In order to study the alkali resistivity of VHA-c in Iris lacteal. (IrlVHA-c), the transgenic tobacco seedlings harboring lrlVHA-c gene from Iris lactea (To), the self-crossed progeny (T1), and the non-transgeni...In order to study the alkali resistivity of VHA-c in Iris lacteal. (IrlVHA-c), the transgenic tobacco seedlings harboring lrlVHA-c gene from Iris lactea (To), the self-crossed progeny (T1), and the non-transgenic lines of tobacco seedlings were grown in Hoagland nutrient solutions supplemented with 0, 100, 200, 300, 400 mmol.L^-1 NaHCO3. The MDA content, CAT, POD and SOD activity, electrical conductivity, chlorophyll content, soluble sugar content, proline content and polyphenol oxidase activity of the seedlings were determined. The results showed that the transgenic lines of tobacco maintained a high activity up to 200 mmol.L^-1 NaHCO3, and activity was slightly lower at 300 mmol.L^-1 NaHCOa. When the concentration of NaHCO3 was as high as 400 mmol.L^-1 the seedlings were badly hurt. In addition, the activity of To and T1 transgentic tobacoo was maintained more or less. While the non- transgenic lines of tobacco could maintain viably up to 100 mmol. L^-1 NaHCO3, and they could not survive at 400 mmol. L^-1 NaHCO3. The conclusion was drawn that the alkali resistance of the tobacoo transformed IrlVHA-c was noticeably improved.展开更多
We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
Flavonoids are important bioactive components in Dendrobium officinale,a medicinal orchid.They are involved in many biological activities,including protecting plants against biotic and abiotic stresses.Research on the...Flavonoids are important bioactive components in Dendrobium officinale,a medicinal orchid.They are involved in many biological activities,including protecting plants against biotic and abiotic stresses.Research on the key genes related to flavonoid biosynthesis in D.officinale is limited.In this study,one of the key flavonoid biosynthesis genes,flavanone 3-hydroxylase(F3H),was characterized from D.officinale.The open reading frame of DoF3H was 1134 bp long and it encoded a 377-amino acid protein.The DoF3H protein showed considerably high homology with F3H proteins from other plant species and shared a common evolutionary ancestor with other F3Hs.DoF3H transcripts were detected in different organs of adult plants and mainly accumulated in flowers,followed by roots,stems and leaves,a pattern that was similar to the content of flavonoids.Recombinant DoF3H protein,which was localized in the cytosol,could convert naringenin to dihydrokaempferol.The mRNA levels of DoF3H were significantly induced by salt and cold stresses.Furthermore,the heterologous expression of DoF3H in Escherichia coli conferred it higher tolerance to salt and cold stresses.These results provide insight into the molecular function of DoF3H in the biosynthesis of flavonoids,and provide a new application for improvement of abiotic tolerance in D.officinale.展开更多
DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-bu...DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.展开更多
Histone H3 lysine 27 trimethylation(H3K27me3) is a histone modification associated with transcriptional repression. However, insights into the genome-wide pattern of H3K27me3 in grapevines are limited. Here, anti-H3K2...Histone H3 lysine 27 trimethylation(H3K27me3) is a histone modification associated with transcriptional repression. However, insights into the genome-wide pattern of H3K27me3 in grapevines are limited. Here, anti-H3K27 chromatin immunoprecipitation(ChIP), high-throughput sequencing, and transcriptome analysis were performed using leaves of Vitis amurensis. The leaves were treated at 4°C for 2 h and 24 h and used to investigate changes in H3K27me3 under chilling treatment. The results show that H3K27me3 is well-distributed both in gene regions(-50%) and in the intergenic region(-50%) in the grapevine genome(Vitis vinifera ‘Pinot Noir PN40024'). H3K27me3 was found to be localized in8 368 annotated gene regions in all detected samples(leaves at normal temperature and under chilling treatments) and mainly enriched in gene bodies with the adjacent promoter and downstream areas. The short-term chilling treatments(4°C for 2 h) induced 2 793 gains and 305losses in H3K27me3 modification. Subsequently, 97.3% of the alterations were restored to original levels after 24 h treatment. The ChIP-qPCR for five differential peaks showed similar results to the data for ChIP-seq, indicating that the chilling-induced H3K27me3 modification is reliable.Integrative analysis of transcriptome and ChIP-seq results showed that the expression of H3K27me3 target genes was significantly lower than those of non-target genes, indicating transcriptional repression of H3K27me3 in grapevine leaves. Furthermore, histone methylation alterations were detected in 82 genes and were related to either repression or activation of their expression during chilling stress. The findings provide the genome-wide H3K27me3 patterns in grapevines and shed light on uncovering its regulation in chilling stress responses.展开更多
Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypot...Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.展开更多
Pyroptosis plays an important role in hemorrhagic stroke.Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization ...Pyroptosis plays an important role in hemorrhagic stroke.Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3(NLRP3)pathway.However,the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear.In this study,we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue.Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress,pyroptosis,and inflammation and protected neurons.The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation.展开更多
Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly...Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.展开更多
The Si_(3)N_(4)/SiC gradient material with a gradient composition structure was prepared by a hot pressing sintering.The sinterability,distribution of residual stress and the effect of residual stress on mechanical pr...The Si_(3)N_(4)/SiC gradient material with a gradient composition structure was prepared by a hot pressing sintering.The sinterability,distribution of residual stress and the effect of residual stress on mechanical properties of Si_(3)N_(4)/SiC gradient materials were studied.The research results show that,at 1750℃,Si_(3)N_(4)/SiC gradient materials with different ratios can achieve co-sintering,and the overall relative density of the sample reaches 98.5%.Interestingly,the flexural strength of Si_(3)N_(4)/SiC gradient material is related to its loading surface.The flexural strength of SiC as the loading surface is about 35%higher than that of Si_(3)N_(4)as the loading surface.The analysis of the residual stress of the material in the gradient structure shows that the gradient stress distribution between the two phases is a vital factor affecting the mechanical properties of the material.With the increase of SiC content in the gradient direction,the fracture toughness of each layer of Si_(3)N_(4)/SiC gradient materials gradually decreases.The surface hardness of the pure SiC side is lower than that reported in other literature.展开更多
Drought has severely affected the yield and quality of commercial crops.The BRI1 family plays an important role in plant response to drought stress,and BRL3 gene plays an important role in the study of drought in Arab...Drought has severely affected the yield and quality of commercial crops.The BRI1 family plays an important role in plant response to drought stress,and BRL3 gene plays an important role in the study of drought in Arabidopsis thaliana.In this study,NtBRL3 was constructed as a vector and genetically transformed to obtain‘N.Tobacco K326’overexpression of NtBRL3.The enzyme activities of transgenic tobacco and wild-type tobacco were measured and transcriptome and metabolome analyses were performed.The results showed that the antioxidant enzymes of transgenic tobacco were more active under drought conditions,and 85 significantly differentially metabolites and 106 significantly differentially expressed genes were identified in the metabolome and transcriptome analyses,respectively.Transgenic tobacco NtBRL3ox demonstrated an excessive accumulation of droughtrelated metabolites,sugars such as sucrose and maltotetraose,and amino acids such as proline,compared with WT.We discovered drought-related differential genes in the root transcriptome,among which LOX6,RD22,WSD1,CCD8,and UGT were key genes which play an important role in plant response to drought stress.Our results demonstrate that NtBRL3 overexpression in K326 enhances drought resistance in transgenic tobacco.展开更多
Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This study investigated the progressive deterioration of olanzapine-induced...Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet(HFD)and explored the involvement of endoplasmic reticulum(ER)stress.Methods Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine(3 mg/kg/day)and the ER stress inhibitor 4-phenylbutyric acid(4-PBA,1 and 0.5 g/kg/day)for 8 days.Changes in body weight,food intake,and plasma lipids were assessed.Hepatic fat accumulation was evaluated using oil red O staining.Western blotting and immunofluorescence assays were employed to examine the expression of ER stress markers,NOD-like receptor pyrin domain-containing protein 3(NLRP3),and proopiomelanocortin(POMC)in the hypothalamus or liver.Results Compared to olanzapine alone,olanzapine+HFD induced greater weight gain,increased hyperlipidemia,and enhanced hepatic fat accumulation(P<0.05).Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects(P<0.05).Further mechanistic investigations revealed that olanzapine alone activated ER stress,upregulated NLRP3 expression in the hypothalamus and liver,and downregulated hypothalamic POMC expression.The HFD exacerbated these effects by 50%–100%.Moreover,co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress,NLRP3,and POMC expression in the hypothalamus and liver(P<0.05).Conclusion HFD worsened olanzapine-induced weight gain and lipid metabolic disorders,possibly through ER stress-POMC and ER stress-NLRP3 signaling.ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.展开更多
In order to solve the problem of asymmetric large deformation of high-stress soft rock crossing roadway under complex geological conditions in deep mines, taking the 2# total return airway of 76.2# section of Wuyang C...In order to solve the problem of asymmetric large deformation of high-stress soft rock crossing roadway under complex geological conditions in deep mines, taking the 2# total return airway of 76.2# section of Wuyang Coal Mine as the engineering background, the causes of asymmetric deformation and failure of soft rock crossing roadway in deep mines were summarized and analyzed by means of field investigation, theoretical analysis and numerical simulation, and the asymmetric high-efficiency support technology with large row spacing was studied. The results show that the lithology of roadway strata is the main cause of asymmetric deformation and failure of roadway. The shape change of roadway is not the main influencing factor of asymmetric deformation of roadway, but for the control of roadway surrounding rock, the straight wall semi-circular arch roadway is better than the rectangular roadway. The field industrial test shows that after adopting the new support design scheme, the displacement of the roof and floor of the roadway is reduced by 86.39% compared with the original support design scheme, and the displacement of the two sides of the roadway is reduced by 86.05% compared with the original support design scheme, which can ensure the normal and safe production of the roadway during the service period, and provide reference for the support design of other similar geological conditions.展开更多
Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like...Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.展开更多
The endoplasmic reticulum plays an extremely important role in the process of cellular protein secretion.The cyclic AMP-responsive element-binding protein 3(CREB3)transcription factor family is closely associated with...The endoplasmic reticulum plays an extremely important role in the process of cellular protein secretion.The cyclic AMP-responsive element-binding protein 3(CREB3)transcription factor family is closely associated with the secretion and transport of proteins within the endoplasmic reticulum.As a member of the CREB3 transcription factor family,cyclic AMP-responsive element-binding protein 3-like protein 2(CREB3L2)stands out as a non-classical sensor within the endoplasmic reticulum.CREB3L2 can detect and regulate endoplasmic reticulum pressure,exert control over the processes of protein transport and secretion,participate in the development of tumor cells,and is also closely linked to the development of certain human tissues and organs.This article aims to review the role of CREB3L2 in tissue development and disease,shedding light on the related mechanisms of CREB3L2 in cancer development.The goal is to provide insights and directions for further analysis of CREB3L2.展开更多
基金Supported by the Post-doctoral research start-up funding of Heilongjiang Province (LBH-210144)Postdoctoral Funds Project of Heilongjiang Province (520-415037)
文摘In order to study the alkali resistivity of VHA-c in Iris lacteal. (IrlVHA-c), the transgenic tobacco seedlings harboring lrlVHA-c gene from Iris lactea (To), the self-crossed progeny (T1), and the non-transgenic lines of tobacco seedlings were grown in Hoagland nutrient solutions supplemented with 0, 100, 200, 300, 400 mmol.L^-1 NaHCO3. The MDA content, CAT, POD and SOD activity, electrical conductivity, chlorophyll content, soluble sugar content, proline content and polyphenol oxidase activity of the seedlings were determined. The results showed that the transgenic lines of tobacco maintained a high activity up to 200 mmol.L^-1 NaHCO3, and activity was slightly lower at 300 mmol.L^-1 NaHCOa. When the concentration of NaHCO3 was as high as 400 mmol.L^-1 the seedlings were badly hurt. In addition, the activity of To and T1 transgentic tobacoo was maintained more or less. While the non- transgenic lines of tobacco could maintain viably up to 100 mmol. L^-1 NaHCO3, and they could not survive at 400 mmol. L^-1 NaHCO3. The conclusion was drawn that the alkali resistance of the tobacoo transformed IrlVHA-c was noticeably improved.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
基金supported by the National Natural Science Foundation of China(Grant No.31871547)。
文摘Flavonoids are important bioactive components in Dendrobium officinale,a medicinal orchid.They are involved in many biological activities,including protecting plants against biotic and abiotic stresses.Research on the key genes related to flavonoid biosynthesis in D.officinale is limited.In this study,one of the key flavonoid biosynthesis genes,flavanone 3-hydroxylase(F3H),was characterized from D.officinale.The open reading frame of DoF3H was 1134 bp long and it encoded a 377-amino acid protein.The DoF3H protein showed considerably high homology with F3H proteins from other plant species and shared a common evolutionary ancestor with other F3Hs.DoF3H transcripts were detected in different organs of adult plants and mainly accumulated in flowers,followed by roots,stems and leaves,a pattern that was similar to the content of flavonoids.Recombinant DoF3H protein,which was localized in the cytosol,could convert naringenin to dihydrokaempferol.The mRNA levels of DoF3H were significantly induced by salt and cold stresses.Furthermore,the heterologous expression of DoF3H in Escherichia coli conferred it higher tolerance to salt and cold stresses.These results provide insight into the molecular function of DoF3H in the biosynthesis of flavonoids,and provide a new application for improvement of abiotic tolerance in D.officinale.
文摘DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.
基金supported by the National Key Research and Development Program of China (Grant No. 2018YFD1000300)the National Natural Science Foundation of China (Grant No. 32025032)+1 种基金the Grape Breeding Project of Ningxia (Grant No. NXNYYZ202101-04)Major Program of Technological Innovation in Hubei Province (Grant No. 2019ABA093).
文摘Histone H3 lysine 27 trimethylation(H3K27me3) is a histone modification associated with transcriptional repression. However, insights into the genome-wide pattern of H3K27me3 in grapevines are limited. Here, anti-H3K27 chromatin immunoprecipitation(ChIP), high-throughput sequencing, and transcriptome analysis were performed using leaves of Vitis amurensis. The leaves were treated at 4°C for 2 h and 24 h and used to investigate changes in H3K27me3 under chilling treatment. The results show that H3K27me3 is well-distributed both in gene regions(-50%) and in the intergenic region(-50%) in the grapevine genome(Vitis vinifera ‘Pinot Noir PN40024'). H3K27me3 was found to be localized in8 368 annotated gene regions in all detected samples(leaves at normal temperature and under chilling treatments) and mainly enriched in gene bodies with the adjacent promoter and downstream areas. The short-term chilling treatments(4°C for 2 h) induced 2 793 gains and 305losses in H3K27me3 modification. Subsequently, 97.3% of the alterations were restored to original levels after 24 h treatment. The ChIP-qPCR for five differential peaks showed similar results to the data for ChIP-seq, indicating that the chilling-induced H3K27me3 modification is reliable.Integrative analysis of transcriptome and ChIP-seq results showed that the expression of H3K27me3 target genes was significantly lower than those of non-target genes, indicating transcriptional repression of H3K27me3 in grapevine leaves. Furthermore, histone methylation alterations were detected in 82 genes and were related to either repression or activation of their expression during chilling stress. The findings provide the genome-wide H3K27me3 patterns in grapevines and shed light on uncovering its regulation in chilling stress responses.
基金supported by the National Natural Science Foundation of China,No.81571120(to ZYH).
文摘Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.
文摘Pyroptosis plays an important role in hemorrhagic stroke.Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3(NLRP3)pathway.However,the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear.In this study,we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue.Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress,pyroptosis,and inflammation and protected neurons.The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation.
基金supported by the Xiamen High-Level Health Talents Introduction and Training Project(Xiaweidang 2021-124)the National Natural Science Foundation of China(No.81774319).
文摘Background:The development and prognosis of breast cancer are intricately linked to psychological stress.In addition,depression is the most common psychological comorbidity among breast cancer survivors,and reportedly,Fang-Xia-Dihuang decoction(FXDH)can effectively manage depression in such patients.However,its pharmacological and molecular mechanisms remain obscure.Methods:Public databases were used for obtaining active components and related targets.Main active components were further verified by ultra-high-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Protein–protein interaction and enrichment analyses were taken to predict potential hub targets and related pathways.Molecule docking was used to understand the interactions between main compounds and hub targets.In addition,an animal model of breast cancer combined with depression was established to evaluate the intervention effect of FXDH and verify the pathways screened by network pharmacology.Results:174 active components of FXDH and 163 intersection targets of FXDH,breast cancer,and depression were identified.Quercetin,methyl ferulate,luteolin,ferulaldehyde,wogonin,and diincarvilone were identified as the principal active components of FXDH.Protein–protein interaction and KEGG enrichment analyses revealed that the phosphoinositide-3-kinase–protein kinase B(PI3K/AKT)and Janus kinase/signal transducer and activator of transcription(JAK2/STAT3)signaling pathways played a crucial role in mediating the efficacy of FXDH for inhibiting breast cancer progression induced by depression.In addition,in vivo experiments revealed that FXDH ameliorated depression-like behavior in mice and inhibited excessive tumor growth in mice with breast cancer and depression.FXDH treatment downregulated the expression of epinephrine,PI3K,AKT,STAT3,and JAK2 compared with the control treatment(p<0.05).Molecular docking verified the relationship between the six primary components of FXDH and the three most important targets,including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),AKT,and STAT3.Conclusion:This study provides a scientific basis to support the clinical application of FXDH for improving depression-like behavior and inhibiting breast cancer progression promoted by chronic stress.The therapeutic effects FXDH may be closely related to the PI3K/AKT and JAK2/STAT3 pathways.This finding helps better understand the regulatory mechanisms underlying the efficacy of FXDH.
基金Funded by the National Natural Science Foundation of China(Nos.43190311,43200301 and 631800611)。
文摘The Si_(3)N_(4)/SiC gradient material with a gradient composition structure was prepared by a hot pressing sintering.The sinterability,distribution of residual stress and the effect of residual stress on mechanical properties of Si_(3)N_(4)/SiC gradient materials were studied.The research results show that,at 1750℃,Si_(3)N_(4)/SiC gradient materials with different ratios can achieve co-sintering,and the overall relative density of the sample reaches 98.5%.Interestingly,the flexural strength of Si_(3)N_(4)/SiC gradient material is related to its loading surface.The flexural strength of SiC as the loading surface is about 35%higher than that of Si_(3)N_(4)as the loading surface.The analysis of the residual stress of the material in the gradient structure shows that the gradient stress distribution between the two phases is a vital factor affecting the mechanical properties of the material.With the increase of SiC content in the gradient direction,the fracture toughness of each layer of Si_(3)N_(4)/SiC gradient materials gradually decreases.The surface hardness of the pure SiC side is lower than that reported in other literature.
基金supported by the Science and Technology Project of Guizhou Tobacco Company(2021XM04)the Creation of“Tobacco T-DNA Activation Insertion Mutant Library and Screening of Important Trait Mutants”Project of Guizhou University Talent Introduction(Guizhou University Hezi[2013]50).
文摘Drought has severely affected the yield and quality of commercial crops.The BRI1 family plays an important role in plant response to drought stress,and BRL3 gene plays an important role in the study of drought in Arabidopsis thaliana.In this study,NtBRL3 was constructed as a vector and genetically transformed to obtain‘N.Tobacco K326’overexpression of NtBRL3.The enzyme activities of transgenic tobacco and wild-type tobacco were measured and transcriptome and metabolome analyses were performed.The results showed that the antioxidant enzymes of transgenic tobacco were more active under drought conditions,and 85 significantly differentially metabolites and 106 significantly differentially expressed genes were identified in the metabolome and transcriptome analyses,respectively.Transgenic tobacco NtBRL3ox demonstrated an excessive accumulation of droughtrelated metabolites,sugars such as sucrose and maltotetraose,and amino acids such as proline,compared with WT.We discovered drought-related differential genes in the root transcriptome,among which LOX6,RD22,WSD1,CCD8,and UGT were key genes which play an important role in plant response to drought stress.Our results demonstrate that NtBRL3 overexpression in K326 enhances drought resistance in transgenic tobacco.
基金the Natural Science Foundation of Hubei Province(No.2021CFB301 and No.2021CFB299)the State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(WUT)(No.2022-KF-27).
文摘Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet(HFD)and explored the involvement of endoplasmic reticulum(ER)stress.Methods Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine(3 mg/kg/day)and the ER stress inhibitor 4-phenylbutyric acid(4-PBA,1 and 0.5 g/kg/day)for 8 days.Changes in body weight,food intake,and plasma lipids were assessed.Hepatic fat accumulation was evaluated using oil red O staining.Western blotting and immunofluorescence assays were employed to examine the expression of ER stress markers,NOD-like receptor pyrin domain-containing protein 3(NLRP3),and proopiomelanocortin(POMC)in the hypothalamus or liver.Results Compared to olanzapine alone,olanzapine+HFD induced greater weight gain,increased hyperlipidemia,and enhanced hepatic fat accumulation(P<0.05).Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects(P<0.05).Further mechanistic investigations revealed that olanzapine alone activated ER stress,upregulated NLRP3 expression in the hypothalamus and liver,and downregulated hypothalamic POMC expression.The HFD exacerbated these effects by 50%–100%.Moreover,co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress,NLRP3,and POMC expression in the hypothalamus and liver(P<0.05).Conclusion HFD worsened olanzapine-induced weight gain and lipid metabolic disorders,possibly through ER stress-POMC and ER stress-NLRP3 signaling.ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.
文摘In order to solve the problem of asymmetric large deformation of high-stress soft rock crossing roadway under complex geological conditions in deep mines, taking the 2# total return airway of 76.2# section of Wuyang Coal Mine as the engineering background, the causes of asymmetric deformation and failure of soft rock crossing roadway in deep mines were summarized and analyzed by means of field investigation, theoretical analysis and numerical simulation, and the asymmetric high-efficiency support technology with large row spacing was studied. The results show that the lithology of roadway strata is the main cause of asymmetric deformation and failure of roadway. The shape change of roadway is not the main influencing factor of asymmetric deformation of roadway, but for the control of roadway surrounding rock, the straight wall semi-circular arch roadway is better than the rectangular roadway. The field industrial test shows that after adopting the new support design scheme, the displacement of the roof and floor of the roadway is reduced by 86.39% compared with the original support design scheme, and the displacement of the two sides of the roadway is reduced by 86.05% compared with the original support design scheme, which can ensure the normal and safe production of the roadway during the service period, and provide reference for the support design of other similar geological conditions.
文摘Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.
基金Hebei Province Medical Science Research Plan Project(20220282)Baoding Science and Technology Plan Project(2141ZF237)。
文摘The endoplasmic reticulum plays an extremely important role in the process of cellular protein secretion.The cyclic AMP-responsive element-binding protein 3(CREB3)transcription factor family is closely associated with the secretion and transport of proteins within the endoplasmic reticulum.As a member of the CREB3 transcription factor family,cyclic AMP-responsive element-binding protein 3-like protein 2(CREB3L2)stands out as a non-classical sensor within the endoplasmic reticulum.CREB3L2 can detect and regulate endoplasmic reticulum pressure,exert control over the processes of protein transport and secretion,participate in the development of tumor cells,and is also closely linked to the development of certain human tissues and organs.This article aims to review the role of CREB3L2 in tissue development and disease,shedding light on the related mechanisms of CREB3L2 in cancer development.The goal is to provide insights and directions for further analysis of CREB3L2.