Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are o...Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the cell.Nevertheless,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.展开更多
A series of 3-nitro-5-nitroimino-1,2,4-oxadiazole-based energetic salts were synthesized from 3-nitro-5-nitroimino-1,2,4-oxadiazole anion and nitrogen-rich cations. They were fully characterized by IR,elemental analys...A series of 3-nitro-5-nitroimino-1,2,4-oxadiazole-based energetic salts were synthesized from 3-nitro-5-nitroimino-1,2,4-oxadiazole anion and nitrogen-rich cations. They were fully characterized by IR,elemental analysis and NMR spectroscopy. The structure of triaminoguanidinium salt（1-e） was confirmed by single crystal X-ray diffraction. All salts showed good thermal stability with decomposed temperature ranging from 155 8C to 258 8C, and positive heats of formation from 226.0 k J/mol to554.1 k J/mol. Thus, the theoretic detonation pressure was predicted from 28.70 GPa to 37.60 GPa and velocities from 8526 m/s to 9354 m/s. Among them, guanidinium salt（1-c） exhibited both high decomposition temperature（258 8C） and detonation velocity（9319 m/s）.展开更多
Huntington’s disease(HD)is a fatal neurodegenerative disorder characterized by a triad of behavioral symptoms:involuntary movement,emotional change,and cognitive dysfunction.Although alterations in WNT signaling have...Huntington’s disease(HD)is a fatal neurodegenerative disorder characterized by a triad of behavioral symptoms:involuntary movement,emotional change,and cognitive dysfunction.Although alterations in WNT signaling have been reported in HD,its precise role in pathogenesis remains unclear.In this study,we found that astrocytic WNT5B mRNA and protein levels are elevated in the striatum of both HD patients and HD model mice.The noncanonical WNT5B signaling pathway induced sustained expression of matrix metallopeptidase 14(MMP14),an extracellular matrix(ECM)-degrading enzyme,via activation of the NFATc2 transcription factor in both human and primary mouse astrocytes.Robust upregulation of MMP14 led to ECM degradation,medium spiny neuron(MSN)damage,and increased mutant huntingtin aggregation in N171-82Q HD transgenic mice.Furthermore,WNT5B gain-offunction exacerbated neuropathology,impaired motor coordination,and shortened the lifespan of N171-82Q mice.We further demonstrated that the overexpression of the estrogen receptorα(ERα)suppresses NFATc2 transcriptional activity in vitro.A targeted therapy for the WNT5B-NFATc2-MMP14 signaling pathway by genistein,a phytoestrogen,reduced MMP14 transcription by antagonizing NFATc2 activity and preventing ECM degradation in N171-82Q mice.Genistein treatment also ameliorated neuropathology and motor deficits and prolonged the lifespan of HD mice.Together,these findings define a molecular pathological mechanism in which astrocytic MMP14 transcription,driven by the noncanonical WNT5B signaling pathway,promotes ECM degradation and MSN damage and accelerates neurodegeneration in HD.Modulation of the noncell-autonomous WNT5BNFATc2-MMP14 signaling pathway by genistein may serve as a potential therapeutic strategy for mitigating HD pathogenesis.展开更多
Over the past decades,there has been an intensive quest for theoretical studies and experimental detection of polynitrogen species (e.g.,N4,N5^+,N8,cyclo-N5^-,and polymeric nitrogen,etc.)that are potentiaUy stable in ...Over the past decades,there has been an intensive quest for theoretical studies and experimental detection of polynitrogen species (e.g.,N4,N5^+,N8,cyclo-N5^-,and polymeric nitrogen,etc.)that are potentiaUy stable in the condensed phase [1-4].As a class of representative polynitrogen species,cyclo-pentazolate (cyclo-N5^-)com- pounds have received significant interest from synthetic chemists.Despite traditional arylpentazole compounds were discovered in 1956 [5],the experimental synthesis of stable cyclo-N;species has encountered great difficulties for subsequent decades.展开更多
Objective To study the severe acute respiratory syndrome (SARS) -associated coronavirus genotype and its characteristics.Methods A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples t...Objective To study the severe acute respiratory syndrome (SARS) -associated coronavirus genotype and its characteristics.Methods A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29 715 bp (GenBank accession: AY297028, version; gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done.Results By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C: G: C: C/T: T: T: T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C: G: A: C: C/T: T: G: T: T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in China's Mainland. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to He in the protein, respectively.Conclusion Attention should be paid to whether these genotype and mutation patterns are related to the virus' s biological activities, epidemic characteristics and host clinical symptoms.展开更多
Cyclopentazolate anions(cyclo-N5-)have been receiving ever-increasing attention as component of energetic explosives since recent fulfilment of the first stable sample in solid phase and ambient conditions.Herein,we p...Cyclopentazolate anions(cyclo-N5-)have been receiving ever-increasing attention as component of energetic explosives since recent fulfilment of the first stable sample in solid phase and ambient conditions.Herein,we present a new strategy to utilize deflagration reactions of cobalt pentazolate in combination with explosive poly(ionic liquid)(EPIL)for the preparation of Co@N-doped carbon materials with homogeneously distributed cobalt nanoparticle encapsulated by the layers of N-doped carbon sheets.The resultant5%Co(N5)2-EPIL-900 exhibits high electrocatalytic activities,excellent stability and tolerance to CH3 OH towards oxygen reduction reaction(ORR).Moreover,the present approach provides a novel routine for preparation of functional materials from energetic and newly-emerging cyclo-N5--derived compounds.展开更多
基金supported by LifeArc Philanthropic Fund(P2019-0004)LifeArc Pathfinder Award+7 种基金along with Wellcome Trust Seed Award(109626/Z/15/Z)FA PESP-UoB Strategic Collaboration FundBirmingham Fellowship(to SS)grants from Laboratoire d'Excellence Revive(Investissement d'AvenirANR-10-LABX-73)the Region lle-de-France via doctoral school Innovation Therapeutique,du Fondamentalàl'Appliqué(ED569)from Universite Paris-Saclay(to LA)Medical Research Council(MRC)Developmental Pathway Funding Scheme(DPFS)grant(MR/P007732/1)(to TB)supported by the Association Fran?aise contre les Myopathies(AFM-Téléthon)。
文摘Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the cell.Nevertheless,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.
基金financial support from the National Natural Science Foundation of China(Nos.21372027 and 21172203)
文摘A series of 3-nitro-5-nitroimino-1,2,4-oxadiazole-based energetic salts were synthesized from 3-nitro-5-nitroimino-1,2,4-oxadiazole anion and nitrogen-rich cations. They were fully characterized by IR,elemental analysis and NMR spectroscopy. The structure of triaminoguanidinium salt（1-e） was confirmed by single crystal X-ray diffraction. All salts showed good thermal stability with decomposed temperature ranging from 155 8C to 258 8C, and positive heats of formation from 226.0 k J/mol to554.1 k J/mol. Thus, the theoretic detonation pressure was predicted from 28.70 GPa to 37.60 GPa and velocities from 8526 m/s to 9354 m/s. Among them, guanidinium salt（1-c） exhibited both high decomposition temperature（258 8C） and detonation velocity（9319 m/s）.
基金funded by multiple grants from the National Research Foundation of Korea(NRF),supported by the Ministry of Education,Science and Technology,including the Sejong Science Fellowship(2021R1C1C2095827,S.J.H.)grants 2020M3E5D9079742,2021M3A9G1015618,and RS-2022-NR070632 awarded to H.R+3 种基金Additional support was provided through the Korea Dementia Research Project(RS2023-KH137130 to H.R.)under the Korea Dementia Research Center(KDRC),funded by the Ministry of Health&Welfare and the Ministry of Science and ICTThis work was also partially supported by the Korea Institute of Science and Technology(KIST)through grants 2E33701,2E33722,2Z07276,and 2Z07368(H.R.)We further acknowledge support from the U.S.National Institutes of Health(NIH R01NS109537,J.L.)English language and stylistic editing were assisted by AI-based proofreading tools(ChatGPT,OpenAI).
文摘Huntington’s disease(HD)is a fatal neurodegenerative disorder characterized by a triad of behavioral symptoms:involuntary movement,emotional change,and cognitive dysfunction.Although alterations in WNT signaling have been reported in HD,its precise role in pathogenesis remains unclear.In this study,we found that astrocytic WNT5B mRNA and protein levels are elevated in the striatum of both HD patients and HD model mice.The noncanonical WNT5B signaling pathway induced sustained expression of matrix metallopeptidase 14(MMP14),an extracellular matrix(ECM)-degrading enzyme,via activation of the NFATc2 transcription factor in both human and primary mouse astrocytes.Robust upregulation of MMP14 led to ECM degradation,medium spiny neuron(MSN)damage,and increased mutant huntingtin aggregation in N171-82Q HD transgenic mice.Furthermore,WNT5B gain-offunction exacerbated neuropathology,impaired motor coordination,and shortened the lifespan of N171-82Q mice.We further demonstrated that the overexpression of the estrogen receptorα(ERα)suppresses NFATc2 transcriptional activity in vitro.A targeted therapy for the WNT5B-NFATc2-MMP14 signaling pathway by genistein,a phytoestrogen,reduced MMP14 transcription by antagonizing NFATc2 activity and preventing ECM degradation in N171-82Q mice.Genistein treatment also ameliorated neuropathology and motor deficits and prolonged the lifespan of HD mice.Together,these findings define a molecular pathological mechanism in which astrocytic MMP14 transcription,driven by the noncanonical WNT5B signaling pathway,promotes ECM degradation and MSN damage and accelerates neurodegeneration in HD.Modulation of the noncell-autonomous WNT5BNFATc2-MMP14 signaling pathway by genistein may serve as a potential therapeutic strategy for mitigating HD pathogenesis.
基金supported by the National Natural Science Foundation of China (21602211 and 11472251)the Thousand Talents Plan (Youth)+1 种基金Dvelopment Foundation of CAEP (2015B0302057 and 2015B0302056)the Science Challenge Project (TZ2018004)
文摘Over the past decades,there has been an intensive quest for theoretical studies and experimental detection of polynitrogen species (e.g.,N4,N5^+,N8,cyclo-N5^-,and polymeric nitrogen,etc.)that are potentiaUy stable in the condensed phase [1-4].As a class of representative polynitrogen species,cyclo-pentazolate (cyclo-N5^-)com- pounds have received significant interest from synthetic chemists.Despite traditional arylpentazole compounds were discovered in 1956 [5],the experimental synthesis of stable cyclo-N;species has encountered great difficulties for subsequent decades.
基金This work was supported by the Administration of Science and Technology of Zhejiang Province,the Administration of Health of Zhejiang Province and Zhejiang University.
文摘Objective To study the severe acute respiratory syndrome (SARS) -associated coronavirus genotype and its characteristics.Methods A SARS-associated coronavirus isolate named ZJ01 was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of ZJ01 consisted of 29 715 bp (GenBank accession: AY297028, version; gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done.Results By bioinformatics processing and analysis, the 5 loci nucleotides at ZJ01 genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C: G: C: C/T: T: T: T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C: G: A: C: C/T: T: G: T: T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the ZJ01 isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in China's Mainland. Phylogenetic analysis of the spike protein gene fragments of these SARS-associated coronavirus strains showed that the GZ01 isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of BJ01 and CUHK-W1 were more closely related to the GZ01 isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to He in the protein, respectively.Conclusion Attention should be paid to whether these genotype and mutation patterns are related to the virus' s biological activities, epidemic characteristics and host clinical symptoms.
基金financially supported by the National Natural Science Foundation of China(21703218 and21875228)Shenzhen Science and Technology Innovation Committee(JCYJ20151013162733704)
文摘Cyclopentazolate anions(cyclo-N5-)have been receiving ever-increasing attention as component of energetic explosives since recent fulfilment of the first stable sample in solid phase and ambient conditions.Herein,we present a new strategy to utilize deflagration reactions of cobalt pentazolate in combination with explosive poly(ionic liquid)(EPIL)for the preparation of Co@N-doped carbon materials with homogeneously distributed cobalt nanoparticle encapsulated by the layers of N-doped carbon sheets.The resultant5%Co(N5)2-EPIL-900 exhibits high electrocatalytic activities,excellent stability and tolerance to CH3 OH towards oxygen reduction reaction(ORR).Moreover,the present approach provides a novel routine for preparation of functional materials from energetic and newly-emerging cyclo-N5--derived compounds.
