The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV(OI-XV)has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteo...The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV(OI-XV)has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteoblasts.Although such aninfluence was supported by subsequent studies,a mouse model of OI-XV remained to be established.Therefore,we introduced a previously identified disease-causing mutation(G177C)into the murine Wnt1 gene.Homozygous Wnt1^(G177C/G177C)mice were viable and did not display defects in brain development,but the majority of 24-week-old Wnt1^(G177C/G177C)mice had skeletal fractures.This increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix quality.Importantly,the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5,the latter mimicking the effect of sclerostin neutralization.Finally,transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix modifiers.Taken together,our data demonstrate that regulating bone matrix quality is a primary function of WNT1.They further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.展开更多
Ethylene plays essential roles in plant growth,development and stress responses.The ethylene signaling pathway and molecular mechanism have been studied extensively in Arabidopsis and rice but limited in peanuts.Here,...Ethylene plays essential roles in plant growth,development and stress responses.The ethylene signaling pathway and molecular mechanism have been studied extensively in Arabidopsis and rice but limited in peanuts.Here,we established a sand-culture method to screen pingyangmycin mutagenized peanut lines based on their specific response to ethylene(“triple response”).An ethylene-insensitive mutant,inhibition of peanut hypocotyl elongation 1(iph1),was identified that showed reduced sensitivity to ethylene in both hypocotyl elongation and root growth.Through bulked segregant analysis sequencing,a major gene related to iph1,named AhIPH1,was preliminarily mapped at the chromosome Arahy.01,and further narrowed to a 450-kb genomic region through substitution mapping strategy.A total of 7014 genes were differentially expressed among the ACC treatment through RNA-seq analysis,of which only the Arahy.5BLU0Q gene in the candidate mapping interval was differentially expressed between WT and mutant iph1.Integrating sequence variations,functional annotation and transcriptome analysis revealed that a predicated gene,Arahy.5BLU0Q,encoding SNF1 protein kinase,may be the candidate gene for AhIPH1.This gene contained two single-nucleotide polymorphisms at promoter region and was more highly expressed in iph1 than WT.Our findings reveal a novel ethylene-responsive gene,which provides a theoretical foundation and new genetic resources for the mechanism of ethylene signaling in peanuts.展开更多
Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role o...The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.展开更多
In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein...In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.展开更多
Aquaporins play important regulatory roles in improving plant abiotic stress tolerance.To better understand whether the Os PIP1 genes collectively dominate the osmotic regulation in rice under salt stress,a cluster ed...Aquaporins play important regulatory roles in improving plant abiotic stress tolerance.To better understand whether the Os PIP1 genes collectively dominate the osmotic regulation in rice under salt stress,a cluster editing of the Os PIP1;1,Os PIP1;2 and Os PIP1;3 genes in rice was performed by CRISPR/Cas9 system.Sequencing showed that two mutants with Cas9-free,line 14 and line 18 were successfully edited.Briefly,line 14 deleted a single C base in both the Os PIP1;1 and Os PIP1;3 genes,and inserted a single T base in the Os PIP1;2 gene,respectively.While line 18 demonstrated an insertion of a single A base in the Os PIP1;1gene and a single T base in both the Os PIP1;2 and Os PIP1;3 genes,respectively.Multiplex editing of the Os PIP1 genes significantly inhibited photosynthetic rate and accumulation of compatible metabolites,but increased MDA contents and osmotic potentials in the mutants,thus delaying rice growth under salt stress.Functional loss of the Os PIP1 genes obviously suppressed the expressions of the Os PIP1,Os SOS1,Os CIPK24 and Os CBL4 genes,and increased the influxes of Na+and effluxes of K^(+)/H^(+)in the roots,thus accumulating more Na+in rice mutants under salt stress.This study suggests that the Os PIP1 genes are essential modulators collectively contributing to the enhancement of rice salt stress tolerance,and multiplex editing of the Os PIP1 genes provides insight into the osmotic regulation of the PIP genes.展开更多
As“Bohai Red”scallops were originated from the hybrids between the Peruvian scallop(Argopecten purpuratus)and the bay scallop(Argopecten irradians)northern subspecies(Argopecten irradians irradians).Twelve Wnt membe...As“Bohai Red”scallops were originated from the hybrids between the Peruvian scallop(Argopecten purpuratus)and the bay scallop(Argopecten irradians)northern subspecies(Argopecten irradians irradians).Twelve Wnt members were identified from the two subspecies of bay scallop,and 13 Wnt genes were found in the genome of the Peruvian scallop.Protein structure analyses showed that most Wnt genes poses all 5 conserved motifs except Wnt1,Wnt2,Wnt6,and Wnt9 in the bay scallops and Wnt2 and Wnt9 in the Peruvian scallop.Unexpectedly,Wnt8 gene was present while Wnt3 was absent in both the bay scallops and the Peruvian scallop.Phylogenetic analysis revealed that Wnt3 might have disappeared in the early evolution of mollusks.The expression profile of Wnt genes in the“Bohai Red”exposed to different temperatures was examined by qRT-PCR.Results show that expression of Wnt genes responded differentially to temperature changes.The Wnt genes such as Wnt1,Wnt6,Wnt7,Wnt11,and WntA that responded slowly to low and high temperature stresses may be related to the maintenance of basic homeostasis.Other Wnt genes such as Wnt4,Wnt9,Wnt5,and Wnt2 that responded rapidly to low temperature may play an important role in organismal protection against low temperature stress.And yet some Wnt genes including Wnt10,Wnt16,and Wnt8 that responded quickly to high temperature stress may play key roles in response to high temperature stress.The results provide new insights into the evolution and function of Wnt genes in bivalves and eventually benefit culture of“Bohai Red”scallops.展开更多
Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is...Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is the best strategy for controlling the disease.In this study,we performed fine mapping and characterization of the all-stage stem rust resistance(Sr)gene Sr8155B1 from the durum wheat line 8155-B1.In seedling tests of biparental populations,Sr8155B1 was effective against six Chinese Pgt races tested.In a segregating population of 5060 gametes,Sr8155B1 was mapped to a 0.06-cM region flanked by markers Pku2772 and Pku43365,corresponding to 1.5-and 2.7-Mb regions in the Svevo and Chinese Spring reference genomes.Both regions include several typical nucleotide-binding leucine-rich repeat(NLR)and protein kinase genes that represent candidate genes.Among them,three NLR genes and three receptor-like protein kinases were highly polymorphic between the parental lines and their transcripts were upregulated in the homozygous resistant line TdR2 relative to its susceptible sister line TdS4.Four markers(Pku2772,Pku43365,Pku2950,and Pku3721)developed in this study,together with seedling resistance responses,correctly predicted Sr8155B1 absence or presence in 78 tetraploid wheat genotypes tested.The presence of Sr8155B1 in tetraploid wheat accessions CItr 14916,PI 197492,and PI 197493 was confirmed by mapping in three F_(2)populations.The genetic map and linked markers developed in this study may accelerate the deployment of Sr8155B1-mediated resistance in wheat breeding programs.展开更多
Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartil...Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartilage remains themajor hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding orreversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development isa critical barrier to progress in OA therapy. Recent studies by the current authors’ group and others have revealedthat the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulatesthe expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. Thisreview mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities ofarticular chondrocytes and its implication in the pathogenesis of OA.展开更多
基金This project has received funding from the Deutsche Forschungsgemeinschaft(SCHI 504/15-1 and YO 299/1-1),the European Community's Seventh Framework Programme under grant agreement no.602300(SYBIL),and the German Federal Ministry of Education and Research(BMBF)within the project"Detection and Individualized Management of Early Onset Osteoporosis(DIMEOS)"Parts of this work were supported by the Deutsche Forschungsgemeinschaft through FOR 2722 to O.S.(SE2373/1-1)W.Z.received funding through the China Scholarship Council.
文摘The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV(OI-XV)has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteoblasts.Although such aninfluence was supported by subsequent studies,a mouse model of OI-XV remained to be established.Therefore,we introduced a previously identified disease-causing mutation(G177C)into the murine Wnt1 gene.Homozygous Wnt1^(G177C/G177C)mice were viable and did not display defects in brain development,but the majority of 24-week-old Wnt1^(G177C/G177C)mice had skeletal fractures.This increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix quality.Importantly,the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5,the latter mimicking the effect of sclerostin neutralization.Finally,transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix modifiers.Taken together,our data demonstrate that regulating bone matrix quality is a primary function of WNT1.They further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.
基金supported by the National Natural Science Foundation of China(32001578)Qingdao Science&Technology Key Projects(22-1-3-1-zyyd-nsh,23-1-3-8-zyyd-nsh)+1 种基金Salt-Alkali Agriculture Industry System of Shandong Province(SDAIT-29-03)Science&Technology Specific Projects in Agricultural High-tech Industrial Demonstration Area of the Yellow River Delta(2022SZX19)。
文摘Ethylene plays essential roles in plant growth,development and stress responses.The ethylene signaling pathway and molecular mechanism have been studied extensively in Arabidopsis and rice but limited in peanuts.Here,we established a sand-culture method to screen pingyangmycin mutagenized peanut lines based on their specific response to ethylene(“triple response”).An ethylene-insensitive mutant,inhibition of peanut hypocotyl elongation 1(iph1),was identified that showed reduced sensitivity to ethylene in both hypocotyl elongation and root growth.Through bulked segregant analysis sequencing,a major gene related to iph1,named AhIPH1,was preliminarily mapped at the chromosome Arahy.01,and further narrowed to a 450-kb genomic region through substitution mapping strategy.A total of 7014 genes were differentially expressed among the ACC treatment through RNA-seq analysis,of which only the Arahy.5BLU0Q gene in the candidate mapping interval was differentially expressed between WT and mutant iph1.Integrating sequence variations,functional annotation and transcriptome analysis revealed that a predicated gene,Arahy.5BLU0Q,encoding SNF1 protein kinase,may be the candidate gene for AhIPH1.This gene contained two single-nucleotide polymorphisms at promoter region and was more highly expressed in iph1 than WT.Our findings reveal a novel ethylene-responsive gene,which provides a theoretical foundation and new genetic resources for the mechanism of ethylene signaling in peanuts.
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
文摘The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.
文摘In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.
基金supported by the National Key Research and Development Program of China (2021YFF1000402-2)the Key Project of Transgenic Crops Cultivation (2016ZX08010005-9)。
文摘Aquaporins play important regulatory roles in improving plant abiotic stress tolerance.To better understand whether the Os PIP1 genes collectively dominate the osmotic regulation in rice under salt stress,a cluster editing of the Os PIP1;1,Os PIP1;2 and Os PIP1;3 genes in rice was performed by CRISPR/Cas9 system.Sequencing showed that two mutants with Cas9-free,line 14 and line 18 were successfully edited.Briefly,line 14 deleted a single C base in both the Os PIP1;1 and Os PIP1;3 genes,and inserted a single T base in the Os PIP1;2 gene,respectively.While line 18 demonstrated an insertion of a single A base in the Os PIP1;1gene and a single T base in both the Os PIP1;2 and Os PIP1;3 genes,respectively.Multiplex editing of the Os PIP1 genes significantly inhibited photosynthetic rate and accumulation of compatible metabolites,but increased MDA contents and osmotic potentials in the mutants,thus delaying rice growth under salt stress.Functional loss of the Os PIP1 genes obviously suppressed the expressions of the Os PIP1,Os SOS1,Os CIPK24 and Os CBL4 genes,and increased the influxes of Na+and effluxes of K^(+)/H^(+)in the roots,thus accumulating more Na+in rice mutants under salt stress.This study suggests that the Os PIP1 genes are essential modulators collectively contributing to the enhancement of rice salt stress tolerance,and multiplex editing of the Os PIP1 genes provides insight into the osmotic regulation of the PIP genes.
基金Supported by the Focally Deployed Program,Center for Ocean Mega-Science,Chinese Academy of Sciences,National Natural Science Foundation(No.COMS2019R03)the National Natural Science Foundation of China(No.31972791)+2 种基金the Earmarked Fund for Agriculture Seed Improvement Project of Shandong Province(No.2020LZGC016)the Earmarked Fund for Shandong Modern Agro-Industry Technology Research System(No.SDAIT-14)the Natural Science Foundation of Shandong Province(No.ZR2020MC192)。
文摘As“Bohai Red”scallops were originated from the hybrids between the Peruvian scallop(Argopecten purpuratus)and the bay scallop(Argopecten irradians)northern subspecies(Argopecten irradians irradians).Twelve Wnt members were identified from the two subspecies of bay scallop,and 13 Wnt genes were found in the genome of the Peruvian scallop.Protein structure analyses showed that most Wnt genes poses all 5 conserved motifs except Wnt1,Wnt2,Wnt6,and Wnt9 in the bay scallops and Wnt2 and Wnt9 in the Peruvian scallop.Unexpectedly,Wnt8 gene was present while Wnt3 was absent in both the bay scallops and the Peruvian scallop.Phylogenetic analysis revealed that Wnt3 might have disappeared in the early evolution of mollusks.The expression profile of Wnt genes in the“Bohai Red”exposed to different temperatures was examined by qRT-PCR.Results show that expression of Wnt genes responded differentially to temperature changes.The Wnt genes such as Wnt1,Wnt6,Wnt7,Wnt11,and WntA that responded slowly to low and high temperature stresses may be related to the maintenance of basic homeostasis.Other Wnt genes such as Wnt4,Wnt9,Wnt5,and Wnt2 that responded rapidly to low temperature may play an important role in organismal protection against low temperature stress.And yet some Wnt genes including Wnt10,Wnt16,and Wnt8 that responded quickly to high temperature stress may play key roles in response to high temperature stress.The results provide new insights into the evolution and function of Wnt genes in bivalves and eventually benefit culture of“Bohai Red”scallops.
基金the National Key Research and Development Program of China(2022YFD1201300)the Key R&D Program of Shandong Province(ZR202211070163)+1 种基金the Provincial Natural Science Foundation of Shandong(ZR2021ZD30,ZR2021MC056)the Young Taishan Scholars Program of Shandong Province.
文摘Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is the best strategy for controlling the disease.In this study,we performed fine mapping and characterization of the all-stage stem rust resistance(Sr)gene Sr8155B1 from the durum wheat line 8155-B1.In seedling tests of biparental populations,Sr8155B1 was effective against six Chinese Pgt races tested.In a segregating population of 5060 gametes,Sr8155B1 was mapped to a 0.06-cM region flanked by markers Pku2772 and Pku43365,corresponding to 1.5-and 2.7-Mb regions in the Svevo and Chinese Spring reference genomes.Both regions include several typical nucleotide-binding leucine-rich repeat(NLR)and protein kinase genes that represent candidate genes.Among them,three NLR genes and three receptor-like protein kinases were highly polymorphic between the parental lines and their transcripts were upregulated in the homozygous resistant line TdR2 relative to its susceptible sister line TdS4.Four markers(Pku2772,Pku43365,Pku2950,and Pku3721)developed in this study,together with seedling resistance responses,correctly predicted Sr8155B1 absence or presence in 78 tetraploid wheat genotypes tested.The presence of Sr8155B1 in tetraploid wheat accessions CItr 14916,PI 197492,and PI 197493 was confirmed by mapping in three F_(2)populations.The genetic map and linked markers developed in this study may accelerate the deployment of Sr8155B1-mediated resistance in wheat breeding programs.
基金supported by the United States National Institutes of Health(NIH)under Award Number R01 AR059088(to J.W.)the Mary A.and Paul R.Harrington Distinguished Professorship Endowment.
文摘Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartilage remains themajor hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding orreversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development isa critical barrier to progress in OA therapy. Recent studies by the current authors’ group and others have revealedthat the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulatesthe expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. Thisreview mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities ofarticular chondrocytes and its implication in the pathogenesis of OA.
