We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the e...We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is detectable.For(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is non-zero.For(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the line-of-sight.We find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and 0.2.Furthermore,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.展开更多
背景:目前运动疗法是非药物治疗腰痛的有效方法,运动疗法可通过骨骼和肌肉之间的机械-化学偶联维持腰椎的稳定,但目前尚无关于运动疗法通过机械-化学偶联缓解慢性非特异性下背痛之间研究进展及最佳治疗方案的明确阐述。目的:综述运动疗...背景:目前运动疗法是非药物治疗腰痛的有效方法,运动疗法可通过骨骼和肌肉之间的机械-化学偶联维持腰椎的稳定,但目前尚无关于运动疗法通过机械-化学偶联缓解慢性非特异性下背痛之间研究进展及最佳治疗方案的明确阐述。目的:综述运动疗法时椎旁肌通过机械-化学偶联影响腰椎稳定性进而缓解慢性非特异性下背痛的相关研究进展,以及目前运动疗法治疗慢性非特异性下背痛的最佳方案。方法:在万方数据库、中国知网、维普、Web of Science和PubMed数据库进行文献检索,以“慢性非特异性下背痛,腰椎稳定,椎旁肌,运动疗法”为中文检索词,以“chronic nonspecific low back pain,lumbar stabilization,paravertebral muscle,exercise therapy”为英文检索词,检索各数据库建库至2024年1月发表的相关文献,最终纳入93篇文献进行归纳总结。结果与结论:运动疗法可以通过适当的机械刺激作用于椎旁肌和骨骼并使其产生相应的变化。运动疗法主要通过机械-化学偶联方式来提高椎旁肌的质量,进而维持腰椎稳定,从而更好地缓解慢性非特异性下背痛,是慢性非特异性下背痛的重要干预措施。但是,对于运动疗法通过腰椎稳定来治疗慢性非特异性下背痛的确切有效方案尚无明确报道。个体化运动方案的制定对于慢性非特异性下背痛的治疗和预后尤为重要。同一个体的肌肉质量与骨骼质量是密切相关的,影像学评估椎旁肌的质量和体积对于疾病的发现和干预具有重要意义。展开更多
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen...Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.展开更多
BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRN...BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.展开更多
基金supported by the National SKA Program of China No.2020SKA0120200the National Key Program for Science and Technology Research and Development No.2022YFC2205201+2 种基金the National Natural Science Foundation of China(NSFC,grant Nos.12288102,12041303,and 12041304)the Major Science and Technology Program of Xinjiang Uygur Autonomous Region No.2022A03013-2the open program of the Key Laboratory of Xinjiang Uygur Autonomous Region No.2020D04049。
文摘We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is detectable.For(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is non-zero.For(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the line-of-sight.We find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and 0.2.Furthermore,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.
文摘背景:目前运动疗法是非药物治疗腰痛的有效方法,运动疗法可通过骨骼和肌肉之间的机械-化学偶联维持腰椎的稳定,但目前尚无关于运动疗法通过机械-化学偶联缓解慢性非特异性下背痛之间研究进展及最佳治疗方案的明确阐述。目的:综述运动疗法时椎旁肌通过机械-化学偶联影响腰椎稳定性进而缓解慢性非特异性下背痛的相关研究进展,以及目前运动疗法治疗慢性非特异性下背痛的最佳方案。方法:在万方数据库、中国知网、维普、Web of Science和PubMed数据库进行文献检索,以“慢性非特异性下背痛,腰椎稳定,椎旁肌,运动疗法”为中文检索词,以“chronic nonspecific low back pain,lumbar stabilization,paravertebral muscle,exercise therapy”为英文检索词,检索各数据库建库至2024年1月发表的相关文献,最终纳入93篇文献进行归纳总结。结果与结论:运动疗法可以通过适当的机械刺激作用于椎旁肌和骨骼并使其产生相应的变化。运动疗法主要通过机械-化学偶联方式来提高椎旁肌的质量,进而维持腰椎稳定,从而更好地缓解慢性非特异性下背痛,是慢性非特异性下背痛的重要干预措施。但是,对于运动疗法通过腰椎稳定来治疗慢性非特异性下背痛的确切有效方案尚无明确报道。个体化运动方案的制定对于慢性非特异性下背痛的治疗和预后尤为重要。同一个体的肌肉质量与骨骼质量是密切相关的,影像学评估椎旁肌的质量和体积对于疾病的发现和干预具有重要意义。
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX)and 81671189(to RX)。
文摘Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
基金Changzhou Sci and Tech Program,No.CJ20220008Young Talent Development Plan of Changzhou Health Commission,No.CZQM2020118+2 种基金Changzhou High-Level Medical Talents Training Project,No.2022CZBJ105Cultivation Project of Changzhou Medical Center,Nanjing Medical University,No.CMCB202211Development Foundation of Affiliated Hospital of Xuzhou Medical University,No.XYFC202304,and No.XYFM202307。
文摘BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.
