PON 1 (Paraoxonase 1) has been proposed as an efficient catalytic bioscavenger to combat against OP (organophosphate) and CWNA (chemical warfare nerve agent) toxicity. Unlike stoichiometric bioscavengers such as...PON 1 (Paraoxonase 1) has been proposed as an efficient catalytic bioscavenger to combat against OP (organophosphate) and CWNA (chemical warfare nerve agent) toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.展开更多
Glaucoma is the second leading cause of irreversible vision impairment affecting more than 70 million people worldwide with approximately 10%suffering from glaucoma-related bilateral blind(Quigley and Broman,2006).I...Glaucoma is the second leading cause of irreversible vision impairment affecting more than 70 million people worldwide with approximately 10%suffering from glaucoma-related bilateral blind(Quigley and Broman,2006).It is a multi-factorial disease that is characterized by optic nerve damage and visual field loss.Progressive loss of retinal ganglion cells(RGCs)resulting in visual field deficits is the hallmark of glaucoma.展开更多
Analysis of nerve agents and their degradation products constitutes an important subject for verifying the compliance to the Chemical Weapons Convention(CWC).In environmental water,the relevant degradation products of...Analysis of nerve agents and their degradation products constitutes an important subject for verifying the compliance to the Chemical Weapons Convention(CWC).In environmental water,the relevant degradation products of nerve agents are usually present at low concentration levels and mixed with a large amount of interferents.In this paper,six different kinds of solid-phase bulk sorbents were respectively investigated to improve the SPE efficiency for nerve agents degradation products from stimulant water samples,in which a large amount of background interferents were spiked.Results showed that the strong anion-exchange sorbent could selectively extract the spiking six target compounds from the matrices and showed a high recovery.展开更多
VX is a highly toxic organophosphorus nerve agent that the Chemical Weapons Convention classifies as a Schedule 1. In our previous study, we developed a method for detecting organophosphorus compounds using peptide se...VX is a highly toxic organophosphorus nerve agent that the Chemical Weapons Convention classifies as a Schedule 1. In our previous study, we developed a method for detecting organophosphorus compounds using peptide self-assembly. Nevertheless, the self-assembly mechanisms of peptides that bind organophosphorus and the roles of each peptide residue remain elusive, restricting the design and application of peptide materials. Here, we use a multi-scale computational combined with experimental approach to illustrate the self-assembly mechanism of peptide-bound VX and the roles played by residues in different peptide sequences. We calculated that the self-assembly of peptides was accelerated after adding VX, and the final size of assembled nanofibers was larger than the original one, aligning with experimental findings. The atomic scale details offered by our approach enabled us to clarify the connection between the peptide sequences and nanostructures formation, as well as the contribution of various residues in binding VX and assembly process. Our investigation revealed a tight correlation between the number of Tyrosine residues and morphology of the assembly. These results indicate a self-assembly mechanism of peptide and VX, which can be used to design functional peptides for binding and hydrolyzing other organophosphorus nerve agents for detoxification and biomedical applications.展开更多
There is a great interest in developing microelectronic devices based on nanostructured conducting polymers that can selectively electro-couple analytes at high sensitivity and low power.Nanostructured conducting poly...There is a great interest in developing microelectronic devices based on nanostructured conducting polymers that can selectively electro-couple analytes at high sensitivity and low power.Nanostructured conducting polymers have emerged as promising candidates for this technology due to their excellent stability with low redox potential,high conductivity,and selectivity endowed by chemical functionalization.However,it remains challenging to develop cost-effective and large-scale assembly approaches for functionalized conducting polymers in the practical fabrication of electronic devices.Here,we reported a straightforward waferscale assembly of nanostructured hexafluoroisopropanol functionalized poly(3,4-ethylenedioxythiophene)(PEDOT-HFIP)on smooth substrates.This approach is template-free,solution-processed,and adaptable to conductive and nonconductive substrates.By this approach,the nanostructured PEDOT-HFIPs could be easily integrated onto interdigitated electrodes with intimate ohmic contact.At the optimized space-to-volume ratio,we demonstrated a low-power,sensitive,and selective nerve agent sensing technology using this platform by detecting sarin vapor with a limit of detection(LOD)of 10 ppb and signal strength of 400 times the water interference at the same concentration,offering significant advantages over existing similar technologies.We envision that its easy scale-up,micro size,small power consumption,and combination of high sensitivity and selectivity make it attractive for various wearable platforms.展开更多
Three fluorescent BINOL-Si complexes(FS1,FS2 and FS3)were rationally designed and synthesized to detect diethyl chlorophosphate(DCP),a mimic of lethal nerve agents.These three fluorescent probes showed green,yellow an...Three fluorescent BINOL-Si complexes(FS1,FS2 and FS3)were rationally designed and synthesized to detect diethyl chlorophosphate(DCP),a mimic of lethal nerve agents.These three fluorescent probes showed green,yellow and orange fluorescence,respectively.Moreover,the series of fluorescent probes has the characteristics of fast response time(4 s),low detection limit(0.0097 mmol/L),high sensitivity and naked eye detection.More important,a fiber optic sensor capable of detecting DCP vapor in real time was also prepared for the first time,the lowest detection limits(down to 4.4 ppb)were all lower than that of the IDLH(immediately dangerous to life or health)concentration of Sarin(7.0 ppb).展开更多
Binding of fluorescent molecules to the porous matrix through noncovalent interactions will synergistically expand their application spectrum. In this regard, we report an integrative self-assembly of molecule 1 with ...Binding of fluorescent molecules to the porous matrix through noncovalent interactions will synergistically expand their application spectrum. In this regard, we report an integrative self-assembly of molecule 1 with benzothiadizole and 9,9-dihexyl fluorene units, and covalent organic frameworks(COFs) via an emulsion-modulated polymerization process, within which molecules of 1 are able to interact with the scaffolds of COFs through CH-π interactions. Thus the π-πinteractions between the fluorescent molecules are largely suppressed, giving rise to their remarkable monomer-like optical properties. Of particular interest is that, given by the specific interaction between COFs and a nerve agent simulant diethyl chlorophosphite(DCP), these assembled composites show the ability of ultrasensitive detection of DCP with a detection limit of ~40 ppb. Moreover, the present integrative assembly strategy can be extended to encapsulate multiple fluorescent molecules, enabling the assemblies with white light emission. Our results highlight opportunities for the development of highly emissive porous materials by molecular selfassembly of fluorophores and molecular units of COFs.展开更多
Nerve agents are used in civil wars and terrorist attacks,posing a threat to public safety.Acute exposure to nerve agents such as soman(GD)causes serious brain damage,leading to death due to intense seizures induced b...Nerve agents are used in civil wars and terrorist attacks,posing a threat to public safety.Acute exposure to nerve agents such as soman(GD)causes serious brain damage,leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation.However,data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited.Here,we evaluated the potential effects of transient receptor vanilloid 4(TRPV4)in the treatment of soman-induced status epilepticus(SE)and secondary brain injury.We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures.Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity.TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure.Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity.The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1βand IL-18 increased in soman-exposed rat hippocampus.However,TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway.In conclusion,our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation.To our knowledge,this is the first study regarding the“dual-switch”function of TRPV4 in the treatment of soman intoxication.展开更多
Developing a versatile etching strategy for constructing hierarchically porous metal-organic frameworks(HP-MOFs)with anticipated mesopores and micropores remains a crucial scientific challenge in probing the enhanced ...Developing a versatile etching strategy for constructing hierarchically porous metal-organic frameworks(HP-MOFs)with anticipated mesopores and micropores remains a crucial scientific challenge in probing the enhanced performance and potential applications of MOF materials.Herein,a universal vapor etching method is implemented to controllably create HP-MOFs.Based on the principle that the concentration of vapor is lower than that of the solution,the etching rate and strength toward MOFs are greatly reduced,enabling us to obtain intermediate products during etching.Using this strategy,a series of desired HP-MOFs with varying metal nodes have been prepared.The resultant HP-MOFs integrate the merits of mesopores(mass transfer facilitation)and micropores(large internal surface area).For the degradation of the nerve agent,dimethyl 4-nitrophenyl phosphate,HP-UiO-66 exhibits better catalytic activity than pristine UiO-66.展开更多
As social media becomes increasingly ubiquitous,many events are recorded and released on social media platforms,including chemical weapon attacks.We develop an objective tool in order to evaluate brief and unstructure...As social media becomes increasingly ubiquitous,many events are recorded and released on social media platforms,including chemical weapon attacks.We develop an objective tool in order to evaluate brief and unstructured social media videos for analysing sarin exposure from a civilian medical pathology perspective.We developed and validated this new questionnaire using a standardized procedure that includes content domain specification,item pool generation,content validity evaluation,a pilot study,and assessment of reliability and validity.In total,51 sarin attacks and 48 matched videos were analysed.Cronbach’s a for all 20 items was 0.75,which indicates adequate internal reliability.The test–retest reliability was 0.96,which indicates good internal reliability.The inter-observer intraclass correlation coefficient was 0.97.After verifying sampling adequacy with the Kaiser–Meyer–Olkin measure and the factorability of the items with Barlett’s test of sphericity,a factor analysis was performed.According to the principal axis factoring,a six-factor solution explained 51.86%of the total variance.The receiver-operating characteristic curve analysis showed that the Video Score Questionnaire has a sensitivity of 0.817,a specificity of 0.478,and an efficiency of 65.3.Therefore,the Video Score Questionnaire is reliable and valid for evaluating sarin attacks from brief and unstructured social media videos.展开更多
文摘PON 1 (Paraoxonase 1) has been proposed as an efficient catalytic bioscavenger to combat against OP (organophosphate) and CWNA (chemical warfare nerve agent) toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.
基金supported by Institut Pengurusan Penyelidikan(RMI)Universiti Teknologi MARA,Malaysia,under the grant No.600-IRMI/MyRA 5/3/LESTARI(0088/2016)and 600-IRMI/DANA 5/3/LESTARI(0076/2016)
文摘Glaucoma is the second leading cause of irreversible vision impairment affecting more than 70 million people worldwide with approximately 10%suffering from glaucoma-related bilateral blind(Quigley and Broman,2006).It is a multi-factorial disease that is characterized by optic nerve damage and visual field loss.Progressive loss of retinal ganglion cells(RGCs)resulting in visual field deficits is the hallmark of glaucoma.
文摘Analysis of nerve agents and their degradation products constitutes an important subject for verifying the compliance to the Chemical Weapons Convention(CWC).In environmental water,the relevant degradation products of nerve agents are usually present at low concentration levels and mixed with a large amount of interferents.In this paper,six different kinds of solid-phase bulk sorbents were respectively investigated to improve the SPE efficiency for nerve agents degradation products from stimulant water samples,in which a large amount of background interferents were spiked.Results showed that the strong anion-exchange sorbent could selectively extract the spiking six target compounds from the matrices and showed a high recovery.
基金supported by the National Key R&D Program of China(No.2020YFF0305002)the Project program of Tianjin Key Laboratory of Food Quality and Health,Tianjin University of Science and Technology(No.TJS202102).
文摘VX is a highly toxic organophosphorus nerve agent that the Chemical Weapons Convention classifies as a Schedule 1. In our previous study, we developed a method for detecting organophosphorus compounds using peptide self-assembly. Nevertheless, the self-assembly mechanisms of peptides that bind organophosphorus and the roles of each peptide residue remain elusive, restricting the design and application of peptide materials. Here, we use a multi-scale computational combined with experimental approach to illustrate the self-assembly mechanism of peptide-bound VX and the roles played by residues in different peptide sequences. We calculated that the self-assembly of peptides was accelerated after adding VX, and the final size of assembled nanofibers was larger than the original one, aligning with experimental findings. The atomic scale details offered by our approach enabled us to clarify the connection between the peptide sequences and nanostructures formation, as well as the contribution of various residues in binding VX and assembly process. Our investigation revealed a tight correlation between the number of Tyrosine residues and morphology of the assembly. These results indicate a self-assembly mechanism of peptide and VX, which can be used to design functional peptides for binding and hydrolyzing other organophosphorus nerve agents for detoxification and biomedical applications.
基金financial support from the National Natural Science Foundation of China(Nos.21474014 and 22175111)Z.G.thanks financial support from the National Natural Science Foundation of China(No.21704013)+1 种基金China Postdoctoral Science Foundation(No.2017M611416)R.B.W.thanks for financial support from the National Postdoctoral Program for Innovative Talents(No.BX201700044).
文摘There is a great interest in developing microelectronic devices based on nanostructured conducting polymers that can selectively electro-couple analytes at high sensitivity and low power.Nanostructured conducting polymers have emerged as promising candidates for this technology due to their excellent stability with low redox potential,high conductivity,and selectivity endowed by chemical functionalization.However,it remains challenging to develop cost-effective and large-scale assembly approaches for functionalized conducting polymers in the practical fabrication of electronic devices.Here,we reported a straightforward waferscale assembly of nanostructured hexafluoroisopropanol functionalized poly(3,4-ethylenedioxythiophene)(PEDOT-HFIP)on smooth substrates.This approach is template-free,solution-processed,and adaptable to conductive and nonconductive substrates.By this approach,the nanostructured PEDOT-HFIPs could be easily integrated onto interdigitated electrodes with intimate ohmic contact.At the optimized space-to-volume ratio,we demonstrated a low-power,sensitive,and selective nerve agent sensing technology using this platform by detecting sarin vapor with a limit of detection(LOD)of 10 ppb and signal strength of 400 times the water interference at the same concentration,offering significant advantages over existing similar technologies.We envision that its easy scale-up,micro size,small power consumption,and combination of high sensitivity and selectivity make it attractive for various wearable platforms.
基金the National Natural Science Foundation of China(Nos.21572091 and 21772078)the Fundamental Research Funds for the Central Universities(Nos.2682019CX70 and 2682019CX71)。
文摘Three fluorescent BINOL-Si complexes(FS1,FS2 and FS3)were rationally designed and synthesized to detect diethyl chlorophosphate(DCP),a mimic of lethal nerve agents.These three fluorescent probes showed green,yellow and orange fluorescence,respectively.Moreover,the series of fluorescent probes has the characteristics of fast response time(4 s),low detection limit(0.0097 mmol/L),high sensitivity and naked eye detection.More important,a fiber optic sensor capable of detecting DCP vapor in real time was also prepared for the first time,the lowest detection limits(down to 4.4 ppb)were all lower than that of the IDLH(immediately dangerous to life or health)concentration of Sarin(7.0 ppb).
基金supported by the National Natural Science Foundation of China (21703120,21972076,51903140 and 21925604)China Postdoctoral Science Foundation (2019M662324)Taishan Scholars Program of Shandong Province (tsqn201812011)。
文摘Binding of fluorescent molecules to the porous matrix through noncovalent interactions will synergistically expand their application spectrum. In this regard, we report an integrative self-assembly of molecule 1 with benzothiadizole and 9,9-dihexyl fluorene units, and covalent organic frameworks(COFs) via an emulsion-modulated polymerization process, within which molecules of 1 are able to interact with the scaffolds of COFs through CH-π interactions. Thus the π-πinteractions between the fluorescent molecules are largely suppressed, giving rise to their remarkable monomer-like optical properties. Of particular interest is that, given by the specific interaction between COFs and a nerve agent simulant diethyl chlorophosphite(DCP), these assembled composites show the ability of ultrasensitive detection of DCP with a detection limit of ~40 ppb. Moreover, the present integrative assembly strategy can be extended to encapsulate multiple fluorescent molecules, enabling the assemblies with white light emission. Our results highlight opportunities for the development of highly emissive porous materials by molecular selfassembly of fluorophores and molecular units of COFs.
基金the Special Fund for Military Medical Science(AWS15J007 and BWS16J007)the National Natural Science Foundation of China(81703505).
文摘Nerve agents are used in civil wars and terrorist attacks,posing a threat to public safety.Acute exposure to nerve agents such as soman(GD)causes serious brain damage,leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation.However,data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited.Here,we evaluated the potential effects of transient receptor vanilloid 4(TRPV4)in the treatment of soman-induced status epilepticus(SE)and secondary brain injury.We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures.Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity.TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure.Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity.The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1βand IL-18 increased in soman-exposed rat hippocampus.However,TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway.In conclusion,our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation.To our knowledge,this is the first study regarding the“dual-switch”function of TRPV4 in the treatment of soman intoxication.
基金financially supported by the National Natural Science Foundation of China(22175030)the Open Project of State Key Laboratory of Supramolecular Structure and Materials(sklssm202205)。
文摘Developing a versatile etching strategy for constructing hierarchically porous metal-organic frameworks(HP-MOFs)with anticipated mesopores and micropores remains a crucial scientific challenge in probing the enhanced performance and potential applications of MOF materials.Herein,a universal vapor etching method is implemented to controllably create HP-MOFs.Based on the principle that the concentration of vapor is lower than that of the solution,the etching rate and strength toward MOFs are greatly reduced,enabling us to obtain intermediate products during etching.Using this strategy,a series of desired HP-MOFs with varying metal nodes have been prepared.The resultant HP-MOFs integrate the merits of mesopores(mass transfer facilitation)and micropores(large internal surface area).For the degradation of the nerve agent,dimethyl 4-nitrophenyl phosphate,HP-UiO-66 exhibits better catalytic activity than pristine UiO-66.
基金This work was supported by the Spiez Laboratory(Federal Office for Civil Protection),Switzerland[grant number 354012624].
文摘As social media becomes increasingly ubiquitous,many events are recorded and released on social media platforms,including chemical weapon attacks.We develop an objective tool in order to evaluate brief and unstructured social media videos for analysing sarin exposure from a civilian medical pathology perspective.We developed and validated this new questionnaire using a standardized procedure that includes content domain specification,item pool generation,content validity evaluation,a pilot study,and assessment of reliability and validity.In total,51 sarin attacks and 48 matched videos were analysed.Cronbach’s a for all 20 items was 0.75,which indicates adequate internal reliability.The test–retest reliability was 0.96,which indicates good internal reliability.The inter-observer intraclass correlation coefficient was 0.97.After verifying sampling adequacy with the Kaiser–Meyer–Olkin measure and the factorability of the items with Barlett’s test of sphericity,a factor analysis was performed.According to the principal axis factoring,a six-factor solution explained 51.86%of the total variance.The receiver-operating characteristic curve analysis showed that the Video Score Questionnaire has a sensitivity of 0.817,a specificity of 0.478,and an efficiency of 65.3.Therefore,the Video Score Questionnaire is reliable and valid for evaluating sarin attacks from brief and unstructured social media videos.