In this research, the absorbance and luminescence response of two osmium(II) phenathrane (phen) carbonyl complexes to various DNA, heparin and i-carrageenan polyanions were studied. The [Os(phen)<sub>2</sub&g...In this research, the absorbance and luminescence response of two osmium(II) phenathrane (phen) carbonyl complexes to various DNA, heparin and i-carrageenan polyanions were studied. The [Os(phen)<sub>2</sub>CO(L)]<sup>2+</sup> complexes with L either a 4-phenyl pyridine (4-phpy) or phenyl imidazole (phimd) group exhibit moderate luminescent intensity in the visible region, their intensities are highly altered by the addition of DNA and other polyanion samples. These luminescent responses to polyanions were also compared with the [Ru(phen)<sub>3</sub>]<sup>2+</sup> complex. In ethanol solution, the presence of polyanions significantly enhanced the luminescent emission intensity of [Os(phen)<sub>2</sub>CO(L)]<sup>2+</sup> complexes with a blue shift. While the polyanions all showed emission enhancement on the highly lumi-nescent [Ru(phen)<sub>3</sub>]<sup>2+</sup> complex in ethanol solution with a red spectra shift. The [Os(phen)<sub>2</sub>CO(L)] <sup>2+</sup> with (phimd) ligand has the lowest emission in ethanol solution, its intensity can be enhanced up to 11 times in the presence of DNA polyanions. This enhancement for all the complexes in ethanol is mainly due to their electrostatic interaction with the anion sites and with some degree of ligand intercalation into the polyanion hydrophobic structure which reduced the solvent quenching of the complexes. The blue shift of the (4-phpy) and particularly (phimd) Os(II)CO complexes indicate an insertion of the (4-phpy) or (phimd) group into the polymer chains. The two new Os(II)CO complexes has great potential to be used as luminescence sensors for DNA and polyanion detection in the low micro molar range with high sensitivity.展开更多
Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thou...Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency.The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system.Specifically,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general population.In this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses.Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection.With respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune environment.The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system.The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating.Finally,we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development.This review may provide valuable information for the development of new immunological treatments for mpox.展开更多
Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase （cGAS） and gamma-in...Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase （cGAS） and gamma-interferon- inducible protein （IFI16）, has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING （stimulator of interferon genes）, to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.展开更多
Nanopore has been developed to be a powerful,single-molecule analytical tool for sensing ions,small organic molecules and biomacromolecules such as proteins and DNAs.Generally,the identity of the analyte can be reveal...Nanopore has been developed to be a powerful,single-molecule analytical tool for sensing ions,small organic molecules and biomacromolecules such as proteins and DNAs.Generally,the identity of the analyte can be revealed by current amplitude changes and mean dwell time of the analyte binding events.In some cases,generation of highly characteristic current events affords an alternative way of analyte determination with high confidence level.However,we found that secondary structures in DNA/RNA hybrids might severely hinder the generation of signature events during their translocation through?-hemolysin nanopore.In this report,we propose a strategy to add a certain concentration of urea in the buffer solution for single channel recordings and validate that low concentration of urea can effectively denature the secondary structures in DNA hybrids and recover the generation of signature events.This finding might be useful in other secondary structure-related nanopore sensing activities.展开更多
The cGAS-MITA pathway of cytosolic DNA sensing plays essential roles in immune response against pathogens that contain DNA or with DNA production in their life cycles. The cGAS-MITA pathway also detects leaked or aber...The cGAS-MITA pathway of cytosolic DNA sensing plays essential roles in immune response against pathogens that contain DNA or with DNA production in their life cycles. The cGAS-MITA pathway also detects leaked or aberrant accumulated self DNA in the cytoplasm under certain pathological conditions, such as virus induced cell death, DNA damage, mitochondria damage, gene mutations, which results in autoimmune diseases. Therefore, the cGAS-MITA pathway must be tightly controlled to ensure proper immune response against pathogens and to avoid autoimmune diseases. The regulation of cGAS-MITA pathway at MITA-level have been extensively explored and reviewed elsewhere,here we provide a summary and perspective on recent advances in understanding of the cGAS regulation.展开更多
Cytosolic DNA is prevalent in cells constituting the tumor microenvironment(TME)and can activate the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)innate im...Cytosolic DNA is prevalent in cells constituting the tumor microenvironment(TME)and can activate the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)innate immune pathway.The initiation,transmission,and execution of the cGAS-STING pathway can take place among different cell types within the TME and thus cGAS-STING may play opposing roles in driving tumor progression in addition to its tumor cell-intrinsic role.Herein,we review recent advances in the cGAS-STING field with a focus on its crosstalk with other signaling pathways in the TME.Future efforts to depict a more detailed picture of the roles of cGAS-STING signaling in the TME wil help design a better cancer treatment regime by targeting the cGAS-STING pathway more precisely.展开更多
Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive immunity.The i...Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive immunity.The identification of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP)synthase(cGAS)as a major cytosolic DNA receptor is a milestone in the field of DNA sensing.The engagement of cGAS by double-stranded DNA from different origins,including invading pathogens,damaged mitochondria,ruptured micronuclei,and genomic DNA results in the generation of cGAMP and activation of stimulator of interferon genes,which thereby activates innate immunity mainly characterized by the activation of type I interferon response.In recent years,great progress has been made in understanding the subcellular localization and novel functions of cGAS.In this review,we particularlyfocus on summarizingthe multifaceted roles ofcGAS in regulating senescence,autophagy,cell stemness,apoptosis,angiogenesis,cell proliferation,antitumor effect,DNA replication,DNA damage repair,micronucleophagy,as well as cell metabolism.展开更多
文摘In this research, the absorbance and luminescence response of two osmium(II) phenathrane (phen) carbonyl complexes to various DNA, heparin and i-carrageenan polyanions were studied. The [Os(phen)<sub>2</sub>CO(L)]<sup>2+</sup> complexes with L either a 4-phenyl pyridine (4-phpy) or phenyl imidazole (phimd) group exhibit moderate luminescent intensity in the visible region, their intensities are highly altered by the addition of DNA and other polyanion samples. These luminescent responses to polyanions were also compared with the [Ru(phen)<sub>3</sub>]<sup>2+</sup> complex. In ethanol solution, the presence of polyanions significantly enhanced the luminescent emission intensity of [Os(phen)<sub>2</sub>CO(L)]<sup>2+</sup> complexes with a blue shift. While the polyanions all showed emission enhancement on the highly lumi-nescent [Ru(phen)<sub>3</sub>]<sup>2+</sup> complex in ethanol solution with a red spectra shift. The [Os(phen)<sub>2</sub>CO(L)] <sup>2+</sup> with (phimd) ligand has the lowest emission in ethanol solution, its intensity can be enhanced up to 11 times in the presence of DNA polyanions. This enhancement for all the complexes in ethanol is mainly due to their electrostatic interaction with the anion sites and with some degree of ligand intercalation into the polyanion hydrophobic structure which reduced the solvent quenching of the complexes. The blue shift of the (4-phpy) and particularly (phimd) Os(II)CO complexes indicate an insertion of the (4-phpy) or (phimd) group into the polymer chains. The two new Os(II)CO complexes has great potential to be used as luminescence sensors for DNA and polyanion detection in the low micro molar range with high sensitivity.
基金supported by the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018 to B.S.)Beijing Key Laboratory for HIV/AIDS Research(BZ0089).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus Orthopoxvirus.Since 2022,MPXV has posed a significant threat to global public health.The emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an emergency.The extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune system.Specifically,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general population.In this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune responses.Two caspase-1 inhibitory proteins and a PKR escape-related protein have been identified as phylogenomic hubs involved in modulating the immune environment during the MPXV infection.With respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune environment.The viral envelope also poses challenges for the neutralizing effects of antibodies and the complement system.The unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth investigating.Finally,we briefly discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine development.This review may provide valuable information for the development of new immunological treatments for mpox.
文摘Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase （cGAS） and gamma-interferon- inducible protein （IFI16）, has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING （stimulator of interferon genes）, to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.
基金the National Basic Research Program of China (2013CB932800)the National Natural Science Foundation of China (21175135, 21375130, 21205119, 21475132)the CAS Hundred Talents Program
文摘Nanopore has been developed to be a powerful,single-molecule analytical tool for sensing ions,small organic molecules and biomacromolecules such as proteins and DNAs.Generally,the identity of the analyte can be revealed by current amplitude changes and mean dwell time of the analyte binding events.In some cases,generation of highly characteristic current events affords an alternative way of analyte determination with high confidence level.However,we found that secondary structures in DNA/RNA hybrids might severely hinder the generation of signature events during their translocation through?-hemolysin nanopore.In this report,we propose a strategy to add a certain concentration of urea in the buffer solution for single channel recordings and validate that low concentration of urea can effectively denature the secondary structures in DNA hybrids and recover the generation of signature events.This finding might be useful in other secondary structure-related nanopore sensing activities.
基金supported by the National Natural Science Foundation of China (31400742)
文摘The cGAS-MITA pathway of cytosolic DNA sensing plays essential roles in immune response against pathogens that contain DNA or with DNA production in their life cycles. The cGAS-MITA pathway also detects leaked or aberrant accumulated self DNA in the cytoplasm under certain pathological conditions, such as virus induced cell death, DNA damage, mitochondria damage, gene mutations, which results in autoimmune diseases. Therefore, the cGAS-MITA pathway must be tightly controlled to ensure proper immune response against pathogens and to avoid autoimmune diseases. The regulation of cGAS-MITA pathway at MITA-level have been extensively explored and reviewed elsewhere,here we provide a summary and perspective on recent advances in understanding of the cGAS regulation.
基金supported by the High-Risk High-Reward Program from the Office of the Director,National Institutes of Health(DP50D026395)the National Cancer Institute(Breast Cancer SPOREP50CA247749 and R01CA256188-01)+4 种基金the Department of Defense Congressionally Directed Medical Research Program,the Burroughs Wellcome Fund Career Award for Medical Scientiststhe Parker Institute for Immunotherapy at MSKCC,the Josie Robertson Foundation,the STARR Cancer Consortium,the Cycle for Survival Fundthe MSKCC core grant(P30-CA008748)the National Institutes of Health/National Cancer Institute MSK Genomic Instability in Breast Cancer SPORE P50CA247749the Translational Research Oncology Training Program(T32 CA 160001).
文摘Cytosolic DNA is prevalent in cells constituting the tumor microenvironment(TME)and can activate the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)innate immune pathway.The initiation,transmission,and execution of the cGAS-STING pathway can take place among different cell types within the TME and thus cGAS-STING may play opposing roles in driving tumor progression in addition to its tumor cell-intrinsic role.Herein,we review recent advances in the cGAS-STING field with a focus on its crosstalk with other signaling pathways in the TME.Future efforts to depict a more detailed picture of the roles of cGAS-STING signaling in the TME wil help design a better cancer treatment regime by targeting the cGAS-STING pathway more precisely.
基金This work was supported by the National Natural Science Foundation of China(81922030 and 81770006 to H.L,32188101,32030038,91842303,and 31730025 to B.G.)the Major Research Plan of National Natural Science Foundation of China(2017YFA0505900 to B.G.),Shanghai Shu Guang Program(205G19)Shanghai Science and Technology Fund(19140900600 and 22S11900700 to H.L.).
文摘Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive immunity.The identification of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP)synthase(cGAS)as a major cytosolic DNA receptor is a milestone in the field of DNA sensing.The engagement of cGAS by double-stranded DNA from different origins,including invading pathogens,damaged mitochondria,ruptured micronuclei,and genomic DNA results in the generation of cGAMP and activation of stimulator of interferon genes,which thereby activates innate immunity mainly characterized by the activation of type I interferon response.In recent years,great progress has been made in understanding the subcellular localization and novel functions of cGAS.In this review,we particularlyfocus on summarizingthe multifaceted roles ofcGAS in regulating senescence,autophagy,cell stemness,apoptosis,angiogenesis,cell proliferation,antitumor effect,DNA replication,DNA damage repair,micronucleophagy,as well as cell metabolism.
