Monopulse slot antenna arrays based on substrate integrated waveguide (SIW) are proposed for the application of 60 GHz mono- pulse tracking systems in this paper. The sum-difference monopulse comparator can provide ...Monopulse slot antenna arrays based on substrate integrated waveguide (SIW) are proposed for the application of 60 GHz mono- pulse tracking systems in this paper. The sum-difference monopulse comparator can provide a high amplitude and phase balance over wide frequency band and no phase delay technique is required for the difference channel. Resonant slot antennas are adopted as the radiating elements since they can be integrated with the sum-difference monopulse comparator in a single layer with a compact size. Two monopulse arrays with 2× 4 and 4×4 slot elements are designed, fabricated, and measured. Measured results show that the proposed antenna arrays have wide bandwidth covering the unlicensed 60-GHz band. The peak sum beam gain is 13.85 dBi for the 2 ×4 element array and 16.24 dBi for the 4×4 element array. The peak difference beam gain is 11.20 dBi for the 2×4 element array and 12.11 dBi for the 4×4 element array and the maximum null depth can reach -40 dB.展开更多
variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades.However,the way by viruses target IFN-signaling extracellularly has not been discovered.Infection by both corona...variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades.However,the way by viruses target IFN-signaling extracellularly has not been discovered.Infection by both coronavirus SARS-CoV-2 and enterovirus 71(EV71 or EV-A71)can cause severe diseases such as neurological disorders and even death in children.展开更多
The latent infection by herpes virus type 1(HSV-1)may be lifelong in trigeminal ganglia and a suspected cause of Alzheimer's Disease(AD)and Amyotrophic lateral sclerosis(ALS).Whether and how N6-methyladenosine(m6A...The latent infection by herpes virus type 1(HSV-1)may be lifelong in trigeminal ganglia and a suspected cause of Alzheimer's Disease(AD)and Amyotrophic lateral sclerosis(ALS).Whether and how N6-methyladenosine(m6A)modification of viral RNAs affects virus infection are poorly understood.Here,we report that HSV-1 infection enhanced the expression of m6A writers(METTL3,METTL14)and readers(YTHDF1/2/3)at the early infection stage and decreased their expression later on,while suppressed the erasers'(FTO,ALBKH5)expression immediately upon infection to facilitate viral replication.Inhibiting m6A modification by 3-deazaadenosine(DAA)significantly decreased viral replication and reduced viral reproduction over 1000 folds.More interestingly,depleting the writers and readers by siRNAs inhibited virus replication and reproduction;whereas depleting the erasers promoted viral replication and reproduction.Silencing YTHDF3 strikingly decreased viral replication by up to 90%,leading to reduction of up to 10-fold viral replication and over 100-fold virus reproduction,respectively.Depletion of m6A initiator METTL3(by 60%–70%)by siRNA correlatedly decreased viral replication 60%–70%,and reduced virus yield over 30-fold.Consistently,ectopic expression of METTL3 largely increased virus yield.METTL3 knockdown suppressed the HSV-1 intermediate early and early genes(ICP0,ICP8 and UL23)and late genes(VP16,UL44,UL49 and ICP47);while ectopic expression of METTL3 upregulated these gene expression.Results from our study shed the lights on the importance for m6A modification to initiate HSV-1 early replication.The components of m6A modification machinery,particularly m6A initiator METTL3 and reader YTHDF3,would be potential important targets for combating HSV-1 infections.展开更多
Tbx3,a transcriptional repressor,is essential in the organogenesis of vertebrates,stem cell self-renewal and differentiation,and the carcinogenesis of multiple tumor types.However,the mechanism by which Tbx3 participa...Tbx3,a transcriptional repressor,is essential in the organogenesis of vertebrates,stem cell self-renewal and differentiation,and the carcinogenesis of multiple tumor types.However,the mechanism by which Tbx3 participates in the metastasis of hepatocellular carcinoma(HCC)remains largely unknown.In this study,we show that Tbx3 was dramatically upregulated in clinical HCC samples and that elevated expression of Tbx3 promoted cancer progression.To determine the underlying mechanism,systematic glycine scan mutagenesis and deletion assays were performed.We identified two critical motifs,^(585)LFSYPYT^(591)and^(604)HRH^(606),that contribute to the repression of transcriptional activity.These motifs are also essential for Tbx3 to promote cell migration and metastasis both in vitro and in vivo via the suppression of E-cadherin expression.More importantly,Tbx3 directly interacts with HDAC5 via these motifs,and an HDAC inhibitor blocks Tbx3-mediated cell migration and the downregulation of E-cadherin in HCC.As Tbx3 is involved in the carcinogenesis of multiple types of human cancers,our findings suggest an important target for anticancer drug development.展开更多
The pandemic COVID-19,caused by a new coronavirus SARS-CoV-2 infection,has infected over 12 million individuals and caused more than 55,200 death worldwide.Currently,there is no specific drug to treating this disease....The pandemic COVID-19,caused by a new coronavirus SARS-CoV-2 infection,has infected over 12 million individuals and caused more than 55,200 death worldwide.Currently,there is no specific drug to treating this disease.Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries.Antiviral chemotherapies have been conducted by in multiple cohorts in different counties.Although FDA has fast approved remdesivir for treating COVID-19,it only speeds up recovery from COVID-19 with mildly reduced mortality.The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects,it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy.In terms of hydroxychloroquine(HCQ)therapy,although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients,large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus.Convalescent plasma(CP)therapy suggested its safety use in SARS-CoV-2 infection;but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin.Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis,suitable animal models or ex vivo human lung tissues aid in studying replication,transmission and spread of the novel viruses,thereby facilitating highly effective therapies.展开更多
Dear Editor,Evidence shows the NSP1’s crucial roles of theβ-coronavirus SARS-CoV-2 in promoting cellular mRNA degradation,inhibiting host cell translation,innate immunity,and inducing inflammatory cytokine storm in ...Dear Editor,Evidence shows the NSP1’s crucial roles of theβ-coronavirus SARS-CoV-2 in promoting cellular mRNA degradation,inhibiting host cell translation,innate immunity,and inducing inflammatory cytokine storm in the pathogenesis of COVID-19.1,2 More interestingly,NSP1 deletion in infectious clones prevents virus infection.3 However,little is known how NSP1 interacts with host factors to disrupt the host’s innate immunity for facilitating virus infection and reproduction.As a(+)ssRNA virus,SARS-CoV-2 completes its life cycle in the cytosol;viral RNA processing is the key for controlling and regulating the virus reproduction and pathogenesis.The ribonucleoproteins hnRNPs are the main factors responsible for RNA processing,including RNA splicing,maturation,decay,and translation,and even innate immunity in some cases.展开更多
Stress proteins(SPs)including heat-shock proteins(HSPs),RNA chaperones,and ER associated stress proteins are molecular chaperones essential for cellular homeostasis.The major functions of HSPs include chaperoning misf...Stress proteins(SPs)including heat-shock proteins(HSPs),RNA chaperones,and ER associated stress proteins are molecular chaperones essential for cellular homeostasis.The major functions of HSPs include chaperoning misfolded or unfolded polypeptides,protecting cells from toxic stress,and presenting immune and inflammatory cytokines.Regarded as a double-edged sword,HSPs also cooperate with numerous viruses and cancer cells to promote their survival.RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins(hnRNPs),which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II.hnRNPs involve in a large number of cellular processes,including chromatin remodelling,transcription regulation,RNP assembly and stabilization,RNA export,virus replication,histonelike nucleoid structuring,and even intracellular immunity.Dysregulation of stress proteins is associated with many human diseases including human cancer,cardiovascular diseases,neurodegenerative diseases(e.g.,Parkinson’s diseases,Alzheimer disease),stroke and infectious diseases.In this review,we summarized the biologic function of stress proteins,and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections.As SPs also attract a great interest as potential antiviral targets(e.g.,COVID-19),we also discuss the present progress and challenges in this area of HSP-based drug development,as well as with compounds already under clinical evaluation.展开更多
Dear Editors,Oncoprotein PIM1 kinase participates in many important biological processes,such as cell proliferation,apoptosis,carcinogenesis and tumorigenesis,by phosphorylating cellular substrates.More recently,sever...Dear Editors,Oncoprotein PIM1 kinase participates in many important biological processes,such as cell proliferation,apoptosis,carcinogenesis and tumorigenesis,by phosphorylating cellular substrates.More recently,several groups discovered that PIM1 affects(+)ssRNA virus transcription and modulates virus infection,such as human rhinovirus(HRV)-16 and hepatitis C virus(HCV).2 We recently reported that PIM1 enhances EV-A71 IRES activity by regulating AUF1 translocation.展开更多
基金supported in part by the Innovation and Technology Support Programme(ITSP)of the Innovation and Technology Commission(ITS/210/19)in part by the Young Scientists Fund of the National Natural Science Foundation of China(62001409)+1 种基金in part by Shenzhen-Hong Kong-Macao Science and Technology Project(Category C)(SGDX20210823104002018)in part by 2022 Guangdong-Hong Kong-Macao Joint Innovation Funding Scheme(2022A0505030021).
基金This project is supported by the National Basic Research Program of China ("973" Program) under Grant No. 2014CB339900 and the National Natural Science Foundation of China under Grant No. 61372056.
文摘Monopulse slot antenna arrays based on substrate integrated waveguide (SIW) are proposed for the application of 60 GHz mono- pulse tracking systems in this paper. The sum-difference monopulse comparator can provide a high amplitude and phase balance over wide frequency band and no phase delay technique is required for the difference channel. Resonant slot antennas are adopted as the radiating elements since they can be integrated with the sum-difference monopulse comparator in a single layer with a compact size. Two monopulse arrays with 2× 4 and 4×4 slot elements are designed, fabricated, and measured. Measured results show that the proposed antenna arrays have wide bandwidth covering the unlicensed 60-GHz band. The peak sum beam gain is 13.85 dBi for the 2 ×4 element array and 16.24 dBi for the 4×4 element array. The peak difference beam gain is 11.20 dBi for the 2×4 element array and 12.11 dBi for the 4×4 element array and the maximum null depth can reach -40 dB.
基金The work was partially supported by grants from The Science Technology and Innovation Committee of Shenzhen Municipality[JCYJ20180507181627057]RGC General Research Fund of Hong Kong Special Administrative Region[11104020]Strategic funds from The City University of Hong Kong to M.He.
文摘variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades.However,the way by viruses target IFN-signaling extracellularly has not been discovered.Infection by both coronavirus SARS-CoV-2 and enterovirus 71(EV71 or EV-A71)can cause severe diseases such as neurological disorders and even death in children.
基金This work was supported by grants from National Science Foundation of China(No.81671995)The Science Technology and Innovation Committee of Shenzhen Municipality(No.JCYJ20180507181627057)and Strategic funds from City University of Hong Kong.
文摘The latent infection by herpes virus type 1(HSV-1)may be lifelong in trigeminal ganglia and a suspected cause of Alzheimer's Disease(AD)and Amyotrophic lateral sclerosis(ALS).Whether and how N6-methyladenosine(m6A)modification of viral RNAs affects virus infection are poorly understood.Here,we report that HSV-1 infection enhanced the expression of m6A writers(METTL3,METTL14)and readers(YTHDF1/2/3)at the early infection stage and decreased their expression later on,while suppressed the erasers'(FTO,ALBKH5)expression immediately upon infection to facilitate viral replication.Inhibiting m6A modification by 3-deazaadenosine(DAA)significantly decreased viral replication and reduced viral reproduction over 1000 folds.More interestingly,depleting the writers and readers by siRNAs inhibited virus replication and reproduction;whereas depleting the erasers promoted viral replication and reproduction.Silencing YTHDF3 strikingly decreased viral replication by up to 90%,leading to reduction of up to 10-fold viral replication and over 100-fold virus reproduction,respectively.Depletion of m6A initiator METTL3(by 60%–70%)by siRNA correlatedly decreased viral replication 60%–70%,and reduced virus yield over 30-fold.Consistently,ectopic expression of METTL3 largely increased virus yield.METTL3 knockdown suppressed the HSV-1 intermediate early and early genes(ICP0,ICP8 and UL23)and late genes(VP16,UL44,UL49 and ICP47);while ectopic expression of METTL3 upregulated these gene expression.Results from our study shed the lights on the importance for m6A modification to initiate HSV-1 early replication.The components of m6A modification machinery,particularly m6A initiator METTL3 and reader YTHDF3,would be potential important targets for combating HSV-1 infections.
基金This study was supported by grants from The Science Technology and Innovation Committee of Shenzhen Municipality(JSGG20151030110921727,JCYJ20170818100531426,JCYJ20170306091121656)the Planned Science and Technology Project of Guangdong Province(2017A020215004)+1 种基金NSFC(No.81471964,81671995,81702510)The Start-up Fund and Match Fund from The City University of Hong Kong(9680149,9610330).
文摘Tbx3,a transcriptional repressor,is essential in the organogenesis of vertebrates,stem cell self-renewal and differentiation,and the carcinogenesis of multiple tumor types.However,the mechanism by which Tbx3 participates in the metastasis of hepatocellular carcinoma(HCC)remains largely unknown.In this study,we show that Tbx3 was dramatically upregulated in clinical HCC samples and that elevated expression of Tbx3 promoted cancer progression.To determine the underlying mechanism,systematic glycine scan mutagenesis and deletion assays were performed.We identified two critical motifs,^(585)LFSYPYT^(591)and^(604)HRH^(606),that contribute to the repression of transcriptional activity.These motifs are also essential for Tbx3 to promote cell migration and metastasis both in vitro and in vivo via the suppression of E-cadherin expression.More importantly,Tbx3 directly interacts with HDAC5 via these motifs,and an HDAC inhibitor blocks Tbx3-mediated cell migration and the downregulation of E-cadherin in HCC.As Tbx3 is involved in the carcinogenesis of multiple types of human cancers,our findings suggest an important target for anticancer drug development.
基金The work was partially supported by grants from The Science Technology and Innovation Committee of Shenzhen Municipality[JCYJ20170818100531426,JCYJ20180507181627057]grants from National Science Foundation of China[81671995]Strategic funds from City University of Hong Kong.
文摘The pandemic COVID-19,caused by a new coronavirus SARS-CoV-2 infection,has infected over 12 million individuals and caused more than 55,200 death worldwide.Currently,there is no specific drug to treating this disease.Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries.Antiviral chemotherapies have been conducted by in multiple cohorts in different counties.Although FDA has fast approved remdesivir for treating COVID-19,it only speeds up recovery from COVID-19 with mildly reduced mortality.The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects,it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy.In terms of hydroxychloroquine(HCQ)therapy,although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients,large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus.Convalescent plasma(CP)therapy suggested its safety use in SARS-CoV-2 infection;but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin.Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis,suitable animal models or ex vivo human lung tissues aid in studying replication,transmission and spread of the novel viruses,thereby facilitating highly effective therapies.
基金The work was partially supported by grants from The Science Technology and Innovation Committee of Shenzhen Municipality[JCYJ20180507181627057]RGC General Research Fund of Hong Kong Special Administrative Region[11104020]Strategic funds from City University of Hong Kong to M.L.H.
文摘Dear Editor,Evidence shows the NSP1’s crucial roles of theβ-coronavirus SARS-CoV-2 in promoting cellular mRNA degradation,inhibiting host cell translation,innate immunity,and inducing inflammatory cytokine storm in the pathogenesis of COVID-19.1,2 More interestingly,NSP1 deletion in infectious clones prevents virus infection.3 However,little is known how NSP1 interacts with host factors to disrupt the host’s innate immunity for facilitating virus infection and reproduction.As a(+)ssRNA virus,SARS-CoV-2 completes its life cycle in the cytosol;viral RNA processing is the key for controlling and regulating the virus reproduction and pathogenesis.The ribonucleoproteins hnRNPs are the main factors responsible for RNA processing,including RNA splicing,maturation,decay,and translation,and even innate immunity in some cases.
基金supported by grants from The Science Technology and Innovation Committee of Shenzhen Municipality[JCYJ20170818100531426,JCYJ20180507181627057]grants from National Science Foundation of China[81671995]+1 种基金the general research grant of Hong Kong[11100215]Strategic funds from City University of Hong Kong.
文摘Stress proteins(SPs)including heat-shock proteins(HSPs),RNA chaperones,and ER associated stress proteins are molecular chaperones essential for cellular homeostasis.The major functions of HSPs include chaperoning misfolded or unfolded polypeptides,protecting cells from toxic stress,and presenting immune and inflammatory cytokines.Regarded as a double-edged sword,HSPs also cooperate with numerous viruses and cancer cells to promote their survival.RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins(hnRNPs),which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II.hnRNPs involve in a large number of cellular processes,including chromatin remodelling,transcription regulation,RNP assembly and stabilization,RNA export,virus replication,histonelike nucleoid structuring,and even intracellular immunity.Dysregulation of stress proteins is associated with many human diseases including human cancer,cardiovascular diseases,neurodegenerative diseases(e.g.,Parkinson’s diseases,Alzheimer disease),stroke and infectious diseases.In this review,we summarized the biologic function of stress proteins,and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections.As SPs also attract a great interest as potential antiviral targets(e.g.,COVID-19),we also discuss the present progress and challenges in this area of HSP-based drug development,as well as with compounds already under clinical evaluation.
基金The work was partially supported by grants from The Science Technology and Innovation Committee of Shenzhen Municipality[JCYJ20180507181627057]grants from National Science Foundation of China[81671995]+1 种基金the general research grant of Hong Kong[11100215]and Strategic funds from City University of Hong Kong.
文摘Dear Editors,Oncoprotein PIM1 kinase participates in many important biological processes,such as cell proliferation,apoptosis,carcinogenesis and tumorigenesis,by phosphorylating cellular substrates.More recently,several groups discovered that PIM1 affects(+)ssRNA virus transcription and modulates virus infection,such as human rhinovirus(HRV)-16 and hepatitis C virus(HCV).2 We recently reported that PIM1 enhances EV-A71 IRES activity by regulating AUF1 translocation.