OBJECTIVE To explore the mechanism of action of Qihuang Zhuyu formula(QHZYF)in improving depression after myocardial infarction(MI),with a focus on revealing its regulatory effect on the inflammatory response of the h...OBJECTIVE To explore the mechanism of action of Qihuang Zhuyu formula(QHZYF)in improving depression after myocardial infarction(MI),with a focus on revealing its regulatory effect on the inflammatory response of the heart and brain.METHODS The active ingredients of QHZYF and the action targets for intervening in depression after MI were analyzed by using ultra-performance liquid chromatography-high-resolution mass spectrometry(UPLC-Q-TOF/MS)combined with network pharmacology and molecular docking.A rat model of depression after MI was established by ligation of the left anterior descending coronary artery combined with chronic restraint stress.Echocardiography was used to evaluate cardiac function,hematoxylin-eosin(HE)and Masson staining were used to evaluate myocardial injury,behavioral tests were used to detect melancholic behaviors,Nissl staining was used to evaluate hippocampal neuron injury.Western blot detection of tumor necrosis factor receptor 2(TNFR2),phosphatidylinositol-3-kinase(PI3K),phosphorylated seronine protein kinase(p-AKT),seronine protein kinase(AKT),tumor necrosis factor receptor 1(TNFR1),phosphorylated nuclear factorκB(p-NF-κB),and nuclear factorκB(NF-κB)in cardiac and hippocampal tissues was conducted.The levels of serum IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of TNFR1 and TNFR2 was detected by immunohistochemical technique(IHC).In vitro experiments,co-culture of rat cardiomyocyte line H9C2 cells and rat adrenal pheochromocytoma cell line with high differentiation PC12 cells was conducted,TNFR1 inhibitor(H398)and TNFR2 agonist(C-6His)were administered for intervention,and the expression of TNFR2,PI3K,p-AKT,AKT,TNFR1,NF-κB,p-NF-κB was detected by Western blot.Observe the apoptosis of cells by TUNEL staining,ELISA was used to detect the levels of IL-6 and IL-10 in the cell supernatant.RESULTS Network pharmacological analysis indicates that the TNF signaling pathway was a key target for the treatment of depression after MI with the QHZYF.In vivo experiments have confirmed that the intervention of QHZYF could significantly improve the cardiac function,myocardial tissue and hippocampal neuron structure damage of depressed rats after MI,and improve their depression-like behaviors.At the molecular level,the high-dose group of QHZYF significantly upregulated TNFR2,p-AKT/AKT,and IL-10 in cardiac and hippocampal tissues(P<0.01),and downregulated TNFR1,p-NF-κB/NF-κB and IL-6(P<0.01).In vitro experiments showed that the drug-containing serum of QHZYF significantly upregulated the expression of TNFR2,p-AKT/AKT and IL-10 in H9C2 and PC12 cells(P<0.01),downregulated the expression of TNFR1,p-NF-κB/NF-κB and IL-6(P<0.01),and significantly inhibited cell apoptosis(P<0.01).Furthermore,experiments on the combined application of H398 or C-6His further confirmed that its protective and anti-inflammatory effects were mediated by regulating the TNFR2/PI3K/AKT and TNFR1/NF-κB pathways.CONCLUSION QHZYF improves the homeostasis of heart and brain inflammation by regulating the TNF pathway,and ameliorates myocardial injury and depressive state in depressed rats after MI.展开更多
OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tiv...OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tive.Here,we hypothesize that dysfunction of central TGR5 may contribute to the pathogene⁃sis of depression.METHODS In well-established chronic social defeat stress(CSDS)and chronic restraint stress(CRS)models of depression,we investigated the functional roles of TGR5 in CA3 pyramidal neurons(PyNs)and underlying mech⁃anisms of the neuronal circuit in depression(for in vivo studies,n=10;for in vitro studies,n=5-10)using fiber photometry;optogenetic,chemoge⁃netic,pharmacological,and molecular profiling techniques;and behavioral tests.RESULTS Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs.Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777,a specific agonist,protected against CSDS and CRS,exerting sig⁃nificant antidepressant-like effects that were mediated via CA3 PyN activation.Conversely,genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behav⁃iors.Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS.Silencing and stimula⁃tion of CA3 PyNs→somatostatin-GABAergic(gamma-aminobutyric acidergic)neurons of the dorsolateral septum circuit bidirectionally regulat⁃ed depression-like behaviors,and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.CON⁃CLUSION TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission,suggesting that TGR5 could be a novel target for developing antidepressants.展开更多
OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stre...OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress(CSDS)-induced depressive-like behaviors and its related mechanism.METHODS AND RE⁃SULTS The daily oral administration of Rb1(35 and 70 mg·kg-1)and imipramine(15 mg·kg-1)for 28 d significantly reversed the social avoidance behavior,anhedonia,and behavioral despair via CSDS exposure,as demonstrated by the consid⁃erable elevation in the time in the zone in social interaction test and consumption of sucrose solu⁃tion in sucrose preference test and decrease of immobility time in forced swim test.Moreover,Rb1 obviously restored the CSDS-induced decrease of BDNF-signaling pathway and hippo⁃campal neurogenesis.Rb1 significantly increased the hippocampal levels of ERK,AKT,and CREB phosphorylation and increased the number of DCX+cells in DG.Importantly,the antidepres⁃sant effects of Rb1 were completely blocked in mice by using K252a(the nonselective tyrosine kinase B inhibitor).CONCLUSION Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression,and its effects was facilitated by enhancing the BDNF signaling cas⁃cade and up-regulation of hippocampal neuro⁃genesis.展开更多
Petrographic analysis combined with various techniques, such as scanning electron microscopy and X-ray diffraction, was used to assess the timing of growth and original mineral cements, the controls on reservoir and r...Petrographic analysis combined with various techniques, such as scanning electron microscopy and X-ray diffraction, was used to assess the timing of growth and original mineral cements, the controls on reservoir and reservoir quality of the fourth member sandstones of Shahejie formation (Es4). The Es4 sandstones are mostly arkose and lithic arkose, rarely feldspathic litharenite, with an average mass fraction of quartz 51.6%, feldspar 33.8% and rock fragments 14.6% (Q51.6F33.8R14.6). They have an average framework composition (mass fraction) of quartz 57.10%, K-feldspar 5.76%, sodium-calcium feldspar 13.00%, calcite 5.77%, dolomite 5.63%, siderite 0.95%, pyrite 0.30%, anhydrite 0.04%, and clay mineral 11.46%. The diagenentic minerals typically include kaolinite, illite-smectite (I/S), illite, chlorite, authigenetic quartz and feldspar, and carbonate and pyrite. Es4 sandstone has undergone stages A and B of eodiagenesis, and now, it is experiencing stage A of mesodiagenesis. Reservoir quality is predominantly controlled by the mechanical compaction, for example, 45.65% of the original porosity loss is related to compaction. The original porosity loss related with cementation is only 26.00%. The reservoir quality is improved as a result of dissolution of feldspar, rock fragment and so forth. The porosity evolved from dissolution varies from 3% to 4%.展开更多
Sediments in the Liushagang Formation of Late Eocene form a group of key hydrocarbon play fairways in the Beibuwan Basin,South China Sea.As an important reservoir-forming combination,the Liushagang Formation consists ...Sediments in the Liushagang Formation of Late Eocene form a group of key hydrocarbon play fairways in the Beibuwan Basin,South China Sea.As an important reservoir-forming combination,the Liushagang Formation consists of deltaic siliciclastic and show clear sedimentary cyclicity.According to paleontology research and stratigraphic correlation,the boundary between Liushagang Formation(Els)and Weizhou Formation(Ewz)is regarded as the Eocene-Oligocene boundary.The oxygen isotope dating for well cores from the top of the first Member of Liushagang Formation(Els1)and the bottom of the third Member of Weizhou Formation(Ewz3)give an isochron age of 35.2 Ma.Here,we use GR logging data as a paleoenvironmental proxy to conduct a detailed cyclostratigraphic study of the Els1 in the Bailian Sag,Fushan Depression.Power spectra,evolutionary fast Fourier transformation and wavelet analysis all reveal significant sedimentary cycles in Els1.The ratios of cycle wavelengths in these stratigraphic units are 21?5?2.8?1.2?1,and are interpreted as Milankovitch cycles of 400 ka and 96 ka eccentricity,52 ka obliquity,22ka and 19 ka precession cycles,respectively.An astronomical time scale is established by tuning filtered 96 ka eccentricity cycles to a target curve of Well L2 in the Bailian Sag.Based on regional stratigraphic framework,combined with seismic,cores and logging data,the HST of the first member of the Liushagang Formation(Els1)delta in Well L2 was divided into six parasequence sets named Ps1-Ps6.According to the spectrum analysis by Simple Lomb periodogram from PAST program packages,the sediment accumulation rate of each parasequence sets first increased and then decreased as time went by.The sediment accumulation rate of Ps4 reached the maximum(0.127 m/ka)during the most prosperous period of delta prograding.Finally,the duration of each period of parasequence sets and more accurate geological age were calculated on the basis of sediment accumulation rate.The ages of each depth are precisely estimated and provide new constraints on the Late Eocene.展开更多
At present,depression is treated with antidepressant drugs and assisted with psychotherapy and physical therapy,and these expensive and time-consuming treatment methods often end prematurely and result in a prolonged ...At present,depression is treated with antidepressant drugs and assisted with psychotherapy and physical therapy,and these expensive and time-consuming treatment methods often end prematurely and result in a prolonged course w ithout effective symptom relief. Therefore,based on the neurofeedback therapy,a novel depression rehabilitation method using a Virtual-Reality(VR) game framew ork is proposed. In this VR game framew ork,an innovative threeelectrode Electroencephalography(EEG) collector is used to record patients' EEG data. The data are processed and converted into feedback features,and the feedback w ill be displayed to patients in real time through a VR headset. Patients can adjust their psychological activity based on the feedback,and relieve their physiological dysfunction effectively. The framew ork also provides a data storage module,w hich may offer therapists w ays to assess patients' rehabilitation results in a long term,as w ell as provide possibility to continue tow ards better algorithm of feedback features w ith data-mining.The prototype system is tested in the framew ork,and the experimental results prove the effectiveness of the framew ork in depression rehabilitation.展开更多
OBJECTIVE Hyperactivityof hypothalamic-pituitary-adrenal(HPA) axis is an important aetiological risk factor for the development of depression. Previous studies have demonstrated that the phenolic monomer baicalin has ...OBJECTIVE Hyperactivityof hypothalamic-pituitary-adrenal(HPA) axis is an important aetiological risk factor for the development of depression. Previous studies have demonstrated that the phenolic monomer baicalin has antidepressant-like effects and decreases serum corticosterone levels.However,the mechanism by which baicalin regulates hyperactivity of HPA axis remains unclear. This work aimed to investigate the effects of baicalin on hyperactivity of HPA axis using the olfactory bulbectomised(OBX) rat model of depression. METHODS Animals were anaesthetised with 10% chloral hydrate(3.3 mL·kg^(-1),ip). Using disinfected surgical equipment,the skull covering the olfactory bulbs was exposed by a midline incision. Two burr holes(2 mm diameter) were drilled 8 mm anterior to the bregma and 2 mm lateral to the midline. Both olfactory bulbs were aspirated and the holes filled with glass ionomer cement. The scalp was sutured closed. Sham-operated rats underwent every surgical procedure except the aspiration of the bulbs. The animals received penicillin(8×10~5U) intramuscularly(0.2 mL/300 g) once per day for 3 d post-surgery to prevent infection,and were subsequently housed alone in polypropylene cages. The experiments continued after 14 d of rehabilitation. The following groups were used for experiments: sham-operated(underwent surgical procedure without aspiratedolfactory bulbs and administration of vehicle only),OBX-model(underwent every surgical procedure and administration of vehicle only),OBX-amitriptyline treated(10 mg·kg^(-1)),and OBX-baicalin treatment(20 and 40 mg·kg^(-1)). Amitriptyline and baicalin were dissolved in physiological saline. RESULTS We examined how baicalin altered OBX-induced changes in serum glucocorticoid level as wel as inflammatory responses,sirtuin 1(SIRT1) expression,and p65 acetylation in the hypothalamus. Similar experiments were performed to analyse the effects of baicalin on lipopolysaccharide-induced inflammatory responses inhypothalamus. CONCLUSION Our results indicate that activation of the SIRT1 in the hypothalamus contributes to hyperactivity of HPA axis,which can be alleviated by baicalin.展开更多
Reservoirs can be developed in the sediment gravity flows.However,high quality reservoirs are found widespread in sediment gravity flows of Gangzhong area,Huanghua depression,Bohai Bay Basin,East China.Characteristics...Reservoirs can be developed in the sediment gravity flows.However,high quality reservoirs are found widespread in sediment gravity flows of Gangzhong area,Huanghua depression,Bohai Bay Basin,East China.Characteristics and formation of these reservoirs are key problems to be solved.Through comprehensive analysis of thin section petrography,scanning electron microscopy and X-ray diffraction,two distinct rules were obtained.1) These high quality reservoirs have apparent characteristics:lithology consists mainly of medium-fine grained sands; moderately-well sorted and rounded; intergranular pores dominating >70% of the entire pores,surface per unit pore volume reaches 15%; average porosity is 21% and average permeability is 55×10-3 μm2.2) Types of sedimentary microfacies and dissolution strongly control on the formation of high quality reservoirs.Main channels and sandy braided bars have the best reservoir properties.Because that sediments are mainly medium-fine grained sands in high-energy environments.The favorable primary porosity and permeability may promote calcite cementation and help to produce more secondary pores.Besides,at the depth of 2500-3200 m,basically matching threshold of oil generation,organic acid expelled when organic matter became mature,and H+ released during clay mineral transformation.These both result in the dissolution of calcite cements and create large volume pores,then physical properties improve correspondingly.Moreover,deep hydrothermal fluid intrusion may also have impacts on the development of secondary pores.展开更多
OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herba...OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.展开更多
Objective:Sleep quality in kidney transplant recipients is closely associated with symptoms of fatigue and depression.Although subjective assessment tools like the Pittsburgh Sleep Quality Index and the Richards-Campb...Objective:Sleep quality in kidney transplant recipients is closely associated with symptoms of fatigue and depression.Although subjective assessment tools like the Pittsburgh Sleep Quality Index and the Richards-Campbell Sleep Questionnaire(RCSQ)are widely used to evaluate sleep quality,there is a lack of studies utilizing polysomnography for objective evaluation.This study aims to investigate the correlation between sleep quality,fatigue,and depression in kidney transplant recipients using both subjective and objective methods,providing scientific evidence for improving their quality of life.Methods:The cross-sectional study conveniently sampled 50 kidney transplant recipients from a transplant center in a general hospital between August 2018 and March 2020.Subjective and objective sleep parameters were evaluated using the RCQS and polysomnography,respectively.The Fatigue Severity Scale was used to assess fatigue,and the Hamilton Depression Scale was employed to measure depression levels.Results:A lower proportion of rapid eye movement(REM)sleep was associated with increased fatigue.Additionally,higher wake time percentages and poorer sleep quality were significantly correlated with greater depression severity.Conclusion:This study underscores the critical importance of effectively managing sleep quality in kidney transplant recipients and addressing their fatigue and depression symptoms.These findings lay a foundation for developing targeted nursing and therapeutic strategies.展开更多
The proposed Tendaho Reservoir and Irrigation site is located at the center of the Afar Depression where the Main Ethiopian Rift(MER),the Red Sea Rift and the Gulf of Aden Rift join at the extensional triple junction....The proposed Tendaho Reservoir and Irrigation site is located at the center of the Afar Depression where the Main Ethiopian Rift(MER),the Red Sea Rift and the Gulf of Aden Rift join at the extensional triple junction.The entire irrigation scheme and the reservoir area lie within the Tendaho Graben and at the west horst of the Graben(Tendaho Goba’ad Dis-展开更多
The glutenite in the fourth member of Shahejie Formation(Es^4) in northern Dongying depression straightforwardly penetrated into the muddy bathyal -abyss facies.The conditions of reservoir is very superior:(1) the hig...The glutenite in the fourth member of Shahejie Formation(Es^4) in northern Dongying depression straightforwardly penetrated into the muddy bathyal -abyss facies.The conditions of reservoir is very superior:(1) the high quality thick bedded oil source rock is developed very well in the Lijin sag and Minfeng sag of the study area,and it has the higher capability of generating hydrocarbon;(2) the展开更多
The Songliao basin in northeast China is a Mesozoic rift basin characterized by Mesozoic and Cenozoic hydrocarbon systems.The Changling fault depression located in the south of the Songliao Basin,
Enrichment of hydrocarbon reservoir relates to the slope break types in continental basin(sag)in China. Division and analysis of genetic types of slope break will help to study the enrichment regularity of hydrocarbon...Enrichment of hydrocarbon reservoir relates to the slope break types in continental basin(sag)in China. Division and analysis of genetic types of slope break will help to study the enrichment regularity of hydrocarbon reservoir and is conducive to the guiding of future development in exploration and enhancing prediction accuracy.This paper,guided by the theory of sequence stratigraphy and using high-resolution three-dimensional seismic data,drilling and other information,takes into account the characteristics展开更多
The deep buried clastic formation of Paleogene is an important hydrocarbon reservoir in the Chezhen depression.There are two types of diagenetic alteration modes in it.The first mode is weak compaction, strong cementa...The deep buried clastic formation of Paleogene is an important hydrocarbon reservoir in the Chezhen depression.There are two types of diagenetic alteration modes in it.The first mode is weak compaction, strong cementation,fracturing and weak dissolution in the sandstone and conglomerate on the steep slope of the depression.The reservoirs are cemented mainly by carbonate minerals strongly。展开更多
Huanghua depression,in the middle of Bohai Bay basin,is a major secondary sedimentary and petroliferous unit.Although this basin has been explored for nearly 50 years,the discovery of new reservoirs increased quickly ...Huanghua depression,in the middle of Bohai Bay basin,is a major secondary sedimentary and petroliferous unit.Although this basin has been explored for nearly 50 years,the discovery of new reservoirs increased quickly in recent years.The subduction of the Pacific Plate to the Eurasia Plate caused the transtensional deformation of the whole basin.During the Paleogene,the depocenters and subsidence centers展开更多
The evolution of the Tarim southwest depression lying at the piedmont of the West Kunlun orogen differs completely from the evolution of the main part of Tarim basin after Later Palaeozoic because the former strongly ...The evolution of the Tarim southwest depression lying at the piedmont of the West Kunlun orogen differs completely from the evolution of the main part of Tarim basin after Later Palaeozoic because the former strongly subsides many times.. Subsidence is related closely to the West Kunlun fold thrust\|belt, thus the evolution of the Depression and the fold\|thrust\|belt reflects clearly the formation and evolution of the West Kunlun and even the Tibet.1 Evolution of the West Kunlun fold\|thrust\|belt\;Thrusting of the fold\|thrust\|belt can be classified into three stages:(1) Devonian thrusting:This is the oldest thrusting distinguished in the northern margin of the West Kunlun while the Silurian—Devonian thrusting was discriminated a few years ago by seismic data in the northern part of the East Kunlun. The Devonian thrusting is proved by the Upper Devonian dynamometamorphic rocks outcropping at the core of the anticline in the Sangzhu lying at the fold\|thrust\|belt. The rocks consist of slightly metamorphic clastic rock and have always been regarded as the Mid\|Proterozoic strata. But they are actually Upper Devonian strata according to the amount of perfect plant fossils that we found recently in the metamorphic rock, and they are overburdened `with an angular unconformity by another reliable Upper\|Devonian conglomerate in the core of the Aqike anticline. A possible explanation for this and its limited lined distribution parallel to the West Kunlun orogen is that they are subjected to metamorphism during the Later Devonian thrusting.展开更多
OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hypnotics.For emergency use,specific antagonists are currently administered to counteract respiratory depression.However,antagonists are of...OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hypnotics.For emergency use,specific antagonists are currently administered to counteract respiratory depression.However,antagonists are often short-lasting and can have multiple unexpected side effects.A novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration.To explore the mechanism and impact of LCX001 on protection against respiratory depression.METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid,propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate potential analgesic effect of LCX001.Binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation.The function of AMPA receptors were determined by location of receptors inthe membrane and state of channel opening,and both processes were impressed by AMPA receptor regulatory proteins.According to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by Western blotting.The variation of receptor surface location were observed by live cell imaging.The regulation on neuronal Ca2+and cell function was investigated intensively by Ca2+imaging to clarify mechanism of LCX001.RESULTS LCX001 effectively rescued and prevented opioid(fentanyl and TH-030418),propofol,and pentobarbitalinduced respiratory depression by strengthening respiratory frequency and minute ventilation by 30%-50% in rats.The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001 on increasing the inhibition rate and %MPE to 80% and 65% respectively,in contrast to some ampakines that did not affect analgesia.Furthermore,LCX001 potentiated[3 H]AMPA and L-glutamate binding affinity to AMPA receptors,and facilitated glutamateevoked inward currents in HEK293 cells stably expressing GluA2(R).At 10 mmol·L^(-1) glutamate evoked amplitudes,LCX001 at 100 μmol·L^(-1) increased the potency of glutamate induced currents by(1120 ± 60) pA,compared with that of(752 ± 35) pA in the control group.LCX001 also prominently promoted steady state/peak amplitude ratio.LCX001 significantly slowed down the desensitization rates of the AMPA ion channel,and inhibited current decay.Importantly,application of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioidinduced abnormal intracel ular Ca2+load,which might participate in breathing modulation.CONCLUSION The typical positive modulatory impact and potential new mechanism of LCX001 might promote ampakines to be a therapeutic option for protection against respiratory depression.展开更多
Lower Devonian is lithologically divided into three thicknesses.Section begins from the carbonate thickness(Ovinparma regional stage),but it has different physical composition.Therefore the thickness is divided into t...Lower Devonian is lithologically divided into three thicknesses.Section begins from the carbonate thickness(Ovinparma regional stage),but it has different physical composition.Therefore the thickness is divided into two lithologic units from below upward:lithologic unit"a"—terrigenous-carbonate; lithologic unit"b"—carbonate.Above it lies terrige-展开更多
The buried hill in the Jizhong depression contains abundant petroleum reserves and are important production areas.The Ordovician buried hill has restricted the discovery of new oil and gas exploration targets because ...The buried hill in the Jizhong depression contains abundant petroleum reserves and are important production areas.The Ordovician buried hill has restricted the discovery of new oil and gas exploration targets because of its strong reservoir heterogeneity and complex reservoir-controlling factors.Based on a large volume of core,thin section,logging,seismic,and geochemical data and numerous geological analyses,the reservoir-forming conditions and modes were systematically analyzed to guide the exploration and achieve important breakthroughs in the Yangshuiwu and Wen an slope buried hills.The study revealed that three sets of source rocks of the third and fourth members of the Shahejie Formation from the Paleogene and Carboniferous-Permian were developed in the Jizhong depression,providing sufficient material basis for the formation of buried hill oil and gas reservoirs.The reservoir control mechanism involving the three major factors of“cloud-karst-fault”was clarified,and karst cave,fracture fissure-pore,and cloud pore type reservoir models were established,thereby expanding the exploration potential.Controlled by the superposition of multi-stage tectonic processes during the Indosinian,Yanshanian,and Himalayan,two genetic buried hill trap types of uplift-depression and depression-uplift were formed.Based on the analysis of reservoir-forming factors of the Ordovician buried hill,three buried hill oil and gas reservoir-forming models were identified:low-level tectonic-lithologic composite quasi-layered buried hill,medium-level paleo-storage paleo-block buried hill,and high-level paleo-storage new-block buried hill.Comprehensive evaluations indicate that the reservoir-forming conditions of the low-level tectonic-lithologic composite quasi-layered buried hill in the northern portion of the Jizhong depression are the most favorable and that the Sicundian and Xinzhen buried hills are favorable areas for future exploration.展开更多
文摘OBJECTIVE To explore the mechanism of action of Qihuang Zhuyu formula(QHZYF)in improving depression after myocardial infarction(MI),with a focus on revealing its regulatory effect on the inflammatory response of the heart and brain.METHODS The active ingredients of QHZYF and the action targets for intervening in depression after MI were analyzed by using ultra-performance liquid chromatography-high-resolution mass spectrometry(UPLC-Q-TOF/MS)combined with network pharmacology and molecular docking.A rat model of depression after MI was established by ligation of the left anterior descending coronary artery combined with chronic restraint stress.Echocardiography was used to evaluate cardiac function,hematoxylin-eosin(HE)and Masson staining were used to evaluate myocardial injury,behavioral tests were used to detect melancholic behaviors,Nissl staining was used to evaluate hippocampal neuron injury.Western blot detection of tumor necrosis factor receptor 2(TNFR2),phosphatidylinositol-3-kinase(PI3K),phosphorylated seronine protein kinase(p-AKT),seronine protein kinase(AKT),tumor necrosis factor receptor 1(TNFR1),phosphorylated nuclear factorκB(p-NF-κB),and nuclear factorκB(NF-κB)in cardiac and hippocampal tissues was conducted.The levels of serum IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of TNFR1 and TNFR2 was detected by immunohistochemical technique(IHC).In vitro experiments,co-culture of rat cardiomyocyte line H9C2 cells and rat adrenal pheochromocytoma cell line with high differentiation PC12 cells was conducted,TNFR1 inhibitor(H398)and TNFR2 agonist(C-6His)were administered for intervention,and the expression of TNFR2,PI3K,p-AKT,AKT,TNFR1,NF-κB,p-NF-κB was detected by Western blot.Observe the apoptosis of cells by TUNEL staining,ELISA was used to detect the levels of IL-6 and IL-10 in the cell supernatant.RESULTS Network pharmacological analysis indicates that the TNF signaling pathway was a key target for the treatment of depression after MI with the QHZYF.In vivo experiments have confirmed that the intervention of QHZYF could significantly improve the cardiac function,myocardial tissue and hippocampal neuron structure damage of depressed rats after MI,and improve their depression-like behaviors.At the molecular level,the high-dose group of QHZYF significantly upregulated TNFR2,p-AKT/AKT,and IL-10 in cardiac and hippocampal tissues(P<0.01),and downregulated TNFR1,p-NF-κB/NF-κB and IL-6(P<0.01).In vitro experiments showed that the drug-containing serum of QHZYF significantly upregulated the expression of TNFR2,p-AKT/AKT and IL-10 in H9C2 and PC12 cells(P<0.01),downregulated the expression of TNFR1,p-NF-κB/NF-κB and IL-6(P<0.01),and significantly inhibited cell apoptosis(P<0.01).Furthermore,experiments on the combined application of H398 or C-6His further confirmed that its protective and anti-inflammatory effects were mediated by regulating the TNFR2/PI3K/AKT and TNFR1/NF-κB pathways.CONCLUSION QHZYF improves the homeostasis of heart and brain inflammation by regulating the TNF pathway,and ameliorates myocardial injury and depressive state in depressed rats after MI.
文摘OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tive.Here,we hypothesize that dysfunction of central TGR5 may contribute to the pathogene⁃sis of depression.METHODS In well-established chronic social defeat stress(CSDS)and chronic restraint stress(CRS)models of depression,we investigated the functional roles of TGR5 in CA3 pyramidal neurons(PyNs)and underlying mech⁃anisms of the neuronal circuit in depression(for in vivo studies,n=10;for in vitro studies,n=5-10)using fiber photometry;optogenetic,chemoge⁃netic,pharmacological,and molecular profiling techniques;and behavioral tests.RESULTS Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs.Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777,a specific agonist,protected against CSDS and CRS,exerting sig⁃nificant antidepressant-like effects that were mediated via CA3 PyN activation.Conversely,genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behav⁃iors.Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS.Silencing and stimula⁃tion of CA3 PyNs→somatostatin-GABAergic(gamma-aminobutyric acidergic)neurons of the dorsolateral septum circuit bidirectionally regulat⁃ed depression-like behaviors,and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.CON⁃CLUSION TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission,suggesting that TGR5 could be a novel target for developing antidepressants.
基金Ministry of Science and Tech⁃nology of China(2017ZX09301029)and Space Medical Experiment Project of China Manned Space Program(HYZHXM05003)。
文摘OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress(CSDS)-induced depressive-like behaviors and its related mechanism.METHODS AND RE⁃SULTS The daily oral administration of Rb1(35 and 70 mg·kg-1)and imipramine(15 mg·kg-1)for 28 d significantly reversed the social avoidance behavior,anhedonia,and behavioral despair via CSDS exposure,as demonstrated by the consid⁃erable elevation in the time in the zone in social interaction test and consumption of sucrose solu⁃tion in sucrose preference test and decrease of immobility time in forced swim test.Moreover,Rb1 obviously restored the CSDS-induced decrease of BDNF-signaling pathway and hippo⁃campal neurogenesis.Rb1 significantly increased the hippocampal levels of ERK,AKT,and CREB phosphorylation and increased the number of DCX+cells in DG.Importantly,the antidepres⁃sant effects of Rb1 were completely blocked in mice by using K252a(the nonselective tyrosine kinase B inhibitor).CONCLUSION Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression,and its effects was facilitated by enhancing the BDNF signaling cas⁃cade and up-regulation of hippocampal neuro⁃genesis.
基金Project(2006AA09Z336) supported by the National High-Tech Research and Development Program of China
文摘Petrographic analysis combined with various techniques, such as scanning electron microscopy and X-ray diffraction, was used to assess the timing of growth and original mineral cements, the controls on reservoir and reservoir quality of the fourth member sandstones of Shahejie formation (Es4). The Es4 sandstones are mostly arkose and lithic arkose, rarely feldspathic litharenite, with an average mass fraction of quartz 51.6%, feldspar 33.8% and rock fragments 14.6% (Q51.6F33.8R14.6). They have an average framework composition (mass fraction) of quartz 57.10%, K-feldspar 5.76%, sodium-calcium feldspar 13.00%, calcite 5.77%, dolomite 5.63%, siderite 0.95%, pyrite 0.30%, anhydrite 0.04%, and clay mineral 11.46%. The diagenentic minerals typically include kaolinite, illite-smectite (I/S), illite, chlorite, authigenetic quartz and feldspar, and carbonate and pyrite. Es4 sandstone has undergone stages A and B of eodiagenesis, and now, it is experiencing stage A of mesodiagenesis. Reservoir quality is predominantly controlled by the mechanical compaction, for example, 45.65% of the original porosity loss is related to compaction. The original porosity loss related with cementation is only 26.00%. The reservoir quality is improved as a result of dissolution of feldspar, rock fragment and so forth. The porosity evolved from dissolution varies from 3% to 4%.
基金Projects(41472084,41172123) supported by the National Natural Science Foundation of China
文摘Sediments in the Liushagang Formation of Late Eocene form a group of key hydrocarbon play fairways in the Beibuwan Basin,South China Sea.As an important reservoir-forming combination,the Liushagang Formation consists of deltaic siliciclastic and show clear sedimentary cyclicity.According to paleontology research and stratigraphic correlation,the boundary between Liushagang Formation(Els)and Weizhou Formation(Ewz)is regarded as the Eocene-Oligocene boundary.The oxygen isotope dating for well cores from the top of the first Member of Liushagang Formation(Els1)and the bottom of the third Member of Weizhou Formation(Ewz3)give an isochron age of 35.2 Ma.Here,we use GR logging data as a paleoenvironmental proxy to conduct a detailed cyclostratigraphic study of the Els1 in the Bailian Sag,Fushan Depression.Power spectra,evolutionary fast Fourier transformation and wavelet analysis all reveal significant sedimentary cycles in Els1.The ratios of cycle wavelengths in these stratigraphic units are 21?5?2.8?1.2?1,and are interpreted as Milankovitch cycles of 400 ka and 96 ka eccentricity,52 ka obliquity,22ka and 19 ka precession cycles,respectively.An astronomical time scale is established by tuning filtered 96 ka eccentricity cycles to a target curve of Well L2 in the Bailian Sag.Based on regional stratigraphic framework,combined with seismic,cores and logging data,the HST of the first member of the Liushagang Formation(Els1)delta in Well L2 was divided into six parasequence sets named Ps1-Ps6.According to the spectrum analysis by Simple Lomb periodogram from PAST program packages,the sediment accumulation rate of each parasequence sets first increased and then decreased as time went by.The sediment accumulation rate of Ps4 reached the maximum(0.127 m/ka)during the most prosperous period of delta prograding.Finally,the duration of each period of parasequence sets and more accurate geological age were calculated on the basis of sediment accumulation rate.The ages of each depth are precisely estimated and provide new constraints on the Late Eocene.
基金National Basic Research Program of China(2014CB744600)National Natural Science Foundation of China(61632014,61210010)+2 种基金Program of Beijing M unicipal Science&Technology Commission(Z171100000117005)Program of International S&T Cooperation of M OST(2013DFA11140)National Key Research and Development Program of China(2016YFC1307203)
文摘At present,depression is treated with antidepressant drugs and assisted with psychotherapy and physical therapy,and these expensive and time-consuming treatment methods often end prematurely and result in a prolonged course w ithout effective symptom relief. Therefore,based on the neurofeedback therapy,a novel depression rehabilitation method using a Virtual-Reality(VR) game framew ork is proposed. In this VR game framew ork,an innovative threeelectrode Electroencephalography(EEG) collector is used to record patients' EEG data. The data are processed and converted into feedback features,and the feedback w ill be displayed to patients in real time through a VR headset. Patients can adjust their psychological activity based on the feedback,and relieve their physiological dysfunction effectively. The framew ork also provides a data storage module,w hich may offer therapists w ays to assess patients' rehabilitation results in a long term,as w ell as provide possibility to continue tow ards better algorithm of feedback features w ith data-mining.The prototype system is tested in the framew ork,and the experimental results prove the effectiveness of the framew ork in depression rehabilitation.
文摘OBJECTIVE Hyperactivityof hypothalamic-pituitary-adrenal(HPA) axis is an important aetiological risk factor for the development of depression. Previous studies have demonstrated that the phenolic monomer baicalin has antidepressant-like effects and decreases serum corticosterone levels.However,the mechanism by which baicalin regulates hyperactivity of HPA axis remains unclear. This work aimed to investigate the effects of baicalin on hyperactivity of HPA axis using the olfactory bulbectomised(OBX) rat model of depression. METHODS Animals were anaesthetised with 10% chloral hydrate(3.3 mL·kg^(-1),ip). Using disinfected surgical equipment,the skull covering the olfactory bulbs was exposed by a midline incision. Two burr holes(2 mm diameter) were drilled 8 mm anterior to the bregma and 2 mm lateral to the midline. Both olfactory bulbs were aspirated and the holes filled with glass ionomer cement. The scalp was sutured closed. Sham-operated rats underwent every surgical procedure except the aspiration of the bulbs. The animals received penicillin(8×10~5U) intramuscularly(0.2 mL/300 g) once per day for 3 d post-surgery to prevent infection,and were subsequently housed alone in polypropylene cages. The experiments continued after 14 d of rehabilitation. The following groups were used for experiments: sham-operated(underwent surgical procedure without aspiratedolfactory bulbs and administration of vehicle only),OBX-model(underwent every surgical procedure and administration of vehicle only),OBX-amitriptyline treated(10 mg·kg^(-1)),and OBX-baicalin treatment(20 and 40 mg·kg^(-1)). Amitriptyline and baicalin were dissolved in physiological saline. RESULTS We examined how baicalin altered OBX-induced changes in serum glucocorticoid level as wel as inflammatory responses,sirtuin 1(SIRT1) expression,and p65 acetylation in the hypothalamus. Similar experiments were performed to analyse the effects of baicalin on lipopolysaccharide-induced inflammatory responses inhypothalamus. CONCLUSION Our results indicate that activation of the SIRT1 in the hypothalamus contributes to hyperactivity of HPA axis,which can be alleviated by baicalin.
基金Project(2006CB202300)supported by the National Basic Research Program of China
文摘Reservoirs can be developed in the sediment gravity flows.However,high quality reservoirs are found widespread in sediment gravity flows of Gangzhong area,Huanghua depression,Bohai Bay Basin,East China.Characteristics and formation of these reservoirs are key problems to be solved.Through comprehensive analysis of thin section petrography,scanning electron microscopy and X-ray diffraction,two distinct rules were obtained.1) These high quality reservoirs have apparent characteristics:lithology consists mainly of medium-fine grained sands; moderately-well sorted and rounded; intergranular pores dominating >70% of the entire pores,surface per unit pore volume reaches 15%; average porosity is 21% and average permeability is 55×10-3 μm2.2) Types of sedimentary microfacies and dissolution strongly control on the formation of high quality reservoirs.Main channels and sandy braided bars have the best reservoir properties.Because that sediments are mainly medium-fine grained sands in high-energy environments.The favorable primary porosity and permeability may promote calcite cementation and help to produce more secondary pores.Besides,at the depth of 2500-3200 m,basically matching threshold of oil generation,organic acid expelled when organic matter became mature,and H+ released during clay mineral transformation.These both result in the dissolution of calcite cements and create large volume pores,then physical properties improve correspondingly.Moreover,deep hydrothermal fluid intrusion may also have impacts on the development of secondary pores.
文摘OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.
基金supported by the Clinical Medical Technology Innovation Guide Project of Hunan Province,China(2020SK53609).
文摘Objective:Sleep quality in kidney transplant recipients is closely associated with symptoms of fatigue and depression.Although subjective assessment tools like the Pittsburgh Sleep Quality Index and the Richards-Campbell Sleep Questionnaire(RCSQ)are widely used to evaluate sleep quality,there is a lack of studies utilizing polysomnography for objective evaluation.This study aims to investigate the correlation between sleep quality,fatigue,and depression in kidney transplant recipients using both subjective and objective methods,providing scientific evidence for improving their quality of life.Methods:The cross-sectional study conveniently sampled 50 kidney transplant recipients from a transplant center in a general hospital between August 2018 and March 2020.Subjective and objective sleep parameters were evaluated using the RCQS and polysomnography,respectively.The Fatigue Severity Scale was used to assess fatigue,and the Hamilton Depression Scale was employed to measure depression levels.Results:A lower proportion of rapid eye movement(REM)sleep was associated with increased fatigue.Additionally,higher wake time percentages and poorer sleep quality were significantly correlated with greater depression severity.Conclusion:This study underscores the critical importance of effectively managing sleep quality in kidney transplant recipients and addressing their fatigue and depression symptoms.These findings lay a foundation for developing targeted nursing and therapeutic strategies.
文摘The proposed Tendaho Reservoir and Irrigation site is located at the center of the Afar Depression where the Main Ethiopian Rift(MER),the Red Sea Rift and the Gulf of Aden Rift join at the extensional triple junction.The entire irrigation scheme and the reservoir area lie within the Tendaho Graben and at the west horst of the Graben(Tendaho Goba’ad Dis-
文摘The glutenite in the fourth member of Shahejie Formation(Es^4) in northern Dongying depression straightforwardly penetrated into the muddy bathyal -abyss facies.The conditions of reservoir is very superior:(1) the high quality thick bedded oil source rock is developed very well in the Lijin sag and Minfeng sag of the study area,and it has the higher capability of generating hydrocarbon;(2) the
文摘The Songliao basin in northeast China is a Mesozoic rift basin characterized by Mesozoic and Cenozoic hydrocarbon systems.The Changling fault depression located in the south of the Songliao Basin,
文摘Enrichment of hydrocarbon reservoir relates to the slope break types in continental basin(sag)in China. Division and analysis of genetic types of slope break will help to study the enrichment regularity of hydrocarbon reservoir and is conducive to the guiding of future development in exploration and enhancing prediction accuracy.This paper,guided by the theory of sequence stratigraphy and using high-resolution three-dimensional seismic data,drilling and other information,takes into account the characteristics
文摘The deep buried clastic formation of Paleogene is an important hydrocarbon reservoir in the Chezhen depression.There are two types of diagenetic alteration modes in it.The first mode is weak compaction, strong cementation,fracturing and weak dissolution in the sandstone and conglomerate on the steep slope of the depression.The reservoirs are cemented mainly by carbonate minerals strongly。
文摘Huanghua depression,in the middle of Bohai Bay basin,is a major secondary sedimentary and petroliferous unit.Although this basin has been explored for nearly 50 years,the discovery of new reservoirs increased quickly in recent years.The subduction of the Pacific Plate to the Eurasia Plate caused the transtensional deformation of the whole basin.During the Paleogene,the depocenters and subsidence centers
文摘The evolution of the Tarim southwest depression lying at the piedmont of the West Kunlun orogen differs completely from the evolution of the main part of Tarim basin after Later Palaeozoic because the former strongly subsides many times.. Subsidence is related closely to the West Kunlun fold thrust\|belt, thus the evolution of the Depression and the fold\|thrust\|belt reflects clearly the formation and evolution of the West Kunlun and even the Tibet.1 Evolution of the West Kunlun fold\|thrust\|belt\;Thrusting of the fold\|thrust\|belt can be classified into three stages:(1) Devonian thrusting:This is the oldest thrusting distinguished in the northern margin of the West Kunlun while the Silurian—Devonian thrusting was discriminated a few years ago by seismic data in the northern part of the East Kunlun. The Devonian thrusting is proved by the Upper Devonian dynamometamorphic rocks outcropping at the core of the anticline in the Sangzhu lying at the fold\|thrust\|belt. The rocks consist of slightly metamorphic clastic rock and have always been regarded as the Mid\|Proterozoic strata. But they are actually Upper Devonian strata according to the amount of perfect plant fossils that we found recently in the metamorphic rock, and they are overburdened `with an angular unconformity by another reliable Upper\|Devonian conglomerate in the core of the Aqike anticline. A possible explanation for this and its limited lined distribution parallel to the West Kunlun orogen is that they are subjected to metamorphism during the Later Devonian thrusting.
基金National Science and Technology Major Project of China (2015ZX09501003).
文摘OBJECTIVE Respiratory depression hinders the use of anaesthetics and sedative hypnotics.For emergency use,specific antagonists are currently administered to counteract respiratory depression.However,antagonists are often short-lasting and can have multiple unexpected side effects.A novel AMPA receptor modulator LCX001,synthesized by our Institute of Medicinal Chemistry,is expected to relieve suppressed respiration.To explore the mechanism and impact of LCX001 on protection against respiratory depression.METHODS LCX001 was tested to alleviate respiratory depression triggered by opioid,propofol and pentobarbital in the plethysmography recording.The acetic acid writhing and hot-plate tests were conducted to evaluate potential analgesic effect of LCX001.Binding assay and whole-cell recording were used to analyze the property of LCX001 on positive modulation.The function of AMPA receptors were determined by location of receptors inthe membrane and state of channel opening,and both processes were impressed by AMPA receptor regulatory proteins.According to the theory,the effect of LCX001 on the expression of stargazin was measured firstly by Western blotting.The variation of receptor surface location were observed by live cell imaging.The regulation on neuronal Ca2+and cell function was investigated intensively by Ca2+imaging to clarify mechanism of LCX001.RESULTS LCX001 effectively rescued and prevented opioid(fentanyl and TH-030418),propofol,and pentobarbitalinduced respiratory depression by strengthening respiratory frequency and minute ventilation by 30%-50% in rats.The acetic acid writhing test and hot-plate test revealed potent anti-nociceptive efficacy of LCX001 on increasing the inhibition rate and %MPE to 80% and 65% respectively,in contrast to some ampakines that did not affect analgesia.Furthermore,LCX001 potentiated[3 H]AMPA and L-glutamate binding affinity to AMPA receptors,and facilitated glutamateevoked inward currents in HEK293 cells stably expressing GluA2(R).At 10 mmol·L^(-1) glutamate evoked amplitudes,LCX001 at 100 μmol·L^(-1) increased the potency of glutamate induced currents by(1120 ± 60) pA,compared with that of(752 ± 35) pA in the control group.LCX001 also prominently promoted steady state/peak amplitude ratio.LCX001 significantly slowed down the desensitization rates of the AMPA ion channel,and inhibited current decay.Importantly,application of LCX001 generated a significant increase in GluA2(R) surface expression in a mechanism of stargazin up-regulation,and restrained opioidinduced abnormal intracel ular Ca2+load,which might participate in breathing modulation.CONCLUSION The typical positive modulatory impact and potential new mechanism of LCX001 might promote ampakines to be a therapeutic option for protection against respiratory depression.
文摘Lower Devonian is lithologically divided into three thicknesses.Section begins from the carbonate thickness(Ovinparma regional stage),but it has different physical composition.Therefore the thickness is divided into two lithologic units from below upward:lithologic unit"a"—terrigenous-carbonate; lithologic unit"b"—carbonate.Above it lies terrige-
基金major science and technology project of PetroChina“Research and application of key technologies for sustainable,effective and stable production exploration and development of North China Oilfield(2017e-15)”。
文摘The buried hill in the Jizhong depression contains abundant petroleum reserves and are important production areas.The Ordovician buried hill has restricted the discovery of new oil and gas exploration targets because of its strong reservoir heterogeneity and complex reservoir-controlling factors.Based on a large volume of core,thin section,logging,seismic,and geochemical data and numerous geological analyses,the reservoir-forming conditions and modes were systematically analyzed to guide the exploration and achieve important breakthroughs in the Yangshuiwu and Wen an slope buried hills.The study revealed that three sets of source rocks of the third and fourth members of the Shahejie Formation from the Paleogene and Carboniferous-Permian were developed in the Jizhong depression,providing sufficient material basis for the formation of buried hill oil and gas reservoirs.The reservoir control mechanism involving the three major factors of“cloud-karst-fault”was clarified,and karst cave,fracture fissure-pore,and cloud pore type reservoir models were established,thereby expanding the exploration potential.Controlled by the superposition of multi-stage tectonic processes during the Indosinian,Yanshanian,and Himalayan,two genetic buried hill trap types of uplift-depression and depression-uplift were formed.Based on the analysis of reservoir-forming factors of the Ordovician buried hill,three buried hill oil and gas reservoir-forming models were identified:low-level tectonic-lithologic composite quasi-layered buried hill,medium-level paleo-storage paleo-block buried hill,and high-level paleo-storage new-block buried hill.Comprehensive evaluations indicate that the reservoir-forming conditions of the low-level tectonic-lithologic composite quasi-layered buried hill in the northern portion of the Jizhong depression are the most favorable and that the Sicundian and Xinzhen buried hills are favorable areas for future exploration.
