Relative reactivities of polyhalofluoroalkanes toward bromophilic or chlorophilic attacks have been evaluated for the first time by comparing the rates of halophilic attacks by a carbanion derived from the addition of...Relative reactivities of polyhalofluoroalkanes toward bromophilic or chlorophilic attacks have been evaluated for the first time by comparing the rates of halophilic attacks by a carbanion derived from the addition of a nucleophile to an olefin with the rate of β-elimination of the same carbanion intermediate. Relative reactivity orders of some polybromofluoroalkanes and polychlorofluoroalkanes are CF_2Br_2>CF_3CFBr_2 ～ CF_2BrCF_2Br>CF_3CBr_3, and CCl_4 > CF_3CCl_3 > CF_2ClCCl_3 > CFCl_3 > CFCl_2CFCl2 ～ CF_2ClCFCl_2. Early transition states for halophilic attacks are speculated.展开更多
It is generally recognized that the formation and accumulation of iron oxides on the surface of zero-valent iron(Fe^(0))resulting in significant decrease of contaminant degradation rates during the long-term reactions...It is generally recognized that the formation and accumulation of iron oxides on the surface of zero-valent iron(Fe^(0))resulting in significant decrease of contaminant degradation rates during the long-term reactions.However,in this study,we found that the removal efficiencies of p-nitrophenol(PNP)by micro zero-valent iron(mFe^(0))could maintain at the satisfactory level in the process of continuous reactions(20 cycles).The removal rate constant(0.1779 min^(-1))of the 5th cycle was 6.74 times higher than that of the 1streaction(0.0264 min^(-1)),even the 20th cycle(0.0371 min^(-1))was higher than that of the 1st reaction.Interestingly,almost no dissolved iron was detected in the solution,and the total iron concentrations decreased dramatically with the process of continuous reactions.The results of scanning electron microscope and energy dispersive spectrometry(SEM-EDS)and X-ray diffraction(XRD)revealed that the structure and composition of corrosion products change from amorphous to highly crystal with the increase of the number of cycles.The corrosion products were mainly magnetite(Fe_(3)O_(4))and a small part of maghemite(γ-Fe_(2)O_(3)),which were in the form of micro sphe res on the surface of mFe^(0).The formation of surface oxidation shell hindered the release of Fe^(2+).X-ray photoelectron spectroscopy(XPS)results illustrated that partial Fe3O_(4) could be converted into y-Fe_(2)O_(3).Electrochemical analysis proved that the electron transfer rate of mFe^(0) increased with the formation of the oxides shell.However,the consumption of iron core and thicker oxide film weakened the electron transfer rate.Besides,the quenching experiments indicated that the reaction activity of mFe^(0) could be enhanced with the addition of scavengers.This study deepened the understanding of the structural transformation and radical production of mFe^(0) in continuous reactions.展开更多
We have generated one possible active site structure of Oxyhemocyanin (Oxy-Hc) and two possible active site structures of Oxytyrosinase (Oxy-Ty) using the EHMO method. Oxy-Hc active site has a plane configuration, whi...We have generated one possible active site structure of Oxyhemocyanin (Oxy-Hc) and two possible active site structures of Oxytyrosinase (Oxy-Ty) using the EHMO method. Oxy-Hc active site has a plane configuration, while Oxy-Ty has boat configuration. When there exist water molecules, two water molecules are connected with the Oxy-Ty active site weakly. Calculations for the reactions of Oxy-Hc and Oxy-Ty (the water-off) with phenol demonstrate that the former reaction is thermodynamically forbidden, while the latter Is realizable.展开更多
Five Shenfu char samples were prepared from Shenfu raw coal at different temperatures （950, 1100, 1200, 1300 and 1400℃） using a muffle furnace. Demineralization of the char samples was performed by treating them wi...Five Shenfu char samples were prepared from Shenfu raw coal at different temperatures （950, 1100, 1200, 1300 and 1400℃） using a muffle furnace. Demineralization of the char samples was performed by treating them with 10% nitric acid for 10 min in a CEM Discover microwave reactor. The gasification of the chars, and corresponding demineralized chars, in a carbon dioxide （CO2） atmosphere was conducted in a Netzsch STA 409Cl31F tempera- ture-programmed thermogravimetry apparatus. The effects of charring temperature and demineralization on the gasification reactivity of chars were systematically investigated. The results show that a char formed at a lower temperature is more reactive except for demineralized char formed at 1100℃, which is less reactive than char formed at 1200℃. Demineralization decreases the char reactivities toward gasification with CO2 to a small extent.展开更多
Considerable efforts have been devoted to characterising the chemical components of vehicle exhaust.However,these components may not accurately reflect the contribution of vehicle exhaust to atmospheric reactivity bec...Considerable efforts have been devoted to characterising the chemical components of vehicle exhaust.However,these components may not accurately reflect the contribution of vehicle exhaust to atmospheric reactivity because of the presence of species not accounted for(“missing species”)given the limitations of analytical instruments.In this study,we improved the laser photolysis–laser-induced fluorescence(LP-LIF)technique and applied it to directly measure the total OH reactivity(TOR)in exhaust gas from light-duty gasoline vehicles in China.The TOR for China Ⅰ to Ⅵ-a vehicles was 15.6,16.3,8.4,2.6,1.5,and 1.6×10^(4) sec^(-1),respectively,reflecting a notable drop as emission standards were upgraded.The TOR was comparable between cold and warm starts.The missing OH reactivity(MOR)values for China Ⅰ to Ⅳ vehicles were close to zero with a cold start but were much higher with a warm start.The variations in oxygenated volatile organic compounds(OVOCs)under different emission standards and for the two start conditions were similar to those of the MOR,indicating that OVOCs and the missing species may have similar production processes.Online measurement revealed that the duration of the stable driving stage was the primary factor leading to the production of OVOCs and missing species.Our findings underscore the importance of direct measurement of TOR from vehicle exhaust and highlight the necessity of adding OVOCs and other organic reactive gases in future upgrades of emission standards,such that the vehicular contribution to atmospheric reactivity can be more effectively controlled.展开更多
Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidat...Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
Condensation of methyl 7-methylcoumarin-4-acetate(2)with primary amines and with an- thranilic acid gave 7-methyl-2-oxo-N-aryl-2H-[1]-benzopyran-4--acetamide(4a—d)and(7),respectively. Compound 7 underwent cyclization...Condensation of methyl 7-methylcoumarin-4-acetate(2)with primary amines and with an- thranilic acid gave 7-methyl-2-oxo-N-aryl-2H-[1]-benzopyran-4--acetamide(4a—d)and(7),respectively. Compound 7 underwent cyclization to give 2-(7-methyl-2-oxo-2H-[1]-benzopyran-4-yl)-methyl-4H-3,1- benzoxazin-4-one(3).The reaction of 3 with aromatic amines gave the corresponding quinazolone derivatives 5 which tautomerises to the thermodynamically more stable isomer 6,whereas its reaction with Grignard reagents and aromatic aldehydes gave 8a,8b,and 9a,9b,respectively.展开更多
The reduced form of the nicotinamide-adenine dinucleotide coenzyme(NAD(P)H)plays an important role in many bio-reductions by transferring a hydride ion or an electronto the surrounding substrate(see eq.(1),R represent...The reduced form of the nicotinamide-adenine dinucleotide coenzyme(NAD(P)H)plays an important role in many bio-reductions by transferring a hydride ion or an electronto the surrounding substrate(see eq.(1),R represents adenine dinucleotide).展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to impr...Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expre...Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.展开更多
To study the volatile organic compounds(VOCs)emission characteristics of industrial enterprises in China,6 typical chemical industries in Yuncheng City were selected as research objects,including the modern coal chemi...To study the volatile organic compounds(VOCs)emission characteristics of industrial enterprises in China,6 typical chemical industries in Yuncheng City were selected as research objects,including the modern coal chemical industry(MCC),pharmaceutical industry(PM),pesticide industry(PE),coking industry(CO)and organic chemical industry(OC).The chemical composition of 91 VOCs was quantitatively analyzed.The results showed that the emission concentration of VOCs in the chemical industry ranged from 1.16 to 155.59 mg/m^(3).Alkanes were the main emission components of MCC(62.0%),PE(55.1%),and OC(58.5%).Alkenes(46.5%)were important components of PM,followed by alkanes(23.8%)and oxygenated volatile organic compounds(OVOCs)(21.2%).Halocarbons(8.6%-71.1%),OVOCs(9.7%-37.6%)and alkanes(11.2%-27.0%)were characteristic components of CO.The largest contributor to OFP was alkenes(0.6%-81.7%),followed by alkanes(9.3%-45.9%),and the lowest onewas alkyne(0%-0.5%).Aromatics(66.9%-85.4%)were the largest contributing components to SOA generation,followed by alkanes(2.6%-28.5%),and the lowest one was alkenes(0%-4.1%).Ethylene and BTEX were the key active species in various chemical industries.The human health risk assessment showed workers long-term exposed to the air in the chemical industrial zone had a high cancer and non-cancer risk during work,and BTEX and dichloromethane were the largest contributors.展开更多
Emission characteristics of biogenic volatile organic compounds(BVOCs)from dominant tree species in the subtropical pristine forests of China are extremely limited.Here we conducted in situ field measurements of BVOCs...Emission characteristics of biogenic volatile organic compounds(BVOCs)from dominant tree species in the subtropical pristine forests of China are extremely limited.Here we conducted in situ field measurements of BVOCs emissions from representative mature evergreen trees by using dynamic branch enclosures at four altitude gradients(600-1690ma.s.l.)in the Nanling Mountains of southern China.Composition characteristics as well as seasonal and altitudinal variations were analyzed.Standardized emission rates and canopyscale emission factors were then calculated.Results showed that BVOCs emission intensities in the wet season were generally higher than those in the dry season.Monoterpenes were the dominant BVOCs emitted from most broad-leaved trees,accounting for over 70%of the total.Schima superba,Yushania basihirsuta and Altingia chinensis had relatively high emission intensities and secondary pollutant formation potentials.The localized emission factors of isoprene were comparable to the defaults in the Model of Emissions of Gases and Aerosols fromNature(MEGAN),while emission factors of monoterpenes and sesquiterpenes were 2 to 58 times of those in the model.Our results can be used to update the current BVOCs emission inventory in MEGAN,thereby reducing the uncertainties of BVOCs emission estimations in forested regions of southern China.展开更多
In the mammalian central nervous system(CNS),astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics.These fascinating cells play essential neurosupportive and homeostat...In the mammalian central nervous system(CNS),astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics.These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological,molecular,and functional changes to adopt so-called‘reactive’states in response to CNS injury or disease.In recent years,interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances.Here,we will review and discuss the wellestablished and emerging astroglial biology and functions,with emphasis on their potential as therapeutic targets for CNS injury,including traumatic and ischemic injury.This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.展开更多
Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in m...Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice.展开更多
文摘Relative reactivities of polyhalofluoroalkanes toward bromophilic or chlorophilic attacks have been evaluated for the first time by comparing the rates of halophilic attacks by a carbanion derived from the addition of a nucleophile to an olefin with the rate of β-elimination of the same carbanion intermediate. Relative reactivity orders of some polybromofluoroalkanes and polychlorofluoroalkanes are CF_2Br_2>CF_3CFBr_2 ～ CF_2BrCF_2Br>CF_3CBr_3, and CCl_4 > CF_3CCl_3 > CF_2ClCCl_3 > CFCl_3 > CFCl_2CFCl2 ～ CF_2ClCFCl_2. Early transition states for halophilic attacks are speculated.
基金the financial support from China Postdoctoral Science Foundation(No.2019T120843)Sichuan Science and Technology Program(No.2019YJ0091)。
文摘It is generally recognized that the formation and accumulation of iron oxides on the surface of zero-valent iron(Fe^(0))resulting in significant decrease of contaminant degradation rates during the long-term reactions.However,in this study,we found that the removal efficiencies of p-nitrophenol(PNP)by micro zero-valent iron(mFe^(0))could maintain at the satisfactory level in the process of continuous reactions(20 cycles).The removal rate constant(0.1779 min^(-1))of the 5th cycle was 6.74 times higher than that of the 1streaction(0.0264 min^(-1)),even the 20th cycle(0.0371 min^(-1))was higher than that of the 1st reaction.Interestingly,almost no dissolved iron was detected in the solution,and the total iron concentrations decreased dramatically with the process of continuous reactions.The results of scanning electron microscope and energy dispersive spectrometry(SEM-EDS)and X-ray diffraction(XRD)revealed that the structure and composition of corrosion products change from amorphous to highly crystal with the increase of the number of cycles.The corrosion products were mainly magnetite(Fe_(3)O_(4))and a small part of maghemite(γ-Fe_(2)O_(3)),which were in the form of micro sphe res on the surface of mFe^(0).The formation of surface oxidation shell hindered the release of Fe^(2+).X-ray photoelectron spectroscopy(XPS)results illustrated that partial Fe3O_(4) could be converted into y-Fe_(2)O_(3).Electrochemical analysis proved that the electron transfer rate of mFe^(0) increased with the formation of the oxides shell.However,the consumption of iron core and thicker oxide film weakened the electron transfer rate.Besides,the quenching experiments indicated that the reaction activity of mFe^(0) could be enhanced with the addition of scavengers.This study deepened the understanding of the structural transformation and radical production of mFe^(0) in continuous reactions.
文摘We have generated one possible active site structure of Oxyhemocyanin (Oxy-Hc) and two possible active site structures of Oxytyrosinase (Oxy-Ty) using the EHMO method. Oxy-Hc active site has a plane configuration, while Oxy-Ty has boat configuration. When there exist water molecules, two water molecules are connected with the Oxy-Ty active site weakly. Calculations for the reactions of Oxy-Hc and Oxy-Ty (the water-off) with phenol demonstrate that the former reaction is thermodynamically forbidden, while the latter Is realizable.
基金Projects 2004CB217704 supported by the Special Fund for Major State Basic Research Project, 104031 by the Key Project of Chinese Ministry of Education JHB05-33 by the Program of the Universities in Jiangsu Province for Development of High-Tech Industries
文摘Five Shenfu char samples were prepared from Shenfu raw coal at different temperatures （950, 1100, 1200, 1300 and 1400℃） using a muffle furnace. Demineralization of the char samples was performed by treating them with 10% nitric acid for 10 min in a CEM Discover microwave reactor. The gasification of the chars, and corresponding demineralized chars, in a carbon dioxide （CO2） atmosphere was conducted in a Netzsch STA 409Cl31F tempera- ture-programmed thermogravimetry apparatus. The effects of charring temperature and demineralization on the gasification reactivity of chars were systematically investigated. The results show that a char formed at a lower temperature is more reactive except for demineralized char formed at 1100℃, which is less reactive than char formed at 1200℃. Demineralization decreases the char reactivities toward gasification with CO2 to a small extent.
基金supported by the National Natural Science Foundation of China(Nos.91644221 and 41627809)the National Key Research and Development Program of China(Nos.2016YFC0202201 and 2018YFC0213904)the Key-Area Research and Development Program of Guangdong Province(No.2019B110206001).
文摘Considerable efforts have been devoted to characterising the chemical components of vehicle exhaust.However,these components may not accurately reflect the contribution of vehicle exhaust to atmospheric reactivity because of the presence of species not accounted for(“missing species”)given the limitations of analytical instruments.In this study,we improved the laser photolysis–laser-induced fluorescence(LP-LIF)technique and applied it to directly measure the total OH reactivity(TOR)in exhaust gas from light-duty gasoline vehicles in China.The TOR for China Ⅰ to Ⅵ-a vehicles was 15.6,16.3,8.4,2.6,1.5,and 1.6×10^(4) sec^(-1),respectively,reflecting a notable drop as emission standards were upgraded.The TOR was comparable between cold and warm starts.The missing OH reactivity(MOR)values for China Ⅰ to Ⅳ vehicles were close to zero with a cold start but were much higher with a warm start.The variations in oxygenated volatile organic compounds(OVOCs)under different emission standards and for the two start conditions were similar to those of the MOR,indicating that OVOCs and the missing species may have similar production processes.Online measurement revealed that the duration of the stable driving stage was the primary factor leading to the production of OVOCs and missing species.Our findings underscore the importance of direct measurement of TOR from vehicle exhaust and highlight the necessity of adding OVOCs and other organic reactive gases in future upgrades of emission standards,such that the vehicular contribution to atmospheric reactivity can be more effectively controlled.
基金supported by the National Natural Science Foundation of China,No.82001325Visiting Scholar Foundation of Shandong Province,No.20236-01(both to CS).
文摘Stroke is the leading cause of mortality globally,ultimately leading to severe,lifelong neurological impairments.Patients often suffer from a secondary cascade of damage,including neuroinflammation,cytotoxicity,oxidative stress,and mitochondrial dysfunction.Regrettably,there is a paucity of clinically available therapeutics to address these issues.Emerging evidence underscores the pivotal roles of astrocytes,the most abundant glial cells in the brain,throughout the various stages of ischemic stroke.In this comprehensive review,we initially provide an overview of the fundamental physiological functions of astrocytes in the brain,emphasizing their critical role in modulating neuronal homeostasis,synaptic activity,and blood-brain barrier integrity.We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke.Their well-established contributions to energy provision,metabolic regulation,and neurotransmitter homeostasis,as well as their emerging roles in mitochondrial recovery,neuroinflammation regulation,and oxidative stress modulation following ischemic injury,are discussed in detail.We also explore the cellular and molecular mechanisms underpinning these functions,with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention.In the final section of this review,we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke.These astrocyte-targeting strategies are categorized into traditional small-molecule drugs,microRNAs(miRNAs),stem cell-based therapies,cellular reprogramming,hydrogels,and extracellular vesicles.By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches,we aim to highlight the critical roles of astrocytes during and after stroke,particularly in the pathophysiological development in ischemic stroke.We also emphasize promising avenues for novel,astrocyte-targeted therapeutics that could become clinically available options,ultimately improving outcomes for patients with stroke.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
文摘Condensation of methyl 7-methylcoumarin-4-acetate(2)with primary amines and with an- thranilic acid gave 7-methyl-2-oxo-N-aryl-2H-[1]-benzopyran-4--acetamide(4a—d)and(7),respectively. Compound 7 underwent cyclization to give 2-(7-methyl-2-oxo-2H-[1]-benzopyran-4-yl)-methyl-4H-3,1- benzoxazin-4-one(3).The reaction of 3 with aromatic amines gave the corresponding quinazolone derivatives 5 which tautomerises to the thermodynamically more stable isomer 6,whereas its reaction with Grignard reagents and aromatic aldehydes gave 8a,8b,and 9a,9b,respectively.
文摘The reduced form of the nicotinamide-adenine dinucleotide coenzyme(NAD(P)H)plays an important role in many bio-reductions by transferring a hydride ion or an electronto the surrounding substrate(see eq.(1),R represents adenine dinucleotide).
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金supported by the Natural Science Fund of Fujian Province,No.2020J011058(to JK)the Project of Fujian Provincial Hospital for High-level Hospital Construction,No.2020HSJJ12(to JK)+1 种基金the Fujian Provincial Finance Department Special Fund,No.(2021)848(to FC)the Fujian Provincial Major Scientific and Technological Special Projects on Health,No.2022ZD01008(to FC).
文摘Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
文摘Nitric oxide(NO)is a gaseous molecule produced by 3 different NO synthase(NOS)isoforms:Neural/brain NOS(nNOS/bNOS,type 1),endothelial NOS(eNOS,type 3)and inducible NOS(type 2).Type 1 and 3 NOS are constitutively expressed.NO can serve different purposes:As a vasoactive molecule,as a neurotransmitter or as an immunomodulator.It plays a key role in cerebral ischemia/reperfusion injury(CIRI).Hypoxic episodes simulate the production of oxygen free radicals,leading to mitochondrial and phospholipid damage.Upon reperfusion,increased levels of oxygen trigger oxide synthases;whose products are associated with neuronal damage by promoting lipid peroxidation,nitrosylation and excitotoxicity.Molecular pathways in CIRI can be altered by NOS.Neuroprotective effects are observed with eNOS activity.While nNOS interplay is prone to endothelial inflammation,oxidative stress and apoptosis.Therefore,nNOS appears to be detrimental.The interaction between NO and other free radicals develops peroxynitrite;which is a cytotoxic agent.It plays a main role in the likelihood of hemorrhagic events by tissue plasminogen activator(t-PA).Peroxynitrite scavengers are currently being studied as potential targets to prevent hemorrhagic transformation in CIRI.
基金supported by the National Natural Science Foundation of China(No.41905108)the National Research Program for Key Issues in Air Pollution Control(No.DQ GG0532).
文摘To study the volatile organic compounds(VOCs)emission characteristics of industrial enterprises in China,6 typical chemical industries in Yuncheng City were selected as research objects,including the modern coal chemical industry(MCC),pharmaceutical industry(PM),pesticide industry(PE),coking industry(CO)and organic chemical industry(OC).The chemical composition of 91 VOCs was quantitatively analyzed.The results showed that the emission concentration of VOCs in the chemical industry ranged from 1.16 to 155.59 mg/m^(3).Alkanes were the main emission components of MCC(62.0%),PE(55.1%),and OC(58.5%).Alkenes(46.5%)were important components of PM,followed by alkanes(23.8%)and oxygenated volatile organic compounds(OVOCs)(21.2%).Halocarbons(8.6%-71.1%),OVOCs(9.7%-37.6%)and alkanes(11.2%-27.0%)were characteristic components of CO.The largest contributor to OFP was alkenes(0.6%-81.7%),followed by alkanes(9.3%-45.9%),and the lowest onewas alkyne(0%-0.5%).Aromatics(66.9%-85.4%)were the largest contributing components to SOA generation,followed by alkanes(2.6%-28.5%),and the lowest one was alkenes(0%-4.1%).Ethylene and BTEX were the key active species in various chemical industries.The human health risk assessment showed workers long-term exposed to the air in the chemical industrial zone had a high cancer and non-cancer risk during work,and BTEX and dichloromethane were the largest contributors.
基金supported by the National Natural Science Foundation of China (NSFC)Projects (Nos.42205105,42121004,and 42077190)the Science and Technology Project of Shaoguan (No.210811164532141)+3 种基金the National Key R&D Program of China (2022YFC3700604)the Science and Technology Program of Guangzhou City (No.202201010400)the Fundamental Research Funds for the Central Universities (No.21622319)the Research Center of Low Carbon Economy for Guangzhou Region (No.22JNZS50).
文摘Emission characteristics of biogenic volatile organic compounds(BVOCs)from dominant tree species in the subtropical pristine forests of China are extremely limited.Here we conducted in situ field measurements of BVOCs emissions from representative mature evergreen trees by using dynamic branch enclosures at four altitude gradients(600-1690ma.s.l.)in the Nanling Mountains of southern China.Composition characteristics as well as seasonal and altitudinal variations were analyzed.Standardized emission rates and canopyscale emission factors were then calculated.Results showed that BVOCs emission intensities in the wet season were generally higher than those in the dry season.Monoterpenes were the dominant BVOCs emitted from most broad-leaved trees,accounting for over 70%of the total.Schima superba,Yushania basihirsuta and Altingia chinensis had relatively high emission intensities and secondary pollutant formation potentials.The localized emission factors of isoprene were comparable to the defaults in the Model of Emissions of Gases and Aerosols fromNature(MEGAN),while emission factors of monoterpenes and sesquiterpenes were 2 to 58 times of those in the model.Our results can be used to update the current BVOCs emission inventory in MEGAN,thereby reducing the uncertainties of BVOCs emission estimations in forested regions of southern China.
基金supported by the National Natural Science Foundation of China(82171386,81971161,and 82201536)the Shanghai Science and Technology Development Foundation(22YF1458600)+1 种基金the Scientifc Foundation from Naval Medical University(2021QN08)the STI2030-Major Projects from Ministry of Science and Technology of China(2022ZD0204700).
文摘In the mammalian central nervous system(CNS),astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics.These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological,molecular,and functional changes to adopt so-called‘reactive’states in response to CNS injury or disease.In recent years,interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances.Here,we will review and discuss the wellestablished and emerging astroglial biology and functions,with emphasis on their potential as therapeutic targets for CNS injury,including traumatic and ischemic injury.This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
基金supported by the National Natural Science Foundation of China(Grant No.32472185)the Key Research and Development Program of Hubei Province,China(Grant No.2022BFE003)the Hubei Agriculture Science and Technology Innovation Center program,and the National Rice Industry Technology System,China(Grant No.CARS-01-07).
文摘Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice.
