Myotonic dystrophy type 1 (DM1),or Steiner’s disease,is an autosomal dominant disorder caused by the expansion of unstable trinucleotide repeats (CTG) in the 3’ untranslated region of the myotonic dystrophy protein ...Myotonic dystrophy type 1 (DM1),or Steiner’s disease,is an autosomal dominant disorder caused by the expansion of unstable trinucleotide repeats (CTG) in the 3’ untranslated region of the myotonic dystrophy protein kinase gene (DMPK) (Brook et al.,1992;Mahadevan et al.,1992).The number of CTG repeats observed in normal individuals is in a range of 5-34,while the individuals with 35-49 CTG repeats are usually asymptomatic but at risk of展开更多
This paper presents a feasible method for rapid detection of the interphase nuclei of uncultured amniocytes for chromosomes 18 by using our modified primed in situ labeling (PRINS) technique. A total of 262 independen...This paper presents a feasible method for rapid detection of the interphase nuclei of uncultured amniocytes for chromosomes 18 by using our modified primed in situ labeling (PRINS) technique. A total of 262 independent, uncultured amniotic fluid samples were analysed in a blind fashion before the karyotype was available. In addition, 62 samples were examined by fluorescence in situ hybridization (FISH) for comparison. In more than 95% of the samples PRINS reactions with primer 18cen were successfully induced. Two samples were properly identified and correctly scored as trisomic 18. PRINS reaction could be performed automatically in less than one hour with a programmable thermocycler. Our studies showed that the PRINS technique is simple, rapid and cost effective. It is as sensitive and specific as FISH; can enhance the accuracy of standard cytogenetic analysis; and allows identification of chromosomes 18 aneuploidies in uncultured amniocytes in significantly less time.展开更多
Subtelomeric rearrangements contribute to idiopathic mental retardation （MR）, but most children with idiopathic MR do not show any chromosome abnormalities with standard cytogenetic analysis. The primed in situ labe...Subtelomeric rearrangements contribute to idiopathic mental retardation （MR）, but most children with idiopathic MR do not show any chromosome abnormalities with standard cytogenetic analysis. The primed in situ labeling （PRINS） technique, using an oligonucleotide primer complementary to the telemetric repeat sequences （TTAGGG）, can identify chromosome telomeric abnormality （deletion） in idiopathic MR children. In this study, seventy children with idiopathic MR were enrolled and subjected to PR1NS. The results showed normal karyotype in all the children, subtelomeric rearrangements （lq del and 4q del） in 2 cases, which was confirmed by fluorescence in situ hybridization （FISH）. It was concluded that PRINS is effective for the detection of subtelomeric rearrangements and may become a routine technique for cytogenetical abnormality screening.展开更多
In response to preharvest priming with exogenous methyl jasmonate(MeJA),tea plants adjust their physiological behavior at the molecular level.The whole-organism reconfiguration of aroma formation from the precursor to...In response to preharvest priming with exogenous methyl jasmonate(MeJA),tea plants adjust their physiological behavior at the molecular level.The whole-organism reconfiguration of aroma formation from the precursor to storage is poorly understood.In this study,we performed iTRAQ proteomic analysis and identified 337,246,and 413 differentially expressed proteins in tea leaves primed with MeJA for 12 h,24h,and 48 h,respectively.Furthermore,a total of 266 nonvolatile and 100 volatile differential metabolites were identified by utilizing MS-based metabolomics.A novel approach that incorporated the integration of extended self-organizing map-based dimensionality was applied.The vivid time-scale changes tracing physiological responses in MeJA-primed tea leaves are marked in these maps.Jasmonates responded quickly to the activation of the jasmonic acid pathway in tea leaves,while hydroxyl and glycosyl jasmonates were biosynthesized simultaneously on a massive scale to compensate for the exhausted defense.The levels ofα-linolenic acid,geranyl diphosphate,farnesyl diphosphate,geranylgeranyl diphosphate,and phenylalanine,which are crucial aroma precursors,were found to be significantly changed in MeJA-primed tea leaves.Green leaf volatiles,volatile terpenoids,and volatile phenylpropanoids/benzenoids were spontaneously biosynthesized from responding precursors and subsequently converted to their corresponding glycosidic forms,which can be stably stored in tea leaves.This study elucidated the physiological response of tea leaves primed with exogenous methyl jasmonate and revealed the molecular basis of source and sink changes on tea aroma biosynthesis and catabolism in response to exogenous stimuli.The results significantly enhance our comprehensive understanding of tea plant responses to exogenous treatment and will lead to the development of promising biotechnologies to improve fresh tea leaf quality.展开更多
Both the primed in situ(PRINS)and the peptide nucleic acid-fluorescence in situ hybridization(PNA-FISH) techniques constitute alternatives to the conventional(fluorescence in situ hybridization,FISH)procedure for chro...Both the primed in situ(PRINS)and the peptide nucleic acid-fluorescence in situ hybridization(PNA-FISH) techniques constitute alternatives to the conventional(fluorescence in situ hybridization,FISH)procedure for chro- mosomal investigations.The PRINS reaction is based on the use of a DNA polymerase and labeled nucleotide in an in situ primer extension reaction.Peptide nucleic acid probes are synthetic DNA analogs with uncharged polyamide backbones.The two procedures present several advantages(specificity,rapidity and discriminating ability)that make them very attractive for cytogenetic purposes.Their adaptation to human spermatozoa has allowed the development of new and fast procedures for the chromosomal screening of male gametes and has provided efficient complements to FISH for in situ assessment of aneuploidy in male gametes.(Asian J Androl 2006 Jul;8:387-392)展开更多
Peltophorum dubium seeds were set to imbibe with four treatments, soaked with solution Captan 0.2% under 10and 27℃,PEG 6000 -1.0 MPa under 10 and 27℃. For each treatment there were four replicates with 40 seeds incu...Peltophorum dubium seeds were set to imbibe with four treatments, soaked with solution Captan 0.2% under 10and 27℃,PEG 6000 -1.0 MPa under 10 and 27℃. For each treatment there were four replicates with 40 seeds incubated in 9-cm Petri dishes with double filter paper moistened with testing solution. The imbibition curves showed that the final weight increase were from 70% to 150% in the treatments when imbibition entered a lag phase. Seeds were tested for effects on germination of five treatments: control group (nonprimed), primed with PEG6000 -1.0 MPa at 10 and 27℃, primed with Captan 0.2% at 10 and 27℃. For each treatment, there were three sub-treatments: seeds were soaked in distilled water for 12, 24 and 36h before the energy test. Germination percentages of nonprimed seeds and primed in PEG 27℃ soaked in distilled water during 12 h were the highest, reaching 100%. The lowest germination percentage occurred primed seeds with PEG6000 27℃ and soaked in distilled water during 36 h, which was only 52%. Germination mean time of primed seeds in PEG at 10℃, soaked 24 h was 1.08 days, mean time of primed seeds in PEG at 27℃ soaked 12 h was 2.42 days. Accelerated ageing results showed low or no germination after ageing 72 h. Control group had a higher germination percentage and seeds were more resistant to deterioration than those in primed groups, both in Petri dish (27℃) and vermiculate (room temperature).展开更多
A Streptomyces cameroonensis based bioformulation (SCaB) has been developed and shown to be stable and effective in controlling the early proliferation of P. megakarya and promoting the growth of cocoa seedlings in nu...A Streptomyces cameroonensis based bioformulation (SCaB) has been developed and shown to be stable and effective in controlling the early proliferation of P. megakarya and promoting the growth of cocoa seedlings in nursery. This study was carried out to explore the molecular mechanisms associated with the interaction of SCaB, cocoa seedlings, and the pathogen during the early stages of seedling growth in the nursery. For this purpose, seedling treatment with 10% W/W SCaB under greenhouse conditions evaluated SCaB’s capacity to stimulate the defense mechanisms in cocoa. Agronomic growth parameters and the level of induction of defense-associated compounds were analyzed. Real-time (rt) PCR was used to assess the level of expression of defense genes. Here, we showed that the application of SCaB as a seedling treatment enhanced the growth of cocoa seedlings in the nursery by an average of 15.6% after 30 days of growth and led to an average reduction in disease severity of 64% when challenged with P. megakarya. The latter led to an increased synthesis of total phenolic compounds, flavonoids, chitinases, peroxidases, and β-1,3-glucanases and an induced up-regulation of TcChiB, TcGlu-1, TcPer-1, and TcMYBPA genes. This research provides a basis for the optimization of beneficial microorganisms as a viable alternative to chemical fungicides used in disease suppression.展开更多
Human primed pluripotent stem cells are capable of generating all the embryonic lineages.However,their extraembryonic trophectoderm potentials are limited.It remains unclear how to expand their developmental potential...Human primed pluripotent stem cells are capable of generating all the embryonic lineages.However,their extraembryonic trophectoderm potentials are limited.It remains unclear how to expand their developmental potential to trophectoderm lineages.Here we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic potential.These chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast lineages.Transcriptomic and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent cells.Mechanistic exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage potential.Our findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.展开更多
N6-methyladenosine(m^(6)A)plays crucial roles in development and cellular reprogramming.During embryonic development,pluripotency transitions from a naïve to a primed state,and modeling the reverse primed-to-na&#...N6-methyladenosine(m^(6)A)plays crucial roles in development and cellular reprogramming.During embryonic development,pluripotency transitions from a naïve to a primed state,and modeling the reverse primed-to-naïve transition(PNT)provides a valuable framework for investigating pluripotency regulation.Here,we show that inhibiting METTL3 significantly promotes PNT in an m^(6)A-dependent manner.Mechanistically,we found that suppressing METTL3 and YTHDF2 prolongs the lifetimes of pluripotency-associated mRNAs,such as Nanog and Sox2,during PNT.In addition,Gstp1 was identified as a downstream target of METTL3 inhibition and YTHDF2 knockout.Gstp1 overexpression enhances PNT,whereas its inhibition impedes the transition.Overall,our findings suggest that YTHDF2 facilitates the removal of pluripotency gene transcripts and Gstp1,thereby promoting PNT reprogramming through m^(6)A-mediated posttranscriptional control.展开更多
Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and...Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naive to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naive–primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naive–primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naive versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naive–primed state conversion of ES cells, which is partially mediated by a Lin28a–let-7–Dnmt3a/b–Dppa3 axis.展开更多
In this paper, transient phenomenon during start up process of a pump fed liquidrocket engine is investigated through numerical simulation. The engine studied in this workis designed such that engine systems are not w...In this paper, transient phenomenon during start up process of a pump fed liquidrocket engine is investigated through numerical simulation. The engine studied in this workis designed such that engine systems are not wetted with propellant until the engine is com-manded to start. This is achieved by positioning the valves for propellant admission at the inter-face of test stand/flight stage and the engine. To evaluate engine performance during starttransient for such systems, unsteady flow simulation was conducted using Method of Charac-teristics and equations for priming. The same has been reported in this work. The results indi-cated a brief period of abrupt pressure rise at pump upstream after opening of the propellantadmission valves, during the process of priming of engine systems at valve downstream.The peak pressure obtained was significantly higher than the propellant tank pressure as wellas the steady state pump suction pressure. The transitory pressure rise was found to occurdue to flow resistance at impeller inlet caused by formation of a forced vortex for orientingthe flow through impeller blades during off design transient regime. The maximum pressureat pump upstream, as computed from start transient simulation, was used as a design inputfor pump inlet feed lines. The engine was realized and subsequently qualified in a ground test facility. Hot test data obtained for pressure and flow rate during transient regime were found tobe in good agreement with the simulation results.展开更多
It is imperative that India and China regain past civilizational glory by showing sensitivity to each other's concerns and reaching goals through cooperation.
Frequent drought events severely restrict global crop productivity,especially those occurring in the reproductive stages.Moderate drought priming during the earlier growth stages is a promising strategy for allowing p...Frequent drought events severely restrict global crop productivity,especially those occurring in the reproductive stages.Moderate drought priming during the earlier growth stages is a promising strategy for allowing plants to resist recurrent severe drought stress.However,the underlying mechanisms remain unclear.Here,we subjected wheat plants to drought priming during the vegetative growth stage and to severe drought stress at 10 days after anthesis.We then collected leaf samples at the ends of the drought priming and recovery periods,and at the end of drought stress for transcriptome sequencing in combination with phenotypic and physiological analyses.The drought-primed wheat plants maintained a lower plant temperature,with higher stomatal openness and photosynthesis,thereby resulting in much lower 1,000-grain weight and grain yield losses under the later drought stress than the non-primed plants.Interestingly,416 genes,including 27 transcription factors(e.g.,MYB,NAC,HSF),seemed to be closely related to the improved drought tolerance as indicated by the dynamic transcriptome analysis.Moreover,the candidate genes showed six temporal expression patterns and were significantly enriched in several stress response related pathways,such as plant hormone signal transduction,starch and sucrose metabolism,arginine and proline metabolism,inositol phosphate metabolism,and wax synthesis.These findings provide new insights into the physiological and molecular mechanisms of the long-term effects of early drought priming that can effectively improve drought tolerance in wheat,and may provide potential approaches for addressing the challenges of increasing abiotic stresses and securing food safety under global warming scenarios.展开更多
Suppose thatλ_(1),λ_(2),λ_(3),λ_(4),λ_(5)are nonzero real numbers,not all of the same sign,andλ_(1)/λ_(2)is irrational and algebraic.Let V be a well-spaced sequence,δ>0.In this paper,it is proved that,for ...Suppose thatλ_(1),λ_(2),λ_(3),λ_(4),λ_(5)are nonzero real numbers,not all of the same sign,andλ_(1)/λ_(2)is irrational and algebraic.Let V be a well-spaced sequence,δ>0.In this paper,it is proved that,for anyε>0,the number of v∈V with v≤N such that the following inequality|λ_(1)p_(1)~2+λ_(2)p_(2)~2+λ_(3)p_(3)~4+λ_(4)p_(4)~4+λ_5p_5~4-v|<v^(-δ)has no solution in prime variables p_(1),p_(2),p_(3),p_(4),p_(5)does not exceed O(N^(29/32+2δ+ε)).展开更多
Let a_(1),a_(2),a_(3)be nonzero integers with gcd(a_(1),a_(2),a_(3))=1,and let k be any positive integer,K=max[3,|a_(1)|,|a_(2)|,|a_(3)|,k].Suppose that l_(1),l_(2),l_(3)are integers each coprime to k.Suppose further ...Let a_(1),a_(2),a_(3)be nonzero integers with gcd(a_(1),a_(2),a_(3))=1,and let k be any positive integer,K=max[3,|a_(1)|,|a_(2)|,|a_(3)|,k].Suppose that l_(1),l_(2),l_(3)are integers each coprime to k.Suppose further that b is any integer satisfying some necessary congruent conditions.The solvability of linear equation a_(1)p_(1)+a_(2)p_(2)+a_(3)p_(3)=b(p_(j)=l_(j)(mod k),1≤j≤3)with prime variables pi,p_(2),ps is investigated.It is proved that if ai,a_(2),a_(3)are all positive,then the above equation is solvable whenever b≥K^(25);if a,a_(2),a_(3)are not all of the same sign,then the above equation has a solution p_(1),p_(2),p_(3)satisfying max(p_(1),p_(2),p_(3))≤3|b|+K^(25).展开更多
基金supported by the National Basic Research Program of China(2010CB529601 and 2013CB945404)to B.L.Wuthe Fudan Young Teacher Funding to Y.An,the higher Education Research Project of Gansu Province(2015B-094)to X.LanShanghai Children’s Hospital Funding(2016YMS001)to X.Lan
文摘Myotonic dystrophy type 1 (DM1),or Steiner’s disease,is an autosomal dominant disorder caused by the expansion of unstable trinucleotide repeats (CTG) in the 3’ untranslated region of the myotonic dystrophy protein kinase gene (DMPK) (Brook et al.,1992;Mahadevan et al.,1992).The number of CTG repeats observed in normal individuals is in a range of 5-34,while the individuals with 35-49 CTG repeats are usually asymptomatic but at risk of
文摘This paper presents a feasible method for rapid detection of the interphase nuclei of uncultured amniocytes for chromosomes 18 by using our modified primed in situ labeling (PRINS) technique. A total of 262 independent, uncultured amniotic fluid samples were analysed in a blind fashion before the karyotype was available. In addition, 62 samples were examined by fluorescence in situ hybridization (FISH) for comparison. In more than 95% of the samples PRINS reactions with primer 18cen were successfully induced. Two samples were properly identified and correctly scored as trisomic 18. PRINS reaction could be performed automatically in less than one hour with a programmable thermocycler. Our studies showed that the PRINS technique is simple, rapid and cost effective. It is as sensitive and specific as FISH; can enhance the accuracy of standard cytogenetic analysis; and allows identification of chromosomes 18 aneuploidies in uncultured amniocytes in significantly less time.
文摘Subtelomeric rearrangements contribute to idiopathic mental retardation （MR）, but most children with idiopathic MR do not show any chromosome abnormalities with standard cytogenetic analysis. The primed in situ labeling （PRINS） technique, using an oligonucleotide primer complementary to the telemetric repeat sequences （TTAGGG）, can identify chromosome telomeric abnormality （deletion） in idiopathic MR children. In this study, seventy children with idiopathic MR were enrolled and subjected to PR1NS. The results showed normal karyotype in all the children, subtelomeric rearrangements （lq del and 4q del） in 2 cases, which was confirmed by fluorescence in situ hybridization （FISH）. It was concluded that PRINS is effective for the detection of subtelomeric rearrangements and may become a routine technique for cytogenetical abnormality screening.
基金the National Natural Science Foundation of China(31270734)the earmarked fund for China Agricultural Research System(CARS-19)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2014-TRICAAS).
文摘In response to preharvest priming with exogenous methyl jasmonate(MeJA),tea plants adjust their physiological behavior at the molecular level.The whole-organism reconfiguration of aroma formation from the precursor to storage is poorly understood.In this study,we performed iTRAQ proteomic analysis and identified 337,246,and 413 differentially expressed proteins in tea leaves primed with MeJA for 12 h,24h,and 48 h,respectively.Furthermore,a total of 266 nonvolatile and 100 volatile differential metabolites were identified by utilizing MS-based metabolomics.A novel approach that incorporated the integration of extended self-organizing map-based dimensionality was applied.The vivid time-scale changes tracing physiological responses in MeJA-primed tea leaves are marked in these maps.Jasmonates responded quickly to the activation of the jasmonic acid pathway in tea leaves,while hydroxyl and glycosyl jasmonates were biosynthesized simultaneously on a massive scale to compensate for the exhausted defense.The levels ofα-linolenic acid,geranyl diphosphate,farnesyl diphosphate,geranylgeranyl diphosphate,and phenylalanine,which are crucial aroma precursors,were found to be significantly changed in MeJA-primed tea leaves.Green leaf volatiles,volatile terpenoids,and volatile phenylpropanoids/benzenoids were spontaneously biosynthesized from responding precursors and subsequently converted to their corresponding glycosidic forms,which can be stably stored in tea leaves.This study elucidated the physiological response of tea leaves primed with exogenous methyl jasmonate and revealed the molecular basis of source and sink changes on tea aroma biosynthesis and catabolism in response to exogenous stimuli.The results significantly enhance our comprehensive understanding of tea plant responses to exogenous treatment and will lead to the development of promising biotechnologies to improve fresh tea leaf quality.
文摘Both the primed in situ(PRINS)and the peptide nucleic acid-fluorescence in situ hybridization(PNA-FISH) techniques constitute alternatives to the conventional(fluorescence in situ hybridization,FISH)procedure for chro- mosomal investigations.The PRINS reaction is based on the use of a DNA polymerase and labeled nucleotide in an in situ primer extension reaction.Peptide nucleic acid probes are synthetic DNA analogs with uncharged polyamide backbones.The two procedures present several advantages(specificity,rapidity and discriminating ability)that make them very attractive for cytogenetic purposes.Their adaptation to human spermatozoa has allowed the development of new and fast procedures for the chromosomal screening of male gametes and has provided efficient complements to FISH for in situ assessment of aneuploidy in male gametes.(Asian J Androl 2006 Jul;8:387-392)
基金This work is supported by CAPES, Brazil. Open research laboratory of forest plant ecology, Northeast Forestry University and The State's tenth five-year "211 Project"-supported key academic discipline program of ECNU
文摘Peltophorum dubium seeds were set to imbibe with four treatments, soaked with solution Captan 0.2% under 10and 27℃,PEG 6000 -1.0 MPa under 10 and 27℃. For each treatment there were four replicates with 40 seeds incubated in 9-cm Petri dishes with double filter paper moistened with testing solution. The imbibition curves showed that the final weight increase were from 70% to 150% in the treatments when imbibition entered a lag phase. Seeds were tested for effects on germination of five treatments: control group (nonprimed), primed with PEG6000 -1.0 MPa at 10 and 27℃, primed with Captan 0.2% at 10 and 27℃. For each treatment, there were three sub-treatments: seeds were soaked in distilled water for 12, 24 and 36h before the energy test. Germination percentages of nonprimed seeds and primed in PEG 27℃ soaked in distilled water during 12 h were the highest, reaching 100%. The lowest germination percentage occurred primed seeds with PEG6000 27℃ and soaked in distilled water during 36 h, which was only 52%. Germination mean time of primed seeds in PEG at 10℃, soaked 24 h was 1.08 days, mean time of primed seeds in PEG at 27℃ soaked 12 h was 2.42 days. Accelerated ageing results showed low or no germination after ageing 72 h. Control group had a higher germination percentage and seeds were more resistant to deterioration than those in primed groups, both in Petri dish (27℃) and vermiculate (room temperature).
文摘A Streptomyces cameroonensis based bioformulation (SCaB) has been developed and shown to be stable and effective in controlling the early proliferation of P. megakarya and promoting the growth of cocoa seedlings in nursery. This study was carried out to explore the molecular mechanisms associated with the interaction of SCaB, cocoa seedlings, and the pathogen during the early stages of seedling growth in the nursery. For this purpose, seedling treatment with 10% W/W SCaB under greenhouse conditions evaluated SCaB’s capacity to stimulate the defense mechanisms in cocoa. Agronomic growth parameters and the level of induction of defense-associated compounds were analyzed. Real-time (rt) PCR was used to assess the level of expression of defense genes. Here, we showed that the application of SCaB as a seedling treatment enhanced the growth of cocoa seedlings in the nursery by an average of 15.6% after 30 days of growth and led to an average reduction in disease severity of 64% when challenged with P. megakarya. The latter led to an increased synthesis of total phenolic compounds, flavonoids, chitinases, peroxidases, and β-1,3-glucanases and an induced up-regulation of TcChiB, TcGlu-1, TcPer-1, and TcMYBPA genes. This research provides a basis for the optimization of beneficial microorganisms as a viable alternative to chemical fungicides used in disease suppression.
基金supported by the National Key Research and Development Program of China(2021YFA1100300)the National Natural Science Foundation of China(32288102,32370843 and 32025006)Part of the data analysis was performed on the High Performance Computing Platform of the Center for Life Sciences,Peking University。
文摘Human primed pluripotent stem cells are capable of generating all the embryonic lineages.However,their extraembryonic trophectoderm potentials are limited.It remains unclear how to expand their developmental potential to trophectoderm lineages.Here we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic potential.These chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast lineages.Transcriptomic and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent cells.Mechanistic exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage potential.Our findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.
基金supported by the National Key R&D Program of China(2021YFA1102200,2024YFA1802300 and 2024YFA1107000)The National Natural Science Foundation of China(32225012)+4 种基金Major Project of Guangzhou National Laboratory(GZNL2023A02005)Guangdong Basic and Applied Basic Research Foundation(2025A1515012426,2023A1515010420)Science and Technology Projects in Guangzhou(2023A04J0724)Science and Technology Planning Project of Guangdong Province,China(2023B1212060050,2023B1212120009)Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong SAR,P.R.China.
文摘N6-methyladenosine(m^(6)A)plays crucial roles in development and cellular reprogramming.During embryonic development,pluripotency transitions from a naïve to a primed state,and modeling the reverse primed-to-naïve transition(PNT)provides a valuable framework for investigating pluripotency regulation.Here,we show that inhibiting METTL3 significantly promotes PNT in an m^(6)A-dependent manner.Mechanistically,we found that suppressing METTL3 and YTHDF2 prolongs the lifetimes of pluripotency-associated mRNAs,such as Nanog and Sox2,during PNT.In addition,Gstp1 was identified as a downstream target of METTL3 inhibition and YTHDF2 knockout.Gstp1 overexpression enhances PNT,whereas its inhibition impedes the transition.Overall,our findings suggest that YTHDF2 facilitates the removal of pluripotency gene transcripts and Gstp1,thereby promoting PNT reprogramming through m^(6)A-mediated posttranscriptional control.
基金the National Natural Science Foundation of China (31771636, 81671734, and 81501528)National Key R&D Plan (2017YFA0103201 and 2011DAV00088)+2 种基金Tianjin Natural Science Foundation (18JCYBJC24400)CAMS Initiative for Innovative Medicine (CAMS-12M 2016-12M-1-017)Program for Changjiang Scholars and Innovative Research Team in University (IRT13023).
文摘Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naive to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naive–primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naive–primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naive versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naive–primed state conversion of ES cells, which is partially mediated by a Lin28a–let-7–Dnmt3a/b–Dppa3 axis.
文摘In this paper, transient phenomenon during start up process of a pump fed liquidrocket engine is investigated through numerical simulation. The engine studied in this workis designed such that engine systems are not wetted with propellant until the engine is com-manded to start. This is achieved by positioning the valves for propellant admission at the inter-face of test stand/flight stage and the engine. To evaluate engine performance during starttransient for such systems, unsteady flow simulation was conducted using Method of Charac-teristics and equations for priming. The same has been reported in this work. The results indi-cated a brief period of abrupt pressure rise at pump upstream after opening of the propellantadmission valves, during the process of priming of engine systems at valve downstream.The peak pressure obtained was significantly higher than the propellant tank pressure as wellas the steady state pump suction pressure. The transitory pressure rise was found to occurdue to flow resistance at impeller inlet caused by formation of a forced vortex for orientingthe flow through impeller blades during off design transient regime. The maximum pressureat pump upstream, as computed from start transient simulation, was used as a design inputfor pump inlet feed lines. The engine was realized and subsequently qualified in a ground test facility. Hot test data obtained for pressure and flow rate during transient regime were found tobe in good agreement with the simulation results.
文摘It is imperative that India and China regain past civilizational glory by showing sensitivity to each other's concerns and reaching goals through cooperation.
基金supported by the projects of the National Key Research and Development Program of China(2023YFD2300202)the Natural Science Foundation of Jiangsu Province,China(BK20241543)+5 种基金the National Natural Science Foundation of China(32272213,32030076,U1803235,and 32021004)the Fundamental Research Funds for the Central Universities,China(XUEKEN2023013)the Jiangsu Innovation Support Program for International Science and Technology Cooperation Project,China(BZ2023049)the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(22)1006)the China Agriculture Research System(CARS-03)the Jiangsu Collaborative Innovation Center for Modern Crop Production,China(JCIC-MCP)。
文摘Frequent drought events severely restrict global crop productivity,especially those occurring in the reproductive stages.Moderate drought priming during the earlier growth stages is a promising strategy for allowing plants to resist recurrent severe drought stress.However,the underlying mechanisms remain unclear.Here,we subjected wheat plants to drought priming during the vegetative growth stage and to severe drought stress at 10 days after anthesis.We then collected leaf samples at the ends of the drought priming and recovery periods,and at the end of drought stress for transcriptome sequencing in combination with phenotypic and physiological analyses.The drought-primed wheat plants maintained a lower plant temperature,with higher stomatal openness and photosynthesis,thereby resulting in much lower 1,000-grain weight and grain yield losses under the later drought stress than the non-primed plants.Interestingly,416 genes,including 27 transcription factors(e.g.,MYB,NAC,HSF),seemed to be closely related to the improved drought tolerance as indicated by the dynamic transcriptome analysis.Moreover,the candidate genes showed six temporal expression patterns and were significantly enriched in several stress response related pathways,such as plant hormone signal transduction,starch and sucrose metabolism,arginine and proline metabolism,inositol phosphate metabolism,and wax synthesis.These findings provide new insights into the physiological and molecular mechanisms of the long-term effects of early drought priming that can effectively improve drought tolerance in wheat,and may provide potential approaches for addressing the challenges of increasing abiotic stresses and securing food safety under global warming scenarios.
基金Supported by NSFC(Nos.12301006,12471009,12071238,11901566,12001047,11971476)Beijing Natural Science Foundation(No.1242003)。
文摘Suppose thatλ_(1),λ_(2),λ_(3),λ_(4),λ_(5)are nonzero real numbers,not all of the same sign,andλ_(1)/λ_(2)is irrational and algebraic.Let V be a well-spaced sequence,δ>0.In this paper,it is proved that,for anyε>0,the number of v∈V with v≤N such that the following inequality|λ_(1)p_(1)~2+λ_(2)p_(2)~2+λ_(3)p_(3)~4+λ_(4)p_(4)~4+λ_5p_5~4-v|<v^(-δ)has no solution in prime variables p_(1),p_(2),p_(3),p_(4),p_(5)does not exceed O(N^(29/32+2δ+ε)).
文摘Let a_(1),a_(2),a_(3)be nonzero integers with gcd(a_(1),a_(2),a_(3))=1,and let k be any positive integer,K=max[3,|a_(1)|,|a_(2)|,|a_(3)|,k].Suppose that l_(1),l_(2),l_(3)are integers each coprime to k.Suppose further that b is any integer satisfying some necessary congruent conditions.The solvability of linear equation a_(1)p_(1)+a_(2)p_(2)+a_(3)p_(3)=b(p_(j)=l_(j)(mod k),1≤j≤3)with prime variables pi,p_(2),ps is investigated.It is proved that if ai,a_(2),a_(3)are all positive,then the above equation is solvable whenever b≥K^(25);if a,a_(2),a_(3)are not all of the same sign,then the above equation has a solution p_(1),p_(2),p_(3)satisfying max(p_(1),p_(2),p_(3))≤3|b|+K^(25).
