Here we fabricate LA103Z Mg-Li alloy via wire-arc directed energy deposition(WA-DED),and subsequent aging treatment is employed to improve its mechanical property.Results show that a typical dual-phase microstructure ...Here we fabricate LA103Z Mg-Li alloy via wire-arc directed energy deposition(WA-DED),and subsequent aging treatment is employed to improve its mechanical property.Results show that a typical dual-phase microstructure is formed upon WA-DED,consisting of α-Mg,β-Li,AlLi and Li_(2)MgAl,with negligible porosity,and the core-shell Li_(2)MgAl/AlLi composite particles are also generated.After aging treatment,the microstructure is slightly coarsened,together with the precipitation of nano-sized D0_(3)-Mg_(3)Al particles,as well as the dissolution and the mergence of α-Mg phases.Negligible strength and ductility anisotropies are found for the as-deposited alloy.Significant strength increment is achieved via aging treatment,and the ultimate strength increases by~20%(~34 MPa),reaching 200±1 MPa.Both as-deposited and aged alloys show acceptable uniform elongation,with a transgranular fracture mode.Precipitation strengthening enabled by nano-sized D0_(3)-Mg_(3)Al precipitates is primarily responsible for the strength increment mediated by aging treatment.Grain refinement strengthening and solid solution strengthening provide additional contributions to the improved strength.Our work thus offers an applicable additive manufacturing pathway for the efficient and safety-guaranteed fabrication of Mg-Li alloy components with decent mechanical property.展开更多
6-（5-Carboxyl-2-methoxyphenyl）-apigenin （1）, a new flavonoid, was isolated from the 60% ethanol extract of Selaginella uncinata （Desv.） Spring. Its structure was established by spectroscopic methods. Compound 1 ...6-（5-Carboxyl-2-methoxyphenyl）-apigenin （1）, a new flavonoid, was isolated from the 60% ethanol extract of Selaginella uncinata （Desv.） Spring. Its structure was established by spectroscopic methods. Compound 1 represents the first example of the flavonoids possessing a benzoic acid substituent at C-6.展开更多
Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal mu...Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood.In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve.RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated.We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1.The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death.In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation.These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy.This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China(approval No.SYXK 2017-C023) on June 1, 2018.展开更多
It has been proven that thermochemical sulfate reduction （TSR） took place extensively in the Lower Triassic carbonate reservoirs in Northeast （NE） Sichuan （四川） basin. We have carried out analyses on bulk rock ...It has been proven that thermochemical sulfate reduction （TSR） took place extensively in the Lower Triassic carbonate reservoirs in Northeast （NE） Sichuan （四川） basin. We have carried out analyses on bulk rock compositions and isotope ratios together with petrography and fluid inclusions to assess the impact of TSR on diagenetic process of Triassic dolomites. In this article, TSR-related burial diagenesis is characterized by precipitation of calcite cement with negative 613C values and high ho- mogenization temperature. The light carbon isotopic compositions of this phase indicate that carbon incorporated in this cement was partly derived from oxidation of hydrocarbon. The high homogeniza- tion temperatures indicate that the thermochemical reduction of sulfates has been taking place in the deep part of NE Sichuan basin. Additional evidence supporting this interpretation is the high Sr values of this calcite cement. Moreover, the calcites have a 6180 of -8.51%o to -2.79%0 PDB and are interpreted to have precipitated from high salinity fluids with 6180 of ＋5%0 to ＋13%o SMOW. Under cathodolumi- nescence, these calcite cements appear dark brown or black, and both Mg concentrations and Mn/Sr ratios are low. It is therefore indicated that seawater was the principal agent of precipitation fluids. Finally, it should be noted that although H2S and CO2 increased as TSR continued, porosity has been ultimately destroyed by calcite cementation.展开更多
BACKGROUND： With developments of tissue engineering and genetic engineering, we aim to culture myoblasts, which are characterized by high purity, high quality and high production, for wide application in neural regen...BACKGROUND： With developments of tissue engineering and genetic engineering, we aim to culture myoblasts, which are characterized by high purity, high quality and high production, for wide application in neural regeneration researches. OBJECTIVE： To modify traditional dissociation method in order to obtain myoblasts, which are characterized by high purity, high quality and high production, and explore the biological properties under in vitro culture. DESIGN： Observational study. SETTING： Basic Institute of Academy of Military Medical Sciences of Chinese PLA. MATERIALS： Four neonatal Wistar rats of 5 days old, both genders and mean body mass of 10 g were selected in this study. The main reagents and devices were detailed as follows： DMEM medium （Gibco Company）, fetus bovine serum （FBS, Hycolne Company）, collagenase Ⅱ （Sigma Company）, trypsin （Sigma Company）, dispase Ⅱ （Sigma Company）, desmin antibody （Fuzhou Maixin Company）, antibody Ⅱ and ABC kit （Wuhan Baster Biotechnology Company）, desk centrifuge （KUBATO, Japan）, and inverted phase contrast microscope （LEICA DMIRB, Germany）. METHODS： The experiment was carried out in the Basic Institute of Academy of Military Medical Sciences of Chinese PLA from June to October 2006. Neonatal rats were sacrificed under sterile condition to obtain skeletal muscles of limbs, which were washed with cold PBS （containing benzylpenicillin and estreptomicina）, and muscular tissue was sheared into pieces. Then, those muscular pieces were added with mixed digestive enzyme （containing 2 g/L collagenase Ⅱ ＋ 5 g/L dispase Ⅱ ＋ 0.28 g/L CaCl2） as twice volume as pieces, dealt with mechanical pipetting for 5 minutes and cultured in CO2 incubator for 10 minutes. The operation was done for three times and the muscular pieces were digested for 45 minutes in total. Moreover, cells were suspended again in order to obtain myoblasts from skeletal muscle of neonatal rats. In addition, myoblasts were purified with differential attachment technique and enzyme digestion so as to observe morphological characteristics and growth, draw growth curve, analyze surface structure under scanning electron microscope, and evaluate with Desmin immunohistochemical staining. MAIN OUTCOME MEASURES： Morphological characteristics and growth ofmyoblasts cultured in vitro. RESULTS： ①Growth of myoblasts of skeletal muscle： Primary cells had well growth, mature and differentiation. The positive rate of Desmin was 94% and purification of cells was ideal. Growth curve of cells demonstrated that myoblasts which were characterized by high purification started proliferation plentiful through transient growth lag phase （about at one or two days after inoculation）. If myoblasts were not dealt with any interventions, they might become sarcotubule gradually at 3 - 5 days after proliferative phase. During this period, myoblasts maintained a monocaryon-bipolarity state under inverted phase contrast microscope. Furthermore, the growth of cells was the strongest and reproductive activity was the most powerful. This suggested that myotube started to form; in addition, muscle fiber of contractility might form under a well culturing condition. ②Immunocytochemical stain with desmin antibody： Interzonal fiber of desmin from myoblasts showed strongly positive reaction. Positive staining existed in cytoplasm had a high nucleus-cytoplasm ratio. However, myoblasts showed negative or mildly positive reaction. CONCLUSION： It is ideal for modified multi-enzymatic digestion and double purification method to dissociate and purify myoblasts of skeletal muscle; meanwhile, these two methods are both the effective ways to provide convenient conditions to obtain seed cells for neural regeneration researches.展开更多
Depositing a cocatalyst has proven to be an important strategy for improving the photoelectrochemical(PEC)water-splitting efficiency of photoanodes.In this study,Ni(OH)2 quantum dots(Ni(OH)2 QDs)were deposited in situ...Depositing a cocatalyst has proven to be an important strategy for improving the photoelectrochemical(PEC)water-splitting efficiency of photoanodes.In this study,Ni(OH)2 quantum dots(Ni(OH)2 QDs)were deposited in situ onto anα-Fe_(2)O_(3)photoanode via a chelation-mediated hydrolysis method.The photocurrent density of the Ni(OH)2 QDs/α-Fe_(2)O_(3)photoanode reached 1.93 mA·cm^(−2)at 1.23 V vs.RHE,which is 3.5 times that ofα-Fe_(2)O_(3),and an onset potential with a negative shift of ca.100 mV was achieved.More importantly,the Ni(OH)2 QDs exhibited excellent stability in maintaining PEC water oxidation at a high current density,which is attributed to the ultra-small crystalline size,allowing for the rapid acceptance of holes fromα-Fe_(2)O_(3)to Ni(OH)_(2)QDs,formation of active sites for water oxidation,and hole transfer from the active sites to water molecules.Further(photo)electrochemical analysis suggests that Ni(OH)_(2)QDs not only provide maximal active sites for water oxidation but also suppress charge recombination by passivating the surface states ofα-Fe_(2)O_(3),thereby significantly enhancing the water oxidation kinetics over theα-Fe_(2)O_(3)surface.展开更多
While inflammatory bowel disease(IBD) might be a risk factor in the development of brain dysfunctions,the underlying mechanisms are largely unknown. Here,mice were treated with 5% dextran sodium sulfate(DSS) in drinki...While inflammatory bowel disease(IBD) might be a risk factor in the development of brain dysfunctions,the underlying mechanisms are largely unknown. Here,mice were treated with 5% dextran sodium sulfate(DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-a levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSSinduced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis.These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here,we provide new information on the impact of colitis on the outcomes of cortical inflammation.展开更多
The hypobaric hypoxic environment in highaltitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unkno...The hypobaric hypoxic environment in highaltitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1（WIP1） plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear.Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.展开更多
Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized ...Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized mouse, rat, rabbit, dog, baboon and monkey were used as animal model for experimental heat stroke. However, anesthetized mammals models have some limitations, such as neuroprotective effect of anesthetic agents, possible disturbance on injury and recovery of stroke animals by anesthetic agents, difficulty of discussing animal behavior before and after heat stroke, it was also difficult for the models to evaluate cognitive function of animal under hot environment. Considering humanitarian, only awaked and unrestrained mouse heat stroke model was accepted so far. Therefore, we also developed an awaked and unrestrained rat heat stroke model, and found it was helpful to evaluate drug effectiveness for animal behavior and cognitive function under hot environment.展开更多
Glycerol monolaurate(GML)is a widely used industrial chemical with excellent emulsification and antibacterial effect.The direct esterification of glycerol with lauric acid is the main method to synthesize GML.In this ...Glycerol monolaurate(GML)is a widely used industrial chemical with excellent emulsification and antibacterial effect.The direct esterification of glycerol with lauric acid is the main method to synthesize GML.In this work,the kinetic process of direct esterification was systematically studied using p-toluenesulfonic acid as catalyst.A complete kinetic model of consecutive esterification reaction has been established,and the kinetic equation of acid catalysis was deduced.The isomerization reactions of GML and glycerol dilaurate were investigated.It was found that the reaction was an equilibrium reaction and the reaction rate was faster than the esterification reaction.The kinetic equations of the consecutive esterification reaction were obtained by experiments as k_(1)=(276+92261Xcat)exp(-37720/RT)and k_(2)=(80+4413Xcat)exp(-32240/RT).The kinetic results are beneficial to the optimization of operating conditions and reactor design in GML production process.展开更多
Neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates that result from conformational changes in proteins. These diseases may result from an imbalance be...Neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates that result from conformational changes in proteins. These diseases may result from an imbalance between the produetion of misfolded proteins and normal chaperone capacity. Molecular chaperones provide a first line of defenee against misfolded, aggragation-prone proteins and are, therefore, promising therapeutic targets for neurodegenerative diseases.展开更多
Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism...Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine （20 and 40 mM） and irradiated them with 50 mW/cm^2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation.展开更多
Mutations of the X-linked methyl-CpG-binding protein 2(MECP2)gene in humans are responsible for most cases of Rett syndrome(RTT),an X-linked progressive neurological disorder.While genome-wide screens in clinical tria...Mutations of the X-linked methyl-CpG-binding protein 2(MECP2)gene in humans are responsible for most cases of Rett syndrome(RTT),an X-linked progressive neurological disorder.While genome-wide screens in clinical trials have revealed several putative RTT-associ-ated mutations in MECP2,their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence.In this study,we demonstrated that MeCP2 was dynamically modified by O-linked-P-N-acetylglucosamine(O-GlcNAc)at threonine 203(T203),an etiologic site in RTT patients.Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons,and disrupted neuronal migration,dendritic spine morphogenesis,and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex.Mechanistically,genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription.Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.展开更多
Motility is an important physiological characteristic of a mature sperm. Nerve growth factor (NGF) is a key protein for the survival, maintenance and development of the central and peripheral nervous systems. It has b...Motility is an important physiological characteristic of a mature sperm. Nerve growth factor (NGF) is a key protein for the survival, maintenance and development of the central and peripheral nervous systems. It has been shown that NGF and its receptors TrkA and p75 are widely expressed in the testis, accessory reproductive organ, and the epididymal sperms. These observation have shifted the attention to the role of NGF on male reproductive physiology. In the present study, we found that NGF remarkably increased testicular coefficient in rats subjected to unpredictable chronic mild stress. Furthermore, we investigated the role of NGF on human sperm motility in vitro by CASA. The results showed that the parameters of sperm motility after NGF treatment had significantly increased, the means of VAP, VSL, VCL, BCF and LIN were significantly increased 32% than those of NGF absence, the means of MAD, STR, ALH and WOB had no notable difference. In addition, NGF promotes the sperm motility in a time- and dose-dependent manner. Taken together, our findings suggest that NGF plays a promoted role in sperm motility.展开更多
Probiotics are live microorganisms which confer a health benefit to the host when present in the correct amounts.They can be ingested as medications or dietary supplements to help maintain a balance in the microbial e...Probiotics are live microorganisms which confer a health benefit to the host when present in the correct amounts.They can be ingested as medications or dietary supplements to help maintain a balance in the microbial environment of the digestive tract.Probiotics can help maintain homeostasis and enhance physical fitness,thereby reducing the adverse effects caused by anti-cancer treatments.Recent studies have shown that probiotics can protect against and alleviate radiation-induced intestinal damage by activating anti-apoptotic pathways via AKT,inhibiting the COX-2 pathway to inhibit inflammatory reactions,protecting the intestine’s barrier function,improving bacterial translocation,and regulating the intestinal micro-environment.Although relevant clinical trials of probiotics have varied in terms of the bacterial species examined,the concentrations of live bacteria administered,and in the research methods used,most have demonstrated that probiotics could prevent radiation-induced adverse effects on the intestines.With the continuous improvements in the comprehensive treatment of cancer,the survival of patients has been prolonged.Therefore,in recent years,there has been increasing interest in ways to alleviate the adverse reactions and pain during and after treatment and to improve the quality of life for patients.Future research should focus on optimizing the probiotic flora(type(s),numbers,and frequency of administration)and addressing the safety of probiotics for immunocompromised patients.展开更多
To the Editor:Coronary artery disease(CAD)remains a leading cause of morbidity and mortality worldwide.[1]Atherosclerosis is a slowly progressive process;therefore,effective secondary prevention is commonly recommende...To the Editor:Coronary artery disease(CAD)remains a leading cause of morbidity and mortality worldwide.[1]Atherosclerosis is a slowly progressive process;therefore,effective secondary prevention is commonly recommended to halt or delay the progression of atherosclerosis toward subsequent cardiovascular events.[2]However,despite recent advances in medical and interventional therapies,patients with coronary atherosclerotic heart disease are still at high risk of cardiovascular events,resulting in an increasing global health expenditure.展开更多
Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effec...Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract （GBE） against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell- astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B （GB）, against oxygenglucose deprivation/reoxygenation and glucose （OGD/R） injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein （Na-F）, and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.展开更多
Background and purpose The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury.Wild-type p53-induced protein phosphatase 1(Wip1),a serine/threonine phosp...Background and purpose The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury.Wild-type p53-induced protein phosphatase 1(Wip1),a serine/threonine phosphatase,is expressed in various tissues.A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue;however,its role in the central nervous system(CNS)remains unclear.This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.Methods A model of middle cerebral artery occlusion and reperfusion was established in mice.CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia.Laser speckle imaging was used to monitor regional cerebral blood flow.Behavioural outcomes were assessed with a TreadScan gait analysis system.TTC staining was used to evaluate the infarct volume,and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia.ELISA was performed to detect the levels of inflammatory factors.Results Wip1 expression was increased after ischaemia/reperfusion.Wip1-knockout(KO)mice displayed more severe brain injury than wild-type mice,as indicated by aggravated motor dysfunction,greater brain infarct volumes and higher expression of inflammatory cytokines(interleukin-6 and tumour necrosis factor alpha)in the brain.We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models,which all showed activation of microglia/macrophages.Lentivirus-Ppm1d reversed the injury induced by Wip1-KO.Conclusions Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.展开更多
基金supported by the National Natural Science Foundation of China(52475320).
文摘Here we fabricate LA103Z Mg-Li alloy via wire-arc directed energy deposition(WA-DED),and subsequent aging treatment is employed to improve its mechanical property.Results show that a typical dual-phase microstructure is formed upon WA-DED,consisting of α-Mg,β-Li,AlLi and Li_(2)MgAl,with negligible porosity,and the core-shell Li_(2)MgAl/AlLi composite particles are also generated.After aging treatment,the microstructure is slightly coarsened,together with the precipitation of nano-sized D0_(3)-Mg_(3)Al particles,as well as the dissolution and the mergence of α-Mg phases.Negligible strength and ductility anisotropies are found for the as-deposited alloy.Significant strength increment is achieved via aging treatment,and the ultimate strength increases by~20%(~34 MPa),reaching 200±1 MPa.Both as-deposited and aged alloys show acceptable uniform elongation,with a transgranular fracture mode.Precipitation strengthening enabled by nano-sized D0_(3)-Mg_(3)Al precipitates is primarily responsible for the strength increment mediated by aging treatment.Grain refinement strengthening and solid solution strengthening provide additional contributions to the improved strength.Our work thus offers an applicable additive manufacturing pathway for the efficient and safety-guaranteed fabrication of Mg-Li alloy components with decent mechanical property.
基金the National Basic Research Program of China(No.2006CB504100).
文摘6-（5-Carboxyl-2-methoxyphenyl）-apigenin （1）, a new flavonoid, was isolated from the 60% ethanol extract of Selaginella uncinata （Desv.） Spring. Its structure was established by spectroscopic methods. Compound 1 represents the first example of the flavonoids possessing a benzoic acid substituent at C-6.
基金supported by the National Natural Science Foundation of China, Nos.31770929(to HTW), 31522029(to HTW), 81902847(to HHY)the Beijing Municipal Science and Technology Commission of China, Nos.Z181100001518001(to HTW), Z161100000216154(to HTW)。
文摘Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood.In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve.RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated.We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1.The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death.In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation.These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy.This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China(approval No.SYXK 2017-C023) on June 1, 2018.
基金supported by the National Natural Science Foundation of China (Nos. 40839908 and 41172099)
文摘It has been proven that thermochemical sulfate reduction （TSR） took place extensively in the Lower Triassic carbonate reservoirs in Northeast （NE） Sichuan （四川） basin. We have carried out analyses on bulk rock compositions and isotope ratios together with petrography and fluid inclusions to assess the impact of TSR on diagenetic process of Triassic dolomites. In this article, TSR-related burial diagenesis is characterized by precipitation of calcite cement with negative 613C values and high ho- mogenization temperature. The light carbon isotopic compositions of this phase indicate that carbon incorporated in this cement was partly derived from oxidation of hydrocarbon. The high homogeniza- tion temperatures indicate that the thermochemical reduction of sulfates has been taking place in the deep part of NE Sichuan basin. Additional evidence supporting this interpretation is the high Sr values of this calcite cement. Moreover, the calcites have a 6180 of -8.51%o to -2.79%0 PDB and are interpreted to have precipitated from high salinity fluids with 6180 of ＋5%0 to ＋13%o SMOW. Under cathodolumi- nescence, these calcite cements appear dark brown or black, and both Mg concentrations and Mn/Sr ratios are low. It is therefore indicated that seawater was the principal agent of precipitation fluids. Finally, it should be noted that although H2S and CO2 increased as TSR continued, porosity has been ultimately destroyed by calcite cementation.
基金the 38th China Postdoctoral Science Foundation, No. 2005038055 the Scientific and Technological Research Projects of Liaoning Province, No. 2005225003-14the Natural Science Foundation of Liaoning Province, No. 20052204
文摘BACKGROUND： With developments of tissue engineering and genetic engineering, we aim to culture myoblasts, which are characterized by high purity, high quality and high production, for wide application in neural regeneration researches. OBJECTIVE： To modify traditional dissociation method in order to obtain myoblasts, which are characterized by high purity, high quality and high production, and explore the biological properties under in vitro culture. DESIGN： Observational study. SETTING： Basic Institute of Academy of Military Medical Sciences of Chinese PLA. MATERIALS： Four neonatal Wistar rats of 5 days old, both genders and mean body mass of 10 g were selected in this study. The main reagents and devices were detailed as follows： DMEM medium （Gibco Company）, fetus bovine serum （FBS, Hycolne Company）, collagenase Ⅱ （Sigma Company）, trypsin （Sigma Company）, dispase Ⅱ （Sigma Company）, desmin antibody （Fuzhou Maixin Company）, antibody Ⅱ and ABC kit （Wuhan Baster Biotechnology Company）, desk centrifuge （KUBATO, Japan）, and inverted phase contrast microscope （LEICA DMIRB, Germany）. METHODS： The experiment was carried out in the Basic Institute of Academy of Military Medical Sciences of Chinese PLA from June to October 2006. Neonatal rats were sacrificed under sterile condition to obtain skeletal muscles of limbs, which were washed with cold PBS （containing benzylpenicillin and estreptomicina）, and muscular tissue was sheared into pieces. Then, those muscular pieces were added with mixed digestive enzyme （containing 2 g/L collagenase Ⅱ ＋ 5 g/L dispase Ⅱ ＋ 0.28 g/L CaCl2） as twice volume as pieces, dealt with mechanical pipetting for 5 minutes and cultured in CO2 incubator for 10 minutes. The operation was done for three times and the muscular pieces were digested for 45 minutes in total. Moreover, cells were suspended again in order to obtain myoblasts from skeletal muscle of neonatal rats. In addition, myoblasts were purified with differential attachment technique and enzyme digestion so as to observe morphological characteristics and growth, draw growth curve, analyze surface structure under scanning electron microscope, and evaluate with Desmin immunohistochemical staining. MAIN OUTCOME MEASURES： Morphological characteristics and growth ofmyoblasts cultured in vitro. RESULTS： ①Growth of myoblasts of skeletal muscle： Primary cells had well growth, mature and differentiation. The positive rate of Desmin was 94% and purification of cells was ideal. Growth curve of cells demonstrated that myoblasts which were characterized by high purification started proliferation plentiful through transient growth lag phase （about at one or two days after inoculation）. If myoblasts were not dealt with any interventions, they might become sarcotubule gradually at 3 - 5 days after proliferative phase. During this period, myoblasts maintained a monocaryon-bipolarity state under inverted phase contrast microscope. Furthermore, the growth of cells was the strongest and reproductive activity was the most powerful. This suggested that myotube started to form; in addition, muscle fiber of contractility might form under a well culturing condition. ②Immunocytochemical stain with desmin antibody： Interzonal fiber of desmin from myoblasts showed strongly positive reaction. Positive staining existed in cytoplasm had a high nucleus-cytoplasm ratio. However, myoblasts showed negative or mildly positive reaction. CONCLUSION： It is ideal for modified multi-enzymatic digestion and double purification method to dissociate and purify myoblasts of skeletal muscle; meanwhile, these two methods are both the effective ways to provide convenient conditions to obtain seed cells for neural regeneration researches.
文摘Depositing a cocatalyst has proven to be an important strategy for improving the photoelectrochemical(PEC)water-splitting efficiency of photoanodes.In this study,Ni(OH)2 quantum dots(Ni(OH)2 QDs)were deposited in situ onto anα-Fe_(2)O_(3)photoanode via a chelation-mediated hydrolysis method.The photocurrent density of the Ni(OH)2 QDs/α-Fe_(2)O_(3)photoanode reached 1.93 mA·cm^(−2)at 1.23 V vs.RHE,which is 3.5 times that ofα-Fe_(2)O_(3),and an onset potential with a negative shift of ca.100 mV was achieved.More importantly,the Ni(OH)2 QDs exhibited excellent stability in maintaining PEC water oxidation at a high current density,which is attributed to the ultra-small crystalline size,allowing for the rapid acceptance of holes fromα-Fe_(2)O_(3)to Ni(OH)_(2)QDs,formation of active sites for water oxidation,and hole transfer from the active sites to water molecules.Further(photo)electrochemical analysis suggests that Ni(OH)_(2)QDs not only provide maximal active sites for water oxidation but also suppress charge recombination by passivating the surface states ofα-Fe_(2)O_(3),thereby significantly enhancing the water oxidation kinetics over theα-Fe_(2)O_(3)surface.
基金supported by grants from the National Natural Science Foundation of China (81430044)the National Basic Research Development Program of China (2012CB518200 and 2011CB910800)
文摘While inflammatory bowel disease(IBD) might be a risk factor in the development of brain dysfunctions,the underlying mechanisms are largely unknown. Here,mice were treated with 5% dextran sodium sulfate(DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-a levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSSinduced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis.These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here,we provide new information on the impact of colitis on the outcomes of cortical inflammation.
基金supported by the National Natural Science Foundation of China(31401000 and 81430044)the Youth Medicine Program of the People’s Liberation Army of China(13QNP148)+1 种基金the National Basic Research Development Program(973 Program)of China(2012CB518200)the Integrated Drug Discovery Technology Platform of National Science and Technology Major Projects for‘‘Major New Drugs Innovation and Development’’,China(2012ZX09J12201-005)
文摘The hypobaric hypoxic environment in highaltitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1（WIP1） plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear.Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.
基金supported by grants from National Natural Science Foundation of China(31071042)Chinese Postdoctoral Scientific Foundation(20100480774)
文摘Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized mouse, rat, rabbit, dog, baboon and monkey were used as animal model for experimental heat stroke. However, anesthetized mammals models have some limitations, such as neuroprotective effect of anesthetic agents, possible disturbance on injury and recovery of stroke animals by anesthetic agents, difficulty of discussing animal behavior before and after heat stroke, it was also difficult for the models to evaluate cognitive function of animal under hot environment. Considering humanitarian, only awaked and unrestrained mouse heat stroke model was accepted so far. Therefore, we also developed an awaked and unrestrained rat heat stroke model, and found it was helpful to evaluate drug effectiveness for animal behavior and cognitive function under hot environment.
基金supported by the National Research and Development Program of China(2021YFC3001100)the National Natural Science Foundation of China(22288102).
文摘Glycerol monolaurate(GML)is a widely used industrial chemical with excellent emulsification and antibacterial effect.The direct esterification of glycerol with lauric acid is the main method to synthesize GML.In this work,the kinetic process of direct esterification was systematically studied using p-toluenesulfonic acid as catalyst.A complete kinetic model of consecutive esterification reaction has been established,and the kinetic equation of acid catalysis was deduced.The isomerization reactions of GML and glycerol dilaurate were investigated.It was found that the reaction was an equilibrium reaction and the reaction rate was faster than the esterification reaction.The kinetic equations of the consecutive esterification reaction were obtained by experiments as k_(1)=(276+92261Xcat)exp(-37720/RT)and k_(2)=(80+4413Xcat)exp(-32240/RT).The kinetic results are beneficial to the optimization of operating conditions and reactor design in GML production process.
文摘Neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates that result from conformational changes in proteins. These diseases may result from an imbalance between the produetion of misfolded proteins and normal chaperone capacity. Molecular chaperones provide a first line of defenee against misfolded, aggragation-prone proteins and are, therefore, promising therapeutic targets for neurodegenerative diseases.
基金supported by the Integrated Drug Discovery Technology Platform of National Science and Technology Major Projects for "Major New Drugs Innovation and Development",No.2012ZX09J12201-005the National Natural Science Foundation of China,No.31071042,31200822a grant of Beijing Natural Science Foundation,No.5122033
文摘Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine （20 and 40 mM） and irradiated them with 50 mW/cm^2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation.
基金supported by the National Natural Science Foundation of China(31770929 and 31522029)the Beijing Municipal Science and Technology Commission(Z181100001518001 and Z161100000216154)of China.
文摘Mutations of the X-linked methyl-CpG-binding protein 2(MECP2)gene in humans are responsible for most cases of Rett syndrome(RTT),an X-linked progressive neurological disorder.While genome-wide screens in clinical trials have revealed several putative RTT-associ-ated mutations in MECP2,their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence.In this study,we demonstrated that MeCP2 was dynamically modified by O-linked-P-N-acetylglucosamine(O-GlcNAc)at threonine 203(T203),an etiologic site in RTT patients.Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons,and disrupted neuronal migration,dendritic spine morphogenesis,and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex.Mechanistically,genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription.Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.
文摘Motility is an important physiological characteristic of a mature sperm. Nerve growth factor (NGF) is a key protein for the survival, maintenance and development of the central and peripheral nervous systems. It has been shown that NGF and its receptors TrkA and p75 are widely expressed in the testis, accessory reproductive organ, and the epididymal sperms. These observation have shifted the attention to the role of NGF on male reproductive physiology. In the present study, we found that NGF remarkably increased testicular coefficient in rats subjected to unpredictable chronic mild stress. Furthermore, we investigated the role of NGF on human sperm motility in vitro by CASA. The results showed that the parameters of sperm motility after NGF treatment had significantly increased, the means of VAP, VSL, VCL, BCF and LIN were significantly increased 32% than those of NGF absence, the means of MAD, STR, ALH and WOB had no notable difference. In addition, NGF promotes the sperm motility in a time- and dose-dependent manner. Taken together, our findings suggest that NGF plays a promoted role in sperm motility.
基金an NSFC grant from the National Natural Science Foundation of China(No.81703070).
文摘Probiotics are live microorganisms which confer a health benefit to the host when present in the correct amounts.They can be ingested as medications or dietary supplements to help maintain a balance in the microbial environment of the digestive tract.Probiotics can help maintain homeostasis and enhance physical fitness,thereby reducing the adverse effects caused by anti-cancer treatments.Recent studies have shown that probiotics can protect against and alleviate radiation-induced intestinal damage by activating anti-apoptotic pathways via AKT,inhibiting the COX-2 pathway to inhibit inflammatory reactions,protecting the intestine’s barrier function,improving bacterial translocation,and regulating the intestinal micro-environment.Although relevant clinical trials of probiotics have varied in terms of the bacterial species examined,the concentrations of live bacteria administered,and in the research methods used,most have demonstrated that probiotics could prevent radiation-induced adverse effects on the intestines.With the continuous improvements in the comprehensive treatment of cancer,the survival of patients has been prolonged.Therefore,in recent years,there has been increasing interest in ways to alleviate the adverse reactions and pain during and after treatment and to improve the quality of life for patients.Future research should focus on optimizing the probiotic flora(type(s),numbers,and frequency of administration)and addressing the safety of probiotics for immunocompromised patients.
基金This work was supported in part by grants from the Chinese Natural Science Foundation(Nos.N82170275 and 82000420)Health Care Science Foundation(No.21BJZ06)+1 种基金Strengthening Foundation Plan(No.23M3001)Shanghai Talent Development Fund(No.2021064).
文摘To the Editor:Coronary artery disease(CAD)remains a leading cause of morbidity and mortality worldwide.[1]Atherosclerosis is a slowly progressive process;therefore,effective secondary prevention is commonly recommended to halt or delay the progression of atherosclerosis toward subsequent cardiovascular events.[2]However,despite recent advances in medical and interventional therapies,patients with coronary atherosclerotic heart disease are still at high risk of cardiovascular events,resulting in an increasing global health expenditure.
文摘Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract （GBE） against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell- astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B （GB）, against oxygenglucose deprivation/reoxygenation and glucose （OGD/R） injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein （Na-F）, and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
基金This study was funded by Incubation foundation of Capital Medical University(PYZ2018061)Nature and Sciences Foundation of China(81430044,81974183,81930054,82072104).
文摘Background and purpose The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury.Wild-type p53-induced protein phosphatase 1(Wip1),a serine/threonine phosphatase,is expressed in various tissues.A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue;however,its role in the central nervous system(CNS)remains unclear.This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.Methods A model of middle cerebral artery occlusion and reperfusion was established in mice.CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia.Laser speckle imaging was used to monitor regional cerebral blood flow.Behavioural outcomes were assessed with a TreadScan gait analysis system.TTC staining was used to evaluate the infarct volume,and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia.ELISA was performed to detect the levels of inflammatory factors.Results Wip1 expression was increased after ischaemia/reperfusion.Wip1-knockout(KO)mice displayed more severe brain injury than wild-type mice,as indicated by aggravated motor dysfunction,greater brain infarct volumes and higher expression of inflammatory cytokines(interleukin-6 and tumour necrosis factor alpha)in the brain.We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models,which all showed activation of microglia/macrophages.Lentivirus-Ppm1d reversed the injury induced by Wip1-KO.Conclusions Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.
