Strong near-field scattering enhancement (NFSE) of polyhedral oligomeric silsesquioxanes(POSS) nanoparticles (NPs) aggregates is found through physical simulation. An aggregation of N,N′-di-[3-(isobutyl polyhedral ol...Strong near-field scattering enhancement (NFSE) of polyhedral oligomeric silsesquioxanes(POSS) nanoparticles (NPs) aggregates is found through physical simulation. An aggregation of N,N′-di-[3-(isobutyl polyhedral oligomeric silsesquioxanes) propyl] perylene diimide(DPP) which possesses POSS as scatteres experimentally performs strong NFSE, which confirms the physical simulation results. Moreover, coherent random laser is triggered from the DPP aggregates in carbon disulfide. It is the NFSE of POSS NPs connected to both ends of DPP through covalent bonds and the NFSE of their aggregation thanks to DPP’s aggregation that is responsible for the coherent random laser. So, this work develops a method to improve weak scattering of system through construction of molecules, and opens a road to a variety of novel interdisciplinary investigations, involving molecular designing for disordered photonics.展开更多
When the bridge components needing maintenance are the world problem at present,and the health monitoring system is considered to be a very helpful tool for solving this problem.In this paper,a large number of s...When the bridge components needing maintenance are the world problem at present,and the health monitoring system is considered to be a very helpful tool for solving this problem.In this paper,a large number of strain data acquired from the structural health monitoring system(SHMS)installed on a continuous rigid frame bridge are adopted to do reliability assessment.Firstly,a calculation method of punctiform time-dependent reliability is proposed based on the basic reliability theory,and introduced how to calculate reliability of the bridge by using the stress data transformed from the strain data.Secondly,combined with“Three Sigma”principle and the basic pressure safety reserve requirement,the critical load effects distribution function of the bridge is defined,and then the maintenance reliability threshold for controlling the unfavorable load state which appears in the early operation stage of this type bridge is suggested,and then the combination of bridge maintenance management and health monitoring system is realized.Finally,the transformed stress distribution certifies that the load effects of concrete bridges practically have a normal distribution;as for the concrete continuous rigid frame bridge with C50 strength grade concrete,the retrofit reliability threshold should be valued at 6.13.The methodology suggested in this article can help bridge engineers do effective maintenance of bridges,which can effectively extend the service life of the bridge and bring better economic and social benefits.展开更多
AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was i...AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.展开更多
A novel water-soluble luminescent complex consisting of Eu(ally-dbm)3-2Tppo and poly(N-isopropyl acrylamide)(PNIPAM)is synthesized through a series of chemical reactions.The structure of the complex is characterized b...A novel water-soluble luminescent complex consisting of Eu(ally-dbm)3-2Tppo and poly(N-isopropyl acrylamide)(PNIPAM)is synthesized through a series of chemical reactions.The structure of the complex is characterized by TGA,GPC,HNMR,and the thermal-responsive uorescence of the complex in aqueous solution is investigated.It is found that PNIPAM collapse above the lower critical solution temperature causes the coordination bond breaking,leading to weakening of the uorescence from Eu3+and enhancing of the uorescence from the ligands.When temperature decreases,the uorescence from Eu3+is found to boost up and the uorescence from ligands weakens accordingly.It is deduced from this phenomenon that the ligands recoordinate with europium ions again along with the temperature decreasing,which is further confirmed by IR measurements.This thermal-responsive uorescence is of reversibility,which can be used as molecular probes for biological imaging and collapse studying of PNIPAM.展开更多
Monitoring of sweat pH plays important roles in physiological health,nutritional balance,psychological stress,and sports performance.However,the combination of functional MOFs with phosphorescent material to acquire t...Monitoring of sweat pH plays important roles in physiological health,nutritional balance,psychological stress,and sports performance.However,the combination of functional MOFs with phosphorescent material to acquire the real-time physiological information,as well as the application of dual mode anti-counterfeiting,has seldom been reported.Herein,we developed multifunctional gel films based on MOFs and phosphorescent dyes which responded to H+ions and the related mechanism was studied in detail.Upon exposure to H+,the composite gel film exhibited decreased fluorescent signal but enhanced room temperature phosphorescence(RTP),which could be utilized for sweat pH sensing through a dual-mode.Moreover,multifunctional gel films exhibited a potential application in information encryption and anti-counterfeiting by designing of stimulus responsive multiple patterns.This research provided a new avenue for portable and non-invasive sweat pH monitoring methods while also offering insights into stimulus-responsive multifunctional materials.展开更多
Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can...Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.展开更多
Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S31...Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against SARS-CoV-2.Notably,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted cells.Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells.This work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not.展开更多
A range-extended acidity detector based on Nile red was designed and analyzed in this work. In light of the good lasing property and solvatochromism characteristic of Nile red/ethanol solution, we have obtained laser ...A range-extended acidity detector based on Nile red was designed and analyzed in this work. In light of the good lasing property and solvatochromism characteristic of Nile red/ethanol solution, we have obtained laser spectra of sulfuric acid in different concentrations doped in this substrate. Moreover, to expand the acidity detection range, we proposed a tandem cuvette system containing rhodamine 6G/ethanol and Nile red/ethanol. Consequently, the detection range could be enlarged from 26 nm to 40 nm, by changing not only the wavelength peak but also by the intensity ratio of dual-wavelength laser output. In addition, by changing the detection and substrate materials, the whole detection range could be expanded, and therefore a wide range of applications in polarity and acidity detection could be implemented via this method.展开更多
CORRECTION TO:PROTEIN CELL 2020,11(10):723–739 HTTPS://DOI.ORG/10.1007/S13238-020-00768-W In the original publication the author’s name‘Dimitri Lavillete’is published incorrectly.The correct author name should be ...CORRECTION TO:PROTEIN CELL 2020,11(10):723–739 HTTPS://DOI.ORG/10.1007/S13238-020-00768-W In the original publication the author’s name‘Dimitri Lavillete’is published incorrectly.The correct author name should be spelt as‘Dimitri Lavillette’is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit http://creativecommons.org/licenses/by/4.0/.展开更多
The recent outbreak of novel coronavirus pneumonia(COVID-19)caused by a new coronavirus has posed a great threat to public health.Identifying safe and effective antivirals is of urgent demand to cure the huge number o...The recent outbreak of novel coronavirus pneumonia(COVID-19)caused by a new coronavirus has posed a great threat to public health.Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients.Virusencoded proteases are considered potential drug targets.The human immunodeficiency virus protease inhibitors(lopinavir/ritonavir)has been recommended in the global Solidarity Trial in March launched by World Health Organization.However,there is currently no experimental evidence to support or against its clinical use.We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro,and discussed the possible inhibitory mechanism in silico.The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical.Among the four tested compounds,lopinavir showed the best inhibitory effect against the novel coronavirus infection.However,further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen[marketed as Kaletraò,contained lopinavir/ritonavir(200 mg/50 mg)tablets,recommended dosage is 400 mg/10 mg(2 tablets)twice daily].This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma concentration.Nevertheless,the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.展开更多
Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis...Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 instrument.Kinetic analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument.展开更多
Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prev...Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.展开更多
基金supported by the National Natural Science Foundation of China(No.51673178,No.51273186,No.21574120,No.11874012,No.11404087,and No.11574070)Basic Research Fund for the Central Universities(No.WK2060200012)+3 种基金Science and Technological Fund of Anhui Province for Outstanding Youth(No.1608085J01)Fundamental Research Funds for the Central Universities of China,Postdoctoral Science Foundation(No.2015M571918 and No.2017T100442)the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sk lodowska-Curie Grant Agreement(No.744817)the Project of State Key Laboratory of Environment-friendly Energy Materials,Southwest University of Science and Technology(No.18zxhk10)
文摘Strong near-field scattering enhancement (NFSE) of polyhedral oligomeric silsesquioxanes(POSS) nanoparticles (NPs) aggregates is found through physical simulation. An aggregation of N,N′-di-[3-(isobutyl polyhedral oligomeric silsesquioxanes) propyl] perylene diimide(DPP) which possesses POSS as scatteres experimentally performs strong NFSE, which confirms the physical simulation results. Moreover, coherent random laser is triggered from the DPP aggregates in carbon disulfide. It is the NFSE of POSS NPs connected to both ends of DPP through covalent bonds and the NFSE of their aggregation thanks to DPP’s aggregation that is responsible for the coherent random laser. So, this work develops a method to improve weak scattering of system through construction of molecules, and opens a road to a variety of novel interdisciplinary investigations, involving molecular designing for disordered photonics.
文摘When the bridge components needing maintenance are the world problem at present,and the health monitoring system is considered to be a very helpful tool for solving this problem.In this paper,a large number of strain data acquired from the structural health monitoring system(SHMS)installed on a continuous rigid frame bridge are adopted to do reliability assessment.Firstly,a calculation method of punctiform time-dependent reliability is proposed based on the basic reliability theory,and introduced how to calculate reliability of the bridge by using the stress data transformed from the strain data.Secondly,combined with“Three Sigma”principle and the basic pressure safety reserve requirement,the critical load effects distribution function of the bridge is defined,and then the maintenance reliability threshold for controlling the unfavorable load state which appears in the early operation stage of this type bridge is suggested,and then the combination of bridge maintenance management and health monitoring system is realized.Finally,the transformed stress distribution certifies that the load effects of concrete bridges practically have a normal distribution;as for the concrete continuous rigid frame bridge with C50 strength grade concrete,the retrofit reliability threshold should be valued at 6.13.The methodology suggested in this article can help bridge engineers do effective maintenance of bridges,which can effectively extend the service life of the bridge and bring better economic and social benefits.
基金Supported by the National Natural Science Foundation of China(No.82060183)Ningxia Natural Science Foundation(No.2022AAC03388)the Key Research and Development Project of Ningxia Hui Autonomous Region(No.2021BEG02045,No.2020BEG03044).
文摘AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
基金supported by the National Natural Science Foundation of China (No.51673178,No.51273186, No.21574120,and No.11404087)the Basic Research Fund for the Central Universities (WK2060200012)+1 种基金the Science and Technological Fund of Anhui Province for Outstanding Youth (No.1608085J01)the Fundamental Research Funds for the Central Universities, China Postdoctoral Science Foundation (No.2015M571918 and No.2017T100442)
文摘A novel water-soluble luminescent complex consisting of Eu(ally-dbm)3-2Tppo and poly(N-isopropyl acrylamide)(PNIPAM)is synthesized through a series of chemical reactions.The structure of the complex is characterized by TGA,GPC,HNMR,and the thermal-responsive uorescence of the complex in aqueous solution is investigated.It is found that PNIPAM collapse above the lower critical solution temperature causes the coordination bond breaking,leading to weakening of the uorescence from Eu3+and enhancing of the uorescence from the ligands.When temperature decreases,the uorescence from Eu3+is found to boost up and the uorescence from ligands weakens accordingly.It is deduced from this phenomenon that the ligands recoordinate with europium ions again along with the temperature decreasing,which is further confirmed by IR measurements.This thermal-responsive uorescence is of reversibility,which can be used as molecular probes for biological imaging and collapse studying of PNIPAM.
基金supported by the Basic Research Fund for the Central Universities(WK3450000006)the National Natural Science Foundation of China(52373122).
文摘Monitoring of sweat pH plays important roles in physiological health,nutritional balance,psychological stress,and sports performance.However,the combination of functional MOFs with phosphorescent material to acquire the real-time physiological information,as well as the application of dual mode anti-counterfeiting,has seldom been reported.Herein,we developed multifunctional gel films based on MOFs and phosphorescent dyes which responded to H+ions and the related mechanism was studied in detail.Upon exposure to H+,the composite gel film exhibited decreased fluorescent signal but enhanced room temperature phosphorescence(RTP),which could be utilized for sweat pH sensing through a dual-mode.Moreover,multifunctional gel films exhibited a potential application in information encryption and anti-counterfeiting by designing of stimulus responsive multiple patterns.This research provided a new avenue for portable and non-invasive sweat pH monitoring methods while also offering insights into stimulus-responsive multifunctional materials.
基金supported by the National Science and Technology Major Project of China(No.2018ZX10201001-010,No.2017ZX10103009-005,No.2018ZX10713001-007)the National Natural Science Fund for Distinguished Young Scholars of China(No.81525023)+4 种基金the National Natural Science Foundation of China(No.81473031)the Program of Shanghai Academic/Technology Research Leader(No.18XD1400300)the Li Ka Shing Oxford Global Health Programme(No.B9RST00-B900.57)the Chinese Preventive Medicine Association(No:20101801)supported by CAS Pioneer Hundred Talents Program
文摘Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.
基金This work was supported in part by the National Key Research and Development Program Grants(2018FYA0900801 and 2018ZX10101004003001 to K.X.2016YFA0502304 to H.L.)the National Natural Science Foundation of China(Grants 31922004 and 81772202 to K.X.,81825020 to H.L.)+2 种基金the National Science&Technology Major Project"Key New Drug Creation and Manufac-turing Program"of China(Grant 2018ZX09711002 to H.L.)Appli-cation&Frontier Research Program of Wuhan Govemment(2019020701011463 to K.X.).Honglin Li is also sponsored by the National Program for Special Supports of Eminent Professionals and National Program for Support of Top-Notch Young ProfessionalsWe are grateful to Taikang Insurance Group Co,Ltd,Beiing Taikang Yicai Foundation,and Special Fund for COVID-19 Research of Wuhan University for their great supports to this work.
文摘Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against SARS-CoV-2.Notably,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted cells.Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells.This work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not.
基金supported by the National Key Research and Development Program of China(No. 2016YFB0401901)Major Science and Technology Special Project in Anhui (No. 17030901001)+2 种基金National Natural Science Foundation of China (Nos. 21574120and 21774115)Fundamental Research Funds for the Central Universities (No. WK2060200025)Science and Technological Fund of Anhui Province for Outstanding Youth (No. 1608085J01)。
文摘A range-extended acidity detector based on Nile red was designed and analyzed in this work. In light of the good lasing property and solvatochromism characteristic of Nile red/ethanol solution, we have obtained laser spectra of sulfuric acid in different concentrations doped in this substrate. Moreover, to expand the acidity detection range, we proposed a tandem cuvette system containing rhodamine 6G/ethanol and Nile red/ethanol. Consequently, the detection range could be enlarged from 26 nm to 40 nm, by changing not only the wavelength peak but also by the intensity ratio of dual-wavelength laser output. In addition, by changing the detection and substrate materials, the whole detection range could be expanded, and therefore a wide range of applications in polarity and acidity detection could be implemented via this method.
文摘CORRECTION TO:PROTEIN CELL 2020,11(10):723–739 HTTPS://DOI.ORG/10.1007/S13238-020-00768-W In the original publication the author’s name‘Dimitri Lavillete’is published incorrectly.The correct author name should be spelt as‘Dimitri Lavillette’is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit http://creativecommons.org/licenses/by/4.0/.
基金supported in part by grants from the National Science and Technology Major Projects(Grant Number 2018ZX09711003)National Key Research and Development Project(2020YFC0841700)+1 种基金the National Natural Science Foundation of China(Grant Number 31621061)the Hubei Science and Technology Project(Grant Number 2020FCA003)。
文摘The recent outbreak of novel coronavirus pneumonia(COVID-19)caused by a new coronavirus has posed a great threat to public health.Identifying safe and effective antivirals is of urgent demand to cure the huge number of patients.Virusencoded proteases are considered potential drug targets.The human immunodeficiency virus protease inhibitors(lopinavir/ritonavir)has been recommended in the global Solidarity Trial in March launched by World Health Organization.However,there is currently no experimental evidence to support or against its clinical use.We evaluated the antiviral efficacy of lopinavir/ritonavir along with other two viral protease inhibitors in vitro,and discussed the possible inhibitory mechanism in silico.The in vitro to in vivo extrapolation was carried out to assess whether lopinavir/ritonavir could be effective in clinical.Among the four tested compounds,lopinavir showed the best inhibitory effect against the novel coronavirus infection.However,further in vitro to in vivo extrapolation of pharmacokinetics suggested that lopinavir/ritonavir could not reach effective concentration under standard dosing regimen[marketed as Kaletraò,contained lopinavir/ritonavir(200 mg/50 mg)tablets,recommended dosage is 400 mg/10 mg(2 tablets)twice daily].This research concluded that lopinavir/ritonavir should be stopped for clinical use due to the huge gap between in vitro IC50 and free plasma concentration.Nevertheless,the structure–activity relationship analysis of the four inhibitors provided further information for de novel design of future viral protease inhibitors of SARS-CoV-2.
文摘Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 instrument.Kinetic analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument.
基金supported by the National Natural Science Foundation of China(NSFC)(81991494 and 82122031)the National Key R&D Program of China(2020YFA0907100)+3 种基金the Chinese Academy of Sciences(YSBR-010)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-026)Beijing Natural Science Foundation(L222076)L.D.is supported by the Youth Innovation Promotion Association CAS,China(2018113).
文摘Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.
