Mitogenomes have been widely used in phylogenetic and taxonomic research,due to their maternal inheritance,accelerated evolutionary rates,compact circular structure,and the absence of introns.Although their utility is...Mitogenomes have been widely used in phylogenetic and taxonomic research,due to their maternal inheritance,accelerated evolutionary rates,compact circular structure,and the absence of introns.Although their utility is well-established,efficient mitogenome sequencing still poses a challenge for evolutionary studies.Here,we presented a novel hybridization capture protocol that enables high-fidelity sequencing of the complete mitogenome(16535 bp)of Odorrana nasuta.This genome exhibits typical anuran characteristics,including an A+T nucleotide bias(56.37%)and conserved gene composition.Notably,we identified a lineage-specific trnH transposition event that reorganizes the typical gene order into a unique trnH-trnL1-trnT-trnP-trnF cluster,which may be a potential synapomorphic trait for the genus Odorrana.Phylogenetic reconstruction using 13 protein-coding genes from 59 anuran species strongly supported the monophyly of Ranidae and its constituent genera(Odorrana,Rana,Lithobates,Amolops,Pelophylax,Glandirana),yet reveals the incongruence in the placement of Hylarana.The conflicting topologies observed for Hylarana and Glandirana across different studies highlight critical methodological limitations,including taxonomic sampling biases and data type dependency,which collectively compromise phylogenetic resolution.By integrating mitogenomic structure signatures with sequence-based phylogenies,this work advances our understanding of the systematics within Odorrana and highlights the need of multi-locus genomic datasets for resolving deep phylogenetic conflicts within Ranidae.展开更多
Lime mud is a kind of solid waste in the papermaking industry,which has been a source of serious environmental pollution.Ceramsites containing anorthite and gehlenite were prepared from lime mud and fly ash through th...Lime mud is a kind of solid waste in the papermaking industry,which has been a source of serious environmental pollution.Ceramsites containing anorthite and gehlenite were prepared from lime mud and fly ash through the solid state reaction method at 1050°C.The objective of this study was to explore the efficiency of Ca^2＋ and OH-release and assess the phosphorus and copper ion removal performance of the ceramsites via batch experiments,X-ray diffraction（XRD） and scanning electron microscopy（SEM）.The results show that Ca^2＋ and OH-were released from the ceramsites due to the dissolution of anorthite,gehlenite and available lime.It is also concluded that gehlenite had stronger capacity for Ca^2＋ and OH-release compared with anorthite.The Ca^2＋ release could be fit well by the Avrami kinetic model.Increases of porosity,dosage and temperature were associated with increases in the concentrations of Ca^2＋ and OH-released.Under different conditions,the ceramsites could maintain aqueous solutions in alkaline conditions（p H = 9.3–10.9） and the release of Ca^2＋ was not affected.The removal rates of phosphorus and copper ions were as high as 96.88% and 96.81%,respectively.The final p H values of both phosphorus and copper ions solutions changed slightly.The reuse of lime mud in the form of ceramsites is an effective strategy.展开更多
Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls we...Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls were obtained from the Gene Expression Omnibus database.Significant differentially expressed genes were screened using the limma package.Correlation pathways were screened by Spearman correlation analysis on the echinoderm microtubule-associated protein-like 4(EML4)and enrichment in endometriosis pathways and estimated by the GSVA package.Immune characteristics were assessed by the“ESTIMATE”R package.Potential regulatory pathways were determined by enrichment analysis.The SWISS-MODE website was used in homology modeling with EML4 and EML4 protein activity was predicted.VarElect was employed in molecular docking for screening potential compound inhibitors targeting endometriosis.Results:Ten endometriosis and 10 normal samples were included.EML4 was significantly upregulated in endometriosis(p<0.05).Thirty significantly correlated pathways involving 18 positive and 12 negative correlations,including GLYCOSAMINOGLYCAN_BIOSYNTHESIS_HEPARAN_SULFATE and GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIO_SERIES were screened between EML4 and endometriosis.Immunocorrelation analysis showed a significant difference in immune-related pathways in endometriosis and normal samples(p<0.05).In endometriosis,EML4 was associated with T-cell CD4 resting memory,activated mast cells,plasma cells,activated NK cells,M2 macrophages,and follicular helper T cells(p<0.05).Molecular docking identified five potential inhibitors of EML4,and compound DB05104(asimadoline)bound well to EML4 protein to exert its physiological effects.Conclusion:Differential gene expression and immune correlation analyses revealed that EML4 may affect endometriosis through multiple targets and pathways,the mechanism of which involved immune cell activation and infiltration.Molecular docking and dynamics simulation verified DB05104 as a potential inhibitor of EML4 and a powerful target for endometriosis treatment.展开更多
Dear Editor,Large-scale phenotyping efforts have shown that placental defects correlate strongly with embryonic lethal mouse mutants(Perez-Garcia et al.,2018).To rescue normal development of these mutant embryos,tetra...Dear Editor,Large-scale phenotyping efforts have shown that placental defects correlate strongly with embryonic lethal mouse mutants(Perez-Garcia et al.,2018).To rescue normal development of these mutant embryos,tetraploid complementation can be a reliable strategy,in which,tetraploid cells form extraembryonic lineages thus providing the embryo with a wild-type placenta(Nagy et al.,1990).展开更多
CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-...CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.展开更多
基金the National Natural Science Foundation of China(NSFC)to Zhuo CHEN(Grant Nos.32270440 and 31601848)and Xiaohong CHEN(Grant No.U21A20192).
文摘Mitogenomes have been widely used in phylogenetic and taxonomic research,due to their maternal inheritance,accelerated evolutionary rates,compact circular structure,and the absence of introns.Although their utility is well-established,efficient mitogenome sequencing still poses a challenge for evolutionary studies.Here,we presented a novel hybridization capture protocol that enables high-fidelity sequencing of the complete mitogenome(16535 bp)of Odorrana nasuta.This genome exhibits typical anuran characteristics,including an A+T nucleotide bias(56.37%)and conserved gene composition.Notably,we identified a lineage-specific trnH transposition event that reorganizes the typical gene order into a unique trnH-trnL1-trnT-trnP-trnF cluster,which may be a potential synapomorphic trait for the genus Odorrana.Phylogenetic reconstruction using 13 protein-coding genes from 59 anuran species strongly supported the monophyly of Ranidae and its constituent genera(Odorrana,Rana,Lithobates,Amolops,Pelophylax,Glandirana),yet reveals the incongruence in the placement of Hylarana.The conflicting topologies observed for Hylarana and Glandirana across different studies highlight critical methodological limitations,including taxonomic sampling biases and data type dependency,which collectively compromise phylogenetic resolution.By integrating mitogenomic structure signatures with sequence-based phylogenies,this work advances our understanding of the systematics within Odorrana and highlights the need of multi-locus genomic datasets for resolving deep phylogenetic conflicts within Ranidae.
基金financially supported by the National Natural Science Foundation of China (Nos.51578289 and 51468053)the Technology Major Projects of China (No.2012ZX04010-032)+1 种基金the Research and innovation program of graduate students in Jiangsu Province (No.KYLX_0347)the Innovation Fund for National Small and Medium Technology Based Firms of China (No.11C26213201410)
文摘Lime mud is a kind of solid waste in the papermaking industry,which has been a source of serious environmental pollution.Ceramsites containing anorthite and gehlenite were prepared from lime mud and fly ash through the solid state reaction method at 1050°C.The objective of this study was to explore the efficiency of Ca^2＋ and OH-release and assess the phosphorus and copper ion removal performance of the ceramsites via batch experiments,X-ray diffraction（XRD） and scanning electron microscopy（SEM）.The results show that Ca^2＋ and OH-were released from the ceramsites due to the dissolution of anorthite,gehlenite and available lime.It is also concluded that gehlenite had stronger capacity for Ca^2＋ and OH-release compared with anorthite.The Ca^2＋ release could be fit well by the Avrami kinetic model.Increases of porosity,dosage and temperature were associated with increases in the concentrations of Ca^2＋ and OH-released.Under different conditions,the ceramsites could maintain aqueous solutions in alkaline conditions（p H = 9.3–10.9） and the release of Ca^2＋ was not affected.The removal rates of phosphorus and copper ions were as high as 96.88% and 96.81%,respectively.The final p H values of both phosphorus and copper ions solutions changed slightly.The reuse of lime mud in the form of ceramsites is an effective strategy.
基金funded by the Role and Mechanism of EML4 in Regulating Oocyte Meiosis and Leading to the Infertility Project(SDFEYJGL2103).
文摘Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls were obtained from the Gene Expression Omnibus database.Significant differentially expressed genes were screened using the limma package.Correlation pathways were screened by Spearman correlation analysis on the echinoderm microtubule-associated protein-like 4(EML4)and enrichment in endometriosis pathways and estimated by the GSVA package.Immune characteristics were assessed by the“ESTIMATE”R package.Potential regulatory pathways were determined by enrichment analysis.The SWISS-MODE website was used in homology modeling with EML4 and EML4 protein activity was predicted.VarElect was employed in molecular docking for screening potential compound inhibitors targeting endometriosis.Results:Ten endometriosis and 10 normal samples were included.EML4 was significantly upregulated in endometriosis(p<0.05).Thirty significantly correlated pathways involving 18 positive and 12 negative correlations,including GLYCOSAMINOGLYCAN_BIOSYNTHESIS_HEPARAN_SULFATE and GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIO_SERIES were screened between EML4 and endometriosis.Immunocorrelation analysis showed a significant difference in immune-related pathways in endometriosis and normal samples(p<0.05).In endometriosis,EML4 was associated with T-cell CD4 resting memory,activated mast cells,plasma cells,activated NK cells,M2 macrophages,and follicular helper T cells(p<0.05).Molecular docking identified five potential inhibitors of EML4,and compound DB05104(asimadoline)bound well to EML4 protein to exert its physiological effects.Conclusion:Differential gene expression and immune correlation analyses revealed that EML4 may affect endometriosis through multiple targets and pathways,the mechanism of which involved immune cell activation and infiltration.Molecular docking and dynamics simulation verified DB05104 as a potential inhibitor of EML4 and a powerful target for endometriosis treatment.
基金supported by the Genome Tagging Project and grants from the National Key Research and Development Program of China(2024YFA1800010,2020YFA0509000)the National Science and Technology Major Project of China(2023ZD0500500)+2 种基金the National Natural Science Foundation of China(32488101,32030029,32293231,32370909)partly supported by Shanghai Municipal Science and Technology Major Project(22YS1400900,23HC1401000)support of the Sanofi Scholarship Program.
文摘Dear Editor,Large-scale phenotyping efforts have shown that placental defects correlate strongly with embryonic lethal mouse mutants(Perez-Garcia et al.,2018).To rescue normal development of these mutant embryos,tetraploid complementation can be a reliable strategy,in which,tetraploid cells form extraembryonic lineages thus providing the embryo with a wild-type placenta(Nagy et al.,1990).
基金the National Natural Science Foundation of China(82171148,51873107,81770999)National Key Research and Development Program of China(2020YFA0908201)+3 种基金Science and Technology Commission of Shanghai Municipality(21S11905100)National Genetically Modified Organisms Breeding Major Projects of China(2016ZX08009003-006)Clinic Research Plan of SHDC(No.SHDC2020CR4083),“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG08)National Research Facility for Phenotypic and Genotypic Analysis of Model Animals(Beijing).
文摘CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.
