In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values w...In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.展开更多
The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regul...The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.展开更多
Objective:To study the influence of targeted inhibition of Notch1 gene on the killing effects of Paclitaxel on triple-negative breast cancer cells.Methods:The triple-negative [estrogen receptor(ER)/progesterone recept...Objective:To study the influence of targeted inhibition of Notch1 gene on the killing effects of Paclitaxel on triple-negative breast cancer cells.Methods:The triple-negative [estrogen receptor(ER)/progesterone receptor(PR)/human epidermal growth factor receptor 2(Her2)] breast cancer cell line MDA-MB-231 and ER/PR/HER-2-positive breast cancer cell line MCF-7 were cultured,transfected with Notch1-si RNA-overexpression plasmid and blank plasmid,and treated with different concentrations of paclitaxel,and then the cell proliferation activity and apoptosis rate as well as the m RNA expression of Caspase-3,Caspase-9 and Bcl-2 were determined.Results:Paclitaxel could decrease the MDA-MB-231 and MCF-7 cell proliferation activity as well as Bcl-2 mRNA expression,and increase MDA-MB-231 and MCF-7 cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression in dosedependent manners;with the same dose of paclitaxel treatment,the inhibitory effects on MDAMB-231 cell proliferation activity and Bcl-2 m RNA expression as well as the promoting effects on MDA-MB-231 cell apoptosis and mR NA expression of Caspase-3 and Caspase-9 were weaker than those on MCF-7 cell;after 0.5 μM paclitaxel combined with Notch1-siRNA treatment,MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression were significantly lower than those after 0.5 μM paclitaxel combined with control plasmid treatment while cell apoptosis rate and mR NA expression of Caspase-3 and Caspase-9 were higher than those after 0.5 μM paclitaxel combined with control plasmid treatment.Conclusions:Targeted inhibition of Notch1 gene may enhance the killing effects of paclitaxel on triple-negative breast cancer cells by up-regulating the expression of Caspase-3 and Caspase-9 and inhibiting the expression of Bcl-2.展开更多
Understanding the interactions between graphene nanomaterials（GNMs） and antibiotics in aqueous solution is critical to both the engineering applications of GNMs and the assessment of their potential impact on the fa...Understanding the interactions between graphene nanomaterials（GNMs） and antibiotics in aqueous solution is critical to both the engineering applications of GNMs and the assessment of their potential impact on the fate and transport of antibiotics in the aquatic environment. In this study, adsorption of one common antibiotic, tetracycline, by graphene oxide（GO） and reduced graphene oxide（RGO） was examined with multi-walled carbon nanotubes（MWCNTs） and graphite as comparison. The results showed that the tetracycline adsorption capacity by the four selected carbonaceous materials on the unit mass basis followed an order of GO ＆gt; RGO ＆gt; MWCNTs ＆gt; graphite. Upon normalization by surface area,graphite, RGO and MWCNTs had almost the same high tetracycline adsorption affinity while GO exhibited the lowest. We proposed π-electron-property dependent interaction mechanisms to explain the observed different adsorption behaviors. Density functional theory（DFT） calculations suggested that the oxygen-containing functional groups on GO surface reduced its π-electron-donating ability, and thus decreased the π-based interactions between tetracycline and GO surface. Comparison of adsorption efficiency at different p H indicated that electrostatic interaction also played an important role in tetracycline-GO interactions. Site energy analysis confirmed a highly heterogeneous distribution of the binding sites and strong tetracycline binding affinity of GO surface.展开更多
OBJECTIVE Based on the methods of microdialysis,HPLC-MS/MS and gene chip tech.nology,the mechanism of Baicalin and Geniposide(BC/GP) against excitatory amino acid toxicity in ce.rebral ischemia was studied.This will p...OBJECTIVE Based on the methods of microdialysis,HPLC-MS/MS and gene chip tech.nology,the mechanism of Baicalin and Geniposide(BC/GP) against excitatory amino acid toxicity in ce.rebral ischemia was studied.This will provide guidance for the clinical application of BC/GP and the study of excitatory amino acid toxicity in cerebral ischemia.METHODS(1) Microdialysis technique and HPLC-MS/MS was performed to study the pharmacodynamics of BC/GP against cerebral ischemia.(1)18 SD rats with body weight of(280±20) g were randomly divided into control group,treatment groups with BC/CP at low dose,medium dose and high dose(equal to the dosage of crude drugs for 30 mg·kg^(-1),45 mg·kg^(-1) and 60 mg·kg^(-1) respectively).Rats in each group were given intragastric administration for seven days to establish cerebral ischemia model.Then,microdialysis probe was applied to collect cerebrospinal fluid from hippocampus before and after cerebral ischemia.(2) First,we established the HPLC-MS/MS method for measuring drugs and excitatory amino acids.Then we detected the microdi.alysis samples and observed their changes in animals.(2) The mechanism of BC/GP against excitatory toxicity of cerebral ischemia were observed at gene level by chip technique.(1) 16 SD rats with body weight of 240±20 g were randomly divided into sham group,model group,treatment group of BC(60 mg·kg^(-1)),treatment group of GP(60 mg·kg^(-1)) and treatment group of BC/GP(7:3)(60 mg·kg^(-1)).Rats in eachgroup were given intragastric administration for seven days to establish cerebral ischemia model.Then the rats were sacrificed,and the hippocampus were rapidly harvested and stored at-80℃ for further detection.(2) After the quality inspection of the hippocampal,the qualified samples were subjected to detect the levels of neurotransmitter receptor gene in the ischemic of rats by gene chip technology.Finally,the results were analyzed by the method of ΔΔCt.RESULTS(1) Only three compounds includ.ed GP,glutamic acid and aspartic acid were detected in microdialysis samples by HPLC-MS/MS.The concentration of GP increased and lasted for 120 min with a significant dose-dependent after cerebral ischemia.Compared with low dose group,the AUC(0-t),MRT(0-∞),Cmax and t1/2 z in high-dose group showed significant difference(P<0.01).Compared with the model group,the levels of glutamic acid and aspartic acid in the treatment groups decreased significantly,especially in the middle and high dose groups.(2)89 genes in the neurotransmitter receptor gene signaling pathway were detected by gene chip technol.ogy.There were 22 genes with |Fold Regulation| >1.5 in the model group,compared with the sham group.Five of the 22 genes showed statistically significant differences,including Grin2 c(2.9026),Chrna7(-1.5877),and Tacr2(-1.7695).Htr3 a(-1.8172) and Grm6(-2.3527).There were 5 genes with |Fold Regulation|>1.5 in the BC group,compared with the model group,Two of them exhibited statistically significant differences,including Brs3(1.797)and Grin2 c(-1.7979).There were 14 genes with |Fold Reg.ulation| >1.5 in the GP group,compared with the model group.Three of them displayed statistically significant differences,including Hcrtr2(-1.6584),Sctr(-3.8524) and Grin2 c(-4.8408).Compared with model group,the genes of |Fold Regulation| >1.5 in BC/GP(7:3) group are 5,and only one of them showed a significant differences.CONCLUSION(1) After administration of BC and GP,GP can cross the blood-brain barrier and reduce the release of excitatory amino acids in the hippocampus.(2) BC/GP can inhibit the interaction between excitatory amino acids and excitatory amino acid receptors and attenuate the toxicity of excitatory amino acids by down-regulating the expression of glutamic acid receptor Grin2 c gene.(3) BC/GP may exert their brain protection effect by reducing the release of excit.atory amino acids and inhibiting the expression of excitatory amino acid receptors.展开更多
Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin wi...Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin without being in contact with it. Some researchers have used this method to treat stroke patients, but strong evidence of its therapeutic effectiveness is lacking. However, the effect of traditional suspended moxibustion has recently been improved with the development of heat-sensitive suspended moxibustion. Our previous studies showed that moxibustion for 35 min provided a more effective treatment strategy than moxibustion for 15 min, and moxibustion by 35 min with tail temperature increase had a better outcome than that without, however, the mechanism underlying the effect is not clear. In this study, we treated the stroke rats with moxibustion by 35min and divided them into non-heat sensitive moxibustion(NHSM) group and heat sensitive moxibustion (HSM) group according to difference in the tail temperature increase, then we compared the effect and investigated the mechanisms between NHSM and HSM. We found that HSM significantly decreased tail-flick latency, increased neurological function score, decreased infarct volume, reduced inflammatory cells, decreased the expression of inflammatory factor ICAM-1 and reduced the expression of NF-κB p65 and p-IKKα/β in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings revealed that HSM exerted its anti-inflammatory and neuroprotective effects from MCAO-induced injury by decreasing the expression of the NF-κB signaling pathway.展开更多
Cataclysmic variables are special celestial bodies because they have particular light curves and spectra.The mechanisms for generating emission lines radiated from dwarf novae in their quiescent phases are studied.We ...Cataclysmic variables are special celestial bodies because they have particular light curves and spectra.The mechanisms for generating emission lines radiated from dwarf novae in their quiescent phases are studied.We assume that the incident radiation field which is emitted by a hot source（white dwarf and boundary layer）irradiates the gaseous layer evaporated from the accretion disk,and the emission lines are radiated from the gas.We model the fluxes of emission lines by using the photoionization code CLOUDY.Using this method,we input some reasonable parameters and get a series of simulated spectra.In order to find a simulated spectrum which is the best fit to an observed spectrum,we use a cross-correlation method to match them.After the calculation,we use the approximation that the parameters of the simulated spectrum can simulate the observed spectrum.Finally,we learn more about the physical conditions of the system.展开更多
Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics betw...Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics between MDD and dyslipidaemia remain elusive.Aims To comprehensively disentangle the genetic causality between MDD and various phenotypes of blood lipids, thereby facilitating the advancement of management strategies for these conditions.Methods We conducted a two-sample univariable Mendelian randomisation (MR) analysis using different models, including the inverse variance weighted (IVW) method and causal analysis using the summary effect (CAUSE) estimates, as well as a multivariable MR analysis. This analysis used summary statistics from genome-wide association studies (GWAS) of MDD and five lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides (TG), encompassing 5 237 893 individuals of European and East Asian ancestries. For MDD, a total of 598 701 individuals were included, with 500 199 individuals of European ancestry (Ncase=170 756, Ncontrol=329 443) and 98 502 of East Asian ancestry (Ncase=12 588, Ncontrol=85 914). Lipid data were collected from 4 639 192 individuals through the Global Lipids Genetics Consortium (European, N=4 096 085;East Asian, N=543 107). Next, we used the two-step MR to explore the mediating factors between MDD and TG, and the risk factors affecting TG through MDD. Finally, we conducted a GWAS meta-analysis and enrichment analysis.Results In univariable MR, we observed a negative causal effect of low-density lipoprotein on MDD in both European populations (IVW: odds ratio (OR): 0.972, 95% confidence interval (CI) 0.947 to 0.998, p=0.037) and East Asian populations (IVW: OR: 0.928, 95% CI 0.864 to 0.997, p=0.042). Additionally, we identified a bidirectional causal relationship between TG and MDD, with TG having a causal effect on MDD (IVW: OR: 1.052, 95% CI 1.020 to 1.085, p=0.001) and MDD having a causal effect on TG (IVW: OR: 1.075, 95% CI 1.047 to 1.104, p<0.001). Multivariable MR analysis further supported the role of TG in MDD (OR: 1.205, 95% CI 1.034 to 1.405, p=0.017). CAUSE estimates indicated that the causal model of MDD on TG provided a better fit than the sharing model (p=0.003), while the association of TG on MDD was more likely due to horizontal correlated pleiotropy than causality. Mediation analyses revealed that waist-hip ratio (WHR) mediated 69% of the total causal effect of MDD on TG, while other identified risk factors exhibited lower mediating proportions either mediated through MDD (≤17%) or originating from MDD (≤29%). The GWAS meta-analysis highlighted potential pathways related to lipid processes and nucleosome assembling, with significant cell types identified in brain regions and liver tissues.Conclusions The findings indicate that genetic proxies of MDD are associated with elevated levels of TG, with WHR serving as a clinical indicator of the association. This suggests that interventions targeting WHR may be effective in reducing TG levels in patients with MDD.展开更多
Hydroformylation of olefins is one of the highest-volume industrial reactions to meet the vast demands for aldehydes as well as their derivatives.Homogeneous Co complexes were the original catalysts industrialized sin...Hydroformylation of olefins is one of the highest-volume industrial reactions to meet the vast demands for aldehydes as well as their derivatives.Homogeneous Co complexes were the original catalysts industrialized since 1960s.Heterogeneous catalysis is considered superior owing to the facile separation of catalysts from products,shorter technical process,and reduced manufacturing costs.Unexpectedly,there has not been a single case of plant using heterogenized Co-based catalyst successfully.To address the separation issue and understand the catalytic mechanism of the reactions,this review summarizes the progress in heterogeneous systems and provides a detailed discussion of their catalytic performance.Strategies for stabilizing Co species through support modification and additive incorporation are carefully considered to elucidate why heterogeneous systems have not yet succeeded on an industrial scale.Furthermore,we provide our insights for the development of heterogeneous catalytic hydroformylation,including the challenges,opportunities,and outlooks.The aim is to deepen the fundamental understanding of heterogeneous alkene hydroformylation,guiding the community's research efforts towards realizing its successful application in the future.展开更多
Surface deformation calculations due to environmental loading typically rely on the Preliminary Reference Earth Model(PREM),which assumes a homogeneous and isotropic Earth structure,leading to noticeable errors.To enh...Surface deformation calculations due to environmental loading typically rely on the Preliminary Reference Earth Model(PREM),which assumes a homogeneous and isotropic Earth structure,leading to noticeable errors.To enhance accuracy,the high-precision crustal model CRUST 1.0 is used to refine calculations of regional surface deformation caused by hydrological and non-tidal atmospheric loading.The improved model is applied to 27 Global Navigation Satellite System(GNSS)reference stations in the first phase of the Crustal Movement Observation Network of China(CMONOC),considering their geographical locations.Green's functions are employed to compute surface deformation at each site.Results indicate relative discrepancies of 11.78%and 14.14%for non-tidal atmospheric and hydrological loading compared to PREM,with vertical deformation differences reaching an average of 18.95%.Additionally,the distinct spatial distribution characteristics of the relative differences in each direction indicate that the improved RPREM model is more responsive to the mass variations derived from Gravity Recovery and Climate Experiment(GRACE).The results suggest that the improved PRREM model demonstrates higher sensitivity to loading variations than the PREM model.Utilizing the enhanced method of calculating surface deformation through the utilization of Green's function at the site could effectively reduce the calculation error caused by regional structure,leading to enhanced uniformity and isotropy of PREM.展开更多
Objective:To evaluate the global liter-ature output on the relationship between brain-derived neurotrophic factor(BDNF)and cognitive function in al-cohol dependence syndrome using bibliometric methods and explore the ...Objective:To evaluate the global liter-ature output on the relationship between brain-derived neurotrophic factor(BDNF)and cognitive function in al-cohol dependence syndrome using bibliometric methods and explore the status and trends in this field.Method:The literature on the application of BDNF in cognitive impairment caused by alcohol dependence syndrome published from 1995 to 2023 were retrieved from Web of Science,and the relevant information(publication characteristics,country and institution,author,number of publications,citation,journal and research field,corresponding author,key words,etc.)was recorded.The bibliometrix R package was used for quantitative and qualitative analysis of publication output and author contributions.Result:A total of 99 articles were included.The overall number of publications in this field has increased over time.The countries and institutions that contributed the most to the field were the United States and the Academy of Medical Sciences of Iranian universities,respectively.Most of the authors were from the United States,followed by Spain,China,and Iran.Ceccanti M,Fiore M were the most productive authors.Publications with Ceccanti M had the highest h-index.The most cited reference author is Haenninen H(227 citations),and the number one published journal is Alcohol.Most articles were published in 2020(n=12)and 2022(n=11),followed by 2019 and 2021(n=10).The corresponding author has the largest number of publications from the United States,and more publications from a single country tend to have more cooperation from other countries.BDNF and alcohol appeared more frequently in various keyword clouds.However,significant differences remained in the author keyword cloud,keyword plus word cloud,and paper topic word cloud.Conclusion:BDNF has great potential in the application of cognitive dysfunction caused by alcohol dependence syndrome.Bibliometric methods and data visualization techniques can help understand the current state of research progress and enable relevant scholars and practitioners to predict the development trends in this field.展开更多
Recent advancements in two-dimensional van der Waals moir´e materials have unveiled the captivating landscape of moir´e physics.In twisted bilayer graphene(TBG)at‘magic angles’,strong electronic correlatio...Recent advancements in two-dimensional van der Waals moir´e materials have unveiled the captivating landscape of moir´e physics.In twisted bilayer graphene(TBG)at‘magic angles’,strong electronic correlations give rise to a diverse array of exotic physical phenomena,including correlated insulating states,superconductivity,magnetism,topological phases,and the quantum anomalous Hall(QAH)effect.Notably,the QAH effect demonstrates substantial promise for applications in electronic and quantum computing devices with low power consumption.This article focuses on the latest developments surrounding the QAH effect in magic-angle TBG.It provides a comprehensive analysis of magnetism and topology—two crucial factors in engineering the QAH effect within magic-angle TBG.Additionally,it offers a detailed overview of the experimental realization of the QAH effect in moir´e superlattices.Furthermore,this review highlights the underlying mechanisms driving these exotic phases in moir´e materials,contributing to a deeper understanding of strongly interacting quantum systems and facilitating the manipulation of new material properties to achieve novel quantum states.展开更多
Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However,...Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequenc- ing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach.展开更多
Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibusti...Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion （usually from 30 minutes to 1 hour） is longer than traditional suspended moxibustion （usually 15 minutes）. However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebra/ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui （GV14） in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxy- lin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the in- jury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expres- sion was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.展开更多
Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis bu...Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy,Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a wellconstructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection,along with strong support at the national industry level.展开更多
Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To invest...Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.展开更多
Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of margin...Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.展开更多
As one of the most effective mechanisms,precipitation-hardening is widely used to strengthen high-entropy alloys.Yet,heavy precipitation-hardened high-entropy alloys usually exhibit serious embrittlement.How to effect...As one of the most effective mechanisms,precipitation-hardening is widely used to strengthen high-entropy alloys.Yet,heavy precipitation-hardened high-entropy alloys usually exhibit serious embrittlement.How to effectively achieve ultra-high strength and maintain reliable ductility remains a challenge.Here,we report a study of doping extremely little boron to meet this target.We found that adding of 30 ppm boron into the heavy Ti and Al alloyed FCC FeCoNiCr high-entropy,(FeCoNiCr)_(88) Ti_(6) Al_(6) HEA(at.%)which is strengthened mainly by both coarse BCC-based(Ni,Co)_(2) TiAl Heusler and fine L12-type FCC-based(Ni,Co)_(3) TiAl precipitates and shows ultrahigh strength but poor ductility,could significantly change the original microstructure and consequently improve mechanical performance,owing to the well-known effect of boron on reducing the energy of grain boundaries.The boron addition can(1)eliminate microcavities formed at Heusler precipitate-matrix interfaces;(2)suppress the formation and segregation of coarse BCC Heusler precipitates;(3)promote the formation of L12 nanoparticles.This changes of microstructure substantially improve the tensile ductility more than by~86%and retain comparable or even better ultimate tensile strength.These findings may provide a simple and costless solution to produce heavy precipitation-strengthened HEAs with ultrahigh strength and prevent accidental brittleness.展开更多
Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）...Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）, and the non-ridge ectoderm regulate the patterning of digits. Although a series of signaling molecules have been characterized as patterning signals from the organizing centers, the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear, Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process. Here, we review the current understanding of the genetic networks governing digit morphogenesis展开更多
基金This work was supported by the Major State Basic Research Development program of Chinathe National High Technology Research and Development Program of China.
文摘In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.
文摘The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.
基金funded by General Project of Department of Education,Anhui Province(Grant No.KJ2015B016by)the Special Scientific Research Fund of Public Welfare Profession by National Health and Family Planning Commission of the PRC(Grant No.201402003)
文摘Objective:To study the influence of targeted inhibition of Notch1 gene on the killing effects of Paclitaxel on triple-negative breast cancer cells.Methods:The triple-negative [estrogen receptor(ER)/progesterone receptor(PR)/human epidermal growth factor receptor 2(Her2)] breast cancer cell line MDA-MB-231 and ER/PR/HER-2-positive breast cancer cell line MCF-7 were cultured,transfected with Notch1-si RNA-overexpression plasmid and blank plasmid,and treated with different concentrations of paclitaxel,and then the cell proliferation activity and apoptosis rate as well as the m RNA expression of Caspase-3,Caspase-9 and Bcl-2 were determined.Results:Paclitaxel could decrease the MDA-MB-231 and MCF-7 cell proliferation activity as well as Bcl-2 mRNA expression,and increase MDA-MB-231 and MCF-7 cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression in dosedependent manners;with the same dose of paclitaxel treatment,the inhibitory effects on MDAMB-231 cell proliferation activity and Bcl-2 m RNA expression as well as the promoting effects on MDA-MB-231 cell apoptosis and mR NA expression of Caspase-3 and Caspase-9 were weaker than those on MCF-7 cell;after 0.5 μM paclitaxel combined with Notch1-siRNA treatment,MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression were significantly lower than those after 0.5 μM paclitaxel combined with control plasmid treatment while cell apoptosis rate and mR NA expression of Caspase-3 and Caspase-9 were higher than those after 0.5 μM paclitaxel combined with control plasmid treatment.Conclusions:Targeted inhibition of Notch1 gene may enhance the killing effects of paclitaxel on triple-negative breast cancer cells by up-regulating the expression of Caspase-3 and Caspase-9 and inhibiting the expression of Bcl-2.
基金supported by the National Natural Science Foundation of China (Nos. 21476130, 21277082, 21337001, 21676161, 41503097)the Natural Science Foundation of Shandong Province (No. ZR2014BP012)+2 种基金the Research Award Fund for Outstanding Young Scientists of Shandong Province, China (No. BS2012HZ008)the Fundamental Research Funds of Shandong University (No. 2015JC020)the China Postdoctoral Science Foundation (No. 2015 M572040)
文摘Understanding the interactions between graphene nanomaterials（GNMs） and antibiotics in aqueous solution is critical to both the engineering applications of GNMs and the assessment of their potential impact on the fate and transport of antibiotics in the aquatic environment. In this study, adsorption of one common antibiotic, tetracycline, by graphene oxide（GO） and reduced graphene oxide（RGO） was examined with multi-walled carbon nanotubes（MWCNTs） and graphite as comparison. The results showed that the tetracycline adsorption capacity by the four selected carbonaceous materials on the unit mass basis followed an order of GO ＆gt; RGO ＆gt; MWCNTs ＆gt; graphite. Upon normalization by surface area,graphite, RGO and MWCNTs had almost the same high tetracycline adsorption affinity while GO exhibited the lowest. We proposed π-electron-property dependent interaction mechanisms to explain the observed different adsorption behaviors. Density functional theory（DFT） calculations suggested that the oxygen-containing functional groups on GO surface reduced its π-electron-donating ability, and thus decreased the π-based interactions between tetracycline and GO surface. Comparison of adsorption efficiency at different p H indicated that electrostatic interaction also played an important role in tetracycline-GO interactions. Site energy analysis confirmed a highly heterogeneous distribution of the binding sites and strong tetracycline binding affinity of GO surface.
基金supported by National Natural Science Foundation of China(81473385) Shaanxi provincial Natural Science Foundation of China(2017JZ027) Shaanxi Provincial Administration of Traditional Chinese Medicine(13-ZY016)
文摘OBJECTIVE Based on the methods of microdialysis,HPLC-MS/MS and gene chip tech.nology,the mechanism of Baicalin and Geniposide(BC/GP) against excitatory amino acid toxicity in ce.rebral ischemia was studied.This will provide guidance for the clinical application of BC/GP and the study of excitatory amino acid toxicity in cerebral ischemia.METHODS(1) Microdialysis technique and HPLC-MS/MS was performed to study the pharmacodynamics of BC/GP against cerebral ischemia.(1)18 SD rats with body weight of(280±20) g were randomly divided into control group,treatment groups with BC/CP at low dose,medium dose and high dose(equal to the dosage of crude drugs for 30 mg·kg^(-1),45 mg·kg^(-1) and 60 mg·kg^(-1) respectively).Rats in each group were given intragastric administration for seven days to establish cerebral ischemia model.Then,microdialysis probe was applied to collect cerebrospinal fluid from hippocampus before and after cerebral ischemia.(2) First,we established the HPLC-MS/MS method for measuring drugs and excitatory amino acids.Then we detected the microdi.alysis samples and observed their changes in animals.(2) The mechanism of BC/GP against excitatory toxicity of cerebral ischemia were observed at gene level by chip technique.(1) 16 SD rats with body weight of 240±20 g were randomly divided into sham group,model group,treatment group of BC(60 mg·kg^(-1)),treatment group of GP(60 mg·kg^(-1)) and treatment group of BC/GP(7:3)(60 mg·kg^(-1)).Rats in eachgroup were given intragastric administration for seven days to establish cerebral ischemia model.Then the rats were sacrificed,and the hippocampus were rapidly harvested and stored at-80℃ for further detection.(2) After the quality inspection of the hippocampal,the qualified samples were subjected to detect the levels of neurotransmitter receptor gene in the ischemic of rats by gene chip technology.Finally,the results were analyzed by the method of ΔΔCt.RESULTS(1) Only three compounds includ.ed GP,glutamic acid and aspartic acid were detected in microdialysis samples by HPLC-MS/MS.The concentration of GP increased and lasted for 120 min with a significant dose-dependent after cerebral ischemia.Compared with low dose group,the AUC(0-t),MRT(0-∞),Cmax and t1/2 z in high-dose group showed significant difference(P<0.01).Compared with the model group,the levels of glutamic acid and aspartic acid in the treatment groups decreased significantly,especially in the middle and high dose groups.(2)89 genes in the neurotransmitter receptor gene signaling pathway were detected by gene chip technol.ogy.There were 22 genes with |Fold Regulation| >1.5 in the model group,compared with the sham group.Five of the 22 genes showed statistically significant differences,including Grin2 c(2.9026),Chrna7(-1.5877),and Tacr2(-1.7695).Htr3 a(-1.8172) and Grm6(-2.3527).There were 5 genes with |Fold Regulation|>1.5 in the BC group,compared with the model group,Two of them exhibited statistically significant differences,including Brs3(1.797)and Grin2 c(-1.7979).There were 14 genes with |Fold Reg.ulation| >1.5 in the GP group,compared with the model group.Three of them displayed statistically significant differences,including Hcrtr2(-1.6584),Sctr(-3.8524) and Grin2 c(-4.8408).Compared with model group,the genes of |Fold Regulation| >1.5 in BC/GP(7:3) group are 5,and only one of them showed a significant differences.CONCLUSION(1) After administration of BC and GP,GP can cross the blood-brain barrier and reduce the release of excitatory amino acids in the hippocampus.(2) BC/GP can inhibit the interaction between excitatory amino acids and excitatory amino acid receptors and attenuate the toxicity of excitatory amino acids by down-regulating the expression of glutamic acid receptor Grin2 c gene.(3) BC/GP may exert their brain protection effect by reducing the release of excit.atory amino acids and inhibiting the expression of excitatory amino acid receptors.
基金We would like to thank the National Natural Science Foun dation of China (81060305, 81660819)the Natural Science Foundation of Jiangxi Province (20151BAB205068), Key Project of Health Commission of Jiangxi province (2014Z003)Natural Science Foundation of Jiangxi University of Traditional Chinese Medicine (2014ZR018,- 2015jzzdxk024) for their supports.
文摘Ischemic stroke is universally acknowledged as a common cause of long-term disability or even death. Suspended moxibustion, an indirect form of moxibustion, is when moxibustion is placed superficially over the skin without being in contact with it. Some researchers have used this method to treat stroke patients, but strong evidence of its therapeutic effectiveness is lacking. However, the effect of traditional suspended moxibustion has recently been improved with the development of heat-sensitive suspended moxibustion. Our previous studies showed that moxibustion for 35 min provided a more effective treatment strategy than moxibustion for 15 min, and moxibustion by 35 min with tail temperature increase had a better outcome than that without, however, the mechanism underlying the effect is not clear. In this study, we treated the stroke rats with moxibustion by 35min and divided them into non-heat sensitive moxibustion(NHSM) group and heat sensitive moxibustion (HSM) group according to difference in the tail temperature increase, then we compared the effect and investigated the mechanisms between NHSM and HSM. We found that HSM significantly decreased tail-flick latency, increased neurological function score, decreased infarct volume, reduced inflammatory cells, decreased the expression of inflammatory factor ICAM-1 and reduced the expression of NF-κB p65 and p-IKKα/β in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings revealed that HSM exerted its anti-inflammatory and neuroprotective effects from MCAO-induced injury by decreasing the expression of the NF-κB signaling pathway.
基金Supported by the National Natural Science Foundation of China (Grant No. 11163005)the Foundation of Ministry of Education (No. 211198)the Foundation of Huoyingdong (No. 121107)
文摘Cataclysmic variables are special celestial bodies because they have particular light curves and spectra.The mechanisms for generating emission lines radiated from dwarf novae in their quiescent phases are studied.We assume that the incident radiation field which is emitted by a hot source（white dwarf and boundary layer）irradiates the gaseous layer evaporated from the accretion disk,and the emission lines are radiated from the gas.We model the fluxes of emission lines by using the photoionization code CLOUDY.Using this method,we input some reasonable parameters and get a series of simulated spectra.In order to find a simulated spectrum which is the best fit to an observed spectrum,we use a cross-correlation method to match them.After the calculation,we use the approximation that the parameters of the simulated spectrum can simulate the observed spectrum.Finally,we learn more about the physical conditions of the system.
基金supported by the National Natural Science Foundation of China(82071500,82271540,32370724,82401759,81871055,32070679)Shanghai Clinical Research Center for Mental Health(19MC1911100)+11 种基金Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)Shanghai Municipal Administrator of Traditional Chinese Medicine(ZY-(2021-2023)-0207-01)Shanghai Municipal Health Commission Collaborative Innovation Group(2024CXJQ03)Shanghai Science and Technology Innovation Action Program(24JS2840400,24ZR1439900,21Y11921100)Shanghai Municipal Science and Technology Major Project,the National Key R&D Program of China(2023YFA0913804,2024YFA0916603,2022FYC2503300)the Program of Shanghai Academic/Technology Research Leader(21XD1423300)Shanghai Pujiang Program(21PJD063)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)Shanghai Municipal Commission of Education(2024AIZD016)the National Key R&D Program of China(2019YFA0905400,2017YFC0908105,2021YFC2702100)National Program for Support of Top-Notch Young Professionals,Taishan Scholar Program of Shandong Province(tstp20240526)the Natural Science Foundation of Shandong Province(ZR2019YQ14,YDZX2021009,2021ZDSYS06).
文摘Background Numerous studies have consistently demonstrated that a considerable proportion of patients with major depressive disorder (MDD) frequently exhibit pronounced dyslipidaemia. However, the causal dynamics between MDD and dyslipidaemia remain elusive.Aims To comprehensively disentangle the genetic causality between MDD and various phenotypes of blood lipids, thereby facilitating the advancement of management strategies for these conditions.Methods We conducted a two-sample univariable Mendelian randomisation (MR) analysis using different models, including the inverse variance weighted (IVW) method and causal analysis using the summary effect (CAUSE) estimates, as well as a multivariable MR analysis. This analysis used summary statistics from genome-wide association studies (GWAS) of MDD and five lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, total cholesterol and triglycerides (TG), encompassing 5 237 893 individuals of European and East Asian ancestries. For MDD, a total of 598 701 individuals were included, with 500 199 individuals of European ancestry (Ncase=170 756, Ncontrol=329 443) and 98 502 of East Asian ancestry (Ncase=12 588, Ncontrol=85 914). Lipid data were collected from 4 639 192 individuals through the Global Lipids Genetics Consortium (European, N=4 096 085;East Asian, N=543 107). Next, we used the two-step MR to explore the mediating factors between MDD and TG, and the risk factors affecting TG through MDD. Finally, we conducted a GWAS meta-analysis and enrichment analysis.Results In univariable MR, we observed a negative causal effect of low-density lipoprotein on MDD in both European populations (IVW: odds ratio (OR): 0.972, 95% confidence interval (CI) 0.947 to 0.998, p=0.037) and East Asian populations (IVW: OR: 0.928, 95% CI 0.864 to 0.997, p=0.042). Additionally, we identified a bidirectional causal relationship between TG and MDD, with TG having a causal effect on MDD (IVW: OR: 1.052, 95% CI 1.020 to 1.085, p=0.001) and MDD having a causal effect on TG (IVW: OR: 1.075, 95% CI 1.047 to 1.104, p<0.001). Multivariable MR analysis further supported the role of TG in MDD (OR: 1.205, 95% CI 1.034 to 1.405, p=0.017). CAUSE estimates indicated that the causal model of MDD on TG provided a better fit than the sharing model (p=0.003), while the association of TG on MDD was more likely due to horizontal correlated pleiotropy than causality. Mediation analyses revealed that waist-hip ratio (WHR) mediated 69% of the total causal effect of MDD on TG, while other identified risk factors exhibited lower mediating proportions either mediated through MDD (≤17%) or originating from MDD (≤29%). The GWAS meta-analysis highlighted potential pathways related to lipid processes and nucleosome assembling, with significant cell types identified in brain regions and liver tissues.Conclusions The findings indicate that genetic proxies of MDD are associated with elevated levels of TG, with WHR serving as a clinical indicator of the association. This suggests that interventions targeting WHR may be effective in reducing TG levels in patients with MDD.
文摘Hydroformylation of olefins is one of the highest-volume industrial reactions to meet the vast demands for aldehydes as well as their derivatives.Homogeneous Co complexes were the original catalysts industrialized since 1960s.Heterogeneous catalysis is considered superior owing to the facile separation of catalysts from products,shorter technical process,and reduced manufacturing costs.Unexpectedly,there has not been a single case of plant using heterogenized Co-based catalyst successfully.To address the separation issue and understand the catalytic mechanism of the reactions,this review summarizes the progress in heterogeneous systems and provides a detailed discussion of their catalytic performance.Strategies for stabilizing Co species through support modification and additive incorporation are carefully considered to elucidate why heterogeneous systems have not yet succeeded on an industrial scale.Furthermore,we provide our insights for the development of heterogeneous catalytic hydroformylation,including the challenges,opportunities,and outlooks.The aim is to deepen the fundamental understanding of heterogeneous alkene hydroformylation,guiding the community's research efforts towards realizing its successful application in the future.
基金supported by the National Natural Science Foundation of China(Grant 42204006)the Education Commission of Hubei Province of China(Grant D20232802)+1 种基金the Open Fund of Wuhan,Gravitationand Solid EarthTides,National Observationand Research Station(Grant WHYWZ202407)the Open Fund of Hubei Luojia Laboratory(Grant 230100020,230100019).
文摘Surface deformation calculations due to environmental loading typically rely on the Preliminary Reference Earth Model(PREM),which assumes a homogeneous and isotropic Earth structure,leading to noticeable errors.To enhance accuracy,the high-precision crustal model CRUST 1.0 is used to refine calculations of regional surface deformation caused by hydrological and non-tidal atmospheric loading.The improved model is applied to 27 Global Navigation Satellite System(GNSS)reference stations in the first phase of the Crustal Movement Observation Network of China(CMONOC),considering their geographical locations.Green's functions are employed to compute surface deformation at each site.Results indicate relative discrepancies of 11.78%and 14.14%for non-tidal atmospheric and hydrological loading compared to PREM,with vertical deformation differences reaching an average of 18.95%.Additionally,the distinct spatial distribution characteristics of the relative differences in each direction indicate that the improved RPREM model is more responsive to the mass variations derived from Gravity Recovery and Climate Experiment(GRACE).The results suggest that the improved PRREM model demonstrates higher sensitivity to loading variations than the PREM model.Utilizing the enhanced method of calculating surface deformation through the utilization of Green's function at the site could effectively reduce the calculation error caused by regional structure,leading to enhanced uniformity and isotropy of PREM.
基金supported by grants from the Scientific Research Fund project of Education Department of Yunnan Province(2024J0314)Joint Special Project on Basic Research of Yunnan Provincial Department of Science and Technology and Kunming Medical University(202501AY070001-206).
文摘Objective:To evaluate the global liter-ature output on the relationship between brain-derived neurotrophic factor(BDNF)and cognitive function in al-cohol dependence syndrome using bibliometric methods and explore the status and trends in this field.Method:The literature on the application of BDNF in cognitive impairment caused by alcohol dependence syndrome published from 1995 to 2023 were retrieved from Web of Science,and the relevant information(publication characteristics,country and institution,author,number of publications,citation,journal and research field,corresponding author,key words,etc.)was recorded.The bibliometrix R package was used for quantitative and qualitative analysis of publication output and author contributions.Result:A total of 99 articles were included.The overall number of publications in this field has increased over time.The countries and institutions that contributed the most to the field were the United States and the Academy of Medical Sciences of Iranian universities,respectively.Most of the authors were from the United States,followed by Spain,China,and Iran.Ceccanti M,Fiore M were the most productive authors.Publications with Ceccanti M had the highest h-index.The most cited reference author is Haenninen H(227 citations),and the number one published journal is Alcohol.Most articles were published in 2020(n=12)and 2022(n=11),followed by 2019 and 2021(n=10).The corresponding author has the largest number of publications from the United States,and more publications from a single country tend to have more cooperation from other countries.BDNF and alcohol appeared more frequently in various keyword clouds.However,significant differences remained in the author keyword cloud,keyword plus word cloud,and paper topic word cloud.Conclusion:BDNF has great potential in the application of cognitive dysfunction caused by alcohol dependence syndrome.Bibliometric methods and data visualization techniques can help understand the current state of research progress and enable relevant scholars and practitioners to predict the development trends in this field.
基金supported by the Science Research Project of Hebei Education Department(Grant No.BJK2024168)the National Natural Science Foundation of China(Grant No.11904076)+1 种基金the Natural Science Foundation of Hebei(Grant No.A2019205313)Science Foundation of Hebei Normal University(Grant No.L2024J02).
文摘Recent advancements in two-dimensional van der Waals moir´e materials have unveiled the captivating landscape of moir´e physics.In twisted bilayer graphene(TBG)at‘magic angles’,strong electronic correlations give rise to a diverse array of exotic physical phenomena,including correlated insulating states,superconductivity,magnetism,topological phases,and the quantum anomalous Hall(QAH)effect.Notably,the QAH effect demonstrates substantial promise for applications in electronic and quantum computing devices with low power consumption.This article focuses on the latest developments surrounding the QAH effect in magic-angle TBG.It provides a comprehensive analysis of magnetism and topology—two crucial factors in engineering the QAH effect within magic-angle TBG.Additionally,it offers a detailed overview of the experimental realization of the QAH effect in moir´e superlattices.Furthermore,this review highlights the underlying mechanisms driving these exotic phases in moir´e materials,contributing to a deeper understanding of strongly interacting quantum systems and facilitating the manipulation of new material properties to achieve novel quantum states.
文摘Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequenc- ing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach.
基金supported by the National Natural Science Foundation of China,No.81060305&81660819the Natural Science Foundation of Jiangxi Province of China,No.2015BAB205068+2 种基金Key Program for Science and Technology Cooperation Projects of Jiangxi Province of China,No.20161BBH80053a grant from the Key Project of Health Commission of Jiangxi Province of China,No.2014Z003the Natural Science Foundation of Jiangxi University of Traditional Chinese Medicine of China,No.2014ZR018&2015jzzdxk024
文摘Heat-sensitive suspended moxibustion has a neuroprotective effect against focal cerebral ischemia/reperfusion injury, but the underly- ing mechanisms remain unclear. The duration of heat-sensitive suspended moxibustion （usually from 30 minutes to 1 hour） is longer than traditional suspended moxibustion （usually 15 minutes）. However, the effects of 15- and 35-minute suspended moxibustion in rats with cerebra/ischemia/reperfusion injury are poorly understood. In this study, we performed 15- or 35-minute suspended moxibustion at acupoint Dazhui （GV14） in an adult rat model of focal cerebral ischemia/reperfusion injury. Infarct volume was evaluated with the 2,3,5-triphenyltetrazolium chloride assay. Histopathological changes and neuronal apoptosis at the injury site were assessed by hematoxy- lin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Caspase-9 and caspase-3 expression at the in- jury site was detected using immunofluorescent staining. Bax and Bcl-2 expression at the injury site was assessed using western blot assay. In the 35-minute moxibustion group, infarct volume was decreased, neuronal apoptosis was reduced, caspase-9, caspase-3 and Bax expres- sion was lower, and Bcl-2 expression was increased, compared with the 15-minute moxibustion group. Our findings show that 35-minute moxibustion has a greater anti-apoptotic effect than 15-minute moxibustion after focal cerebral ischemia/reperfusion injury.
基金supported by Ministry of Science and Technology Project (2017YFC1001302 and 2016YFC0906400)the Grant of Shanghai Brain-Intelligence Project from the Shanghai Science and Technology Committee (STCSM) (16JC1420500)Shanghai Jiao Tong University Medical Engineering Cross Research Foundation (YG2014MS07)
文摘Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy,Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a wellconstructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection,along with strong support at the national industry level.
基金supported by the National Natural Science Foundation of ChinaNational Basic Research Pro-gram of China (973 Program)+5 种基金National High-tech R&D Program (863 Program)the Chinese Nutrition Soci-ety (No. 05015)the Dannon Institute, the Shanghai-Unilever Research and Development Fund (No. 06SU07007)the Shanghai Municipality Science & Tech-nology Commission (No. 05JC14090)the Shanghai Leading Academic Discipline Project (No. B205)the Knowledge Innovation Program of the Chinese Academy of Sciences (No. KSCX2-YW-R-01)
文摘Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.
文摘Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.
基金the National Natural Science Foundation of China(NSFC)under Grant Nos.51871178。
文摘As one of the most effective mechanisms,precipitation-hardening is widely used to strengthen high-entropy alloys.Yet,heavy precipitation-hardened high-entropy alloys usually exhibit serious embrittlement.How to effectively achieve ultra-high strength and maintain reliable ductility remains a challenge.Here,we report a study of doping extremely little boron to meet this target.We found that adding of 30 ppm boron into the heavy Ti and Al alloyed FCC FeCoNiCr high-entropy,(FeCoNiCr)_(88) Ti_(6) Al_(6) HEA(at.%)which is strengthened mainly by both coarse BCC-based(Ni,Co)_(2) TiAl Heusler and fine L12-type FCC-based(Ni,Co)_(3) TiAl precipitates and shows ultrahigh strength but poor ductility,could significantly change the original microstructure and consequently improve mechanical performance,owing to the well-known effect of boron on reducing the energy of grain boundaries.The boron addition can(1)eliminate microcavities formed at Heusler precipitate-matrix interfaces;(2)suppress the formation and segregation of coarse BCC Heusler precipitates;(3)promote the formation of L12 nanoparticles.This changes of microstructure substantially improve the tensile ductility more than by~86%and retain comparable or even better ultimate tensile strength.These findings may provide a simple and costless solution to produce heavy precipitation-strengthened HEAs with ultrahigh strength and prevent accidental brittleness.
基金the National Basic Research Program of China (973 Program) (No. 2007CB947301).
文摘Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）, and the non-ridge ectoderm regulate the patterning of digits. Although a series of signaling molecules have been characterized as patterning signals from the organizing centers, the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear, Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process. Here, we review the current understanding of the genetic networks governing digit morphogenesis
