by inhibition of SARS-CoV-2 replication and viral-induced inflammation through upregulating let-7

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Signal Transduction and Targeted Therapy 2021年第3期6卷 605-607页

作者： Chen Xie Yanlian Chen Dongling Luo zhen zhuang Heping Jin Haoxian Zhou Xiaocui Li Haijun Lin Xiaohui zheng Jing Zhang Peihui Wang Jincun Zhao Yong Zhao Hui Huang Key Laboratory of Gene Engineering of the Ministry of Education School of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina Cardiovascular Department The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Xiamen Innodx Biotech Co. Ltd.XiamenFujianChina School of Pharmaceutical Sciences Wenzhou Medical UniversityWenzhouZhejiangChina Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandongChina

Dear Editor,The COVID-19 pandemic caused by SARS-CoV-2 has led to acute respiratory distress syndrome(ARDS)with a high rate of death.An excessive inflammatory response,caused by virus infection,is associated with severe clinical manifestations that may lead to death of patients.1 Therefore,the blockage of virus replication and suppression of hyper-inflammatory response are beneficial for COVID-19 treatment.However,the drug targeting both virus and hyper-inflammation,as far as we know,is not available yet.

关键词： inflammation distress acute

Immune responses to SARS-CoV-2 infection in Humans and ACE2 humanized mice

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Fundamental Research 2021年第2期1卷 124-130页

作者： Airu Zhu Zhao Chen Yanqun Wang Qiuhui Zeng Jing Sun zhen zhuang Fang Li Jingxian Zhao Jincun Zhao Nanshan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represents a major public health threat worldwide.Insight into protective and pathogenic aspects of SARS-CoV-2 immune responses is critical to work out effective therapeutics and develop vaccines for controlling the disease.Here,we review the present literature describing the innate and adaptive immune responses including innate immune cells,cytokine responses,antibody responses and T cell responses against SARS-CoV-2 in human infection,as well as in AEC2-humanized mouse infection.We also summarize the now known and unknown about the role of the SARS-CoV-2 immune responses.By better understanding the mechanisms that drive the immune responses,we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.

关键词： SARS-CoV-2 Innate immune response Humoral immune responses T cell response Mouse model

Repurposing carrimycin as an antiviral agent against human coronaviruses,including the currently pandemic SARS-CoV-2

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2850-2858页

作者： Haiyan Yan Jing Sun Kun Wang Huiqiang Wang Shuo Wu Linlin Bao Weiqing He Dong Wang Airu Zhu Tian Zhang Rongmei Gao Biao Dong Jianrui Li Lu Yang Ming Zhong Qi Lv Feifei Qin zhen zhuang Xiaofang Huang Xinyi Yang Yuhuan Li Yongsheng Che Jiandong Jiang Sciences and Peking Union Medical College Beijing 100050China State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510182China Institute of Medicinal Biotechnology Chinese Academy of Medical ScienceBeijing 100050China Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityBenxi 117004China

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development.No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections.We report herein that a macrolide antibiotic,carrimycin,potently inhibited the cytopathic effects(CPE)and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229 E,OC43,and SARS-CoV-2.Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection.In support of this notion,metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA.Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

关键词： Coronavirus SARS-CoV-2 HCoV-229E HCoV-OC43 COVID-19 Carrimycin

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基于FPGA的锻锤安全控制模块设计

电脑与电信 2024年第4期 73-75,96页

作者：李响庄振伟姚海燕李静姚琏安阳工学院电子信息与电气工程学院安阳河南455000 河南省鼎鼎实业有限公司安阳河南455000

近年来,随着工业化进程的发展,工业控制系统对安全操作的需求也随之提升。FPGA以响应时间短、功耗低、安全可靠等特点得到广泛应用。基于FPGA设计了一种锻锤操作的安全控制模块,可以同时对锻锤设备的多个控制信号进行实时监测,在设备发... 详细信息

近年来,随着工业化进程的发展,工业控制系统对安全操作的需求也随之提升。FPGA以响应时间短、功耗低、安全可靠等特点得到广泛应用。基于FPGA设计了一种锻锤操作的安全控制模块,可以同时对锻锤设备的多个控制信号进行实时监测,在设备发生故障时及时提醒工作人员停止操作,避免生产事故的发生。

关键词：安全控制模块 FPGA 锻锤