Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium ch...Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames （ORFs） were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them （penT） was selected and cloned. The deduced protein ofpenTbelongs to the major facilitator superfamily （MFS） and contains 12 transmembrane spanning domains （TMS）. During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid （PAA） and phenoxyacetic acid （POA）. Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenurn doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane. Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames （ORFs） were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them （penT） was selected and cloned. The deduced protein ofpenTbelongs to the major facilitator superfamily （MFS） and contains 12 transmembrane spanning domains （TMS）. During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid （PAA） and phenoxyacetic acid （POA）. Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenurn doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane.展开更多
OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mic...OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.展开更多
The transition of traits between genetically related lineages is a fascinating topic that provides clues to understanding the drivers of speciation and diversification.Much can be learned about this process from phylo...The transition of traits between genetically related lineages is a fascinating topic that provides clues to understanding the drivers of speciation and diversification.Much can be learned about this process from phylogeny-based trait evolution.However,such inference is often plagued by genome-wide gene-tree discordance(GTD),mostly due to incomplete lineage sorting(ILS)and/or introgressive hybridization,especially when the genes underlying the traits appear discordant.Here,by collecting transcriptomes,whole chloroplast genomes(cpDNA),and population genetic datasets,we used the coalescent model to turn GTD into a source of information for ILS and employed hemiplasy to explain specific cases of apparent“phylogenetic discordance”between different morphological traits and probable species phylogeny in the Allium subg.Cyathophora.Both concatenation and coalescence methods consistently showed the same phylogenetic topology for species tree inference based on single-copy genes(SCGs),as supported by the KS distribution.However,GTD was high across the genomes of subg.Cyathophora:~27%e38.9%of the SCG trees were in conflict with the species tree.Plasmid and nuclear incongruence was also present.Our coalescent simulations indicated that such GTD was mainly a product of ILS.Our hemiplasy risk factor calculations supported that random fixation of ancient polymorphisms in different populations during successive speciation events along the subg.Cyathophora phylogeny may have caused the character transition,as well as the anomalous cpDNA tree.Our study exemplifies how phylogenetic noise can be transformed into evolutionary information for understanding character state transitions along species phylogenies.展开更多
OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and iden...OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.展开更多
OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people,could not be prevented,halted,or reversed up till now.A large body of pharmacological study has revealed that Liuwei Dihuang(LW) pos...OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people,could not be prevented,halted,or reversed up till now.A large body of pharmacological study has revealed that Liuwei Dihuang(LW) possesses potential therapeutic effects on AD.LW-AFC is key fractions fromLW.In the present study,we investigated the effect of LW-AFC on AD mouse models.METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain(SAMP8),classic AD animal models,were employed.After the treatment of LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ)deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an AlphaLISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 and SAMP8 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed amyloid-β(Αβ) deposition in the brain,and reduced the concentration of Aβ1-42 in the hippo.campus and plasma of APP/PS1 mice.LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal(HPA) and hypothalamic-pituitary-gonadal(HPG) axis,enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice.Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman.tine and donepezil.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network,which supports the use of LW-AFC as a potential agent for AD therapy.展开更多
OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor acti...OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor activity test was performed to investigate the spontaneous motor activity of mice.The Morris water maze test and shuttle box test were performed to investigate the spatial learning and memory and active avoidance response respectively.The Αβ deposits and neuron loss in the hippocampus was detected by immunofluorescence staining and nissl staining respectively.The flow cytometry was employed to investigate the lymphocyte subsets of the mice.The 3 H-thymidine incorporation was performed to investigate the splenocytes proliferation.RESULTS The treatment of LW ameliorated the impairments of spatial learning and memory and active and passive avoidance in APP/PS1 mice.The administration of LW alleviated neuron loss in the brain,suppressed amyloid-β(Αβ) deposits in the hippocampus of APP/PS1 mice.The treatment of LW significantly increased ConAand LPS-induced proliferation of splenocytes,increased CD3+ T cells and CD19+ B cells in the spleen lymphocytes and reduced Gr1+ cells in APP/PS1 mice.CONCLUSION This data indicated the adminis.tration of LW ameliorated behavioral and pathological deterioration via regulating immune function.展开更多
BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of re...BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of recombinant human thrombopoietin(rhTPO)in patients with ACLF with concomitant severe thrombocytopenia.METHODS This was a prospective,open-label study.We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group,with 35 patients in each group.Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days,while patients in the control group did not receive rhTPO treatment.The primary endpoint was the proportion of patients with platelet count>50×10^(9)/L on day 14.RESULTS The proportion of patients with platelet count>50×10^(9)/L on day 14 was 60.7%in the rhTPO group,which was significantly higher than that(12.0%)in the control group(P<0.001).The platelet count in the rhTPO group on day 14 was 64×10^(9)/L,exceeding the baseline of 28×10^(9)/L.Compared to the control group,the rhTPO group exhibited a significant increase in platelet count from baseline(P<0.05).Model for end-stage liver disease score,albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection.The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL,respectively,showing a significant increase from baseline(P<0.05).Eight(22.9%)patients had bleeding events in the control group compared with four(11.4%)in the rhTPO group.The incidence of 90-day mortality was also higher in the control group(6,17.1%)than that in the rhTPO group(3,8.6%).CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events,with a good safety profile.展开更多
The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to d...The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to develop artificial visual synapses that integrate optical sensing and synaptic functions.This study fully leverages the excellent photoresponsivity proper-ties of the PM6:Y6 system to construct a vertical photo-tunable organic memristor and conducts in-depth research on its resis-tive switching performance,photodetection capability,and simulation of photo-synaptic behavior,showcasing its excellent per-formance in processing visual information and simulating neuromorphic behaviors.The device achieves stable and gradual resis-tance change,successfully simulating voltage-controlled long-term potentiation/depression(LTP/LTD),and exhibits various photo-electric synergistic regulation of synaptic plasticity.Moreover,the device has successfully simulated the image percep-tion and recognition functions of the human visual nervous system.The non-volatile Au/PM6:Y6/ITO memristor is used as an artificial synapse and neuron modeling,building a hierarchical coordinated processing SLP-CNN cascade neural network for visual image recognition training,its linear tunable photoconductivity characteristic serves as the weight update of the net-work,achieving a recognition accuracy of up to 93.4%.Compared with the single-layer visual target recognition model,this scheme has improved the recognition accuracy by 19.2%.展开更多
The models constructed by particle flow simulation method can effectively simulate the heterogeneous substance characteristics and failure behaviors of rocks.However,existing contact models overlook the rock cracks,an...The models constructed by particle flow simulation method can effectively simulate the heterogeneous substance characteristics and failure behaviors of rocks.However,existing contact models overlook the rock cracks,and the various simulation methods that do consider cracks still exhibit certain limitations.In this paper,based on Flat-Joint model and Linear Parallel Bond model,a crack contact model considering linked substance in the crack is proposed by splitting the crack contact into two portions:linked portion and unlinked portion for calculation.The new contact model considers the influence of crack closure on the contact force-displacement law.And a better compressive tensile strength ratio(UCS/T)was obtained by limiting the failure of the contact bond to be solely controlled by the contact force and moment of the linked portion.Then,by employing the FISH Model tool within the Particle Flow Code,the contact model was constructed and verified through contact force–displacement experiments and loading-unloading tests with cracked model.Finally,the contact model was tested through simulations of rock mechanics experiments.The results indicate that the contact model can effectively simulate the axial and lateral strain laws of rocks simultaneously and has a relatively good reproduction of the bi-modularity of rocks.展开更多
Cast CrCoNiAIx （x=0-1.2） medium-entropy alloys （MEAs） were produced by arc melting and flip cast to investigate the alloying effect of AI addition on the microstructure, phase constituent and mechanical properties...Cast CrCoNiAIx （x=0-1.2） medium-entropy alloys （MEAs） were produced by arc melting and flip cast to investigate the alloying effect of AI addition on the microstructure, phase constituent and mechanical properties. The crystal structure changes from an initial face-centered cubic （FCC） to duplex FCC and body-centered cubic （BCC） and finally a single BCC with increasing AI content. In the duplex region, FCC and BCC phases form under a eutectic reaction in the interdendrite region. In the single BCC region, the dendrites transform to ordered B2 and disordered A2 BCC phases resulting from spinodal decomposition. Corresponding to their phase constituents, yield strength increases accompanied with an elongation reduction with increasing AI addition. A very interesting phenomenon of very weak ordered FCC （001） spots appearing in AI-0.4 alloy was observed, indicating a local ordering of FCC phase. The changes of fracture surfaces after the tensile deformation are also corresponding to the variations in mechanical properties.展开更多
随着高通量SNP芯片技术的快速发展和测序成本的大幅降低,SNP基因芯片和基因组重测序等技术被广泛地应用于畜禽基因组研究中。在基因组某一段区域内,当一定数量和一定密度的SNPs表现为纯合时,可以判定该区域存在连续性纯合片段(runs of h...随着高通量SNP芯片技术的快速发展和测序成本的大幅降低,SNP基因芯片和基因组重测序等技术被广泛地应用于畜禽基因组研究中。在基因组某一段区域内,当一定数量和一定密度的SNPs表现为纯合时,可以判定该区域存在连续性纯合片段(runs of homozygosity, ROH)。目前,连续性纯合片段已经逐渐成为分析畜禽群体近交程度、遗传结构等方面的重要指标之一。但是,ROH计算应用的评价标准还相对匮乏。本文系统介绍了连续性纯合片段的发展历史、原理、鉴定方法以及在畜禽群体结构解析、基因组功能分析和种畜禽品质检测等方面的应用情况,以期为畜禽遗传资源保种区和保种场在遗传多样性等动态监测方面提供参考。展开更多
South and north-dipping nodal planes from the U.S. Geological Survey moment tensor solution were used to invert global teleseismic body waves to reveal the source rupture process of the December 8, 2016, Mw6.0 Hutubi ...South and north-dipping nodal planes from the U.S. Geological Survey moment tensor solution were used to invert global teleseismic body waves to reveal the source rupture process of the December 8, 2016, Mw6.0 Hutubi earthquake. The results show that a compact pattern is the main feature of this event for only one main slip zone located at the hypocenter for both models, The slip distributions are dominated by a nearly pure-thrust fault, and there is no apparent surface rupture. The inversion revealed that the slip zone extends 10 km along strike and 12 km along dip. The released total seismic moment was about 9.0 -1017 Nm, corresponding to a magnitude of Mw6.0. It is difficult to solve for a best-fit rupture plane due to the sample slip pattern without obvious rupture directivity. This makes the far- field teleseismic data not sensitive enough to determine the fault geometric parameters. The source model of the reverse north-dipping plane fits well with the observed waveforms, and the results of the aftershock relocation outline a trend of north-dipping profiles, indicating the possibility of a reverse event. The inverted normal fault beneath the Qigu fold, interpreted by geological and seismic studies, may be the seismogenic fault for this reverse event.展开更多
RNA interference(RNAi)is a post-transcriptional gene-silencing technique induced by the introduction of double-stranded RNA(dsRNA)or small interfering RNA(siRNA)[1].RNAi-based strategies have been extensively applied ...RNA interference(RNAi)is a post-transcriptional gene-silencing technique induced by the introduction of double-stranded RNA(dsRNA)or small interfering RNA(siRNA)[1].RNAi-based strategies have been extensively applied in the treatment of human diseases and crop protection against insect pests[2-4].With the availability of the full genome sequences of major mosquito vectors,RNAi has become increasingly used as a novel means of mosquito control[5].展开更多
基金supported by the grants from the Ministry of Science and Technology of China(Nos.2009CB118905 and 2010ZX09401-403)the Knowledge Innovation Program of the Chinese Academy of Sciences(Nos.KSCX2-EW-G-6 and KSCX2-EW-J-6)
文摘Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames （ORFs） were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them （penT） was selected and cloned. The deduced protein ofpenTbelongs to the major facilitator superfamily （MFS） and contains 12 transmembrane spanning domains （TMS）. During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid （PAA） and phenoxyacetic acid （POA）. Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenurn doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane. Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames （ORFs） were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them （penT） was selected and cloned. The deduced protein ofpenTbelongs to the major facilitator superfamily （MFS） and contains 12 transmembrane spanning domains （TMS）. During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid （PAA） and phenoxyacetic acid （POA）. Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenurn doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane.
基金supported by National Science and Technology Major Projects Initiative(2013ZX09508104)National Natural Science Foundation of China(81473191)
文摘OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.
基金supported by the Key Science & Technology Project of Gansu Province (22ZD6NA007)the National Key Research and Development Program of China (2021YFD2200202)Computing support was provided by the Supercomputing Center of Lanzhou University
文摘The transition of traits between genetically related lineages is a fascinating topic that provides clues to understanding the drivers of speciation and diversification.Much can be learned about this process from phylogeny-based trait evolution.However,such inference is often plagued by genome-wide gene-tree discordance(GTD),mostly due to incomplete lineage sorting(ILS)and/or introgressive hybridization,especially when the genes underlying the traits appear discordant.Here,by collecting transcriptomes,whole chloroplast genomes(cpDNA),and population genetic datasets,we used the coalescent model to turn GTD into a source of information for ILS and employed hemiplasy to explain specific cases of apparent“phylogenetic discordance”between different morphological traits and probable species phylogeny in the Allium subg.Cyathophora.Both concatenation and coalescence methods consistently showed the same phylogenetic topology for species tree inference based on single-copy genes(SCGs),as supported by the KS distribution.However,GTD was high across the genomes of subg.Cyathophora:~27%e38.9%of the SCG trees were in conflict with the species tree.Plasmid and nuclear incongruence was also present.Our coalescent simulations indicated that such GTD was mainly a product of ILS.Our hemiplasy risk factor calculations supported that random fixation of ancient polymorphisms in different populations during successive speciation events along the subg.Cyathophora phylogeny may have caused the character transition,as well as the anomalous cpDNA tree.Our study exemplifies how phylogenetic noise can be transformed into evolutionary information for understanding character state transitions along species phylogenies.
基金supported by National Science and Technology Major Project(2013ZX09508104,2012ZX09301003-002-001)
文摘OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
基金supported by National Science and Technology Major Projects Initiative(2013ZX09508104) National Natural Science Foundation of China(81473191)
文摘OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people,could not be prevented,halted,or reversed up till now.A large body of pharmacological study has revealed that Liuwei Dihuang(LW) possesses potential therapeutic effects on AD.LW-AFC is key fractions fromLW.In the present study,we investigated the effect of LW-AFC on AD mouse models.METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain(SAMP8),classic AD animal models,were employed.After the treatment of LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ)deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an AlphaLISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 and SAMP8 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed amyloid-β(Αβ) deposition in the brain,and reduced the concentration of Aβ1-42 in the hippo.campus and plasma of APP/PS1 mice.LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal(HPA) and hypothalamic-pituitary-gonadal(HPG) axis,enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice.Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman.tine and donepezil.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network,which supports the use of LW-AFC as a potential agent for AD therapy.
基金supported by Chinese National Technology Major Project of New Drug Development (2012ZX09301003-002-001 2013ZX09508104)
文摘OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor activity test was performed to investigate the spontaneous motor activity of mice.The Morris water maze test and shuttle box test were performed to investigate the spatial learning and memory and active avoidance response respectively.The Αβ deposits and neuron loss in the hippocampus was detected by immunofluorescence staining and nissl staining respectively.The flow cytometry was employed to investigate the lymphocyte subsets of the mice.The 3 H-thymidine incorporation was performed to investigate the splenocytes proliferation.RESULTS The treatment of LW ameliorated the impairments of spatial learning and memory and active and passive avoidance in APP/PS1 mice.The administration of LW alleviated neuron loss in the brain,suppressed amyloid-β(Αβ) deposits in the hippocampus of APP/PS1 mice.The treatment of LW significantly increased ConAand LPS-induced proliferation of splenocytes,increased CD3+ T cells and CD19+ B cells in the spleen lymphocytes and reduced Gr1+ cells in APP/PS1 mice.CONCLUSION This data indicated the adminis.tration of LW ameliorated behavioral and pathological deterioration via regulating immune function.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of recombinant human thrombopoietin(rhTPO)in patients with ACLF with concomitant severe thrombocytopenia.METHODS This was a prospective,open-label study.We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group,with 35 patients in each group.Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days,while patients in the control group did not receive rhTPO treatment.The primary endpoint was the proportion of patients with platelet count>50×10^(9)/L on day 14.RESULTS The proportion of patients with platelet count>50×10^(9)/L on day 14 was 60.7%in the rhTPO group,which was significantly higher than that(12.0%)in the control group(P<0.001).The platelet count in the rhTPO group on day 14 was 64×10^(9)/L,exceeding the baseline of 28×10^(9)/L.Compared to the control group,the rhTPO group exhibited a significant increase in platelet count from baseline(P<0.05).Model for end-stage liver disease score,albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection.The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL,respectively,showing a significant increase from baseline(P<0.05).Eight(22.9%)patients had bleeding events in the control group compared with four(11.4%)in the rhTPO group.The incidence of 90-day mortality was also higher in the control group(6,17.1%)than that in the rhTPO group(3,8.6%).CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events,with a good safety profile.
基金the National Natural Science Foundation of China(62111540271)Natural Science Foundation of Anhui Province(2308085MF207).
文摘The hierarchical and coordinated processing of visual information by the brain demonstrates its superior ability to min-imize energy consumption and maximize signal transmission efficiency.Therefore,it is crucial to develop artificial visual synapses that integrate optical sensing and synaptic functions.This study fully leverages the excellent photoresponsivity proper-ties of the PM6:Y6 system to construct a vertical photo-tunable organic memristor and conducts in-depth research on its resis-tive switching performance,photodetection capability,and simulation of photo-synaptic behavior,showcasing its excellent per-formance in processing visual information and simulating neuromorphic behaviors.The device achieves stable and gradual resis-tance change,successfully simulating voltage-controlled long-term potentiation/depression(LTP/LTD),and exhibits various photo-electric synergistic regulation of synaptic plasticity.Moreover,the device has successfully simulated the image percep-tion and recognition functions of the human visual nervous system.The non-volatile Au/PM6:Y6/ITO memristor is used as an artificial synapse and neuron modeling,building a hierarchical coordinated processing SLP-CNN cascade neural network for visual image recognition training,its linear tunable photoconductivity characteristic serves as the weight update of the net-work,achieving a recognition accuracy of up to 93.4%.Compared with the single-layer visual target recognition model,this scheme has improved the recognition accuracy by 19.2%.
基金supported by the Natural Science Foundation of Heilongjiang Province(No.ZD2021E006)the National Natural Science Foundation of China(Nos.52174075 and 52074110).
文摘The models constructed by particle flow simulation method can effectively simulate the heterogeneous substance characteristics and failure behaviors of rocks.However,existing contact models overlook the rock cracks,and the various simulation methods that do consider cracks still exhibit certain limitations.In this paper,based on Flat-Joint model and Linear Parallel Bond model,a crack contact model considering linked substance in the crack is proposed by splitting the crack contact into two portions:linked portion and unlinked portion for calculation.The new contact model considers the influence of crack closure on the contact force-displacement law.And a better compressive tensile strength ratio(UCS/T)was obtained by limiting the failure of the contact bond to be solely controlled by the contact force and moment of the linked portion.Then,by employing the FISH Model tool within the Particle Flow Code,the contact model was constructed and verified through contact force–displacement experiments and loading-unloading tests with cracked model.Finally,the contact model was tested through simulations of rock mechanics experiments.The results indicate that the contact model can effectively simulate the axial and lateral strain laws of rocks simultaneously and has a relatively good reproduction of the bi-modularity of rocks.
基金financially supported by the National Nature Science Foundation of China(51775204 and 51604222)the Analytical and Testing Center,HUSTChina Postdoctoral Science Foundation Funded Project
文摘Cast CrCoNiAIx （x=0-1.2） medium-entropy alloys （MEAs） were produced by arc melting and flip cast to investigate the alloying effect of AI addition on the microstructure, phase constituent and mechanical properties. The crystal structure changes from an initial face-centered cubic （FCC） to duplex FCC and body-centered cubic （BCC） and finally a single BCC with increasing AI content. In the duplex region, FCC and BCC phases form under a eutectic reaction in the interdendrite region. In the single BCC region, the dendrites transform to ordered B2 and disordered A2 BCC phases resulting from spinodal decomposition. Corresponding to their phase constituents, yield strength increases accompanied with an elongation reduction with increasing AI addition. A very interesting phenomenon of very weak ordered FCC （001） spots appearing in AI-0.4 alloy was observed, indicating a local ordering of FCC phase. The changes of fracture surfaces after the tensile deformation are also corresponding to the variations in mechanical properties.
文摘随着高通量SNP芯片技术的快速发展和测序成本的大幅降低,SNP基因芯片和基因组重测序等技术被广泛地应用于畜禽基因组研究中。在基因组某一段区域内,当一定数量和一定密度的SNPs表现为纯合时,可以判定该区域存在连续性纯合片段(runs of homozygosity, ROH)。目前,连续性纯合片段已经逐渐成为分析畜禽群体近交程度、遗传结构等方面的重要指标之一。但是,ROH计算应用的评价标准还相对匮乏。本文系统介绍了连续性纯合片段的发展历史、原理、鉴定方法以及在畜禽群体结构解析、基因组功能分析和种畜禽品质检测等方面的应用情况,以期为畜禽遗传资源保种区和保种场在遗传多样性等动态监测方面提供参考。
基金supported by the Director Foundation of Institute of Seismology, CEA (Grant Number: IS201326127)the National Natural Science Foundation of China (Grant Numbers: 41404016, 41474097)
文摘South and north-dipping nodal planes from the U.S. Geological Survey moment tensor solution were used to invert global teleseismic body waves to reveal the source rupture process of the December 8, 2016, Mw6.0 Hutubi earthquake. The results show that a compact pattern is the main feature of this event for only one main slip zone located at the hypocenter for both models, The slip distributions are dominated by a nearly pure-thrust fault, and there is no apparent surface rupture. The inversion revealed that the slip zone extends 10 km along strike and 12 km along dip. The released total seismic moment was about 9.0 -1017 Nm, corresponding to a magnitude of Mw6.0. It is difficult to solve for a best-fit rupture plane due to the sample slip pattern without obvious rupture directivity. This makes the far- field teleseismic data not sensitive enough to determine the fault geometric parameters. The source model of the reverse north-dipping plane fits well with the observed waveforms, and the results of the aftershock relocation outline a trend of north-dipping profiles, indicating the possibility of a reverse event. The inverted normal fault beneath the Qigu fold, interpreted by geological and seismic studies, may be the seismogenic fault for this reverse event.
基金supported by grants from the National Key Research and Development Program(2023YFE0113600).
文摘RNA interference(RNAi)is a post-transcriptional gene-silencing technique induced by the introduction of double-stranded RNA(dsRNA)or small interfering RNA(siRNA)[1].RNAi-based strategies have been extensively applied in the treatment of human diseases and crop protection against insect pests[2-4].With the availability of the full genome sequences of major mosquito vectors,RNAi has become increasingly used as a novel means of mosquito control[5].
