目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将...目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。展开更多
Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies th...Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different organs.However,little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various organs.Through transcriptomic and proteomic analyses,we observed heterogenous peroxisomal components among different organs,as well as between testicular somatic cells and different developmental stages of germ cells.As Pex3 is expressed in both germ cells and Sertoli cells,we generated Pex3 germ cell-and Sertoli cell-specific knockout mice.While Pex3 deletion in Sertoli cells did not affect spermatogenesis,the deletion in germ cells resulted in male sterility,manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells.Proteomic analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related proteins.These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis,but not for Sertoli cells.展开更多
This work develops a Hermitian C^(2) differential reproducing kernel interpolation meshless(DRKIM)method within the consistent couple stress theory(CCST)framework to study the three-dimensional(3D)microstructuredepend...This work develops a Hermitian C^(2) differential reproducing kernel interpolation meshless(DRKIM)method within the consistent couple stress theory(CCST)framework to study the three-dimensional(3D)microstructuredependent static flexural behavior of a functionally graded(FG)microplate subjected to mechanical loads and placed under full simple supports.In the formulation,we select the transverse stress and displacement components and their first-and second-order derivatives as primary variables.Then,we set up the differential reproducing conditions(DRCs)to obtain the shape functions of the Hermitian C^(2) differential reproducing kernel(DRK)interpolant’s derivatives without using direct differentiation.The interpolant’s shape function is combined with a primitive function that possesses Kronecker delta properties and an enrichment function that constituents DRCs.As a result,the primary variables and their first-and second-order derivatives satisfy the nodal interpolation properties.Subsequently,incorporating ourHermitianC^(2)DRKinterpolant intothe strong formof the3DCCST,we develop a DRKIM method to analyze the FG microplate’s 3D microstructure-dependent static flexural behavior.The Hermitian C^(2) DRKIM method is confirmed to be accurate and fast in its convergence rate by comparing the solutions it produces with the relevant 3D solutions available in the literature.Finally,the impact of essential factors on the transverse stresses,in-plane stresses,displacements,and couple stresses that are induced in the loaded microplate is examined.These factors include the length-to-thickness ratio,the material length-scale parameter,and the inhomogeneity index,which appear to be significant.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
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
Accurate 3-dimensional(3-D)reconstruction technology for nondestructive testing based on digital radiography(DR)is of great importance for alleviating the drawbacks of the existing computed tomography(CT)-based method...Accurate 3-dimensional(3-D)reconstruction technology for nondestructive testing based on digital radiography(DR)is of great importance for alleviating the drawbacks of the existing computed tomography(CT)-based method.The commonly used Monte Carlo simulation method ensures well-performing imaging results for DR.However,for 3-D reconstruction,it is limited by its high time consumption.To solve this problem,this study proposes a parallel computing method to accelerate Monte Carlo simulation for projection images with a parallel interface and a specific DR application.The images are utilized for 3-D reconstruction of the test model.We verify the accuracy of parallel computing for DR and evaluate the performance of two parallel computing modes-multithreaded applications(G4-MT)and message-passing interfaces(G4-MPI)-by assessing parallel speedup and efficiency.This study explores the scalability of the hybrid G4-MPI and G4-MT modes.The results show that the two parallel computing modes can significantly reduce the Monte Carlo simulation time because the parallel speedup increment of Monte Carlo simulations can be considered linear growth,and the parallel efficiency is maintained at a high level.The hybrid mode has strong scalability,as the overall run time of the 180 simulations using 320 threads is 15.35 h with 10 billion particles emitted,and the parallel speedup can be up to 151.36.The 3-D reconstruction of the model is achieved based on the filtered back projection(FBP)algorithm using 180 projection images obtained with the hybrid G4-MPI and G4-MT.The quality of the reconstructed sliced images is satisfactory because the images can reflect the internal structure of the test model.This method is applied to a complex model,and the quality of the reconstructed images is evaluated.展开更多
3-dimension(3-D)printing technology is growing strongly with many applications,one of which is the garment industry.The application of human body models to the garment industry is necessary to respond to the increasin...3-dimension(3-D)printing technology is growing strongly with many applications,one of which is the garment industry.The application of human body models to the garment industry is necessary to respond to the increasing personalization demand and still guarantee aesthetics.This paper proposes amethod to construct 3-D human models by applying deep learning.We calculate the location of the main slices of the human body,including the neck,chest,belly,buttocks,and the rings of the extremities,using pre-existing information.Then,on the positioning frame,we find the key points(fixed and unaltered)of these key slices and update these points tomatch the current parameters.To add points to a star slice,we use a deep learning model tomimic the form of the human body at that slice position.We use interpolation to produce sub-slices of different body sections based on the main slices to create complete body parts morphologically.We combine all slices to construct a full 3-D representation of the human body.展开更多
Cucumber seedlings were sprayed with different concentrations of LaCl_3 for 3 d continuously. After 7 d of this treatment, the plants were treated with 1200 mg·L^(-1) 2,4-dichlorophennoxy(2,4-D) for 24 h. The lea...Cucumber seedlings were sprayed with different concentrations of LaCl_3 for 3 d continuously. After 7 d of this treatment, the plants were treated with 1200 mg·L^(-1) 2,4-dichlorophennoxy(2,4-D) for 24 h. The leaves were harvested and rinsed with 5 mmol·L^(-1) EDTA. The concentrations of photosynthetic pigments, soluble protein and metabolites related to oxidative stress and the activities of antioxidant enzymes in leaves were assayed. The results show that the treatment with appropriate concentration of LaCl_3 has resistant effect on oxidative stress induced by 2, 4-D. Proper concentration of LaCl_3 promotes the activity of antioxidant system in plants and alleviates the damage caused by 2, 4-D.展开更多
文摘目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。
基金supported by grants from the National Natural Science Foundation of China(Grant No.31890784 to J.S.)National Key R&D Program(Grant No.2021YFC2700200 to X.G.)+2 种基金National Natural Science Foundation of China(Grant Nos.92068109 and 82122025 to Yan Yuan)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.21KJA310007 to Yan Yuan)Science Foundation of Gusu School(Grant No.GSKY20220101 to J.S.).
文摘Peroxisomes are organelles enclosed by a single membrane and are present in various species.The abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different organs.However,little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various organs.Through transcriptomic and proteomic analyses,we observed heterogenous peroxisomal components among different organs,as well as between testicular somatic cells and different developmental stages of germ cells.As Pex3 is expressed in both germ cells and Sertoli cells,we generated Pex3 germ cell-and Sertoli cell-specific knockout mice.While Pex3 deletion in Sertoli cells did not affect spermatogenesis,the deletion in germ cells resulted in male sterility,manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant cells.Proteomic analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related proteins.These findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis,but not for Sertoli cells.
基金supported by a grant from the National Science and Technology Council of the Republic of China(Grant Number:MOST 112-2221-E-006-048-MY2).
文摘This work develops a Hermitian C^(2) differential reproducing kernel interpolation meshless(DRKIM)method within the consistent couple stress theory(CCST)framework to study the three-dimensional(3D)microstructuredependent static flexural behavior of a functionally graded(FG)microplate subjected to mechanical loads and placed under full simple supports.In the formulation,we select the transverse stress and displacement components and their first-and second-order derivatives as primary variables.Then,we set up the differential reproducing conditions(DRCs)to obtain the shape functions of the Hermitian C^(2) differential reproducing kernel(DRK)interpolant’s derivatives without using direct differentiation.The interpolant’s shape function is combined with a primitive function that possesses Kronecker delta properties and an enrichment function that constituents DRCs.As a result,the primary variables and their first-and second-order derivatives satisfy the nodal interpolation properties.Subsequently,incorporating ourHermitianC^(2)DRKinterpolant intothe strong formof the3DCCST,we develop a DRKIM method to analyze the FG microplate’s 3D microstructure-dependent static flexural behavior.The Hermitian C^(2) DRKIM method is confirmed to be accurate and fast in its convergence rate by comparing the solutions it produces with the relevant 3D solutions available in the literature.Finally,the impact of essential factors on the transverse stresses,in-plane stresses,displacements,and couple stresses that are induced in the loaded microplate is examined.These factors include the length-to-thickness ratio,the material length-scale parameter,and the inhomogeneity index,which appear to be significant.
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.
基金the China Natural Science Fund(No.52171253)the Natural Science Foundation of Sichuan(No.2022NSFSCO949).
文摘Accurate 3-dimensional(3-D)reconstruction technology for nondestructive testing based on digital radiography(DR)is of great importance for alleviating the drawbacks of the existing computed tomography(CT)-based method.The commonly used Monte Carlo simulation method ensures well-performing imaging results for DR.However,for 3-D reconstruction,it is limited by its high time consumption.To solve this problem,this study proposes a parallel computing method to accelerate Monte Carlo simulation for projection images with a parallel interface and a specific DR application.The images are utilized for 3-D reconstruction of the test model.We verify the accuracy of parallel computing for DR and evaluate the performance of two parallel computing modes-multithreaded applications(G4-MT)and message-passing interfaces(G4-MPI)-by assessing parallel speedup and efficiency.This study explores the scalability of the hybrid G4-MPI and G4-MT modes.The results show that the two parallel computing modes can significantly reduce the Monte Carlo simulation time because the parallel speedup increment of Monte Carlo simulations can be considered linear growth,and the parallel efficiency is maintained at a high level.The hybrid mode has strong scalability,as the overall run time of the 180 simulations using 320 threads is 15.35 h with 10 billion particles emitted,and the parallel speedup can be up to 151.36.The 3-D reconstruction of the model is achieved based on the filtered back projection(FBP)algorithm using 180 projection images obtained with the hybrid G4-MPI and G4-MT.The quality of the reconstructed sliced images is satisfactory because the images can reflect the internal structure of the test model.This method is applied to a complex model,and the quality of the reconstructed images is evaluated.
基金Funding for this study from Sai Gon University(Grant No.CSA2021–08).
文摘3-dimension(3-D)printing technology is growing strongly with many applications,one of which is the garment industry.The application of human body models to the garment industry is necessary to respond to the increasing personalization demand and still guarantee aesthetics.This paper proposes amethod to construct 3-D human models by applying deep learning.We calculate the location of the main slices of the human body,including the neck,chest,belly,buttocks,and the rings of the extremities,using pre-existing information.Then,on the positioning frame,we find the key points(fixed and unaltered)of these key slices and update these points tomatch the current parameters.To add points to a star slice,we use a deep learning model tomimic the form of the human body at that slice position.We use interpolation to produce sub-slices of different body sections based on the main slices to create complete body parts morphologically.We combine all slices to construct a full 3-D representation of the human body.
文摘Cucumber seedlings were sprayed with different concentrations of LaCl_3 for 3 d continuously. After 7 d of this treatment, the plants were treated with 1200 mg·L^(-1) 2,4-dichlorophennoxy(2,4-D) for 24 h. The leaves were harvested and rinsed with 5 mmol·L^(-1) EDTA. The concentrations of photosynthetic pigments, soluble protein and metabolites related to oxidative stress and the activities of antioxidant enzymes in leaves were assayed. The results show that the treatment with appropriate concentration of LaCl_3 has resistant effect on oxidative stress induced by 2, 4-D. Proper concentration of LaCl_3 promotes the activity of antioxidant system in plants and alleviates the damage caused by 2, 4-D.
