Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
Horticultural plants play various and critical roles for humans by providing fruits,vegetables,materials for beverages,and herbal medicines and by acting as ornamentals.They have also shaped human art,culture,and envi...Horticultural plants play various and critical roles for humans by providing fruits,vegetables,materials for beverages,and herbal medicines and by acting as ornamentals.They have also shaped human art,culture,and environments and thereby have influenced the lifestyles of humans.With the advent of sequencing technologies,there has been a dramatic increase in the number of sequenced genomes of horticultural plant species in the past decade.The genomes of horticultural plants are highly diverse and complex,often with a high degree of heterozygosity and a high ploidy due to their long and complex history of evolution and domestication.Here we summarize the advances in the genome sequencing of horticultural plants,the reconstruction of pan-genomes,and the development of horticultural genome databases.We also discuss past,present,and future studies related to genome sequencing,data storage,data quality,data sharing,and data visualization to provide practical guidance for genomic studies of horticultural plants.Finally,we propose a horticultural plant genome project as well as the roadmap and technical details toward three goals of the project.展开更多
Beany flavor induced by three lipoxygenases(LOXs, including LOX1, LOX2, and LOX3)restricts human consumption of soybean. It is desirable to generate lipoxygenase-free new mutant lines to improve the eating quality of ...Beany flavor induced by three lipoxygenases(LOXs, including LOX1, LOX2, and LOX3)restricts human consumption of soybean. It is desirable to generate lipoxygenase-free new mutant lines to improve the eating quality of soybean oil and protein products. In this study, a pooled clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPRassociated protein 9(Cas9) strategy targeting three GmLox genes(GmLox1, GmLox2, and GmLox3) was applied and 60 T_0 positive transgenic plants were generated, carrying combinations of sg RNAs and mutations. Among them, GmLox-28 and GmLox-60 were gmlox1 gmlox2 gmlox3 triple mutants and GmLox-40 was a gmlox1 gmlox2 double mutant.Sequencing of T_1 mutant plants derived from GmLox-28, GmLox-60, and GmLox-40 showed that mutation in the GmLox gene was inherited by the next generation. Colorimetric assay revealed that plants carrying different combinations of mutations lost the corresponding lipoxygenase activities. Transgene-free mutants were obtained by screening the T_2 generation of lipoxygenase-free mutant lines(GmLox-28 and GmLox-60). These transgeneand lipoxygenase-free mutants could be used for soybean beany flavor reduction without restriction by regulatory frameworks governing transgenic organisms.展开更多
AIM:To explore the potential risk factors related to gastrointestinal cancer in northern China.METHODS:A total of 3314 cases of gastrointestinal cancer(esophageal,gastric,pancreatic and biliary) and 2223 controls(incl...AIM:To explore the potential risk factors related to gastrointestinal cancer in northern China.METHODS:A total of 3314 cases of gastrointestinal cancer(esophageal,gastric,pancreatic and biliary) and 2223 controls(including healthy individuals,glioma and thyroid cancer) were analyzed by case-control study.Multivariable logistic regression analysis was applied to evaluate the association between different cancers and hepatitis B surface antigen,sex,age,blood type,diabetes,or family history of cancer.RESULTS:Type 2 diabetes was significantly associated with gastric,biliary and pancreatic cancer with an OR of 2.0-3.0.Blood type B was significantly associated with esophageal cancer [odd ratio(OR) = 1.53,95% confidence interval(CI) = 1.10-2.14] and biliary cancer(OR = 1.49,95% CI = 1.09-2.05).The prevalence of type 2 diabetes was significantly higher in gastric,biliary and pancreatic cancers compared with other groups,with ORs ranging between 2.0 and 3.0.Family history of cancer was strongly associated with gastrointestinal compared with other cancers.CONCLUSION:Blood type B individuals are susceptible to esophageal and biliary cancer.Type 2 diabetes is significantly associated with gastric,biliary and especially pancreatic cancer.展开更多
Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygos...Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.展开更多
Tea plants(Camellia sinensis)are commercially cultivated in>60 countries,and their fresh leaves are processed into tea,which is the most widely consumed beverage in the world.Although several chromosome-level tea p...Tea plants(Camellia sinensis)are commercially cultivated in>60 countries,and their fresh leaves are processed into tea,which is the most widely consumed beverage in the world.Although several chromosome-level tea plant genomes have been published,they collapsed the two haplotypes and ignored a large number of allelic variations that may underlie important biological functions in this species.Here,we present a phased chromosome-scale assembly for an elite oolong tea cultivar,"Huangdan",that is well known for its high levels of aroma.Based on the two sets of haplotype genome data,we identi fi ed numerous genetic variations and a substantial proportion of allelic imbalance related to important traits,including aroma-and stress-related alleles.Comparative genomics revealed extensive structural variations as well as expansion of some gene families,such as terpene synthases(TPSs),that likely contribute to the high-aroma characteristics of the backbone parent,underlying the molecular basis for the biosynthesis of aroma-related chemicals in oolong tea.Our results uncovered the genetic basis of special features of this oolong tea cultivar,providing fundamental genomic resources to study evolution and domestication for the economically important tea crop.展开更多
The southward expansion of East Asian farmers profoundly influenced the social evolution of Southeast Asia by introducing cereal agriculture.However,the timing and routes of cereal expansion in key regions are unclear...The southward expansion of East Asian farmers profoundly influenced the social evolution of Southeast Asia by introducing cereal agriculture.However,the timing and routes of cereal expansion in key regions are unclear due to limited empirical evidence.Here we report macrofossil,microfossil,multiple isotopic(C/N/Sr/O)and paleoproteomic data directly from radiocarbon-dated human samples,which were unearthed from a site in Xingyi in central Yunnan and which date between 7000 and 3300 a BP.Dietary isotopes reveal the earliest arrival of millet ca.4900 a BP,and greater reliance on plant and animal agriculture was indicated between 3800 and 3300 a BP.The dietary differences between hunter-gatherer and agricultural groups are also evident in the metabolic and immune system proteins analysed from their skeletal remains.The results of paleoproteomic analysis indicate that humans had divergent biological adaptations,with and without farming.The combined application of isotopes,archaeobotanical data and proteomics provides a new approach to documenting dietary and health changes across major subsistence transitions.展开更多
The ripening of papaya is a physiological and metabolic process associated with accumulation of carotenoids,alternation of flesh color and flavor,which depending on genotype and external factors such as light and horm...The ripening of papaya is a physiological and metabolic process associated with accumulation of carotenoids,alternation of flesh color and flavor,which depending on genotype and external factors such as light and hormone.Transcription factors regulating carotenoid biosynthesis have not been analyzed during papaya fruit ripening.RNA-Seq experiments were implemented using different ripening stages of papaya fruit from two papaya varieties.Cis-elements in lycopeneβ-cyclase genes(CpCYC-B and CpLCY-B)were identified,and followed by genome-wide analysis to identify transcription factors binding to these cis-elements,resulting in the identification of CpbHLH1 and CpbHLH2,two bHLH genes.The expressions of CpbHLH1/2 were changed during fruit development,coupled with transcript increase of carotenoid biosynthesis-related genes including CpCYC-B,CpLCY-B,CpPDS2,CpZDS,CpLCY-E,and CpCHY-B.Yeast onehybrid(Y1H)and transient expression assay revealed that CpbHLH1/2 could bind to the promoters of CpCYC-B and CpLCY-B,and regulate their transcriptions.In response to strong light,the results of elevated expression of carotenoid biosynthesis-related genes and the changed expression of CpbHLH1/2 indicated that CpbHLH1/2 were involved in light-mediated mechanisms of regulating critical genes in the carotenoid biosynthesis pathway.Collectively,our findings demonstrated several TF family members participating in the regulation of carotenoid genes and proved that CpbHLH1 and CpbHLH2 individually regulated the transcription of lycopeneβ-cyclase genes(CpCYC-B and CpLCY-B).This study yielded novel findings on regulatory mechanism of carotenoid biosynthesis during papaya fruit ripening.展开更多
Mechanistic target of rapamycin （mTOR） complex 1 （mTORC1） integrates signals from growth factors, cel- lular energy levels, stress and amino acids to control cell growth and proliferation through regulating trans-...Mechanistic target of rapamycin （mTOR） complex 1 （mTORC1） integrates signals from growth factors, cel- lular energy levels, stress and amino acids to control cell growth and proliferation through regulating trans- lation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 A resolution. The mTORCI comprises a dimer of heterotrimer （mTOR-Raptor-mLST8） mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase- like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for sub- strate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance forsubstrate entry to the catalytic cavity of mTORCI. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regu- latory mechanism of mTORC1 pathway.展开更多
Epithelial–mesenchymal transition(EMT) is a complex nonlinear biological process that plays essential roles in fundamental biological processes such as embryogenesis, wounding healing, tissue regeneration,and cancer ...Epithelial–mesenchymal transition(EMT) is a complex nonlinear biological process that plays essential roles in fundamental biological processes such as embryogenesis, wounding healing, tissue regeneration,and cancer metastasis. A hallmark of EMT is the switch-like behavior during state transition, which is characteristic of phase transitions. Hence, detecting the tipping point just before mesenchymal state transition is critical for understanding molecular mechanism of EMT. Through dynamic network biomarkers(DNB) model, a DNB group with 37 genes was identified which can provide the early-warning signals of EMT. Particularly, we found that two DNB genes, i.e., SMAD7 and SERPINE1 promoted EMT by switching their regulatory network which was further validated by biological experiments. Survival analyses revealed that SMAD7 and SERPINE1 as DNB genes further acted as prognostic biomarkers for lung adenocarcinoma.展开更多
The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approa...The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.展开更多
Cell walls in plants,particularly forest trees,are the major carbon sink of the terrestrial ecosystem.Chemical and biosynthetic features of plant cell walls were revealed early on,focusing mostly on herbaceous model s...Cell walls in plants,particularly forest trees,are the major carbon sink of the terrestrial ecosystem.Chemical and biosynthetic features of plant cell walls were revealed early on,focusing mostly on herbaceous model species.Recent developments in genomics,transcriptomics,epigenomics,transgenesis,and associated analytical techniques are enabling novel insights into formation of woody cell walls.Here,we review multilevel regulation of cell wall biosynthesis in forest tree species.We highlight current approaches to engineering cell walls as potential feedstock for materials and energy and survey reported field tests of such engineered transgenic trees.We outline opportunities and challenges in future research to better understand cell type biogenesis for more efficient wood cell wall modification and utilization for biomaterials or for enhanced carbon capture and storage.展开更多
Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently.Its leaves have been traditionally used to treat obesity and diabetes with the well-known a...Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently.Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B.Here,we presented three C.paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly.Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids.Resequencing analysis of 45 C.paliurus individuals uncovered two bottlenecks,consistent with the known events of environmental changes,and many selectively swept genes involved in critical biological functions,including plant defense and secondary metabolite biosynthesis.We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes,in particular gibberellinrelated genes,associated with the heterodichogamy in C.paliurus species.Our study sheds light on evolutionary history of C.paliurus and provides genomic resources to study the medicinal herbs.展开更多
This is a continuity of a series of taxonomic and phylogenetic papers on the fungi where materials were collected from many countries,examined and described.In addition to extensive morphological descriptions and appr...This is a continuity of a series of taxonomic and phylogenetic papers on the fungi where materials were collected from many countries,examined and described.In addition to extensive morphological descriptions and appropriate asexual and sexual connections,DNA sequence data are also analysed from concatenated datasets to infer phylogenetic relationships and substantiate systematic positions of taxa within appropriate ranks.Wherever new species or combinations are proposed,we apply an integrative approach using morphological and molecular data as well as ecological features wherever applicable.Notes on 112 fungal taxa are compiled in this paper including Biatriosporaceae and Roussoellaceae,Didysimulans gen.nov.,81 new species,18 new host records and new country records,five reference specimens,two new combinations,and three sexual and asexual morph reports.The new species are Amanita cornelii,A.emodotrygon,Angustimassarina alni,A.arezzoensis,A.italica,A.lonicerae,A.premilcurensis,Ascochyta italica,A.rosae,Austroboletus appendiculatus,Barriopsis thailandica,Berkleasmium ariense,Calophoma petasitis,Camarosporium laburnicola,C.moricola,C.grisea,C.ossea,C.paraincrustata,Colletotrichum sambucicola,Coprinopsis cerkezii,Cytospora gelida,Dacrymyces chiangraiensis,Didysimulans italica,D.mezzanensis,Entodesmium italica,Entoloma magnum,Evlachovaea indica,Exophiala italica,Favolus gracilisporus,Femsjonia monospora,Fomitopsis flabellata,F.roseoalba,Gongronella brasiliensis,Helvella crispoides,Hermatomyces chiangmaiensis,H.chromolaenae,Hysterium centramurum,Inflatispora caryotae,Inocybe brunneosquamulosa,I.luteobrunnea,I.rubrobrunnea,Keissleriella cirsii,Lepiota cylindrocystidia,L.flavocarpa,L.maerimensis,Lophiotrema guttulata,Marasmius luculentus,Morenoina calamicola,Moelleriella thanathonensis,Mucor stercorarius,Myrmecridium fluviae,Myrothecium septentrionale,Neosetophoma garethjonesii,Nigrograna cangshanensis,Nodulosphaeria guttulatum,N.multiseptata,N.sambuci,Panus subfasciatus,Paraleptosphaeria padi,Paraphaeosphaeri展开更多
Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neova...Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.展开更多
Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and...Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.展开更多
Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from th...Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from the canonical adaptor complex, AP-2, plant cells rely on the TPLATE complex （TPC） to execute CME （Gadeyne et al., 2014）. FT160100218, DP110100410）, the Ministry of Education, Culture, Sports, Science, and Technology of Japan （24114003, 15H04382, and 17K19412）, the European Research Council （ERC grant 682436）, the IRRTF-RNC （no. 501892） and a USA National Science Foundation CAREER Award.展开更多
This study elaborates on the design,fabrication,and data analysis details of SPEED,a recently proposed smartphonebased digital polymerase chain reaction(dPCR)device.The dPCR chips incorporate partition diameters rangi...This study elaborates on the design,fabrication,and data analysis details of SPEED,a recently proposed smartphonebased digital polymerase chain reaction(dPCR)device.The dPCR chips incorporate partition diameters ranging from 50μm to 5μm,and these partitions are organized into six distinct blocks to facilitate image processing.Due to the superior thermal conductivity of Si and its potential for mass production,the dPCR chips were fabricated on a Si substrate.A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time.The optical design employs four 470 nm light-emitting diodes as light sources,with filters and mirrors effectively managing the light emitted during PCR.An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format,partition identification,skew correction,and the generation of an image correction mask.We validated the device using a range of deoxyribonucleic acid targets,demonstrating its potential applicability across multiple fields.Therefore,we provide guidance and verification of the design and testing of the recently proposed SPEED device.展开更多
JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a ...JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a nearly complete genome assembly of JUJUNCAO and reveal that JUJUNCAO is an allopolyploid that originated2.7 million years ago(mya).Its genome consists of two subgenomes,and subgenome A shares high collinear synteny with pearl millet.We also investigated the genome evolution of JUJUNCAO and suggest that the ancestral karyotype of Cenchrus split into the A and B ancestral karyotypes of JUJUNCAO.Comparative transcriptome and DNA methylome analyses revealed functional divergence of homeologous gene pairs between the two subgenomes,which was a further indication of asymmetric DNA methylation.The three types of centromeric repeat in the JUJUNCAO genome(CEN137,CEN148,and CEN156)may have evolved independently within each subgenome,with some introgressions of CEN156 from the B to the A subgenome.We investigated the photosynthetic characteristics of JUJUNCAO,revealing its typical C4 Kranz anatomy and high photosynthetic efficiency.NADP-ME and PEPCK appear to cooperate in the major C4 decarboxylation reaction of JUJUNCAO,which is different from other C4 photosynthetic subtypes and may contribute to its high photosynthetic efficiency and biomass yield.Taken together,our results provide insights into the highly efficient photosynthetic mechanism of JUJUNCAO and provide a valuable reference genome for future genetic and evolutionary studies,as well as genetic improvement of Cenchrus grasses.展开更多
Although Activin/Nodal signaling regulates pluripotency of human embryonic stem （ES） cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells po...Although Activin/Nodal signaling regulates pluripotency of human embryonic stem （ES） cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells possess active Smad2-mediated Activin/Nodal signaling and found that Smad2-mediated Activin/Nodal signaling is dispensable for self-renewal maintenance but is required for proper differentiation toward the mesendoderm lineage. To gain insights into the underlying mechanisms, Smad2-associated genes were identified by genome-wide chromatin immu- noprecipitation-chip analysis. The results showed that there is a transcriptional correlation between Smad2 binding and Activin/Nodal signaling modulation, and that the development-related genes were enriched among the Smad2- bound targets. We further identified Tapbp as a key player in mesendoderm differentiation of mouse ES cells acting downstream of the Activin/Nodal-Smad2 pathway. Taken together, our findings suggest that Smad2-mediated Activin/Nodal signaling orchestrates mesendoderm lineage commitment of mouse ES cells through direct modulation of corresponding developmental regulator expression.展开更多
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+9 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA14
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金supported by the National Natural Science Foundation of China(31801898)the Natural Science Foundation of Fujian Province,China(Kjd18033A)+2 种基金open funds of the State Key Laboratory of Crop Genetics and Germplasm Enhancement(ZW201909)the State Key Laboratory of Tree Genetics and Breeding(TGB2018004)the Outstanding Youth Program of Fujian Agriculture and Forestry University.
文摘Horticultural plants play various and critical roles for humans by providing fruits,vegetables,materials for beverages,and herbal medicines and by acting as ornamentals.They have also shaped human art,culture,and environments and thereby have influenced the lifestyles of humans.With the advent of sequencing technologies,there has been a dramatic increase in the number of sequenced genomes of horticultural plant species in the past decade.The genomes of horticultural plants are highly diverse and complex,often with a high degree of heterozygosity and a high ploidy due to their long and complex history of evolution and domestication.Here we summarize the advances in the genome sequencing of horticultural plants,the reconstruction of pan-genomes,and the development of horticultural genome databases.We also discuss past,present,and future studies related to genome sequencing,data storage,data quality,data sharing,and data visualization to provide practical guidance for genomic studies of horticultural plants.Finally,we propose a horticultural plant genome project as well as the roadmap and technical details toward three goals of the project.
基金supported by funds from the National Key Research and Development Program of China(2016YFD0100700)to Y.G。
文摘Beany flavor induced by three lipoxygenases(LOXs, including LOX1, LOX2, and LOX3)restricts human consumption of soybean. It is desirable to generate lipoxygenase-free new mutant lines to improve the eating quality of soybean oil and protein products. In this study, a pooled clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPRassociated protein 9(Cas9) strategy targeting three GmLox genes(GmLox1, GmLox2, and GmLox3) was applied and 60 T_0 positive transgenic plants were generated, carrying combinations of sg RNAs and mutations. Among them, GmLox-28 and GmLox-60 were gmlox1 gmlox2 gmlox3 triple mutants and GmLox-40 was a gmlox1 gmlox2 double mutant.Sequencing of T_1 mutant plants derived from GmLox-28, GmLox-60, and GmLox-40 showed that mutation in the GmLox gene was inherited by the next generation. Colorimetric assay revealed that plants carrying different combinations of mutations lost the corresponding lipoxygenase activities. Transgene-free mutants were obtained by screening the T_2 generation of lipoxygenase-free mutant lines(GmLox-28 and GmLox-60). These transgeneand lipoxygenase-free mutants could be used for soybean beany flavor reduction without restriction by regulatory frameworks governing transgenic organisms.
基金Supported by The National Basic Research Program,973 Pro-gram No. 2010CB912802 and No. 2006CB910700the China National Science Foundation,No. 81071953,No. 30890033 and No. 30620120433+1 种基金the Chinese Academy of Sciences No.KSCX1-YW-R-40the 44 Postdoctoral Fund of China,No.20080441314
文摘AIM:To explore the potential risk factors related to gastrointestinal cancer in northern China.METHODS:A total of 3314 cases of gastrointestinal cancer(esophageal,gastric,pancreatic and biliary) and 2223 controls(including healthy individuals,glioma and thyroid cancer) were analyzed by case-control study.Multivariable logistic regression analysis was applied to evaluate the association between different cancers and hepatitis B surface antigen,sex,age,blood type,diabetes,or family history of cancer.RESULTS:Type 2 diabetes was significantly associated with gastric,biliary and pancreatic cancer with an OR of 2.0-3.0.Blood type B was significantly associated with esophageal cancer [odd ratio(OR) = 1.53,95% confidence interval(CI) = 1.10-2.14] and biliary cancer(OR = 1.49,95% CI = 1.09-2.05).The prevalence of type 2 diabetes was significantly higher in gastric,biliary and pancreatic cancers compared with other groups,with ORs ranging between 2.0 and 3.0.Family history of cancer was strongly associated with gastrointestinal compared with other cancers.CONCLUSION:Blood type B individuals are susceptible to esophageal and biliary cancer.Type 2 diabetes is significantly associated with gastric,biliary and especially pancreatic cancer.
基金supported by the National Key Research and Development Program of China(grant no.2019YFD1000500)the 2020 Research Program of Sanya Yazhou Bay Science and Technology City(grant no.SKJC-2020-02-002)+2 种基金the Central Public-Interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences(grant nos.1630012019009,1630052016005,1630052016006,1630052017021,and 1630052019023)the Central Public-Interest Scientific Institution Basal Research Fund for Innovative Research Team Program of CATAS(grant nos.17CXTD-28 and 1630052017017)the ear-marked fund for Modern Agro-industry Technology Research System(grant no.nycytx-11).
文摘Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.
基金This research was funded by the Fujian Province"2011 Collaborative Innovation Center",the Chinese Oolong Tea Industry Innovation Center special project(J 2015-75)the National Natural Science Foundation of China(31701874)+3 种基金the Major Special Project of Scientific and Technological Innovation on Anxi Tea(AX2021001)the Earmarked Fund for the China Agriculture Research System(CARS-19)the Scientific Research Foundation of the Graduate School of Fujian Agriculture and Forestry University(324-1122yb060)the Scientific Research Foundation of Horticulture College of Fujian Agriculture and Forestry University(2018B02).
文摘Tea plants(Camellia sinensis)are commercially cultivated in>60 countries,and their fresh leaves are processed into tea,which is the most widely consumed beverage in the world.Although several chromosome-level tea plant genomes have been published,they collapsed the two haplotypes and ignored a large number of allelic variations that may underlie important biological functions in this species.Here,we present a phased chromosome-scale assembly for an elite oolong tea cultivar,"Huangdan",that is well known for its high levels of aroma.Based on the two sets of haplotype genome data,we identi fi ed numerous genetic variations and a substantial proportion of allelic imbalance related to important traits,including aroma-and stress-related alleles.Comparative genomics revealed extensive structural variations as well as expansion of some gene families,such as terpene synthases(TPSs),that likely contribute to the high-aroma characteristics of the backbone parent,underlying the molecular basis for the biosynthesis of aroma-related chemicals in oolong tea.Our results uncovered the genetic basis of special features of this oolong tea cultivar,providing fundamental genomic resources to study evolution and domestication for the economically important tea crop.
基金the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0601)the Priority Research Program of the Chinese Academy of Sciences(XDA2004010101)+6 种基金the National Natural Science Foundation of China(42271160,32060208,31801040,and 32270667)the Major Project of National Social Science Foundation of China(21&ZD285and 20&ZD248)the National Key Research&Development Program of China(2020YFE0202200)Westlake Education FoundationNanqiang Outstanding Young Talents Program of Xiamen University(X2123302)the European Research Council Grant(ERC-2019-ADG-883700-TRAM)the Academician and Expert Workstation of Yunnan Province(202305AF150183)。
文摘The southward expansion of East Asian farmers profoundly influenced the social evolution of Southeast Asia by introducing cereal agriculture.However,the timing and routes of cereal expansion in key regions are unclear due to limited empirical evidence.Here we report macrofossil,microfossil,multiple isotopic(C/N/Sr/O)and paleoproteomic data directly from radiocarbon-dated human samples,which were unearthed from a site in Xingyi in central Yunnan and which date between 7000 and 3300 a BP.Dietary isotopes reveal the earliest arrival of millet ca.4900 a BP,and greater reliance on plant and animal agriculture was indicated between 3800 and 3300 a BP.The dietary differences between hunter-gatherer and agricultural groups are also evident in the metabolic and immune system proteins analysed from their skeletal remains.The results of paleoproteomic analysis indicate that humans had divergent biological adaptations,with and without farming.The combined application of isotopes,archaeobotanical data and proteomics provides a new approach to documenting dietary and health changes across major subsistence transitions.
基金supported by the grant 2015N20002-1 from the Department of Science and Technology of Fujian Province,US National Science Foundation(NSF)Plant Genome Research Program Award DBI-1546890the National Natural Science Foundation of China(Grant No.31701889).
文摘The ripening of papaya is a physiological and metabolic process associated with accumulation of carotenoids,alternation of flesh color and flavor,which depending on genotype and external factors such as light and hormone.Transcription factors regulating carotenoid biosynthesis have not been analyzed during papaya fruit ripening.RNA-Seq experiments were implemented using different ripening stages of papaya fruit from two papaya varieties.Cis-elements in lycopeneβ-cyclase genes(CpCYC-B and CpLCY-B)were identified,and followed by genome-wide analysis to identify transcription factors binding to these cis-elements,resulting in the identification of CpbHLH1 and CpbHLH2,two bHLH genes.The expressions of CpbHLH1/2 were changed during fruit development,coupled with transcript increase of carotenoid biosynthesis-related genes including CpCYC-B,CpLCY-B,CpPDS2,CpZDS,CpLCY-E,and CpCHY-B.Yeast onehybrid(Y1H)and transient expression assay revealed that CpbHLH1/2 could bind to the promoters of CpCYC-B and CpLCY-B,and regulate their transcriptions.In response to strong light,the results of elevated expression of carotenoid biosynthesis-related genes and the changed expression of CpbHLH1/2 indicated that CpbHLH1/2 were involved in light-mediated mechanisms of regulating critical genes in the carotenoid biosynthesis pathway.Collectively,our findings demonstrated several TF family members participating in the regulation of carotenoid genes and proved that CpbHLH1 and CpbHLH2 individually regulated the transcription of lycopeneβ-cyclase genes(CpCYC-B and CpLCY-B).This study yielded novel findings on regulatory mechanism of carotenoid biosynthesis during papaya fruit ripening.
基金We thank staff members Biomedical Core Facility, Fudan University and National Center for Protein Science Shanghai for their help on Mass Spectrometry analyses. We thank the Tsinghua Cryo-EM Facility and High Performance Computation Facility of National Center for Protein Science Beijing for their support in cryo-EM data collection and processing. This work was supported by Grants from the National Natural Science Foundation of China （Grant Nos. U1432242, 31425008, 91419301）, Basic Research Project of Shanghai Science and Technology Commission （No. 12JC1402700）, the Program of Shanghai Subject Chief Scientist （,No. 14XD1400500）.
文摘Mechanistic target of rapamycin （mTOR） complex 1 （mTORC1） integrates signals from growth factors, cel- lular energy levels, stress and amino acids to control cell growth and proliferation through regulating trans- lation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 A resolution. The mTORCI comprises a dimer of heterotrimer （mTOR-Raptor-mLST8） mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase- like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for sub- strate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance forsubstrate entry to the catalytic cavity of mTORCI. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regu- latory mechanism of mTORC1 pathway.
基金supported by the National Key Research and Development Program of China (2017YFA0505500)the National Natural Science Foundation of China (31930022, 31771476, 61773196)+5 种基金Shanghai Municipal Science and Technology Major Project (2017SHZDZX01)Key Project of Zhangjiang National Innovation Demonstration Zone Special Development Fund (ZJ2018ZD-013)Ministry of Science and Technology Project (2017YFC0907505)Guangdong Provincial Key Laboratory Funds (2017B030301018, 2019B030301001)Shenzhen Research Funds (JCYJ20170307104535585, ZDSYS20140509142721429)Shenzhen Peacock Plan (KQTD2016053117035204)
文摘Epithelial–mesenchymal transition(EMT) is a complex nonlinear biological process that plays essential roles in fundamental biological processes such as embryogenesis, wounding healing, tissue regeneration,and cancer metastasis. A hallmark of EMT is the switch-like behavior during state transition, which is characteristic of phase transitions. Hence, detecting the tipping point just before mesenchymal state transition is critical for understanding molecular mechanism of EMT. Through dynamic network biomarkers(DNB) model, a DNB group with 37 genes was identified which can provide the early-warning signals of EMT. Particularly, we found that two DNB genes, i.e., SMAD7 and SERPINE1 promoted EMT by switching their regulatory network which was further validated by biological experiments. Survival analyses revealed that SMAD7 and SERPINE1 as DNB genes further acted as prognostic biomarkers for lung adenocarcinoma.
文摘The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.
基金supported by the National Key Research and Development Program of China(2021YFD2200700)the Fundamental Research Funds for the Central Universities of China(grant 2572022DQ01)+6 种基金the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)the 111 Project(B16010)supported by the Young Scholar Fellowship Columbus Program from the Ministry of Science and Technology of Taiwan,China(111-2311-B-002-021)the National Science and Technology Council(112-2636-B-006-006)MEXT KAKENHI(JP18H05484,JP18H05489)the Research Foundation Flanders for proving the predoctoral fellowship.D.M.O.is indebted to the Research Foundation Flanders(FWO,grant 1246123N)for a postdoctoral fellowshipsupported by the Energy Transition Fund projects AdLibio and AdvBio,the interuniversity iBOF project NextBioRef,and the FWO project G011620N。
文摘Cell walls in plants,particularly forest trees,are the major carbon sink of the terrestrial ecosystem.Chemical and biosynthetic features of plant cell walls were revealed early on,focusing mostly on herbaceous model species.Recent developments in genomics,transcriptomics,epigenomics,transgenesis,and associated analytical techniques are enabling novel insights into formation of woody cell walls.Here,we review multilevel regulation of cell wall biosynthesis in forest tree species.We highlight current approaches to engineering cell walls as potential feedstock for materials and energy and survey reported field tests of such engineered transgenic trees.We outline opportunities and challenges in future research to better understand cell type biogenesis for more efficient wood cell wall modification and utilization for biomaterials or for enhanced carbon capture and storage.
基金funded by the National Natural Science Foundation of China(Grant Nos.31971642,32271859,32071750,31470637,and 32222019)This work was also supported by the Key R&D Program of Jiangsu Province(Grant No.BE2019388)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China.
文摘Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently.Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B.Here,we presented three C.paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly.Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids.Resequencing analysis of 45 C.paliurus individuals uncovered two bottlenecks,consistent with the known events of environmental changes,and many selectively swept genes involved in critical biological functions,including plant defense and secondary metabolite biosynthesis.We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes,in particular gibberellinrelated genes,associated with the heterodichogamy in C.paliurus species.Our study sheds light on evolutionary history of C.paliurus and provides genomic resources to study the medicinal herbs.
基金Saowaluck Tibpromma would like to thank the Molecular Biology Experimental Center at Kunming Institute of Botany for facilities for molecular work,the Mushroom Research Foundation(MRF)Chiang Rai,Thailand for the financial support of her study and Shaun Pennycook is thanked for nomenclatural advice.K.D.Hyde would like to thank the Thailand Research Fund Grant No.RSA5980068 entitled“Biodiversity,phylogeny and role of fungal endophytes on above parts of Rhizophora apiculata and Nypa fruticans”+6 种基金the Chinese Academy of Sciences,Project Number 2013T2S0030for the award of Visiting Professorship for Senior International Scientists at Kunming Institute of Botany and National Research Council of Thailand(Mae Fah Luang University)for a grants“Biodiversity,phylogeny and role of fungal endophytes of Pandanaceae”(Grant No.:592010200112)“Diseases of mangrove trees and maintenance of good forestry practice”(Grant No.:60201000201)for supporting this study.S.C.Karunarathna,P.E.Mortimer and J.C.Xu would like to thank the World Agroforestry Centre,East and Central Asia OfficeKey Laboratory for Plant Diversity and Biogeography of East Asia,Kunming Institute of Botany,Chinese Academy of Sciencethe ChineseMinistry of Science and Technology,under the 12th 5-year National Key Technology Support Program(NKTSP)2013 BAB07B06 integration and comprehensive demonstration of key technologies on Green Phosphate-mountaion Construction and the CGIAR Research Program 6:Forest,Trees and Agroforestry for partial funding.The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research group NO(RG-1436-025)Financial support by the German Academic Exchange Service(DAAD)and the Thai Royal Golden Ph.D.Jubilee-Industry program(RGJ)for a joint TRFDAAD PPP(2012-2014)academic exchange grant to K.D.Hyde and M.Stadler,and the RGJ for a personal grant to B.Thongbai(No.Ph.D/0138/2553 in 4.S.MF/53/A.3)is gratefully acknowledged.Chayanard Phukhamsakda(PHD/0020/25
文摘This is a continuity of a series of taxonomic and phylogenetic papers on the fungi where materials were collected from many countries,examined and described.In addition to extensive morphological descriptions and appropriate asexual and sexual connections,DNA sequence data are also analysed from concatenated datasets to infer phylogenetic relationships and substantiate systematic positions of taxa within appropriate ranks.Wherever new species or combinations are proposed,we apply an integrative approach using morphological and molecular data as well as ecological features wherever applicable.Notes on 112 fungal taxa are compiled in this paper including Biatriosporaceae and Roussoellaceae,Didysimulans gen.nov.,81 new species,18 new host records and new country records,five reference specimens,two new combinations,and three sexual and asexual morph reports.The new species are Amanita cornelii,A.emodotrygon,Angustimassarina alni,A.arezzoensis,A.italica,A.lonicerae,A.premilcurensis,Ascochyta italica,A.rosae,Austroboletus appendiculatus,Barriopsis thailandica,Berkleasmium ariense,Calophoma petasitis,Camarosporium laburnicola,C.moricola,C.grisea,C.ossea,C.paraincrustata,Colletotrichum sambucicola,Coprinopsis cerkezii,Cytospora gelida,Dacrymyces chiangraiensis,Didysimulans italica,D.mezzanensis,Entodesmium italica,Entoloma magnum,Evlachovaea indica,Exophiala italica,Favolus gracilisporus,Femsjonia monospora,Fomitopsis flabellata,F.roseoalba,Gongronella brasiliensis,Helvella crispoides,Hermatomyces chiangmaiensis,H.chromolaenae,Hysterium centramurum,Inflatispora caryotae,Inocybe brunneosquamulosa,I.luteobrunnea,I.rubrobrunnea,Keissleriella cirsii,Lepiota cylindrocystidia,L.flavocarpa,L.maerimensis,Lophiotrema guttulata,Marasmius luculentus,Morenoina calamicola,Moelleriella thanathonensis,Mucor stercorarius,Myrmecridium fluviae,Myrothecium septentrionale,Neosetophoma garethjonesii,Nigrograna cangshanensis,Nodulosphaeria guttulatum,N.multiseptata,N.sambuci,Panus subfasciatus,Paraleptosphaeria padi,Paraphaeosphaeri
基金the National Natural Science Foundation of China(Nos.81891002,81971178,32200806)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16040701)+2 种基金the Youth Innovation Promotion Association CAS(No.2021319)the Natural Science Foundation of Jiangsu Province(No.BK20210127)the High-level Innovation and Entrepreneurship Talent Introduction Plan of Jiangsu Province.We acknowledge the CapitalBio Technology Inc.(Beijing,China)for RNA sequencing and proteomic sequencing.Schematic in Fig.2A and 6C were created with BioRender.com and were granted publication permission.We acknowledge a kind gift of PEGDA from Prof.Y.Du(Tsinghua University,Beijing,China)and help from PhD candiate WJ.Li in his lab on schematic preparation.
文摘Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.
基金Y.Yin including the National Natural Science Foundation of China(82030081 and 81874235)the National Key Research and Development Program of China(2021YFA1300601)the Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project(JCYJ20220818102811024).
文摘Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.
基金This work was supported by the Max-Planck Gesellschaft, the Deutsche Forschungsgemeinschaft, the National Natural Science Foundation of China （grants 31530051）, the Swiss Federal Institute of Technology of Zurich （ETH-Z）, the Swiss National Foundation （SNF 2-77212-15）, the University of Melbourne, the Australian Research Council （CE1101007,
文摘Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from the canonical adaptor complex, AP-2, plant cells rely on the TPLATE complex （TPC） to execute CME （Gadeyne et al., 2014）. FT160100218, DP110100410）, the Ministry of Education, Culture, Sports, Science, and Technology of Japan （24114003, 15H04382, and 17K19412）, the European Research Council （ERC grant 682436）, the IRRTF-RNC （no. 501892） and a USA National Science Foundation CAREER Award.
基金support from grant no.52150710541 provided by the National Natural Science Foundation of P.R.Chinagrant no.2018YFE0109000 provided by the Ministry of Science and Technology of the P.R.China+6 种基金H.Z.was supported by grant no.62301412 from the Natural Science Foundation of Chinagrant no.2023-JCQN-0130 from the Natural Science Basic Research Program of Shaanxi Province,P.R.Chinagrant no.2023M732815 from the P.R.China Postdoctoral Science Foundationgrant no.2023BSHEDZZ18 from the Postdoctoral Science Foundation of Shaanxi provinceM.K.was supported by grant no.LTACH19005 from the Ministry of Education,YouthSports of the Czech Republic and grant no.RVO-VFN 64165 from the Ministry of Health of the Czech RepublicMinistry of Health,Czech Republic-conceptual development of research organization 00064165,General University Hospital in Prague.
文摘This study elaborates on the design,fabrication,and data analysis details of SPEED,a recently proposed smartphonebased digital polymerase chain reaction(dPCR)device.The dPCR chips incorporate partition diameters ranging from 50μm to 5μm,and these partitions are organized into six distinct blocks to facilitate image processing.Due to the superior thermal conductivity of Si and its potential for mass production,the dPCR chips were fabricated on a Si substrate.A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time.The optical design employs four 470 nm light-emitting diodes as light sources,with filters and mirrors effectively managing the light emitted during PCR.An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format,partition identification,skew correction,and the generation of an image correction mask.We validated the device using a range of deoxyribonucleic acid targets,demonstrating its potential applicability across multiple fields.Therefore,we provide guidance and verification of the design and testing of the recently proposed SPEED device.
基金supported by grants from the Major Special Project of Fujian Province(2021NZ029009)the Natural Science foundation of Fujian Province(2019J01665).
文摘JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a nearly complete genome assembly of JUJUNCAO and reveal that JUJUNCAO is an allopolyploid that originated2.7 million years ago(mya).Its genome consists of two subgenomes,and subgenome A shares high collinear synteny with pearl millet.We also investigated the genome evolution of JUJUNCAO and suggest that the ancestral karyotype of Cenchrus split into the A and B ancestral karyotypes of JUJUNCAO.Comparative transcriptome and DNA methylome analyses revealed functional divergence of homeologous gene pairs between the two subgenomes,which was a further indication of asymmetric DNA methylation.The three types of centromeric repeat in the JUJUNCAO genome(CEN137,CEN148,and CEN156)may have evolved independently within each subgenome,with some introgressions of CEN156 from the B to the A subgenome.We investigated the photosynthetic characteristics of JUJUNCAO,revealing its typical C4 Kranz anatomy and high photosynthetic efficiency.NADP-ME and PEPCK appear to cooperate in the major C4 decarboxylation reaction of JUJUNCAO,which is different from other C4 photosynthetic subtypes and may contribute to its high photosynthetic efficiency and biomass yield.Taken together,our results provide insights into the highly efficient photosynthetic mechanism of JUJUNCAO and provide a valuable reference genome for future genetic and evolutionary studies,as well as genetic improvement of Cenchrus grasses.
基金Acknowledgments We thank Gaoyang Zhu for technical assistance. This work was supported by grants from the National Natural Science Foundation of China （30930050, 30921004）, the 973 Program （2006CB943401, 2010CB833706） to YGC, and grants from the China National Science Foundation （Grant # 30890033, 30588001 and 30620120433）, Chinese Ministry of Science and Technology（Grant # 2006CB910700） to JDH.
文摘Although Activin/Nodal signaling regulates pluripotency of human embryonic stem （ES） cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells possess active Smad2-mediated Activin/Nodal signaling and found that Smad2-mediated Activin/Nodal signaling is dispensable for self-renewal maintenance but is required for proper differentiation toward the mesendoderm lineage. To gain insights into the underlying mechanisms, Smad2-associated genes were identified by genome-wide chromatin immu- noprecipitation-chip analysis. The results showed that there is a transcriptional correlation between Smad2 binding and Activin/Nodal signaling modulation, and that the development-related genes were enriched among the Smad2- bound targets. We further identified Tapbp as a key player in mesendoderm differentiation of mouse ES cells acting downstream of the Activin/Nodal-Smad2 pathway. Taken together, our findings suggest that Smad2-mediated Activin/Nodal signaling orchestrates mesendoderm lineage commitment of mouse ES cells through direct modulation of corresponding developmental regulator expression.
