Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia.Inhibiting oxidative stress has been considered as an effective approach for stroke treatment.Edaravone,a free radical scavenger,ha...Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia.Inhibiting oxidative stress has been considered as an effective approach for stroke treatment.Edaravone,a free radical scavenger,has been shown to prevent cerebral ischemic injury.However,the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions(O_2-(·-)).Here,we report that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine,a novel small-molecule compound structurally related to edaravone,showed a stronger inhibitory effect on oxidative stress in vitro.In vivo,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde,two proteins crucial for oxidative stress,suggesting a strengthened antioxidant system.Moreover,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability.Then,we found that 2-methyl-5 Hbenzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone.More importantly,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period,indicating enhanced neuroprotection,sensorimotor function and spatial memory.Together,these findings suggest that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.展开更多
Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly prod...Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.展开更多
Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke.The narrow treatment time window is still to be solved.Given that the ischemic core expanded ove...Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke.The narrow treatment time window is still to be solved.Given that the ischemic core expanded over days,treatment with an extended time window is anticipated.Bestrophin1(BEST1)belongs to a bestrophin family of calcium-activated chloride channels.We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice.Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits.Using electrophysiological recordings,we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity.Finally,we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6—72 h post-ischemia in rodents.This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions.Our study identifies the glutamatereleasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.展开更多
In order to assess the dynamics of molecular conversion,scientists simulated the low-temperature synthesis of polycyclic aromatic hydrocarbons(PAHs)in Titan’s atmosphere[1],and noticed the transformation(hydrogenatio...In order to assess the dynamics of molecular conversion,scientists simulated the low-temperature synthesis of polycyclic aromatic hydrocarbons(PAHs)in Titan’s atmosphere[1],and noticed the transformation(hydrogenation,oxygenation,and hydroxylation to complex molecules)of PAHs under interstellar medium conditions.Geological hydrothermal systems have also drawn attention as potential key sites for various organic synthesis and transformation reactions[2,3].Thus the formation of abiotic CH4[4],which has proven to be an important component of deep hydrothermal fluids that are generated outside the temperature regime envisaged for thermogenic gases,have long been reported in a range of global hydrothermal sites,including mid-ocean ridges,continental rifts,pre-orogenic and subduction zones,back-arcs,hot springs,and volcanically-active areas.These transformation processes have been suggested to occur at the water–mineral interface.There is compelling evidence for the generation of C-H chain molecules from inorganic chemicals via abiotic reactions(e.g.,Fischer-Tropsch synthesis of CH4)in laboratory and field studies[5,6].However,a huge gap remains in the understanding of carbon and hydrogen evolution and heterocyclization from C-H chain molecules to complex heterocyclic materials and then possible hydrophobic or hydrophilic macromolecules,and the corresponding reaction mechanism(s).The occurrence of abundant and complex heterocyclic molecules formed through abiotic processes is rare in natural regions associated with deep fluid movement and activity。展开更多
Background Poststroke depression and anxiety,independent predictor of poor functional outcomes,are common in the acute phase of stroke.Up to now,there is no fast-onset antidepressive and anxiolytic agents suitable for...Background Poststroke depression and anxiety,independent predictor of poor functional outcomes,are common in the acute phase of stroke.Up to now,there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke.ZL006-05,a dual-target analgesic we developed,dissociates nitric oxide synthase from postsynaptic density-95 while potentiatesα2-containingγ-aminobutyric acid type A receptor.This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.Methods Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice.Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride)staining or Nissl staining.Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores.Grid-walking,cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions.Spatial learning was assessed using Morris water maze task.Depression and anxiety were induced by unpredictable chronic mild stress.Depressive behaviours were assessed by tail suspension,forced swim and sucrose preference tests.Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests.Pharmacokinetics,toxicokinetics and long-term toxicity studies were performed in rats.Results Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly,with a treatment window of 12 hours after ischemia,and reduced plasminogen activato-induced haemorrhagic transformation.ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice,had antidepressant and anxiolytic effects in stroke mice.ZL006-05 crossed the blood-brain barrier and distributed into the brain rapidly,and had a high safety profile in toxicokinetics and long-term toxicological studies.Conclusion ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy,safety and targeting of clinical issues.展开更多
As a relatively stable craton block in the earth system, the petroliferous basin is influenced by the evolution of the earth system from the early development environment of source rocks, hydrocarbon formation, and re...As a relatively stable craton block in the earth system, the petroliferous basin is influenced by the evolution of the earth system from the early development environment of source rocks, hydrocarbon formation, and reservoir dissolution to hydrocarbon accumulation or destruction. As a link between the internal and external factors of the basin, deep fluids run through the whole process of hydrocarbon formation and accumulation through organic-inorganic interaction. The nutrients carried by deep fluids promote the bloom of hydrocarbon-generating organisms and extra addition of carbon and hydrogen source, which are beneficial to the development of high-quality source rock and enhancement of the hydrocarbon generation potential. The energy carried by the deep fluid promotes the early maturation of the source rock and facilitates the hydrocarbon generation by activation and hydrogenation in high-mature hydrocarbon sources. The dissolution alteration of carbonate rocks and clastic reservoirs by CO_2-rich deep fluids improves the deep reservoir space, thus extending the oil and gas reservoir space into greater depth. The extraction of deeply retained crude oil by deep supercritical CO_2 and the displacement of CH_4 in shale have both improved the hydrocarbon fluidity in deep and tight reservoirs. Simultaneously, the energy and material carried by deep fluids(C, H, and catalytic substances) not only induce inorganic CH_4 formation by Fischer-Tropsch(F-T) synthesis and "hydrothermal petroleum" generation from organic matter by thermal activity but also cause the hydrothermal alteration of crude oil from organic sources. Therefore, from the perspective of the interaction of the earth's sphere, deep fluids not only input a significant amount of exogenous C and H into sedimentary basins but also improve the reservoir space for oil and gas, as well as their enrichment and accumulation efficiencies.展开更多
Helium gas is a scarce but important strategic resource,which is usually associated with natural gas.Presently,only one extra-large helium-rich gas field has been found in China:the Hetianhe Gas Field in the Tarim Bas...Helium gas is a scarce but important strategic resource,which is usually associated with natural gas.Presently,only one extra-large helium-rich gas field has been found in China:the Hetianhe Gas Field in the Tarim Basin.This paper reports a new example,the Dongsheng Gas Field(DGF)in the Ordos Basin.In this study,92 natural gas samples from the DGF were analyzed for helium content and isotope composition using isotope mass spectrometry.The natural gas samples were found to have an average helium content of 0.133%,with 65(70.7%)of the samples having a helium content of 0.1%or more.Based on the proven natural gas reserves of the DGF,the proven geological helium reserves were calculated to be 1.96×10^(8)m^(3),suggesting that it represents the first extra-large helium-rich natural gas reservoir to be hosted in tight sandstone in China.The ^(3)He/^(4)He ratios of 5 natural gas samples from the DGF are within the range of 3.03×10^(−8)–3.44×10^(−8).Therefore,the helium in the gas field is thought to be of typical crustal origin and to have formed in the granitic basement that is rich in uranium and thorium.The accumulation of helium-rich natural gas was controlled by regional tectonic activities.Activity along the fault connecting the reservoir with the basement caused release of the helium gas,which entered the overlying strata along the fault and accumulated with conventional hydrocarbon gas.Based on the structural background and the distribution of helium source rocks in the Ordos Basin,the main helium source rocks with high exploration potential are located in deep strata within the north and middle parts of the basin.展开更多
Phosphofructokinase-1(PFK-1),a major regulatory glycolytic enzyme,has been implicated in the functions of astrocytes and neurons.Here,we report that PFK-1 negatively regulates neurogenesis from neural stem cells(N...Phosphofructokinase-1(PFK-1),a major regulatory glycolytic enzyme,has been implicated in the functions of astrocytes and neurons.Here,we report that PFK-1 negatively regulates neurogenesis from neural stem cells(NSCs)by targeting pro-neural transcriptional factors.Using in vitro assays,we found that PFK-1 knockdown enhanced,and PFK-1 overexpression inhibited the neuronal differentiation of NSCs,which was consistent with the findings from NSCs subjected to 5 h of hypoxia.Meanwhile,the neurogenesis induced by PFK-1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage.Similarly,in vivo knockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus.Finally,we demonstrated that the neurogenesis mediated by PFK-1 was likely achieved by targeting mammalian achaete-scute homologue-1(Mash 1),neuronal differentiation factor(NeuroD),and sex-determining region Y(SRY)-related HMG box 2(Sox2).All together,our results reveal PFK-1 as an important regulator of neurogenesis.展开更多
Lacustrine shale is an important target for the exploration of unconventional oil and gas in China beyond marine shale gas.However,the formation environment of lacustrine shale differs from that of marine shale,result...Lacustrine shale is an important target for the exploration of unconventional oil and gas in China beyond marine shale gas.However,the formation environment of lacustrine shale differs from that of marine shale,resulting in a different reservoir composition,organic matter,oil and gas content,and hydrocarbon mobility.In this study,the Chang 7 shale of the Yanchang Formation in the Ordos Basin was used to analyze the effect of volcanic activity on the paleoproductivity and preservation conditions during the formation of lacustrine shale.The results show that algae and bacteria were developed before the eruption.After the eruption,the number of bacteria declined,but the increased prosperity of algae reflects that the volcanic activity enhanced ancient productivity.The sulfate generated by volcanic activity promotes bacterial sulfate reduction,and the produced H_(2)S leads to a strong reducing environment in the waterbody,which is conducive to the preservation of organic matter.Organic geochemical analysis shows that the black shale in the shale strata has a high total organic carbon(TOC)content and strong hydrocarbon generation potential,whereas the tuff has a low TOC content and can scarcely generate hydrocarbons,indicating that the tuff deposited by volcanic activity cannot be considered as effective source rock.In terms of storage space,shale is mainly laminar and dispersed,and it includes organic and inorganic pores.The development of organic pores is affected by thermal maturity,whereas inorganic pores mainly occur between detrital particles and crystals.Tuff is mainly supported by heterogeneous matrix and associated with alteration.Its pores include inter-and intragranular mineral pores.The development of tight sandstone pores is affected by compaction,cementation,and dissolution,which mainly consist of intra-and intergranular pores.The Chang 7 lacustrine shale generally contains oil,but different lithologies have different oil drainage efficiencies.Sandstone and shale exhibit the best and worst oil drainage efficiency,respectively.It is mainly affected by the pore size distribution,fluid properties,and rock wettability.Therefore,the development of shale oil should mainly focus on lacustrine shale formations with interbeds.The mutual dissolution of organic matter and hydrocarbons in the shale section leads to the poor mobility and difficult development of hydrocarbons.展开更多
基金supported by grants from NationalNatural Science Foundation of China(31530091,91232304)National Key Research and Development Program of China(2016YFC1306703)+1 种基金Natural Science Foundation of Jiangsu Province(BK20140905)by the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine
文摘Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia.Inhibiting oxidative stress has been considered as an effective approach for stroke treatment.Edaravone,a free radical scavenger,has been shown to prevent cerebral ischemic injury.However,the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions(O_2-(·-)).Here,we report that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine,a novel small-molecule compound structurally related to edaravone,showed a stronger inhibitory effect on oxidative stress in vitro.In vivo,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde,two proteins crucial for oxidative stress,suggesting a strengthened antioxidant system.Moreover,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability.Then,we found that 2-methyl-5 Hbenzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone.More importantly,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period,indicating enhanced neuroprotection,sensorimotor function and spatial memory.Together,these findings suggest that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.
基金supported by grants from National Natural Science Foundation of China (82090042, 31530091,81870912)National Key Research and Development Program of China (2016YFC1306703)。
文摘Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.
基金supported by STI2030-Major Project(2022ZD0211700,China)National Natural Science Foundation of China(82171293,82090042 and 82171368)Natural Science Foundation of Jiangsu Province(BK20211255,China)。
文摘Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke.The narrow treatment time window is still to be solved.Given that the ischemic core expanded over days,treatment with an extended time window is anticipated.Bestrophin1(BEST1)belongs to a bestrophin family of calcium-activated chloride channels.We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice.Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits.Using electrophysiological recordings,we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity.Finally,we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6—72 h post-ischemia in rodents.This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions.Our study identifies the glutamatereleasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.
基金supported by the National Natural Science Foundation of China(41625009 and U20B6001)Research support to Qi Fu from United States National Science Foundation CAREER program(OCE-1652481)+1 种基金American Chemical Society Petroleum Research Fund(54474-DNI2)the support from the Tencent Foundation through the XPLORER PRIZE,China。
文摘In order to assess the dynamics of molecular conversion,scientists simulated the low-temperature synthesis of polycyclic aromatic hydrocarbons(PAHs)in Titan’s atmosphere[1],and noticed the transformation(hydrogenation,oxygenation,and hydroxylation to complex molecules)of PAHs under interstellar medium conditions.Geological hydrothermal systems have also drawn attention as potential key sites for various organic synthesis and transformation reactions[2,3].Thus the formation of abiotic CH4[4],which has proven to be an important component of deep hydrothermal fluids that are generated outside the temperature regime envisaged for thermogenic gases,have long been reported in a range of global hydrothermal sites,including mid-ocean ridges,continental rifts,pre-orogenic and subduction zones,back-arcs,hot springs,and volcanically-active areas.These transformation processes have been suggested to occur at the water–mineral interface.There is compelling evidence for the generation of C-H chain molecules from inorganic chemicals via abiotic reactions(e.g.,Fischer-Tropsch synthesis of CH4)in laboratory and field studies[5,6].However,a huge gap remains in the understanding of carbon and hydrogen evolution and heterocyclization from C-H chain molecules to complex heterocyclic materials and then possible hydrophobic or hydrophilic macromolecules,and the corresponding reaction mechanism(s).The occurrence of abundant and complex heterocyclic molecules formed through abiotic processes is rare in natural regions associated with deep fluid movement and activity。
基金the National Natural Science Foundation of China(82090042,81870912,82171293)the National Key Research and Development Program of China(2021YFA1101803)the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine.
文摘Background Poststroke depression and anxiety,independent predictor of poor functional outcomes,are common in the acute phase of stroke.Up to now,there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke.ZL006-05,a dual-target analgesic we developed,dissociates nitric oxide synthase from postsynaptic density-95 while potentiatesα2-containingγ-aminobutyric acid type A receptor.This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.Methods Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice.Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride)staining or Nissl staining.Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores.Grid-walking,cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions.Spatial learning was assessed using Morris water maze task.Depression and anxiety were induced by unpredictable chronic mild stress.Depressive behaviours were assessed by tail suspension,forced swim and sucrose preference tests.Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests.Pharmacokinetics,toxicokinetics and long-term toxicity studies were performed in rats.Results Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly,with a treatment window of 12 hours after ischemia,and reduced plasminogen activato-induced haemorrhagic transformation.ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice,had antidepressant and anxiolytic effects in stroke mice.ZL006-05 crossed the blood-brain barrier and distributed into the brain rapidly,and had a high safety profile in toxicokinetics and long-term toxicological studies.Conclusion ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy,safety and targeting of clinical issues.
基金supported by Na-tional Natural Science Foundation of China (Grant Nos. 41625009,U1663201 and 41872122)Strategic Priority Research Program of theChinese Academy of Sciences (Grant No. XDA14010404)National KeyFoundational Research and Development Project (Grant No.2017YFC0603102)
文摘As a relatively stable craton block in the earth system, the petroliferous basin is influenced by the evolution of the earth system from the early development environment of source rocks, hydrocarbon formation, and reservoir dissolution to hydrocarbon accumulation or destruction. As a link between the internal and external factors of the basin, deep fluids run through the whole process of hydrocarbon formation and accumulation through organic-inorganic interaction. The nutrients carried by deep fluids promote the bloom of hydrocarbon-generating organisms and extra addition of carbon and hydrogen source, which are beneficial to the development of high-quality source rock and enhancement of the hydrocarbon generation potential. The energy carried by the deep fluid promotes the early maturation of the source rock and facilitates the hydrocarbon generation by activation and hydrogenation in high-mature hydrocarbon sources. The dissolution alteration of carbonate rocks and clastic reservoirs by CO_2-rich deep fluids improves the deep reservoir space, thus extending the oil and gas reservoir space into greater depth. The extraction of deeply retained crude oil by deep supercritical CO_2 and the displacement of CH_4 in shale have both improved the hydrocarbon fluidity in deep and tight reservoirs. Simultaneously, the energy and material carried by deep fluids(C, H, and catalytic substances) not only induce inorganic CH_4 formation by Fischer-Tropsch(F-T) synthesis and "hydrothermal petroleum" generation from organic matter by thermal activity but also cause the hydrothermal alteration of crude oil from organic sources. Therefore, from the perspective of the interaction of the earth's sphere, deep fluids not only input a significant amount of exogenous C and H into sedimentary basins but also improve the reservoir space for oil and gas, as well as their enrichment and accumulation efficiencies.
基金supported by the National Natural Science Foundation of China (Grant Nos. U20B6001, 42141021, 41625009, U19B6003, 41902160, 42172149 and 41872112)the China Postdoctoral Science Foundation (Grant Nos. 2019M650967, 2020T130721)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA14010404)
文摘Helium gas is a scarce but important strategic resource,which is usually associated with natural gas.Presently,only one extra-large helium-rich gas field has been found in China:the Hetianhe Gas Field in the Tarim Basin.This paper reports a new example,the Dongsheng Gas Field(DGF)in the Ordos Basin.In this study,92 natural gas samples from the DGF were analyzed for helium content and isotope composition using isotope mass spectrometry.The natural gas samples were found to have an average helium content of 0.133%,with 65(70.7%)of the samples having a helium content of 0.1%or more.Based on the proven natural gas reserves of the DGF,the proven geological helium reserves were calculated to be 1.96×10^(8)m^(3),suggesting that it represents the first extra-large helium-rich natural gas reservoir to be hosted in tight sandstone in China.The ^(3)He/^(4)He ratios of 5 natural gas samples from the DGF are within the range of 3.03×10^(−8)–3.44×10^(−8).Therefore,the helium in the gas field is thought to be of typical crustal origin and to have formed in the granitic basement that is rich in uranium and thorium.The accumulation of helium-rich natural gas was controlled by regional tectonic activities.Activity along the fault connecting the reservoir with the basement caused release of the helium gas,which entered the overlying strata along the fault and accumulated with conventional hydrocarbon gas.Based on the structural background and the distribution of helium source rocks in the Ordos Basin,the main helium source rocks with high exploration potential are located in deep strata within the north and middle parts of the basin.
基金supported by grants from the National Natural Science Foundation of China(91232304,31530091,and 81571188)the National Basic Research Development Program(973 Program)of China(2011CB504404)+1 种基金the Natural Science Foundation of Jiangsu Province,China(BK2011029 and BK20130040)the Collaborative Innovation Center For Cardiovascular Disease Translational Medicine
文摘Phosphofructokinase-1(PFK-1),a major regulatory glycolytic enzyme,has been implicated in the functions of astrocytes and neurons.Here,we report that PFK-1 negatively regulates neurogenesis from neural stem cells(NSCs)by targeting pro-neural transcriptional factors.Using in vitro assays,we found that PFK-1 knockdown enhanced,and PFK-1 overexpression inhibited the neuronal differentiation of NSCs,which was consistent with the findings from NSCs subjected to 5 h of hypoxia.Meanwhile,the neurogenesis induced by PFK-1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage.Similarly,in vivo knockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus.Finally,we demonstrated that the neurogenesis mediated by PFK-1 was likely achieved by targeting mammalian achaete-scute homologue-1(Mash 1),neuronal differentiation factor(NeuroD),and sex-determining region Y(SRY)-related HMG box 2(Sox2).All together,our results reveal PFK-1 as an important regulator of neurogenesis.
基金supported by the National Natural Science Foundation of China(Grant Nos.41625009,U20B6001,42002139,42090025)the Strategic Priority Research Program of the Chinese Academy of Sciences,China(Grant No.XDA14010404)Tencent Xplorer Prize。
文摘Lacustrine shale is an important target for the exploration of unconventional oil and gas in China beyond marine shale gas.However,the formation environment of lacustrine shale differs from that of marine shale,resulting in a different reservoir composition,organic matter,oil and gas content,and hydrocarbon mobility.In this study,the Chang 7 shale of the Yanchang Formation in the Ordos Basin was used to analyze the effect of volcanic activity on the paleoproductivity and preservation conditions during the formation of lacustrine shale.The results show that algae and bacteria were developed before the eruption.After the eruption,the number of bacteria declined,but the increased prosperity of algae reflects that the volcanic activity enhanced ancient productivity.The sulfate generated by volcanic activity promotes bacterial sulfate reduction,and the produced H_(2)S leads to a strong reducing environment in the waterbody,which is conducive to the preservation of organic matter.Organic geochemical analysis shows that the black shale in the shale strata has a high total organic carbon(TOC)content and strong hydrocarbon generation potential,whereas the tuff has a low TOC content and can scarcely generate hydrocarbons,indicating that the tuff deposited by volcanic activity cannot be considered as effective source rock.In terms of storage space,shale is mainly laminar and dispersed,and it includes organic and inorganic pores.The development of organic pores is affected by thermal maturity,whereas inorganic pores mainly occur between detrital particles and crystals.Tuff is mainly supported by heterogeneous matrix and associated with alteration.Its pores include inter-and intragranular mineral pores.The development of tight sandstone pores is affected by compaction,cementation,and dissolution,which mainly consist of intra-and intergranular pores.The Chang 7 lacustrine shale generally contains oil,but different lithologies have different oil drainage efficiencies.Sandstone and shale exhibit the best and worst oil drainage efficiency,respectively.It is mainly affected by the pore size distribution,fluid properties,and rock wettability.Therefore,the development of shale oil should mainly focus on lacustrine shale formations with interbeds.The mutual dissolution of organic matter and hydrocarbons in the shale section leads to the poor mobility and difficult development of hydrocarbons.