目的:总结MAB21L2基因的变异和临床特点,并与高度同源的MAB21L1基因进行比较。方法:对中山眼科中心临床基因数据库中MAB21L2基因变异患者进行基因型和表型分析,回顾性分析既往文献报道的MAB21L2基因和高度同源基因MAB21L1变异的表型-基...目的:总结MAB21L2基因的变异和临床特点,并与高度同源的MAB21L1基因进行比较。方法:对中山眼科中心临床基因数据库中MAB21L2基因变异患者进行基因型和表型分析,回顾性分析既往文献报道的MAB21L2基因和高度同源基因MAB21L1变异的表型-基因型的关系。结果:在2个小眼畸形家系中发现2个MAB21L2基因杂合变异:先证者1携带已知变异c.151C>G/p.(Arg51Gly),患者双眼小眼畸形伴虹膜脉络膜缺损,伴骨关节屈曲。母亲携带相同杂合变异但表型正常;先证者2携带未报道的变异c.1042G>T/p.(Glu348*),左眼小眼畸形,右眼正常且无全身异常。结合文献回顾发现,在显性遗传模式下,80%的MAB21L2杂合致病变异(20/25)和100%的MAB21L1杂合致病变异(25/25)发生在氨基酸49-52区域,导致小眼无眼或眼缺损异常(microphthalmia,anophthalmia or coloboma,MAC);携带该区域MAB21L2基因杂合突变的患者除MAC外,部分还伴骨骼关节发育异常(12/24,50%);杂合截短变异发生在MAB21L2基因可导致MAC(5/5,100%),而发生在MAB21L1则不致病。结论:在2个小眼畸形家系中发现了MAB21L2基因1个新致病变异和1个已知热点致病变异,通过文献综述比较和总结了MAB21L1和MAB21L2基因的突变频谱以及基因型-表型相互关系,为此类基因缺陷导致遗传病的诊断和鉴别诊断提供依据。展开更多
The long-range periodically ordered atomic structures in intermetallic nanoparticles(INPs)can significantly enhance both the electrocatalytic activity and electrochemical stability toward the oxygen reduction reaction...The long-range periodically ordered atomic structures in intermetallic nanoparticles(INPs)can significantly enhance both the electrocatalytic activity and electrochemical stability toward the oxygen reduction reaction(ORR)compared to the disordered atomic structures in ordinary solid-solution alloy NPs.Accordingly,through a facile and scalable synthetic method,a series of carbon-supported ultrafine Pt_3Co_(x)Mn_(1-x)ternary INPs are prepared in this work,which possess the"skin-like"ultrathin Pt shells,the ordered L1_(2) atomic structure,and the high-even dispersion on supports(L1_(2)-Pt_3Co_(x)Mn_(1-x)/~SPt INPs/C).Electrochemical results present that the composition-optimized L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C exhibits the highest electrocata lytic activity among the series,which are also much better than those of the pristine ultrafine Pt/C.Besides,it also has a greatly enhanced electrochemical stability.In addition,the effects of annealing temperature and time are further investigated.More importantly,such superior ORR electrocatalytic performance of L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C are also well demonstrated in practical fuel cells.Physicochemical characterization analyses further reveal the major origins of the greatly enhanced ORR electrocata lytic performance:the Pt-Co-Mn alloy-induced geometric and ligand effects as well as the extremely high L1_(2) atomic-ordering degree.This work not only successfully develops a highly active and stable ordered ternary intermetallic ORR electrocatalyst,but also elucidates the corresponding"structure-function"relationship,which can be further applied in designing other intermetallic(electro)catalysts.展开更多
Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation...Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.展开更多
Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against ...Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).展开更多
文摘目的:总结MAB21L2基因的变异和临床特点,并与高度同源的MAB21L1基因进行比较。方法:对中山眼科中心临床基因数据库中MAB21L2基因变异患者进行基因型和表型分析,回顾性分析既往文献报道的MAB21L2基因和高度同源基因MAB21L1变异的表型-基因型的关系。结果:在2个小眼畸形家系中发现2个MAB21L2基因杂合变异:先证者1携带已知变异c.151C>G/p.(Arg51Gly),患者双眼小眼畸形伴虹膜脉络膜缺损,伴骨关节屈曲。母亲携带相同杂合变异但表型正常;先证者2携带未报道的变异c.1042G>T/p.(Glu348*),左眼小眼畸形,右眼正常且无全身异常。结合文献回顾发现,在显性遗传模式下,80%的MAB21L2杂合致病变异(20/25)和100%的MAB21L1杂合致病变异(25/25)发生在氨基酸49-52区域,导致小眼无眼或眼缺损异常(microphthalmia,anophthalmia or coloboma,MAC);携带该区域MAB21L2基因杂合突变的患者除MAC外,部分还伴骨骼关节发育异常(12/24,50%);杂合截短变异发生在MAB21L2基因可导致MAC(5/5,100%),而发生在MAB21L1则不致病。结论:在2个小眼畸形家系中发现了MAB21L2基因1个新致病变异和1个已知热点致病变异,通过文献综述比较和总结了MAB21L1和MAB21L2基因的突变频谱以及基因型-表型相互关系,为此类基因缺陷导致遗传病的诊断和鉴别诊断提供依据。
基金supported by the National Key Research and Development Program of China(2021YFB4001301)the Science and Technology Commission of Shanghai Municipality(21DZ1208600)the Oceanic Interdisciplinary Program of Shanghai Jiao Tong University(SL2021ZD105)。
文摘The long-range periodically ordered atomic structures in intermetallic nanoparticles(INPs)can significantly enhance both the electrocatalytic activity and electrochemical stability toward the oxygen reduction reaction(ORR)compared to the disordered atomic structures in ordinary solid-solution alloy NPs.Accordingly,through a facile and scalable synthetic method,a series of carbon-supported ultrafine Pt_3Co_(x)Mn_(1-x)ternary INPs are prepared in this work,which possess the"skin-like"ultrathin Pt shells,the ordered L1_(2) atomic structure,and the high-even dispersion on supports(L1_(2)-Pt_3Co_(x)Mn_(1-x)/~SPt INPs/C).Electrochemical results present that the composition-optimized L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C exhibits the highest electrocata lytic activity among the series,which are also much better than those of the pristine ultrafine Pt/C.Besides,it also has a greatly enhanced electrochemical stability.In addition,the effects of annealing temperature and time are further investigated.More importantly,such superior ORR electrocatalytic performance of L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C are also well demonstrated in practical fuel cells.Physicochemical characterization analyses further reveal the major origins of the greatly enhanced ORR electrocata lytic performance:the Pt-Co-Mn alloy-induced geometric and ligand effects as well as the extremely high L1_(2) atomic-ordering degree.This work not only successfully develops a highly active and stable ordered ternary intermetallic ORR electrocatalyst,but also elucidates the corresponding"structure-function"relationship,which can be further applied in designing other intermetallic(electro)catalysts.
文摘Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.
基金supported by the Natural Science Foundation of Gansu Province[Grant Numbers 22JR5RA930,22JR5RA894]the Talent Project of Lanzhou Science and Technology Bureau[Grant Number 2022-3-44]+1 种基金the projects managed by the Administration of Traditional Chinese Medicine[Grant Number GZKG-2022-54]Intra Hospital Fund of the First Hospital of Lanzhou University[Grant Number ldyyyn2021101].
文摘Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).
文摘列表L(2,1)-标号是一个重要的可以应用到信道分配问题中的优化问题,k-L(2,1)-标号是指对于一个平面图G满足映射ϕ :V (G)→{0,1,…,k},使得若d(u,v)=1,则|ϕ(u)−ϕ(v)|≥2;若d(u,v)=2,则|ϕ(u)−ϕ(v)|≥1,其中d(u,v)是图中点u和点v之间的距离。记λ(2,1)l(G)=min{k|G有一列k-L(2,1)-标号}是列表L(2,1)-标号数。在2018年,Zhu and Bu等人在全局最优化杂志中得出这样一个结论:对于不含4-圈和6-圈的平面图G有λ(2,1)l(G)≤max{Δ+15,29}。本文改进了这个结论的上界λ(2,1)l(G)≤max{Δ+12,24}。
