Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the targe...Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.展开更多
[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mo...[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mongolian horse, Sanhe horse and Thoroughbred, and then analyzed by PCR-SSCP. [Result] Three genotypes (AA, BB and AB) were detected by PCR-SSCP and the distribution of genotypes of all research objects except Xinihe horse and Baerhu horse were in line with the "Hardy-Weinberg Law". [Conclusion] There was a polymorphic locus in the 3′ flank region of IGF-Ⅰ gene, which might affect the equine growth and development mechanism. The study is of important theoretical and practical significance to improve the performance and to develop equine industry.展开更多
Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is deter...Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is determined, incorporating with previous deep geophysical data. In the upper crust, a positive anomaly velocity zone exists in the Sichuan basin, whereas a negative anomaly velocity zone exists in the western Sichuan plateau. The boundary between the positive and negative anomaly zones is the Longmenshan fault zone. The images of lower crust and upper mantle in the Longmenshan fault, Xianshuihe fault, Honghe fault and others show the characteristic of tectonic boundary, indicating that the faults likely penetrate the Moho discontinuity. The negative velocity anomalies at the depth of 50 km in the Tengchong volcanic area and the Panxi tectonic zone appear to be associated with the temperature and composition variations in the upper mantle. The overall features of the crustal and the upper mantle structures in the SichuanYunnan region are the lower average velocity in both crust and uppermost mantle, the large crustal thickness variations, and the existence of high conductivity layer in the crust or/and upper mantle, and higher geothermal value. All these features are closely related to the collision between the India and the Asia plates. The crustal velocity in the SichuanYunnan rhombic block generally shows normal value or positive anomaly, while the negative anomaly exists in the area along the large strike-slip faults as the block boundary. It is conducive to the crustal block side-pressing out along the faults. In the major seismic zones, the seismicity is relative to the negative anomaly velocity. Most strong earthquakes occurred in the upper-mid crust with positive anomaly or normal velocity, where the negative anomaly zone generally exists below.展开更多
AIM:To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island(cag PAI).METHODS:One hundred and forty-nine clinical isolates of Helicobacter pylori(H.pylori)cultured from gastric...AIM:To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island(cag PAI).METHODS:One hundred and forty-nine clinical isolates of Helicobacter pylori(H.pylori)cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material.Antimicrobial susceptibility was determined by the agar dilution method.Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping(cagA,vacA alleles s and m),Glu-Pro-Ile-Tyr-Ala(EPIYA)polymerase chain reaction and random amplified polymorphic DNA(RAPD).Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5program.Cluster analyses was done using SPSS 15.0statistical package,where each of the fingerprint bands were denoted as variables.Dendrograms were designed by following Ward’s clustering method and the estimation of distances between each pair of H.pylori isolates was calculated with the squared Euclidean distance.RESULTS:Resistance rates were 4%for amoxicillin and 2.7%for clarithromycin with 2%double resistances.Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1.The 3’region of cagA gene was successfully amplified in 92.3%(12/13)of the baseline resistant isolates and in 60%(36/60)of the resistant isolates growing in antibiotic dilutions.Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates,it was found that in 61.5%(8/13)of the baseline isolates,a change in the number of EPIYA repetitions lowered antibiotic pressure.The gain and loss of EPIYA motifs resulted in a diversity of H.pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure.RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions.CONCLUSION:Antibiotic pressure does not induce loss of the cag pathogenicity island,but it can leadin most cases-to genetic rearrangements within the3’region cagA of the founding bacteria that can affect the level of tyrosine phosphorylation impacting on its cellular effects and lead to divergence of cagA-positive subclones.展开更多
The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbe...The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.展开更多
The changes of CD4^＋CD25^＋ regulatory T cells （CD4^＋CD25^＋ Treg） and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） from patients with asthma were investigated in order to elucidate the possible role...The changes of CD4^＋CD25^＋ regulatory T cells （CD4^＋CD25^＋ Treg） and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） from patients with asthma were investigated in order to elucidate the possible roles of CD4^＋CD25^＋ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls （normal control group） and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups （P〈0.05）. Although the CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them （P〉0.05）. As compared with persistent group, exacerbation group had lower CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA （P〈0.05）. It was indicated that the decrease of CD4^＋CD25^＋ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.展开更多
The special seismic tectonic environment and frequent seismicity in the southeastern margin of the Qinghai-Tibet Plateau show that this area is an ideal location to study the present tectonic movement and background o...The special seismic tectonic environment and frequent seismicity in the southeastern margin of the Qinghai-Tibet Plateau show that this area is an ideal location to study the present tectonic movement and background of strong earthquakes in China's Mainland and to predict future strong earthquake risk zones. Studies of the structural environment and physical characteristics of the deep structure in this area are helpful to explore deep dynamic effects and deformation field characteristics, to strengthen our understanding of the roles of anisotropy and tectonic deformation and to study the deep tectonic background of the seismic origin of the block＇s interior. In this paper, the three-dimensional （3D） P-wave velocity structure of the crust and upper mantle under the southeastern margin of the Qinghai-Tibet Plateau is obtained via observational data from 224 permanent seismic stations in the regional digital seismic network of Yunnan and Sichuan Provinces and from 356 mobile China seismic arrays in the southern section of the north-south seismic belt using a joint inversion method of the regional earthquake and teleseismic data. The results indicate that the spatial distribution of the P-wave velocity anomalies in the shallow upper crust is closely related to the surface geological structure, terrain and lithology. Baoxing and Kangding, with their basic volcanic rocks and volcanic clastic rocks, present obvious high-velocity anomalies. The Chengdu Basin shows low-velocity anomalies associated with the Quaternary sediments. The Xichang Mesozoic Basin and the Butuo Basin are characterised by low- velocity anomalies related to very thick sedimentary layers. The upper and middle crust beneath the Chuan-Dian and Songpan-Ganzi Blocks has apparent lateral heterogeneities, including low-velocity zones of different sizes. There is a large range of low-velocity layers in the Songpan-Ganzi Block and the sub-block northwest of Sichuan Province, showing that the middle and lower crust is relatively weak. The Sichuan Basin, which is located in the western margin of the Yangtze platform, shows high-velocity characteristics. The results also reveal that there are continuous low-velocity layer distributions in the middle and lower crust of the Daliangshan Block and that the distribution direction of the low-velocity anomaly is nearly SN, which is consistent with the trend of the Daliangshan fault. The existence of the low-velocity layer in the crust also provides a deep source for the deep dynamic deformation and seismic activity of the Daliangshan Block and its boundary faults. The results of the 3D P-wave velocity structure show that an anomalous distribution of high-density, strong-magnetic and high-wave velocity exists inside the crust in the Panxi region. This is likely related to late Paleozoic mantle plume activity that led to a large number of mafic and ultra-mafic intrusions into the crust. In the crustal doming process, the massive intrusion of mantle-derived material enhanced the mechanical strength of the crustal medium. The P-wave velocity structure also revealed that the upper mantle contains a low-velocity layer at a depth of 80-120 km in the Panxi region. The existence of deep faults in the Panxi region, which provide conditions for transporting mantle thermal material into the crust, is the deep tectonic background for the area＇s strong earthquake activity.展开更多
Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistoc...Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.展开更多
The impacts of land cover changes on regional climate with RegCM3. Sensitivity experiments were conducted by in Shaan-Gan-Ning （SGN） in western China were simulated replacing crop grids with different new land cover...The impacts of land cover changes on regional climate with RegCM3. Sensitivity experiments were conducted by in Shaan-Gan-Ning （SGN） in western China were simulated replacing crop grids with different new land cover types in the key area of SGN, where the returning cropland to tree/grass project has been carried out since 1999. The modified new land cover types include desert, forest, shrub and grass. They represent degraded, improved, and maintained vegetation cover with natural canopy in the key area. Results from three individual case studies show that the land cover change causes changes in temperature and terrestrial water variables especially within the key area, while changes in precipitation are found for a larger area. The strongest changes appear where the cropland is degraded to bare soil, leading to increasing temperature and decreases in rainfall, evaporation and soil water. Opposite changes occur when cropland changed into forests, especially with strong increases in soil water. When cropland changed to grass and shrub land, the climatic changes are closer to those with forest cover. This shows the importance of improving and maintaining the vegetation in SGN for the ecosystem and regional climate.展开更多
In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve ...In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold （paw withdrawal latency） was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptJc cleft width and thinning of the postsynaptJc density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kJnase II expression in the hippocampal CA3 region.展开更多
Glatiramer acetate （GA） is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, ...Glatiramer acetate （GA） is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, graft re- jection and hepatic fibrosis. Here, we report that GA was effective in altering the clinical course of diabetes in cyclo- phosphamide （CY）-potentiated non-obese diabetic （CY-NOD） mice. Treatment with GA significantly reduced the dia- betic rate in the mice and ameliorated insulitis, which coincided with increased CD4＋CD25＋Foxp3＋ T cell response in treated mice. GA treatment led to increased expression of transcription factor Foxp3 and elevated production of interleukin-4 （IL-4） both in vivo and in vitro. It was evident that the effect of GA on up-regulation of Foxp3 was me- diated partially through IL-4. IL-4 was found to maintain Foxp3 expression and regulatory function of CD4＋CD25＋ regulatory T cells （Tregs）. This study provides new evidence that GA has treatment potential for type 1 diabetes through the induction of Tregs and that increased IL-4 production is partially responsible for the enhanced Treg＇s function in GA treatment.展开更多
Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We use...Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9(CRISPR-associated protein9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na^+ /K^+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na^+ efflux but also of K^+ and Ca^(2+) influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes.展开更多
The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation ...The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation of these genes remain largely unknown.Here,through comparative transcriptome and chromatin immunoprecipitation sequencing(ChIP-seq)analyses of the methyltransferase PoKmt6 in rice blast fungus Pyricularia oryzae(syn.Magnaporthe oryzae),we found that PoKmt6-mediated H3K27me3 deposition was enriched mainly at fast-evolving regions and contributed to the silencing of a subset of secreted proteins(SP)and transposable element(TE)families during the vegetative growth of P.oryzae.Intriguingly,we observed that a group of SP genes,which were depleted of H3K27me3 modification,could also be silenced via the H3K27me3-mediated repression of the nearby TEs.In conclusion,our results indicate that H3K27me3 modification mediated by PoKmt6 regulates the expression of some SP genes in fast-evolving regions through the suppression of nearby TEs.展开更多
Regional Geological Information System combines the multi-dimensional and dynamic spatial information into an integrated spatial information system. 3D geological modeling and its preprocessing or post-processing are ...Regional Geological Information System combines the multi-dimensional and dynamic spatial information into an integrated spatial information system. 3D geological modeling and its preprocessing or post-processing are the most difficult problems for constructing the system. Based on the current 3D GIS technique, some basic problems in establishing the system are discussed in this paper, including 3D spatial data model, 3D geological modeling, and visu- alization of 3D geological data. A kind of 3D vector data model based on boundary representation for geological object and its topology was developed in order to model and visualize complex geological structures. In addition, some key techniques are pointed out for further study.展开更多
Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stres...Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits as well as sustained cerebral iniurv in the adult hippocampus.展开更多
The development of 3D geological models involves the integration of large amounts of geological data,as well as additional accessible proprietary lithological, structural,geochemical,geophysical,and borehole data.Luan...The development of 3D geological models involves the integration of large amounts of geological data,as well as additional accessible proprietary lithological, structural,geochemical,geophysical,and borehole data.Luanchuan,the case study area,southwestern Henan Province,is an important molybdenum-tungsten -lead-zinc polymetallic belt in China.展开更多
基金supported by grants from the National Natural Science Foundation of China (82070676)Jiangsu Provincial Medi-cal Innovation Center (CXZX202203)Jiangsu Provincial Medi-cal Key Laboratory (ZDXYS202201)。
文摘Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.
文摘[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mongolian horse, Sanhe horse and Thoroughbred, and then analyzed by PCR-SSCP. [Result] Three genotypes (AA, BB and AB) were detected by PCR-SSCP and the distribution of genotypes of all research objects except Xinihe horse and Baerhu horse were in line with the "Hardy-Weinberg Law". [Conclusion] There was a polymorphic locus in the 3′ flank region of IGF-Ⅰ gene, which might affect the equine growth and development mechanism. The study is of important theoretical and practical significance to improve the performance and to develop equine industry.
基金Foundation item: National Scientific and Technological Development Program (95-973-02-02) the Climb Program (95-S-05-01) of National Scientific and Technological Ministry of China and the State Natural Sciences Foundation of China (49874021).
文摘Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is determined, incorporating with previous deep geophysical data. In the upper crust, a positive anomaly velocity zone exists in the Sichuan basin, whereas a negative anomaly velocity zone exists in the western Sichuan plateau. The boundary between the positive and negative anomaly zones is the Longmenshan fault zone. The images of lower crust and upper mantle in the Longmenshan fault, Xianshuihe fault, Honghe fault and others show the characteristic of tectonic boundary, indicating that the faults likely penetrate the Moho discontinuity. The negative velocity anomalies at the depth of 50 km in the Tengchong volcanic area and the Panxi tectonic zone appear to be associated with the temperature and composition variations in the upper mantle. The overall features of the crustal and the upper mantle structures in the SichuanYunnan region are the lower average velocity in both crust and uppermost mantle, the large crustal thickness variations, and the existence of high conductivity layer in the crust or/and upper mantle, and higher geothermal value. All these features are closely related to the collision between the India and the Asia plates. The crustal velocity in the SichuanYunnan rhombic block generally shows normal value or positive anomaly, while the negative anomaly exists in the area along the large strike-slip faults as the block boundary. It is conducive to the crustal block side-pressing out along the faults. In the major seismic zones, the seismicity is relative to the negative anomaly velocity. Most strong earthquakes occurred in the upper-mid crust with positive anomaly or normal velocity, where the negative anomaly zone generally exists below.
基金Supported by The Administrative Department on Science and Innovation of the Republic of Colombia-COLCIENCIAS,No.RC-1106-408-20549,RC-1106-493-26237its program:Jóvenes Investigadores e Innovadores"Virginia Gutiérrez de Pineda",and by the Universidad del Valle,Cali,Colombia
文摘AIM:To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag pathogenicity island(cag PAI).METHODS:One hundred and forty-nine clinical isolates of Helicobacter pylori(H.pylori)cultured from gastric biopsies from 206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric cancer were included as study material.Antimicrobial susceptibility was determined by the agar dilution method.Resistant isolates at baseline and in amoxicillin and clarithromycin serial dilutions were subjected to genotyping(cagA,vacA alleles s and m),Glu-Pro-Ile-Tyr-Ala(EPIYA)polymerase chain reaction and random amplified polymorphic DNA(RAPD).Images of the RAPD amplicons were analyzed by Gel-Pro Analyzer 4.5program.Cluster analyses was done using SPSS 15.0statistical package,where each of the fingerprint bands were denoted as variables.Dendrograms were designed by following Ward’s clustering method and the estimation of distances between each pair of H.pylori isolates was calculated with the squared Euclidean distance.RESULTS:Resistance rates were 4%for amoxicillin and 2.7%for clarithromycin with 2%double resistances.Genotyping evidenced a high prevalence of the genotype cagA-positive/vacA s1m1.The 3’region of cagA gene was successfully amplified in 92.3%(12/13)of the baseline resistant isolates and in 60%(36/60)of the resistant isolates growing in antibiotic dilutions.Upon observing the distribution of the number of EPIYA repetitions in each dilution with respect to baseline isolates,it was found that in 61.5%(8/13)of the baseline isolates,a change in the number of EPIYA repetitions lowered antibiotic pressure.The gain and loss of EPIYA motifs resulted in a diversity of H.pylori subclones after bacterial adjustment to changing conditions product of antibiotic pressure.RAPD PCR evidenced the close clonal relationship between baseline isolates and isolates growing in antibiotic dilutions.CONCLUSION:Antibiotic pressure does not induce loss of the cag pathogenicity island,but it can leadin most cases-to genetic rearrangements within the3’region cagA of the founding bacteria that can affect the level of tyrosine phosphorylation impacting on its cellular effects and lead to divergence of cagA-positive subclones.
文摘The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.
基金This project was supported by a program of Science Project of Hubei Province (No.2003AA301C10).
文摘The changes of CD4^＋CD25^＋ regulatory T cells （CD4^＋CD25^＋ Treg） and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） from patients with asthma were investigated in order to elucidate the possible roles of CD4^＋CD25^＋ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls （normal control group） and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups （P〈0.05）. Although the CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them （P〉0.05）. As compared with persistent group, exacerbation group had lower CD4^＋CD25^＋ Treg ratio and Foxp3 mRNA （P〈0.05）. It was indicated that the decrease of CD4^＋CD25^＋ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.
基金supported by China earthquake scientific array exploration Southern section of North South seismic belt(201008001)Northern section of North South seismic belt(20130811)+1 种基金National Natural Science Foundation of China(41474057)Science for Earthquake Resllience of China Earthquake Administration(XH15040Y)
文摘The special seismic tectonic environment and frequent seismicity in the southeastern margin of the Qinghai-Tibet Plateau show that this area is an ideal location to study the present tectonic movement and background of strong earthquakes in China's Mainland and to predict future strong earthquake risk zones. Studies of the structural environment and physical characteristics of the deep structure in this area are helpful to explore deep dynamic effects and deformation field characteristics, to strengthen our understanding of the roles of anisotropy and tectonic deformation and to study the deep tectonic background of the seismic origin of the block＇s interior. In this paper, the three-dimensional （3D） P-wave velocity structure of the crust and upper mantle under the southeastern margin of the Qinghai-Tibet Plateau is obtained via observational data from 224 permanent seismic stations in the regional digital seismic network of Yunnan and Sichuan Provinces and from 356 mobile China seismic arrays in the southern section of the north-south seismic belt using a joint inversion method of the regional earthquake and teleseismic data. The results indicate that the spatial distribution of the P-wave velocity anomalies in the shallow upper crust is closely related to the surface geological structure, terrain and lithology. Baoxing and Kangding, with their basic volcanic rocks and volcanic clastic rocks, present obvious high-velocity anomalies. The Chengdu Basin shows low-velocity anomalies associated with the Quaternary sediments. The Xichang Mesozoic Basin and the Butuo Basin are characterised by low- velocity anomalies related to very thick sedimentary layers. The upper and middle crust beneath the Chuan-Dian and Songpan-Ganzi Blocks has apparent lateral heterogeneities, including low-velocity zones of different sizes. There is a large range of low-velocity layers in the Songpan-Ganzi Block and the sub-block northwest of Sichuan Province, showing that the middle and lower crust is relatively weak. The Sichuan Basin, which is located in the western margin of the Yangtze platform, shows high-velocity characteristics. The results also reveal that there are continuous low-velocity layer distributions in the middle and lower crust of the Daliangshan Block and that the distribution direction of the low-velocity anomaly is nearly SN, which is consistent with the trend of the Daliangshan fault. The existence of the low-velocity layer in the crust also provides a deep source for the deep dynamic deformation and seismic activity of the Daliangshan Block and its boundary faults. The results of the 3D P-wave velocity structure show that an anomalous distribution of high-density, strong-magnetic and high-wave velocity exists inside the crust in the Panxi region. This is likely related to late Paleozoic mantle plume activity that led to a large number of mafic and ultra-mafic intrusions into the crust. In the crustal doming process, the massive intrusion of mantle-derived material enhanced the mechanical strength of the crustal medium. The P-wave velocity structure also revealed that the upper mantle contains a low-velocity layer at a depth of 80-120 km in the Panxi region. The existence of deep faults in the Panxi region, which provide conditions for transporting mantle thermal material into the crust, is the deep tectonic background for the area＇s strong earthquake activity.
文摘Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.
基金supported by the Spe-cial Research Program for Public-Welfare Forestry(No.200804001)Meteorology(No.GYHY2011060114-3)the 863 Project(No.2009AA122005)
文摘The impacts of land cover changes on regional climate with RegCM3. Sensitivity experiments were conducted by in Shaan-Gan-Ning （SGN） in western China were simulated replacing crop grids with different new land cover types in the key area of SGN, where the returning cropland to tree/grass project has been carried out since 1999. The modified new land cover types include desert, forest, shrub and grass. They represent degraded, improved, and maintained vegetation cover with natural canopy in the key area. Results from three individual case studies show that the land cover change causes changes in temperature and terrestrial water variables especially within the key area, while changes in precipitation are found for a larger area. The strongest changes appear where the cropland is degraded to bare soil, leading to increasing temperature and decreases in rainfall, evaporation and soil water. Opposite changes occur when cropland changed into forests, especially with strong increases in soil water. When cropland changed to grass and shrub land, the climatic changes are closer to those with forest cover. This shows the importance of improving and maintaining the vegetation in SGN for the ecosystem and regional climate.
基金supported by the National Natural Science Foundation of China,No.30472241,90709031 and 30973796the Ministry of Science and Technology of China("973"Project),No.2007CB512505+1 种基金provided by the Foundation of Hainan Province,No.310054the Health Department of Hainan Province,Qiong-Wei-45
文摘In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold （paw withdrawal latency） was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptJc cleft width and thinning of the postsynaptJc density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kJnase II expression in the hippocampal CA3 region.
文摘Glatiramer acetate （GA） is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, graft re- jection and hepatic fibrosis. Here, we report that GA was effective in altering the clinical course of diabetes in cyclo- phosphamide （CY）-potentiated non-obese diabetic （CY-NOD） mice. Treatment with GA significantly reduced the dia- betic rate in the mice and ameliorated insulitis, which coincided with increased CD4＋CD25＋Foxp3＋ T cell response in treated mice. GA treatment led to increased expression of transcription factor Foxp3 and elevated production of interleukin-4 （IL-4） both in vivo and in vitro. It was evident that the effect of GA on up-regulation of Foxp3 was me- diated partially through IL-4. IL-4 was found to maintain Foxp3 expression and regulatory function of CD4＋CD25＋ regulatory T cells （Tregs）. This study provides new evidence that GA has treatment potential for type 1 diabetes through the induction of Tregs and that increased IL-4 production is partially responsible for the enhanced Treg＇s function in GA treatment.
基金supported by the National Key Research and Development Program of China(2016YFC0501203)the National Genetically Modified Organism Project(2016ZX08010005-9)。
文摘Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9(CRISPR-associated protein9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na^+ /K^+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na^+ efflux but also of K^+ and Ca^(2+) influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes.
基金the grants from the National Natural Science Foundation of China(U1805232,31770156,and 32172365)the China Postdoctoral Science Foundation(2021M690637)。
文摘The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation of these genes remain largely unknown.Here,through comparative transcriptome and chromatin immunoprecipitation sequencing(ChIP-seq)analyses of the methyltransferase PoKmt6 in rice blast fungus Pyricularia oryzae(syn.Magnaporthe oryzae),we found that PoKmt6-mediated H3K27me3 deposition was enriched mainly at fast-evolving regions and contributed to the silencing of a subset of secreted proteins(SP)and transposable element(TE)families during the vegetative growth of P.oryzae.Intriguingly,we observed that a group of SP genes,which were depleted of H3K27me3 modification,could also be silenced via the H3K27me3-mediated repression of the nearby TEs.In conclusion,our results indicate that H3K27me3 modification mediated by PoKmt6 regulates the expression of some SP genes in fast-evolving regions through the suppression of nearby TEs.
基金Project 2001AA135170 supported by the National High-Tech Research and Development 863 Program of China
文摘Regional Geological Information System combines the multi-dimensional and dynamic spatial information into an integrated spatial information system. 3D geological modeling and its preprocessing or post-processing are the most difficult problems for constructing the system. Based on the current 3D GIS technique, some basic problems in establishing the system are discussed in this paper, including 3D spatial data model, 3D geological modeling, and visu- alization of 3D geological data. A kind of 3D vector data model based on boundary representation for geological object and its topology was developed in order to model and visualize complex geological structures. In addition, some key techniques are pointed out for further study.
基金the Natural Science Research Project from Bureau of Public Health of Sichuan Province,No. 090194the Natural Science Research Project of Science Technology Bureau of Luzhou,No. 090102
文摘Our preliminary study demonstrated that neuropeptide Y （NPY）/nestin-positive cells exhibit a consistent spatial distribution in the hippocampus of normal adult rats. However, following severe acute and chronic stress-induced impaired learning and memory, synchronous decreased expression of nestin and NPY takes place in the hippocampus, and the underlying mechanisms remain unclear. In the present study, acute and chronic stress rat models were established using combined restrained and inverted stress. Results showed that learning and memory significantly decreased in acute and chronic stress rats. In addition, hippocampal cells were damaged, in particular in the acute stress rats, and nestin and NPY expression, as well as the number of NPY/nestin-positive cells in the CA3 region, significantly decreased. Furthermore, mature neurofilament 200-positive neurons were absent in the chronic stress rats. The NPY and cytoskeletal protein system equally contributed to stress-induced early learning and memory deficits as well as sustained cerebral iniurv in the adult hippocampus.
文摘The development of 3D geological models involves the integration of large amounts of geological data,as well as additional accessible proprietary lithological, structural,geochemical,geophysical,and borehole data.Luanchuan,the case study area,southwestern Henan Province,is an important molybdenum-tungsten -lead-zinc polymetallic belt in China.
