The Chengjiang Formation is the earliest continental clastic deposit after the Jinning Orogeny in central Yunnan Province,and therefore its accurate depositional age is significant for understanding the formation and ...The Chengjiang Formation is the earliest continental clastic deposit after the Jinning Orogeny in central Yunnan Province,and therefore its accurate depositional age is significant for understanding the formation and evolution of the Neoproterozoic rift basins in southern China.However,hampered by accuracy of the dating technique,the existing age data for the Chengjiang Formation are not very reliable.A large number of magmatic zircons were obtained from the tuff interbed in the lower part of the Chengjiang Formation in Jinyang area and the bottom part of the Chengjiang Formation in Dongchuan area,central Yunnan Province,and high-precision SHRIMP U-Pb dating was carried out on these zircons.The results show that the weighted mean 206 Pb/238 U ages are 797.8±8.2 and 803.1±8.7 Ma respectively.In combination with related geological evidence,it has been demonstrated that the bottom boundary age of the Chengjiang Formation should be 800±5 Ma,whereas the top boundary age could be ca 725 Ma.By synthetically analyzing the latest age data for the relevant strata,it has been confirmed that the Chengjiang Formation should be correlated with the Suxiong Formation and the Kaijianqiao Formation in western Sichuan Province,the Liantuo Formation in the middle and lower Yangtze,the Hongchicun Formation and the Shangshu Formation in northern Zhejiang Province,the Puling Formation in southern Anhui Province,the Luokedong Formation and the Majianqiao Formation in northwestern Jiangxi Province,the Wuqiangxi Formation in northwestern Hunan Province,the Fanzhao Formation and the Qingshuijiang Formation in southeastern Guizhou Province,and the Sanmenjie Formation and the Gongdong Formation in northern Guangxi Province.Sedimentary cycle analysis shows that the sedimentary filling sequence of the Neoproterozoic rift basins in southern China can be divided into four cycles.Among them,Cycle II began at ca.800 Ma,accompanied by intensive tectonic-thermal events.The zircon U-Pb ages from the bottom of the Chengjiang Formation reported in t展开更多
Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the cranio...Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues.The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells.Initially,we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells.Moreover,Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line.In addition,micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo.Unexpectedly,Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2,Dlx5,Msx2,and Osterix,but led to upregulation of Alp and Osteocalcin (OCN),both of which play critical roles in promoting osteoblast maturation.Importantly,luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity.Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis,we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes.Based on these findings,we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene,suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.展开更多
The Neoproterozoic Kangdian Rift Basin is a continental rift basin in the western Yangtze Continent.Determining its time of opening and subsequent filling pattern is an important aspect of understanding the formation ...The Neoproterozoic Kangdian Rift Basin is a continental rift basin in the western Yangtze Continent.Determining its time of opening and subsequent filling pattern is an important aspect of understanding the formation and evolution of the Yangtze Continent,South China.The Luliang Formation is the early filling in the eastern part of this rift basin,and its deposition age and filling sequence are significant for studies of the regional stratigraphic correlation,opening time,and filling pattern of this basin.Having been correlated to the upper part of the Mesoproterozoic Kunyang Group or to the Neoproterozoic Chengjiang Formation,the age and regional stratigraphic correlation of the Luliang Formation have long been uncertain.This is due to a lack of reliable absolute age constraints.To address this issue,the first zircon SHRIMP U-Pb geochronology has been established for this formation,yielding two high-precision isotopic ages of 818.6±9.2 and 805±14 Ma for the tuff layers at the bottoms of the lower and upper members of the Luliang Formation,respectively.Given the error factor,the bottom age of the lower member of the Luliang Formation can be interpreted as ca.820 Ma,corresponding to the bottom age of the lower part of the Banxi Group,which is the early filling of the Neoproterozoic Xianggui Rift Basin,a representative basin of the Neoproterozoic rift basins in the Yangtze Continent,South China.The bottom age of the upper member of the Luliang Formation can be interpreted as ca.800±5 Ma,corresponding to the bottom age of the Chengjiang Formation in the western part of the Neoproterozoic Kangdian Rift Basin and also corresponding to the bottom age of the upper part of the Banxi Group in the Neoproterozoic Xianggui Rift Basin.These ages indicate that the Neoproterozoic Kangdian Rift Basin shares the same opening time and filling sequences as those of the other Neoproterozoic rift basins in South China.Basin analysis shows that the Neoproterozoic Kangdian Rift Basin is a typical half-graben basin,with its main boun展开更多
The effects of different chlorides and operational conditions on the distribution and speciation of six heavy metals（Pb, Zn, Cr, Cu, Mn and Ni） during sludge incineration were investigated using a simulated laborato...The effects of different chlorides and operational conditions on the distribution and speciation of six heavy metals（Pb, Zn, Cr, Cu, Mn and Ni） during sludge incineration were investigated using a simulated laboratory tubular-furnace reactor. A thermodynamic equilibrium investigation using the Fact Sage software was performed to compare the experimental results. The results indicate that the volatility of the target metals was enhanced as the chlorine concentration increased. Inorganic-Cl influenced the volatilization of heavy metals in the order of Pb 〉 Zn 〉 Cr 〉 Cu 〉 Mn 〉 Ni. However, the effects of organic-Cl on the volatility of Mn, Pb and Cu were greater than the effects on Zn, Cr and Ni.With increasing combustion temperature, the presence of organic-Cl（PVC） and inorganic-Cl（NaCl） improved the transfer of Pb and Zn from bottom ash to fly ash or fuse gas. However,the presence of chloride had no obvious influence on Mn, Cu and Ni. Increased retention time could increase the volatilization rate of heavy metals; however, this effect was insignificant. During the incineration process, Pb readily formed Pb SiO4 and remained in the bottom ash. Different Pb compounds, primarily the volatile PbCl2, were found in the gas phase after the addition of NaCl; the dominant Pb compounds in the gas phase after the addition of PVC were PbCl2, Pb（ClO4）2and Pb Cl2O4.展开更多
Chimeric antigen receptor(CAR) T cell is a novel approach, which utilizes anti-tumor immunity for cancer treatment. As compared to the traditional cell-mediated immunity, CAR-T possesses the improved specificity of tu...Chimeric antigen receptor(CAR) T cell is a novel approach, which utilizes anti-tumor immunity for cancer treatment. As compared to the traditional cell-mediated immunity, CAR-T possesses the improved specificity of tumor antigens and independent cytotoxicity from major histocompatibility complex molecules through a monoclonal antibody in addition to the Tcell receptor. CAR-T cell has proven its effectiveness, primarily in hematological malignancies, specifically where the CD19 CAR-T cells were used to treat B-cell acute lymphoblastic leukemia and B-cell lymphomas. Nevertheless, there is little progress in the treatment of solid tumors despite the fact that many CAR agents have been created to target tumor antigens such as CEA,EGFR/EGFRvIII, GD2, HER2, MSLN, MUC1, and other antigens. The main obstruction against the progress of research in solid tumors is the tumor microenvironment, in which several elements, such as poor locating ability, immunosuppressive cells,cytokines, chemokines, immunosuppressive checkpoints, inhibitory metabolic factors, tumor antigen loss, and antigen heterogeneity, could affect the potency of CAR-T cells. To overcome these hurdles, researchers have reconstructed the CAR-T cells in various ways. The purpose of this review is to summarize the current research in this field, analyze the mechanisms of the major barriers mentioned above, outline the main solutions, and discuss the outlook of this novel immunotherapeutic modality.展开更多
Ti-Cu alloys with different Cu contents(3, 5 and 7 wt%) were fabricated and studied as novel antibacterial biomaterials for dental application. The Ti-Cu alloys were annealing treated at different temperatures(740℃, ...Ti-Cu alloys with different Cu contents(3, 5 and 7 wt%) were fabricated and studied as novel antibacterial biomaterials for dental application. The Ti-Cu alloys were annealing treated at different temperatures(740℃, 830℃ and 910℃) in order to obtain three typical microstructures, β-Ti + Ti2Cu, β-Ti + transformed α-Ti, and transformed α-Ti. Mechanical, antibacterial and biocorrosion properties of Ti-Cu alloys with different microstructures were well analyzed by scanning electron microscopy(SEM),X-ray diffraction(XRD), transmission electron microscopy(TEM), tensile test, electrochemical test and antibacterial test. The results indicated that the Ti-Cu alloys with microstructure of β-Ti + Ti2 Cu showed the best ductility compared with other Ti-Cu alloys with microstructures of β-Ti + transformed α-Ti and complete transformed α-Ti, and meanwhile, increase of the Cu content significantly contributed to the decreased ductility due to the increasing amount of Ti2 Cu, which brought both solid solution strengthening and precipitation strengthening. Finally, the Ti-5 Cu alloy with microstructure of β-Ti + Ti2 Cu exhibited excellent ductility, antibacterial property and corrosion resistance, providing a great potential in clinical application for dental implants.展开更多
OBJECTIVE: To address the optimal Chinese herbal injections(CHIs) against liver cancer, the present network Meta-analysis is designed to investigate the comparative efficacy and safety of different CHIs.METHODS: Sever...OBJECTIVE: To address the optimal Chinese herbal injections(CHIs) against liver cancer, the present network Meta-analysis is designed to investigate the comparative efficacy and safety of different CHIs.METHODS: Several electronic databases were searched up to June 1 st, 2017. The quality assessment was conducted and network Meta-analysis was performed to compare the efficacy and safety of different CHIs plus transcatheter hepatic arterial chemoembolization(TACE). Primary outcomes were 1-year and 2-year survival rate, the secondary outcomes includes the clinical effective rate, performance status and the adverse reactions(ADRs). Data analysis was applied Stata 13.0 and Win BUGS 1.4 software.RESULTS: A total of 105 randomized controlled trials(RCTs) were identified for inclusion in this analysis, with data for 7683 patients and 13 CHIs. The results suggested that Javanica oil emulsion,Huachansu injection plus TACE were more favorable for 1-year and 2-year survival rate than other CHIs. Kanglaite, Astragalus polysaccharide injection plus TACE showed superiority in the clinical effective rate and performance status over other CHIs.And Shenmai injection plus TACE was superior to reducing ADRs than other CHIs for patients with liver cancer.CONCLUSION: Our findings indicated that receiving CHIs combined with TACE may have therapeutic benefits for patients with liver cancer in improving survival rate, clinical effective rate, the performance status and alleviating the ADRs.展开更多
We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an ext...We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral genome replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.展开更多
In order to develop clinical diagnostic tools for rapid detection of SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal porti...In order to develop clinical diagnostic tools for rapid detection of SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal portion of the nucleocapsid (NC) gene was amplified using RT-PCR from the SARS-CoV genome, cloned into a yeast expression vector (pEGH), and expressed as a glutathione S-transferase (GST) and Hisx6 double-tagged fusion protein under the control of an inducible promoter. Western analysis on the purified protein confirmed the expression and purification of the NC fusion proteins from yeast. To determine its antigenicity, the fusion protein was challenged with serum samples from SARS patients and normal controls. The NC fusion protein demonstrated high antigenicity with high specificity, and therefore, it should have great potential in designing clinical diagnostic tools and provide useful information for vaccine development.展开更多
The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of th...The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of the N protein of SARS-CoV is that it is a typical basic protein with a high predicted pI and high hydrophilicity, which is consistent with its function of binding to the ribophosphate backbone of the RNA molecule. The predicted high extent of phosphorylation of the N protein on multiple candidate phosphorylation sites demonstrates that it would be related to important functions, such as RNA-binding and localization to the nucleolus of host cells. Subsequent study shows that there is an SR-rich region in the N protein and this region might be involved in the protein-protein interaction. The abundant antigenic sites predicted in the N protein, as well as experimental evidence with synthesized polypeptides, indicate that the N protein is one of the major antigens of the SARS-CoV. Compared with other viral structural proteins, the low variation rate of the N protein with regards to its size suggests its importance to the survival of the virus.展开更多
Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of...Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.展开更多
CO_(2)hydrogenation to methanol has become one of the most promising ways for CO_(2)utilization,however,the CO_(2)conversion rate and methanol selectivity of this reaction still need to be improved for industrial appl...CO_(2)hydrogenation to methanol has become one of the most promising ways for CO_(2)utilization,however,the CO_(2)conversion rate and methanol selectivity of this reaction still need to be improved for industrial application.Here we investigated the structure-activity relationship for CO_(2)conversion to methanol of In_(2)O_(3)-based catalysts by modulating morphology and decorating Au.Three different Au/In_(2)O_(3)catalysts were prepared,their activity follow the sequence of Au/In_(2)O_(3)-nanosphere(Au/In_(2)O_(3)-NS)>Au/In_(2)O_(3)-nanoplate(Au/In_(2)O_(3)-NP)>Au/In_(2)O_(3)-hollow microsphere(Au/In_(2)O_(3)-HM).Au/In_(2)O_(3)-NS exhibited the best performance with good CO_(2)conversion of 12.7%,high methanol selectivity of 59.8%,and large space time yield of 0.32 g CH_(3)OH/(hr·gcat)at 300℃.The high performance of Au/In_(2)O_(3)-NS was considered as the presence of Au.It contributes to the creation of more surface oxygen vacancies,which further promoted the CO_(2)adsorption and facilitated CO_(2)activation to form the formate intermediates towards methanol.This work clearly suggests that the activity of In_(2)O_(3)catalyst can be effective enhanced by structure engineering and Au decorating.展开更多
The Coriolis force method is a recently developed and highly regarded direct measurement technique that enables high-precision measurement of bulk materials.The operational parameters and variations thereof directly i...The Coriolis force method is a recently developed and highly regarded direct measurement technique that enables high-precision measurement of bulk materials.The operational parameters and variations thereof directly influence the measurement accuracy of the equipment.In this study,a measurement correction coefficient is introduced to improve the calculation method for mass flow rate of the materials.The DEM is employed to simulate the motion of particle groups within the Coriolis force scale under different parameters,and the effects of various structural and operational parameters on the measurement results are compared.The research findings indicate that a lower rotational speed leads to more stable instantaneous measurement results,although the measurement error is relatively large.When the rotational speed exceeds 300 rpm,the measurement error remains within 15%.For materials with a radius of 1–2 mm,the variation range of precision error is approximately 0.4%.Among the structural parameters,the radius of the measurement wheel has the most significant impact on the measurement results,wherein a larger measurement wheel radius corresponds to a smaller measurement error.The horizontal angle of the blades follows as the next influential parameter,with a clockwise rotation and a horizontal angle of 30°resulting in a measurement error below 2%.展开更多
The insurmountable charge transfer impedance at the Li metal/solid polymer electrolytes(SPEs)interface at room temperature as well as the ascending risk of short circuits at the operating temperature higher than the m...The insurmountable charge transfer impedance at the Li metal/solid polymer electrolytes(SPEs)interface at room temperature as well as the ascending risk of short circuits at the operating temperature higher than the melting point,dominantly limits their applications in solid-state batteries(SSBs).Although the inorganic filler such as CeO_(2)nanoparticle content of composite solid polymer electrolytes(CSPEs)can significantly reduce the enormous charge transfer impedance at the Li metal/SPEs interface,we found that the required content of CeO_(2)nanoparticles in SPEs varies for achieving a decent interfacial charge transfer impedance and the bulk ionic conductivity in CSPEs.In this regard,a sandwich-type composited solid polymer electrolyte with a 10%CeO_(2)CSPEs interlayer sandwiched between two 50%CeO_(2)CSPEs thin layers(sandwiched CSPEs)is constructed to simultaneously achieve low charge transfer impedance and superior ionic conductivity at 30℃.The sandwiched CSPEs allow for stable cycling of Li plating and stripping for 1000 h with 129 mV polarized voltage at 0.1 mA cm^(-2)and 30℃.In addition,the LiFePO_(4)/Sandwiched CSPEs/Li cell also exhibits exceptional cycle performance at 30℃and even elevated120℃without short circuits.Constructing multi-layered CSPEs with optimized contents of the inorganic fillers can be an efficient method for developing all solid-state PEO-based batteries with high performance at a wide range of temperatures.展开更多
Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-e...Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.展开更多
Bragg filters are of essential importance for chip-scale photonic systems.However,the implementation of filters with sub-nanometer bandwidth and rejection beyond 70 dB is hindered by the high index contrast of the sil...Bragg filters are of essential importance for chip-scale photonic systems.However,the implementation of filters with sub-nanometer bandwidth and rejection beyond 70 dB is hindered by the high index contrast of the siliconon-insulator platform,which makes filters prone to fabrication imperfections.In this paper,we propose to combine coherency-broken cascading architecture and cladding modulation to circumvent the intrinsic limitation.The cascading architecture effectively prevents the accumulation of phase errors,while the cladding modulation offers additional design freedom to reduce the coupling coefficient.A bimodal Bragg filter with a testingequipment-limited rejection level of 74 dB and a 40 dB bandwidth of 0.44 nm is experimentally demonstrated.The minimum feature size is 90 nm,which significantly relieves the fabrication constraints.展开更多
Lateral roots play essential roles in drought tolerance in maize(Zea mays L.). However, the genetic basis for the variation in the number of lateral roots in maize remains elusive. Here, we identified a major quantita...Lateral roots play essential roles in drought tolerance in maize(Zea mays L.). However, the genetic basis for the variation in the number of lateral roots in maize remains elusive. Here, we identified a major quantitative trait locus(QTL),q LRT5-1, controlling lateral root number using a recombinant inbred population from a cross between the maize lines Zong3(with many lateral roots) and 87-1(with few lateral roots).Fine-mapping and functional analysis determined that the candidate gene for qLRT5-1,ZmLRT, expresses the primary transcript for the microRNA miR166a. ZmLRT was highly expressed in root tips and lateral root primordia,and knockout and overexpression of ZmLRT increased and decreased lateral root number,respectively. Compared with 87-1, the ZmLRT gene model of Zong3 lacked the second and third exons and contained a 14 bp deletion at the junction between the first exon and intron,which altered the splicing site. In addition,ZmLRT expression was significantly lower in Zong3 than in 87-1, which might be attributed to the insertions of a transposon and over large DNA fragments in the Zong3 ZmLRT promoter region. These mutations decreased the abundance of mature miR166a in Zong3, resulting in increased lateral roots at the seedling stage.Furthermore, miR166a post-transcriptionally repressed five development-related class-Ⅲ homeodomain-leucine zipper genes. Moreover,knockout of ZmLRT enhanced drought tolerance of maize seedlings. Our study furthers our understanding of the genetic basis of lateral root number variation in maize and highlights ZmLRT as a target for improving drought tolerance in maize.展开更多
Polish wheat (Triticum polonicum) is a unique tetraploid wheat species characterized by an elongated outer glume. The genetic control of the long-glume trait by a single semi-dominant locus, P1 (from Polish wheat), wa...Polish wheat (Triticum polonicum) is a unique tetraploid wheat species characterized by an elongated outer glume. The genetic control of the long-glume trait by a single semi-dominant locus, P1 (from Polish wheat), was established more than 100 years ago, but the underlying causal gene and molecular nature remain elusive. Here, we report the isolation of VRT-A2, encoding an SVP-clade MADS-box transcription factor, as the P1 candidate gene. Genetic evidence suggests that in T. polonicum, a naturally occurring sequence rearrangement in the intron-1 region of VRT-A2 leads to ectopic expression of VRT-A2 in floral organs where the long-glume phenotype appears. Interestingly, we found that the intron-1 region is a key ON/OFF molecular switch for VRT-A2 expression, not only because it recruits transcriptional repressors, but also because it confers intron-mediated transcriptional enhancement. Genotypic analyses using wheat accessions indicated that the P1 locus is likely derived from a single natural mutation in tetraploid wheat, which was subsequently inherited by hexaploid T. petropavlovskyi. Taken together, our findings highlight the promoter-proximal intron variation as a molecular basis for phenotypic differentiation, and thus species formation in Triticum plants.展开更多
Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely...Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.展开更多
Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucia...Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.展开更多
基金supported by National Natural Science Foundation of China (Grant Nos. 41030315,41072088)the China Geological Survey(Grant No. 1212011121105)
文摘The Chengjiang Formation is the earliest continental clastic deposit after the Jinning Orogeny in central Yunnan Province,and therefore its accurate depositional age is significant for understanding the formation and evolution of the Neoproterozoic rift basins in southern China.However,hampered by accuracy of the dating technique,the existing age data for the Chengjiang Formation are not very reliable.A large number of magmatic zircons were obtained from the tuff interbed in the lower part of the Chengjiang Formation in Jinyang area and the bottom part of the Chengjiang Formation in Dongchuan area,central Yunnan Province,and high-precision SHRIMP U-Pb dating was carried out on these zircons.The results show that the weighted mean 206 Pb/238 U ages are 797.8±8.2 and 803.1±8.7 Ma respectively.In combination with related geological evidence,it has been demonstrated that the bottom boundary age of the Chengjiang Formation should be 800±5 Ma,whereas the top boundary age could be ca 725 Ma.By synthetically analyzing the latest age data for the relevant strata,it has been confirmed that the Chengjiang Formation should be correlated with the Suxiong Formation and the Kaijianqiao Formation in western Sichuan Province,the Liantuo Formation in the middle and lower Yangtze,the Hongchicun Formation and the Shangshu Formation in northern Zhejiang Province,the Puling Formation in southern Anhui Province,the Luokedong Formation and the Majianqiao Formation in northwestern Jiangxi Province,the Wuqiangxi Formation in northwestern Hunan Province,the Fanzhao Formation and the Qingshuijiang Formation in southeastern Guizhou Province,and the Sanmenjie Formation and the Gongdong Formation in northern Guangxi Province.Sedimentary cycle analysis shows that the sedimentary filling sequence of the Neoproterozoic rift basins in southern China can be divided into four cycles.Among them,Cycle II began at ca.800 Ma,accompanied by intensive tectonic-thermal events.The zircon U-Pb ages from the bottom of the Chengjiang Formation reported in t
基金supported by grant (81771036) from National Natural Science Foundation of China (to S.G.S.)grant (81741028) from National Natural Science Foundation of China (to J.D.)grant (17410710500) Shanghai International Scientific and Technological Cooperation Projects Laser Micromachine and Vascularization of TCP/PCL Scaffolds (to W.Z.)
文摘Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation,and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues.The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells.Initially,we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells.Moreover,Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line.In addition,micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo.Unexpectedly,Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2,Dlx5,Msx2,and Osterix,but led to upregulation of Alp and Osteocalcin (OCN),both of which play critical roles in promoting osteoblast maturation.Importantly,luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity.Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis,we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes.Based on these findings,we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene,suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.
基金supported by National Natural Science Foundation of China(Grant Nos.4103031541072088)China Geological Survey(Grant No.1212011121105)
文摘The Neoproterozoic Kangdian Rift Basin is a continental rift basin in the western Yangtze Continent.Determining its time of opening and subsequent filling pattern is an important aspect of understanding the formation and evolution of the Yangtze Continent,South China.The Luliang Formation is the early filling in the eastern part of this rift basin,and its deposition age and filling sequence are significant for studies of the regional stratigraphic correlation,opening time,and filling pattern of this basin.Having been correlated to the upper part of the Mesoproterozoic Kunyang Group or to the Neoproterozoic Chengjiang Formation,the age and regional stratigraphic correlation of the Luliang Formation have long been uncertain.This is due to a lack of reliable absolute age constraints.To address this issue,the first zircon SHRIMP U-Pb geochronology has been established for this formation,yielding two high-precision isotopic ages of 818.6±9.2 and 805±14 Ma for the tuff layers at the bottoms of the lower and upper members of the Luliang Formation,respectively.Given the error factor,the bottom age of the lower member of the Luliang Formation can be interpreted as ca.820 Ma,corresponding to the bottom age of the lower part of the Banxi Group,which is the early filling of the Neoproterozoic Xianggui Rift Basin,a representative basin of the Neoproterozoic rift basins in the Yangtze Continent,South China.The bottom age of the upper member of the Luliang Formation can be interpreted as ca.800±5 Ma,corresponding to the bottom age of the Chengjiang Formation in the western part of the Neoproterozoic Kangdian Rift Basin and also corresponding to the bottom age of the upper part of the Banxi Group in the Neoproterozoic Xianggui Rift Basin.These ages indicate that the Neoproterozoic Kangdian Rift Basin shares the same opening time and filling sequences as those of the other Neoproterozoic rift basins in South China.Basin analysis shows that the Neoproterozoic Kangdian Rift Basin is a typical half-graben basin,with its main boun
基金spported by the National Natural Science Foundation of China (No. 5130813)the Scientific and Technological Planning Project of Guangzhou, China (No. 201510010033)+1 种基金the natural Science Foundation of Guangdong Province (No. S2013040013022)the Excellent Youth Development Project of Universities in Guangdong Province (No. 2015-261532111)
文摘The effects of different chlorides and operational conditions on the distribution and speciation of six heavy metals（Pb, Zn, Cr, Cu, Mn and Ni） during sludge incineration were investigated using a simulated laboratory tubular-furnace reactor. A thermodynamic equilibrium investigation using the Fact Sage software was performed to compare the experimental results. The results indicate that the volatility of the target metals was enhanced as the chlorine concentration increased. Inorganic-Cl influenced the volatilization of heavy metals in the order of Pb 〉 Zn 〉 Cr 〉 Cu 〉 Mn 〉 Ni. However, the effects of organic-Cl on the volatility of Mn, Pb and Cu were greater than the effects on Zn, Cr and Ni.With increasing combustion temperature, the presence of organic-Cl（PVC） and inorganic-Cl（NaCl） improved the transfer of Pb and Zn from bottom ash to fly ash or fuse gas. However,the presence of chloride had no obvious influence on Mn, Cu and Ni. Increased retention time could increase the volatilization rate of heavy metals; however, this effect was insignificant. During the incineration process, Pb readily formed Pb SiO4 and remained in the bottom ash. Different Pb compounds, primarily the volatile PbCl2, were found in the gas phase after the addition of NaCl; the dominant Pb compounds in the gas phase after the addition of PVC were PbCl2, Pb（ClO4）2and Pb Cl2O4.
文摘Chimeric antigen receptor(CAR) T cell is a novel approach, which utilizes anti-tumor immunity for cancer treatment. As compared to the traditional cell-mediated immunity, CAR-T possesses the improved specificity of tumor antigens and independent cytotoxicity from major histocompatibility complex molecules through a monoclonal antibody in addition to the Tcell receptor. CAR-T cell has proven its effectiveness, primarily in hematological malignancies, specifically where the CD19 CAR-T cells were used to treat B-cell acute lymphoblastic leukemia and B-cell lymphomas. Nevertheless, there is little progress in the treatment of solid tumors despite the fact that many CAR agents have been created to target tumor antigens such as CEA,EGFR/EGFRvIII, GD2, HER2, MSLN, MUC1, and other antigens. The main obstruction against the progress of research in solid tumors is the tumor microenvironment, in which several elements, such as poor locating ability, immunosuppressive cells,cytokines, chemokines, immunosuppressive checkpoints, inhibitory metabolic factors, tumor antigen loss, and antigen heterogeneity, could affect the potency of CAR-T cells. To overcome these hurdles, researchers have reconstructed the CAR-T cells in various ways. The purpose of this review is to summarize the current research in this field, analyze the mechanisms of the major barriers mentioned above, outline the main solutions, and discuss the outlook of this novel immunotherapeutic modality.
基金financially supported by the National Natural Science Foundation of China (Nos. 51631009 and 51811530320)the National Key Research and Development Program of China (Nos. 2018YFC1106600 and 2016YFC1100600)+1 种基金the Innovation Fund Project of Institute of Metal Research, Chinese Academy of Sciences (No. 2017-ZD01)the Key Projects for Foreign Cooperation of Bureau of International Cooperation Chinese Academy of Sciences (No. 174321KYSB2018000)
文摘Ti-Cu alloys with different Cu contents(3, 5 and 7 wt%) were fabricated and studied as novel antibacterial biomaterials for dental application. The Ti-Cu alloys were annealing treated at different temperatures(740℃, 830℃ and 910℃) in order to obtain three typical microstructures, β-Ti + Ti2Cu, β-Ti + transformed α-Ti, and transformed α-Ti. Mechanical, antibacterial and biocorrosion properties of Ti-Cu alloys with different microstructures were well analyzed by scanning electron microscopy(SEM),X-ray diffraction(XRD), transmission electron microscopy(TEM), tensile test, electrochemical test and antibacterial test. The results indicated that the Ti-Cu alloys with microstructure of β-Ti + Ti2 Cu showed the best ductility compared with other Ti-Cu alloys with microstructures of β-Ti + transformed α-Ti and complete transformed α-Ti, and meanwhile, increase of the Cu content significantly contributed to the decreased ductility due to the increasing amount of Ti2 Cu, which brought both solid solution strengthening and precipitation strengthening. Finally, the Ti-5 Cu alloy with microstructure of β-Ti + Ti2 Cu exhibited excellent ductility, antibacterial property and corrosion resistance, providing a great potential in clinical application for dental implants.
基金Supported by the National Natural Science Foundation of China(Study on the Key Influential Factors of Anaphylaxis Induced by Chinese Herbal Injection Based on Three-dimensional Database and Multi-dimensional Data Mining,No.81473547Establishment of Multi-dimensional Clinical Evaluation Model of Danshen Injection for Treating Unstable Angina Pectoris Based on Bayesian Network Meta Analysis,No.81673829)。
文摘OBJECTIVE: To address the optimal Chinese herbal injections(CHIs) against liver cancer, the present network Meta-analysis is designed to investigate the comparative efficacy and safety of different CHIs.METHODS: Several electronic databases were searched up to June 1 st, 2017. The quality assessment was conducted and network Meta-analysis was performed to compare the efficacy and safety of different CHIs plus transcatheter hepatic arterial chemoembolization(TACE). Primary outcomes were 1-year and 2-year survival rate, the secondary outcomes includes the clinical effective rate, performance status and the adverse reactions(ADRs). Data analysis was applied Stata 13.0 and Win BUGS 1.4 software.RESULTS: A total of 105 randomized controlled trials(RCTs) were identified for inclusion in this analysis, with data for 7683 patients and 13 CHIs. The results suggested that Javanica oil emulsion,Huachansu injection plus TACE were more favorable for 1-year and 2-year survival rate than other CHIs. Kanglaite, Astragalus polysaccharide injection plus TACE showed superiority in the clinical effective rate and performance status over other CHIs.And Shenmai injection plus TACE was superior to reducing ADRs than other CHIs for patients with liver cancer.CONCLUSION: Our findings indicated that receiving CHIs combined with TACE may have therapeutic benefits for patients with liver cancer in improving survival rate, clinical effective rate, the performance status and alleviating the ADRs.
文摘We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral genome replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.
文摘In order to develop clinical diagnostic tools for rapid detection of SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal portion of the nucleocapsid (NC) gene was amplified using RT-PCR from the SARS-CoV genome, cloned into a yeast expression vector (pEGH), and expressed as a glutathione S-transferase (GST) and Hisx6 double-tagged fusion protein under the control of an inducible promoter. Western analysis on the purified protein confirmed the expression and purification of the NC fusion proteins from yeast. To determine its antigenicity, the fusion protein was challenged with serum samples from SARS patients and normal controls. The NC fusion protein demonstrated high antigenicity with high specificity, and therefore, it should have great potential in designing clinical diagnostic tools and provide useful information for vaccine development.
文摘The Coronaviridae family is characterized by a nucleocapsid that is composed of the genome RNA molecule in combination with the nucleoprotein (N protein) within a virion. The most striking physiochemical feature of the N protein of SARS-CoV is that it is a typical basic protein with a high predicted pI and high hydrophilicity, which is consistent with its function of binding to the ribophosphate backbone of the RNA molecule. The predicted high extent of phosphorylation of the N protein on multiple candidate phosphorylation sites demonstrates that it would be related to important functions, such as RNA-binding and localization to the nucleolus of host cells. Subsequent study shows that there is an SR-rich region in the N protein and this region might be involved in the protein-protein interaction. The abundant antigenic sites predicted in the N protein, as well as experimental evidence with synthesized polypeptides, indicate that the N protein is one of the major antigens of the SARS-CoV. Compared with other viral structural proteins, the low variation rate of the N protein with regards to its size suggests its importance to the survival of the virus.
文摘Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.
基金supported by the Fundamental Research Funds for Central Universities(No.BLX202151)the National Natural Science Foundation of China(Nos.22208021 and 52225003)the National Key Research and Development Program(No.2022YFA1506200)。
文摘CO_(2)hydrogenation to methanol has become one of the most promising ways for CO_(2)utilization,however,the CO_(2)conversion rate and methanol selectivity of this reaction still need to be improved for industrial application.Here we investigated the structure-activity relationship for CO_(2)conversion to methanol of In_(2)O_(3)-based catalysts by modulating morphology and decorating Au.Three different Au/In_(2)O_(3)catalysts were prepared,their activity follow the sequence of Au/In_(2)O_(3)-nanosphere(Au/In_(2)O_(3)-NS)>Au/In_(2)O_(3)-nanoplate(Au/In_(2)O_(3)-NP)>Au/In_(2)O_(3)-hollow microsphere(Au/In_(2)O_(3)-HM).Au/In_(2)O_(3)-NS exhibited the best performance with good CO_(2)conversion of 12.7%,high methanol selectivity of 59.8%,and large space time yield of 0.32 g CH_(3)OH/(hr·gcat)at 300℃.The high performance of Au/In_(2)O_(3)-NS was considered as the presence of Au.It contributes to the creation of more surface oxygen vacancies,which further promoted the CO_(2)adsorption and facilitated CO_(2)activation to form the formate intermediates towards methanol.This work clearly suggests that the activity of In_(2)O_(3)catalyst can be effective enhanced by structure engineering and Au decorating.
基金Natural Science Foundation of jilin Province(grant No.20230101329JC).
文摘The Coriolis force method is a recently developed and highly regarded direct measurement technique that enables high-precision measurement of bulk materials.The operational parameters and variations thereof directly influence the measurement accuracy of the equipment.In this study,a measurement correction coefficient is introduced to improve the calculation method for mass flow rate of the materials.The DEM is employed to simulate the motion of particle groups within the Coriolis force scale under different parameters,and the effects of various structural and operational parameters on the measurement results are compared.The research findings indicate that a lower rotational speed leads to more stable instantaneous measurement results,although the measurement error is relatively large.When the rotational speed exceeds 300 rpm,the measurement error remains within 15%.For materials with a radius of 1–2 mm,the variation range of precision error is approximately 0.4%.Among the structural parameters,the radius of the measurement wheel has the most significant impact on the measurement results,wherein a larger measurement wheel radius corresponds to a smaller measurement error.The horizontal angle of the blades follows as the next influential parameter,with a clockwise rotation and a horizontal angle of 30°resulting in a measurement error below 2%.
基金supported by the National Key R&D Program of China(2021YFB2400400)the National Natural Science Foundation of China(Grant No.22379120,22179085)+5 种基金the Key Research and Development Plan of Shanxi Province(China,Grant No.2018ZDXM-GY-135,2021JLM-36)the National Natural Science Foundation of China(Grant No.22108218)the“Young Talent Support Plan”of Xi’an Jiaotong University(71211201010723)the Qinchuangyuan Innovative Talent Project(QCYRCXM-2022-137)the“Young Talent Support Plan”of Xi’an Jiaotong University(HG6J003)the“1000-Plan program”of Shaanxi Province。
文摘The insurmountable charge transfer impedance at the Li metal/solid polymer electrolytes(SPEs)interface at room temperature as well as the ascending risk of short circuits at the operating temperature higher than the melting point,dominantly limits their applications in solid-state batteries(SSBs).Although the inorganic filler such as CeO_(2)nanoparticle content of composite solid polymer electrolytes(CSPEs)can significantly reduce the enormous charge transfer impedance at the Li metal/SPEs interface,we found that the required content of CeO_(2)nanoparticles in SPEs varies for achieving a decent interfacial charge transfer impedance and the bulk ionic conductivity in CSPEs.In this regard,a sandwich-type composited solid polymer electrolyte with a 10%CeO_(2)CSPEs interlayer sandwiched between two 50%CeO_(2)CSPEs thin layers(sandwiched CSPEs)is constructed to simultaneously achieve low charge transfer impedance and superior ionic conductivity at 30℃.The sandwiched CSPEs allow for stable cycling of Li plating and stripping for 1000 h with 129 mV polarized voltage at 0.1 mA cm^(-2)and 30℃.In addition,the LiFePO_(4)/Sandwiched CSPEs/Li cell also exhibits exceptional cycle performance at 30℃and even elevated120℃without short circuits.Constructing multi-layered CSPEs with optimized contents of the inorganic fillers can be an efficient method for developing all solid-state PEO-based batteries with high performance at a wide range of temperatures.
基金supported by the National Natural Science Foundation of China, Nos.81971151 (to YW), 82102528 (to XL), 82102583 (to LW)the Natural Science Foundation of Guangdong Province, China, Nos.2020A1515010265 (to YW), 2020A1515110679 (to XL), and 2021A1515010358 (to XL)
文摘Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.
基金Basic and Applied Basic Research Foundation of Guangdong Province(2020B1515130006,2021B515120056,2023A1515011944)Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20210324131614040,JCYJ20220531095604009)National Natural Science Foundation of China(U22A2093)。
文摘Bragg filters are of essential importance for chip-scale photonic systems.However,the implementation of filters with sub-nanometer bandwidth and rejection beyond 70 dB is hindered by the high index contrast of the siliconon-insulator platform,which makes filters prone to fabrication imperfections.In this paper,we propose to combine coherency-broken cascading architecture and cladding modulation to circumvent the intrinsic limitation.The cascading architecture effectively prevents the accumulation of phase errors,while the cladding modulation offers additional design freedom to reduce the coupling coefficient.A bimodal Bragg filter with a testingequipment-limited rejection level of 74 dB and a 40 dB bandwidth of 0.44 nm is experimentally demonstrated.The minimum feature size is 90 nm,which significantly relieves the fabrication constraints.
基金financially supported by the National Key Research and Development Program of China (Grant No. 2016YFD0100801)the National Transgenic Key Project of the Ministry of Agriculture of China (Grant No. 2016ZX08009002)the Natural Science Foundation of Shandong Province (Grant No. ZR2018PC017)。
文摘Lateral roots play essential roles in drought tolerance in maize(Zea mays L.). However, the genetic basis for the variation in the number of lateral roots in maize remains elusive. Here, we identified a major quantitative trait locus(QTL),q LRT5-1, controlling lateral root number using a recombinant inbred population from a cross between the maize lines Zong3(with many lateral roots) and 87-1(with few lateral roots).Fine-mapping and functional analysis determined that the candidate gene for qLRT5-1,ZmLRT, expresses the primary transcript for the microRNA miR166a. ZmLRT was highly expressed in root tips and lateral root primordia,and knockout and overexpression of ZmLRT increased and decreased lateral root number,respectively. Compared with 87-1, the ZmLRT gene model of Zong3 lacked the second and third exons and contained a 14 bp deletion at the junction between the first exon and intron,which altered the splicing site. In addition,ZmLRT expression was significantly lower in Zong3 than in 87-1, which might be attributed to the insertions of a transposon and over large DNA fragments in the Zong3 ZmLRT promoter region. These mutations decreased the abundance of mature miR166a in Zong3, resulting in increased lateral roots at the seedling stage.Furthermore, miR166a post-transcriptionally repressed five development-related class-Ⅲ homeodomain-leucine zipper genes. Moreover,knockout of ZmLRT enhanced drought tolerance of maize seedlings. Our study furthers our understanding of the genetic basis of lateral root number variation in maize and highlights ZmLRT as a target for improving drought tolerance in maize.
基金This work was supported by grants from the National Natural Science Foundation of China(32072055,31991210,and 91935304).
文摘Polish wheat (Triticum polonicum) is a unique tetraploid wheat species characterized by an elongated outer glume. The genetic control of the long-glume trait by a single semi-dominant locus, P1 (from Polish wheat), was established more than 100 years ago, but the underlying causal gene and molecular nature remain elusive. Here, we report the isolation of VRT-A2, encoding an SVP-clade MADS-box transcription factor, as the P1 candidate gene. Genetic evidence suggests that in T. polonicum, a naturally occurring sequence rearrangement in the intron-1 region of VRT-A2 leads to ectopic expression of VRT-A2 in floral organs where the long-glume phenotype appears. Interestingly, we found that the intron-1 region is a key ON/OFF molecular switch for VRT-A2 expression, not only because it recruits transcriptional repressors, but also because it confers intron-mediated transcriptional enhancement. Genotypic analyses using wheat accessions indicated that the P1 locus is likely derived from a single natural mutation in tetraploid wheat, which was subsequently inherited by hexaploid T. petropavlovskyi. Taken together, our findings highlight the promoter-proximal intron variation as a molecular basis for phenotypic differentiation, and thus species formation in Triticum plants.
基金supported by the National Natural Science Foundation of China(82173054,82222029,82203085)the Guangdong Basic and Applied Basic Research Foundation(2022B1515020048,2022B1515020101,China)Guangzhou Science,Technology and Innovation Commission(202102010148,China).
文摘Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant behavior.Long non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely unexplored.In this study,microarray was leveraged for the first time to investigate the role of lncRNA in PT.We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse prognosis.Furthermore,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in vitro.Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in vivo.Mechanistically,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of TNFRSF19.In conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.
基金supported by the National Natural Science Foundation of China(Youth Program),No.81901282(to XC)the National Natural Science Foundation of China,Nos.81401416(to PX),81870992(to PX),81870856(to XC and MZ)+3 种基金Guangdong Basic and Applied Basic Research Foundation the Science Foundation,No.2019A1515011189(to XC)Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)Key Project of Guangzhou Health Commission,No.2019-ZD-09(to PX)Science and Technology Planning Project of Guangzhou,Nos.202102020029(to XC),202102010010(to PX)。
文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.
