Powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that seriously threatens wheat yield and quality.To control this disease,host resistance is the most effective measure.Compared wit...Powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that seriously threatens wheat yield and quality.To control this disease,host resistance is the most effective measure.Compared with the resistance genes from common wheat,alien resistance genes can better withstand infection of this highly variable pathogen.Development of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat breeding.In this study,three wheat-rye germplasm lines YT4-1,YT4-2,and YT4-3 were developed through hybridization between octoploid triticale and common wheat,out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance(APR)to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth stages.Using genomic in situ hybridization,multi-color fluorescence in situ hybridization,multi-color GISH,and molecular marker analysis,YT4-1,YT4-2,and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS.1BL translocation line,6RL ditelosomic addition and T1RS.1BL translocation line,and T1RS.1BL translocation line,respectively.Compared with previously reported wheat-rye derivative lines carrying chromosome 6R,YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic traits.Therefore,these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.展开更多
Total spikelet number per spike(TSS)is a crucial yield component in wheat.Dissecting and characterizing major stable quantitative trait loci(QTL)associated with TSS can significantly enhance the genetic improvement of...Total spikelet number per spike(TSS)is a crucial yield component in wheat.Dissecting and characterizing major stable quantitative trait loci(QTL)associated with TSS can significantly enhance the genetic improvement of yield potential.In a previous study,we identified a stable major QTL for TSS,named QTss.cas-3D.In the present study,we conducted fine mapping of QTss.cas-3D,interval to approximately 6.35 Mb,ranging from 105.03 to 111.38 Mb,based on the IWGSC RefSeq v2.1.Through genome resequencing and gene function annotation,we identified TraesCS3D03G0308000(TaFT-D2)as the candidate gene.Phenotypic evaluation with paired near-isogenic lines revealed that this locus predominantly increases kernel number per spike by enhancing TSS and fertile spikelet number per spike,without significantly affecting thousand-kernel weight or tiller number.The presence of the TaFT-D2 allele in the parent P3228,which is rare in nature populations,highlights its potential value.This study provides a valuable gene resource and functional marker for wheat molecular breeding aimed at improving TSS and establishes a foundation for gene functional analysis of TaFT-D2.展开更多
Introduction: Choriocarcinoma is an aggressive tumor, whose incidence is 0.18 per 100,000 women between the ages of 15 and 49 years [1]. Although its prognosis has improved with the development of chemotherapy regimen...Introduction: Choriocarcinoma is an aggressive tumor, whose incidence is 0.18 per 100,000 women between the ages of 15 and 49 years [1]. Although its prognosis has improved with the development of chemotherapy regimens, the mortality rate of patients with brain metastases is reportedly 29.7% [2]. After chemotherapy, most often, the reappearance of masses in pulmonary is considered to be a sign of relapse. Case presentation: The patient was a 32-year-old Asian Chinese female who delivered a dead male infant at 33 weeks gestation. The placenta appeared to be normal. The major presentation was a haemorrhage of the vagina. The patient received combined treatment with systematic multi-agent chemotherapy and whole-brain radiation therapy at the General Hospital of Hebei Province and achieved complete remission. Two years after remission, a chest CT scan revealed a mass in the right lung that had become larger over 6 months. The patient’s serum β-human chorionic gonadotropin (β-HCG) level was normal, and the tuberculosis infected T lymphocyte spot (T-SPOT.TB) tests were positive. The patient was started on anti-tuberculosis therapy, after which the size of her right lung mass decreased. Conclusion: Lung masses after choriocarcinoma require extensive laboratory and imaging exams to exclude recurrence. This case highlights the importance of differential diagnoses of lung masses in patients with choriocarcinomas. Imaging studies, β-HCG and local lesion resection should be employed to rule out choriocarcinoma recurrence.展开更多
Mix-dimensional van der Waals heterostructures(vdWHs)have inspired worldwide interests and efforts in the field of ad-vanced electronics and optoelectronics.The fundamental understanding of interfacial charge transfer...Mix-dimensional van der Waals heterostructures(vdWHs)have inspired worldwide interests and efforts in the field of ad-vanced electronics and optoelectronics.The fundamental understanding of interfacial charge transfer is of vital import-ance for guiding the design of functional optoelectronic applications.In this work,type-Ⅱ0D-2D CdSe/ZnS quantum dots/MoS_(2)vdWHs are designed to study the light-triggered interfacial charge behaviors and enhanced optoelectronic performances.From spectral measurements in both steady and transient states,the phenomena of suppressed photolu-minescence(PL)emissions,shifted Raman signals and changed PL lifetimes provide strong evidences of efficient charge transfer at the 0D-2D interface.A series of spectral evolutions of heterostructures with various QDs overlapping concentrations at different laser powers are analyzed in details,which clarifies the dynamic competition between exciton and trion during an efficient doping of 3.9×10^(13)cm^(−2).The enhanced photoresponses(1.57×10^(4)A·W^(-1))and detectivities(2.86×10^(11)Jones)in 0D/2D phototransistors further demonstrate that the light-induced charge transfer is still a feasible way to optimize the performance of optoelectronic devices.These results are expected to inspire the basic understand-ing of interfacial physics at 0D/2D interfaces,and shed the light on promoting the development of mixed-dimensional op-toelectronic devices in the near future.展开更多
As an important wild relative of wheat, Agropyron cristatum has been successfully used for wheat improvement. Currently, a few useful agronomic traits of A. cristatum, such as high grain number per spike and resistanc...As an important wild relative of wheat, Agropyron cristatum has been successfully used for wheat improvement. Currently, a few useful agronomic traits of A. cristatum, such as high grain number per spike and resistance to diseases, have been transferred into common wheat.However, the effective detection of small A. cristatum segmental introgressions in common wheat is still difficult. The objective of this study was to identify A. cristatum-specific single nucleotide polymorphisms(SNPs) for the detection of small alien segments in wheat. The transcriptome sequences of A. cristatum were aligned against wheat coding DNA sequences(CDS) for SNP calling. As a result, we discovered a total of 167,613 putative SNPs specific to the P genome of A. cristatum compared with the common wheat genomes. Among 230 selected SNPs with functional annotations related to inflorescence development and stress resistance,68 were validated as P genome-specific SNPs in multiple wheat backgrounds using Kompetitive Allele Specific PCR(KASP) assays. Among them, 55 SNPs were assigned to six homoeologous groups of the P genome using wheat-A. cristatum addition lines, and 6 P-specific SNP markers were further physically mapped on different segments of chromosome 6 P in 6 P translocation lines. The P genome-specific SNPs were also validated by Sanger sequencing and used to detect the P chromatin in wheat-A. cristatum cryptic introgression lines. Two SNP markers(Unigene20217-182 and Unigene20307-1420) were detected in two wheat-A. cristatum introgression lines that showed enhanced grain number per spike and high resistance to powdery mildew. Together, the developed P genome-specific SNP markers will accelerate the detection of large numbers of wheat-A. cristatum derivatives and will be helpful for marker-assisted transfer of desirable traits from A. cristatum into adapted wheat cultivars in wheat breeding programs.展开更多
Reef limestone is a biogenic sedimentary rock widely distributed in coral reef areas, acting as an important foundation for coast construction. Due to its special biogenic origin, reef limestone is different from conv...Reef limestone is a biogenic sedimentary rock widely distributed in coral reef areas, acting as an important foundation for coast construction. Due to its special biogenic origin, reef limestone is different from conventional rocks both in terms of rock structure and mechanical properties. In this study, mesoscale uniaxial compression experiments with five different loading directions were conducted on two kinds of reef limestones from the Maldives Islands and the South China Sea, respectively. The real-time high-resolution videos and images of failure processes were recorded simultaneously to investigate the fracture evolution and fracture surface roughness of reef limestones. It demonstrated that the reef limestones belonged to extremely soft to soft rocks, and their uniaxial compressive strength (UCS) values fluctuated with high discreteness. The mesoscale mechanical properties of reef limestones were highly anisotropic and mainly controlled by pore structure. The occurrence of dissolution pores in reef limestone tended to intensify mechanical anisotropy. With the integration of the fracture initiation and propagation features of reef limestones, it is supposed that the intrinsic mechanism of anisotropy was probably attributed to the differences in coral growth direction and dissolution. Furthermore, the quantified fracture surface roughness was revealed to have a good consistency with density and UCS for the reef limestones from the South China Sea. The findings are helpful for providing theoretical and experimental references for engineering construction in coral reef areas.展开更多
Long-term stability of large-span caverns is a challenging issue for design and construction of underground rock engineering.The Heidong cavern group consisting of 21 caverns was constructed about 1400 years ago for q...Long-term stability of large-span caverns is a challenging issue for design and construction of underground rock engineering.The Heidong cavern group consisting of 21 caverns was constructed about 1400 years ago for quarrying in massive Cretaceous tuff.The cavern No.5 of the Heidong cavern group is characterized by an unsupported span up to 92 m,with the overburden thickness of only 3-25 m.To analyze its long-term stability,a detailed investigation was conducted to obtain its geometry and rock mass characteristics,and to monitor surrounding rock displacements.Based on field survey and laboratory tests,numerical simulations were performed using the finite difference code FLAC;.The analysis results revealed that for the long-term stability of the cavern No.5,some major factors should be carefully considered,such as cavern excavation method in hard massive rocks,site investigation using trial pits,tools like short iron chisel and hammer for manual excavation,geometric dome roof,and waste rocks within abutment or on the floor.The highlights of the technologies obtained from this large-scale ancient underground project can provide reference for other similar project excavations in practice.展开更多
The diagnosis of the recurrent optic neuritis is commonly established clinically,and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional cont...The diagnosis of the recurrent optic neuritis is commonly established clinically,and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging(CE-T1W1).In this paper,we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging(CET2FLAIR).The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1W1.This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.展开更多
Agropyron cristatum(2n=4x=28,PPPP),which harbours many high-yield and disease-resistance genes,is a promising donor for wheat improvement.Narrow genetic diversity and the trade-off between grain weight and grain numbe...Agropyron cristatum(2n=4x=28,PPPP),which harbours many high-yield and disease-resistance genes,is a promising donor for wheat improvement.Narrow genetic diversity and the trade-off between grain weight and grain number have become bottlenecks for increasing grain yield in wheat.In this study,a novel translocation line,WAT650l,was derived from the chromosome 6P addition line 4844–12,which can simultaneously increase both grain number per spike(GNS)and thousand-grain weight(TGW).Cytological analysis and molecular marker analysis revealed that WAT650l was a 5BL.5BS-6PL(bin 12–17)translocation line.Assessment of agronomic traits and analysis of the BC4F2 and BC5F2 populations suggested that the 6PL terminal chromosome segment in WAT650l resulted in increased grain number per spike(average increased by 14.07 grains),thousand-grain weight(average increased by 4.31 g),flag leaf length,plant height,spikelet number per spike and kernel number per spikelet during the two growing seasons of 2020–2021 and 2021–2022.Additionally,the increased GNS locus and high-TGW locus of WAT650l were mapped to the bins 16–17 and 12–13,respectively,on chromosome 6PL by genetic population analysis of three translocation lines.In summary,we provide a valuable germplasm resource for broadening the genetic base of wheat and overcoming the negative relationship between GNS and TGW in wheat breeding.展开更多
Objective:The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target.We aimed to study whether NEDD8(neural precursor cell expressed,developmentall...Objective:The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target.We aimed to study whether NEDD8(neural precursor cell expressed,developmentally down-regulated 8)might serve as a therapeutic target in esophageal squamous cell carcinoma(ESCC).Methods:The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas(TCGA)database and tissue arrays.NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms.Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways.The cell cycle and apoptosis were assessed with fluorescence activated cell sorting.A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing in vivo.Results:NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC,and NEDD8 overexpression was associated with poorer overall patient survival(mRNA level:P=0.028,protein level:P=0.026,log-rank test).Downregulation of NEDD8 significantly suppressed tumor growth both in vitro and in vivo.Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest,DNA damage,and apoptosis in ESCC cells.Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases(CRLs)substrates through inactivation of CRLs,thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC.Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.Conclusions:Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown,and validated NEDD8 as a potential target for ESCC therapy.展开更多
Wide hybridization is a strategy for broadening the genetic basis of wheat. Because an efficient method for inducing wheat–alien chromosome translocations will allow producing useful germplasm, it is desirable to dis...Wide hybridization is a strategy for broadening the genetic basis of wheat. Because an efficient method for inducing wheat–alien chromosome translocations will allow producing useful germplasm, it is desirable to discover new genes that induce chromosomal variation. In this study, chromosome 5P from A.cristatum was shown to induce many types of chromosomal structural variation in a common wheat background, including nonhomoeologous chromosome translocations, as revealed by genomic in situ hybridization, fluorescence in situ hybridization, and DNA marker analysis. Aberrant meiosis was associated with chromosomal structural variation, and aberrant meiotic behavior was observed in wheat–A.cristatum 5P monosomic and disomic addition lines, suggesting that the effect of chromosome 5P was independent of the number of chromosome 5P copies. Chromosome 5P disturbed homologous chromosome pairing at pachytene stage in a common wheat background, resulting in a high frequency of univalent formation and reduced crossing over. Thirteen genes involved in DNA repair or chromatin remodeling, including RAD52-like and MSH6 genes, were differentially expressed(upregulated) in wheat–A. cristatum 5P addition lines according to transcriptome analysis, implicating chromosome 5P in the process of meiotic double-strand break repair. These findings provide a new, efficient tool for inducing wheat–alien chromosome translocations and producing new germplasm.展开更多
Lead halide perovskites have received tremendous attentions recently for their excellent properties such as high light absorption coefficient and long charge carrier diffusion length. However, the stability issues and...Lead halide perovskites have received tremendous attentions recently for their excellent properties such as high light absorption coefficient and long charge carrier diffusion length. However, the stability issues and the existence of toxic lead cations have largely limited their applications in optoelectronic area. Herein, we report the synthesis and investigation of highly stable and lead-free Cs3Bi2I9 perovskite nanoplates for visible light photodetection applications. The Cs3Bi2I9 nanoplates were synthesized through a facile solution-processed method, which is also applicable to various substrates. The achieved nanoplates present very good crystal quality and exhibit excellent long-term stability even exposed in moist air for several months. Photodetectors were constructed based on these high-quality perovskite nanoplates for the first time, and display a maximum photoresponsivity of 33.1 mA/W under the illumination of 450 nm laser, which is six times higher than the solution-synthesized CH3NH3PbI3 nanowire photodetectors. The specific detectivity of these devices can reach up to 10^10 Jones. Additionally, the devices exhibit fast rise and decay time of 10.2 and 37.2 ms, respectively, and highly stable photoswitching behavior with their photoresponse well retaining under alternating light and darkness. This work opens up a new opportunity for stable and low-toxic perovskite-based optoelectronic applications.展开更多
Optoelectronic synaptic elements are emerging functional devices for the vigorous development of advanced neuromorphic computing technology in the post-Moore era.However,optoelectronic devices based on transition meta...Optoelectronic synaptic elements are emerging functional devices for the vigorous development of advanced neuromorphic computing technology in the post-Moore era.However,optoelectronic devices based on transition metal dichalcogenides(TMDs)are limited to their poor mobilities and weak light-matter interactions,which still hardly exhibit superior device performances in the application of artificial synapses.Here,we demonstrate the successful fabrication of Au nanoparticle-coupled MoS_(2)heterostructures via chemical vapor deposition(CVD),where the light absorption of MoS_(2)is greatly enhanced and engineered by plasmonic effects.Hot electrons are excited from Au nanoparticles,and then injected into MoS_(2)semiconductors under the light illumination.The plasmonically-engineered photo-gating effect at the metal-semiconductor junction is demonstrated to create optoelectronic devices with excellent synaptic behaviors,especially in ultra-sensitive excitatory postsynaptic current(EPSC,9.6×10^(-3)nA@3.4 nW·cm^(-2)),ultralow energy consumption(34.7 pJ),long-state retention time(>1,000 s),and tunable synaptic plasticity transitions.The material system of Au-nanoparticles coupled TMDs presents unique advantages for building artificial synapses,which may lead the future development of neuromorphic electronics in optical information sensing and learning.展开更多
Barley is a diploid species with a genome smaller than those of other members of the Triticeae tribe,making it an attractive model for genetic studies in Triticeae crops.The recent development of barley genomics has c...Barley is a diploid species with a genome smaller than those of other members of the Triticeae tribe,making it an attractive model for genetic studies in Triticeae crops.The recent development of barley genomics has created a need for a high-throughput platform to identify genetically uniform mutants for gene function investigations.In this study,we report an ethyl methanesulfonate(EMS)-mutagenized population consisting of 8525M_(3) lines in the barley landrace“Hatiexi”(HTX),which we complement with a high-quality de novo assembly of a reference genome for this genotype.The mutation rate within the population ranged from 1.51 to 4.09 mutations per megabase,depending on the treatment dosage of EMS and the mutation discrimination platform used for genotype analysis.We implemented a three-dimensional DNA pooling strategy combined with multiplexed amplicon sequencing to create a highly efficient and cost-effective TILLING(targeting induced locus lesion in genomes)platform in barley.Mutations were successfully identified from 72 mixed amplicons within a DNA pool containing 64 individual mutants and from 56 mixed amplicons within a pool containing 144 individuals.We discovered abundant allelic mutants for dozens of genes,including the barley Green Revolution contributor gene Brassinosteroid insensitive 1(BRI1).As a proof of concept,we rapidly determined the causal gene responsible for a chlorotic mutant by following the MutMap strategy,demonstrating the value of this resource to support forward and reverse genetic studies in barley.展开更多
Tumor necrosis factor alpha-induced protein 1(TNFAIP1)modulates a plethora of important biological processes,including tumorigenesis and cancer cell migration.However,the regulatory mechanism of TNFAIP1 degradation re...Tumor necrosis factor alpha-induced protein 1(TNFAIP1)modulates a plethora of important biological processes,including tumorigenesis and cancer cell migration.However,the regulatory mechanism of TNFAIP1 degradation remains largely elusive.In the present study,with a label-free quantitative proteomic approach,TNFAIP1 was identified as a novel ubiquitin target of the Cullin-RING E3 ubiquitin ligase(CRL)complex.More importantly,Cul3-ROC1(CRL3),a subfamily of CRLs,was identified to specifically interact with TNFAIP1 and promote its polyubiquitination and degradation.Mechanistically,BTBD9,a specific adaptor component of CRL3 complex,was further defined to bind and promote the ubiquitination and degradation of TNFAIP1 in cells.As such,downregulation of BTBD9 promoted lung cancer cell migration by upregulating the expression of TNFAIP1,whereas TNFAIP1 deletion abrogated this effect.Finally,bioinformatics and clinical sample analyses revealed that BTBD9 was downregulated while TNFAIP1 was overexpressed in human lung cancer,which was associated with poor overall survival of patients.Taken together,these findings reveal a previously unrecognized mechanism by which the CRL3^(BTBD9) ubiquitin ligase controls TNFAIP1 degradation to regulate cancer cell migration.展开更多
Inorganic phosphate(Pi)availability is an important factor which affects the growth and yield of crops,thus an appropriate and effective response to Pi fluctuation is critical.However,how crops orchestrate Pi signalin...Inorganic phosphate(Pi)availability is an important factor which affects the growth and yield of crops,thus an appropriate and effective response to Pi fluctuation is critical.However,how crops orchestrate Pi signaling and growth under Pi starvation conditions to optimize the growth defense tradeoff remains unclear.Here we show that a Pi starvationinduced transcription factor NIGT1(NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1)controls plant growth and prevents a hyper-response to Pi starvation by directly repressing the expression of growth-related and Pisignaling genes to achieve a balance between growth and response under a varying Pi environment.NIGT1 directly binds to the promoters of Pi starvation signaling marker genes,like IPS1,mi R827,and SPX2,under Pi-deficient conditions to mitigate the Pi-starvation responsive(PSR).It also directly represses the expression of vacuolar Pi efflux transporter genes VPE1/2 to regulate plant Pi homeostasis.We further demonstrate that NIGT1 constrains shoot growth by repressing the expression of growth-related regulatory genes,including brassinolide signal transduction master regulator BZR1,cell division regulator CYCB1;1,and DNA replication regulator PSF3.Our findings reveal the function of NIGT1 in orchestrating plant growth and Pi starvation signaling,and also provide evidence that NIGT1 acts as a safeguard to avoid hyper-response during Pi starvation stress in rice.展开更多
Dear Editor,S phase kinase-associated protein 2(SKP2),a substrate recognition component of the SCFSKP2 ubiquitin ligase complex,plays an oncogenic role in tumorigenesis by targeting a variety of tumor suppressors(e.g....Dear Editor,S phase kinase-associated protein 2(SKP2),a substrate recognition component of the SCFSKP2 ubiquitin ligase complex,plays an oncogenic role in tumorigenesis by targeting a variety of tumor suppressors(e.g.,p21,p27,and p130)for ubiquitina-tion and subsequent degradation.1 As a well-characterized oncoprotein,the aberrant expression and dysregulation of SKP2 are frequently observed in different human cancers.Given its critical role in governing tumorigenesis and progression,SKP2 has emerged as a potential pharmacological target for anticancer therapy.展开更多
Peanut(Arachis hypogaea L.)is an important leguminous oil and economic crop that produces flowers aboveground and fruits belowground.Subterranean fruit-pod development,which significantly affects peanut production,inv...Peanut(Arachis hypogaea L.)is an important leguminous oil and economic crop that produces flowers aboveground and fruits belowground.Subterranean fruit-pod development,which significantly affects peanut production,involves complex molecular mechanisms that likely require the coordinated regulation of multiple genes in different tissues.To investigate the molecular mechanisms that underlie peanut fruitpod development,we characterized the anatomical features of early fruit-pod development and integrated single-nucleus RNA-sequencing(snRNA-seq)and single-nucleus assay for transposase-accessible chromatin with sequencing(snATAC-seq)data at the single-cell level.We identified distinct cell types,such as meristem,embryo,vascular tissue,cuticular layer,and stele cells within the shell wall.These specific cell types were used to examine potential molecular changes unique to each cell type during pivotal stages of fruit-pod development.snRNA-seq analyses of differentially expressed genes revealed cell-type-specific insights that were not previously obtainable from transcriptome analyses of bulk RNA.For instance,we identified MADS-box genes that contributes to the formation of parenchyma cells and gravity-related genes that are present in the vascular cells,indicating an essential role for the vascular cells in peg gravitropism.Overall,our single-nucleus analysis provides comprehensive and novel information on specific cell types,gene expression,and chromatin accessibility during the early stages of fruit-pod development.This information will enhance our understanding of the mechanisms that underlie fruit-pod development in peanut and contribute to efforts aimed at improving peanut production.展开更多
Dear Editor,Esophageal squamous cell carcinoma(ESCC)is the major histologic subtype of esophageal cancer with high incidence and mortality.1 However,few achievements have been made in the development of targeted drugs...Dear Editor,Esophageal squamous cell carcinoma(ESCC)is the major histologic subtype of esophageal cancer with high incidence and mortality.1 However,few achievements have been made in the development of targeted drugs.2 Neddylation,a reversible post-translational modification,attaches ubiquitin-like molecule NEDD8 to substrates in a three-step enzymatic reaction catalyzed by NEDD8-activating enzyme E1(NAE,NAE1 and UBA3 heterodimer),NEDD8-conjugating enzyme E2s(UBE2M/UBC12 or UBE2F)and substrate-specific NEDD8-E3 ligases.3 The best-characterized substrates of neddylation are cullin family proteins,the essential components of multiunit Cullin-RING ubiquitin ligases(CRLs).4 Currently,the inhibition of cullin neddylation by targeting overactivated neddylation pathway has emerged as an attractive approach for anticancer therapy.5,6 Our previous study reported that MLN4924,a specific inhibitor of NAE,significantly inhibited the tumor growth of ESCC by blocking cullin neddylation and inactivating CRLs activity.7 However,recent studies found that MLN4924 treatment-emergent NAE mutations would confer the drug resistance.8,9 Therefore,it is urgent to identify other neddylation enzymes(E2s or E3s)as alternative anticancer targets and develop novel anti-ESCC strategies.展开更多
Five complete caverns were discovered in Longyou in 1992.They were manually caved in argillaceous siltstone at shallow depths more than 2000 years ago.When they were un-watered,their integrity was maintained completel...Five complete caverns were discovered in Longyou in 1992.They were manually caved in argillaceous siltstone at shallow depths more than 2000 years ago.When they were un-watered,their integrity was maintained completely,and their interior rock surfaces were free of old cracks.Since then,however,the rock's interior faces have initiated and propagated more and more cracks.This paper attempts to address the question of why the rock interior faces were free of old cracks once they were unearthed.To address this question,this paper proposes a hypothesis that the argillaceous siltstone has the ability of self-healing its cracks over a short period of time under weak acid water environment.Data and evidence are presented herewith to prove the hypothesis.They include observations and measurements in the field and test results in the laboratory.Specifically,a three-point bending test is used to form a tensile crack in a rectangular rock specimen and a deadload test for the specimen immersed in initially weak acid water is used for self-healing its crack.The results have shown that the argillaceous siltstone is in a state of weak alkalinity and the rain water at the site is in a state of weak acidity.Therefore,when it is immersed in weak acid water for some time,the argillaceous siltstone would be able to make chemical reactions to generate new minerals such as calcite.The new minerals would be able to infill the cracks and then heal the crack within a few years.Once the crack is self-healed,the rock can regain its strength and integrity.Consequently,the rock interior surfaces could be free of old cracks when the water was pumped out of the caverns.展开更多
基金This research was supported by the National Key Research and Development Program of China(2021YFD1200600)the National Natural Science Foundation of China(32272105).
文摘Powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that seriously threatens wheat yield and quality.To control this disease,host resistance is the most effective measure.Compared with the resistance genes from common wheat,alien resistance genes can better withstand infection of this highly variable pathogen.Development of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat breeding.In this study,three wheat-rye germplasm lines YT4-1,YT4-2,and YT4-3 were developed through hybridization between octoploid triticale and common wheat,out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance(APR)to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth stages.Using genomic in situ hybridization,multi-color fluorescence in situ hybridization,multi-color GISH,and molecular marker analysis,YT4-1,YT4-2,and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS.1BL translocation line,6RL ditelosomic addition and T1RS.1BL translocation line,and T1RS.1BL translocation line,respectively.Compared with previously reported wheat-rye derivative lines carrying chromosome 6R,YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic traits.Therefore,these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.
基金supported by the National Natural Science Foundation of China (32101686)the Hebei Province Key Research and Development Program (22326306D).
文摘Total spikelet number per spike(TSS)is a crucial yield component in wheat.Dissecting and characterizing major stable quantitative trait loci(QTL)associated with TSS can significantly enhance the genetic improvement of yield potential.In a previous study,we identified a stable major QTL for TSS,named QTss.cas-3D.In the present study,we conducted fine mapping of QTss.cas-3D,interval to approximately 6.35 Mb,ranging from 105.03 to 111.38 Mb,based on the IWGSC RefSeq v2.1.Through genome resequencing and gene function annotation,we identified TraesCS3D03G0308000(TaFT-D2)as the candidate gene.Phenotypic evaluation with paired near-isogenic lines revealed that this locus predominantly increases kernel number per spike by enhancing TSS and fertile spikelet number per spike,without significantly affecting thousand-kernel weight or tiller number.The presence of the TaFT-D2 allele in the parent P3228,which is rare in nature populations,highlights its potential value.This study provides a valuable gene resource and functional marker for wheat molecular breeding aimed at improving TSS and establishes a foundation for gene functional analysis of TaFT-D2.
文摘Introduction: Choriocarcinoma is an aggressive tumor, whose incidence is 0.18 per 100,000 women between the ages of 15 and 49 years [1]. Although its prognosis has improved with the development of chemotherapy regimens, the mortality rate of patients with brain metastases is reportedly 29.7% [2]. After chemotherapy, most often, the reappearance of masses in pulmonary is considered to be a sign of relapse. Case presentation: The patient was a 32-year-old Asian Chinese female who delivered a dead male infant at 33 weeks gestation. The placenta appeared to be normal. The major presentation was a haemorrhage of the vagina. The patient received combined treatment with systematic multi-agent chemotherapy and whole-brain radiation therapy at the General Hospital of Hebei Province and achieved complete remission. Two years after remission, a chest CT scan revealed a mass in the right lung that had become larger over 6 months. The patient’s serum β-human chorionic gonadotropin (β-HCG) level was normal, and the tuberculosis infected T lymphocyte spot (T-SPOT.TB) tests were positive. The patient was started on anti-tuberculosis therapy, after which the size of her right lung mass decreased. Conclusion: Lung masses after choriocarcinoma require extensive laboratory and imaging exams to exclude recurrence. This case highlights the importance of differential diagnoses of lung masses in patients with choriocarcinomas. Imaging studies, β-HCG and local lesion resection should be employed to rule out choriocarcinoma recurrence.
基金This work is supported by National Natural Science Foundation of China(No.92163135,11904098,51972105,U19A2090 and 62090035)Hunan Provincial Natural Science Foundation of China(No.2019JJ30004)+1 种基金Hunan International Innovation Cooperation Platform(No.2018WK4004)Key Program of Science and Technology Department of Hunan Province(Nos.2019XK2001,2020XK2001).
文摘Mix-dimensional van der Waals heterostructures(vdWHs)have inspired worldwide interests and efforts in the field of ad-vanced electronics and optoelectronics.The fundamental understanding of interfacial charge transfer is of vital import-ance for guiding the design of functional optoelectronic applications.In this work,type-Ⅱ0D-2D CdSe/ZnS quantum dots/MoS_(2)vdWHs are designed to study the light-triggered interfacial charge behaviors and enhanced optoelectronic performances.From spectral measurements in both steady and transient states,the phenomena of suppressed photolu-minescence(PL)emissions,shifted Raman signals and changed PL lifetimes provide strong evidences of efficient charge transfer at the 0D-2D interface.A series of spectral evolutions of heterostructures with various QDs overlapping concentrations at different laser powers are analyzed in details,which clarifies the dynamic competition between exciton and trion during an efficient doping of 3.9×10^(13)cm^(−2).The enhanced photoresponses(1.57×10^(4)A·W^(-1))and detectivities(2.86×10^(11)Jones)in 0D/2D phototransistors further demonstrate that the light-induced charge transfer is still a feasible way to optimize the performance of optoelectronic devices.These results are expected to inspire the basic understand-ing of interfacial physics at 0D/2D interfaces,and shed the light on promoting the development of mixed-dimensional op-toelectronic devices in the near future.
基金supported by the China Agriculture Research System(CARS-03)the National Key Research and Development Program of China(2016YFD0102000)
文摘As an important wild relative of wheat, Agropyron cristatum has been successfully used for wheat improvement. Currently, a few useful agronomic traits of A. cristatum, such as high grain number per spike and resistance to diseases, have been transferred into common wheat.However, the effective detection of small A. cristatum segmental introgressions in common wheat is still difficult. The objective of this study was to identify A. cristatum-specific single nucleotide polymorphisms(SNPs) for the detection of small alien segments in wheat. The transcriptome sequences of A. cristatum were aligned against wheat coding DNA sequences(CDS) for SNP calling. As a result, we discovered a total of 167,613 putative SNPs specific to the P genome of A. cristatum compared with the common wheat genomes. Among 230 selected SNPs with functional annotations related to inflorescence development and stress resistance,68 were validated as P genome-specific SNPs in multiple wheat backgrounds using Kompetitive Allele Specific PCR(KASP) assays. Among them, 55 SNPs were assigned to six homoeologous groups of the P genome using wheat-A. cristatum addition lines, and 6 P-specific SNP markers were further physically mapped on different segments of chromosome 6 P in 6 P translocation lines. The P genome-specific SNPs were also validated by Sanger sequencing and used to detect the P chromatin in wheat-A. cristatum cryptic introgression lines. Two SNP markers(Unigene20217-182 and Unigene20307-1420) were detected in two wheat-A. cristatum introgression lines that showed enhanced grain number per spike and high resistance to powdery mildew. Together, the developed P genome-specific SNP markers will accelerate the detection of large numbers of wheat-A. cristatum derivatives and will be helpful for marker-assisted transfer of desirable traits from A. cristatum into adapted wheat cultivars in wheat breeding programs.
基金supported by the National Natural Science Foundation of China(Grant Nos.41977248 and 42207219)the Key Research Program of the Institute of Geology and Geophysics,Chinese Academy of Sciences(CAS)(Grant No.IGGCAS-201903).
文摘Reef limestone is a biogenic sedimentary rock widely distributed in coral reef areas, acting as an important foundation for coast construction. Due to its special biogenic origin, reef limestone is different from conventional rocks both in terms of rock structure and mechanical properties. In this study, mesoscale uniaxial compression experiments with five different loading directions were conducted on two kinds of reef limestones from the Maldives Islands and the South China Sea, respectively. The real-time high-resolution videos and images of failure processes were recorded simultaneously to investigate the fracture evolution and fracture surface roughness of reef limestones. It demonstrated that the reef limestones belonged to extremely soft to soft rocks, and their uniaxial compressive strength (UCS) values fluctuated with high discreteness. The mesoscale mechanical properties of reef limestones were highly anisotropic and mainly controlled by pore structure. The occurrence of dissolution pores in reef limestone tended to intensify mechanical anisotropy. With the integration of the fracture initiation and propagation features of reef limestones, it is supposed that the intrinsic mechanism of anisotropy was probably attributed to the differences in coral growth direction and dissolution. Furthermore, the quantified fracture surface roughness was revealed to have a good consistency with density and UCS for the reef limestones from the South China Sea. The findings are helpful for providing theoretical and experimental references for engineering construction in coral reef areas.
基金financial support by the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection,Chengdu University of Technology(Grant No.SKLGP2011K007)the Key Research Program of the Chinese Academy of Sciences(KZZD-EW05-02)the National Natural Science Foundation of China (Nos.41372324,40972198 and 41172269)
文摘Long-term stability of large-span caverns is a challenging issue for design and construction of underground rock engineering.The Heidong cavern group consisting of 21 caverns was constructed about 1400 years ago for quarrying in massive Cretaceous tuff.The cavern No.5 of the Heidong cavern group is characterized by an unsupported span up to 92 m,with the overburden thickness of only 3-25 m.To analyze its long-term stability,a detailed investigation was conducted to obtain its geometry and rock mass characteristics,and to monitor surrounding rock displacements.Based on field survey and laboratory tests,numerical simulations were performed using the finite difference code FLAC;.The analysis results revealed that for the long-term stability of the cavern No.5,some major factors should be carefully considered,such as cavern excavation method in hard massive rocks,site investigation using trial pits,tools like short iron chisel and hammer for manual excavation,geometric dome roof,and waste rocks within abutment or on the floor.The highlights of the technologies obtained from this large-scale ancient underground project can provide reference for other similar project excavations in practice.
文摘The diagnosis of the recurrent optic neuritis is commonly established clinically,and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging(CE-T1W1).In this paper,we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging(CET2FLAIR).The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1W1.This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.
基金financially supported by the National Natural Science Foundation of China(32171961)the Agricultural Science and Technology Innovation Program of CAAS(CAASASTIP-2021-ICS)。
文摘Agropyron cristatum(2n=4x=28,PPPP),which harbours many high-yield and disease-resistance genes,is a promising donor for wheat improvement.Narrow genetic diversity and the trade-off between grain weight and grain number have become bottlenecks for increasing grain yield in wheat.In this study,a novel translocation line,WAT650l,was derived from the chromosome 6P addition line 4844–12,which can simultaneously increase both grain number per spike(GNS)and thousand-grain weight(TGW).Cytological analysis and molecular marker analysis revealed that WAT650l was a 5BL.5BS-6PL(bin 12–17)translocation line.Assessment of agronomic traits and analysis of the BC4F2 and BC5F2 populations suggested that the 6PL terminal chromosome segment in WAT650l resulted in increased grain number per spike(average increased by 14.07 grains),thousand-grain weight(average increased by 4.31 g),flag leaf length,plant height,spikelet number per spike and kernel number per spikelet during the two growing seasons of 2020–2021 and 2021–2022.Additionally,the increased GNS locus and high-TGW locus of WAT650l were mapped to the bins 16–17 and 12–13,respectively,on chromosome 6PL by genetic population analysis of three translocation lines.In summary,we provide a valuable germplasm resource for broadening the genetic base of wheat and overcoming the negative relationship between GNS and TGW in wheat breeding.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81602072,81902380,81820108022,and 81625018)Innovation Program of Shanghai Municipal Education Commission(Grant No.2019-01-07-00-10-E00056)+5 种基金Program of Shanghai Academic/Technology Research Leader(Grant No.18XD1403800)National High Technology Research and Development Program of China(Grant No.2015AA021107-019)Scientific Research Project of Shanghai Science and Technology Commission(Grant No.18411960600)Shanghai Technological Innovation Action Projects(Grant No.18411950800)Shanghai‘Rising Stars of Medical Talent’Youth Development Program,Outstanding Youth Medical Talents,2018the Shanghai Sailing Program(Grant No.17YF1405000).
文摘Objective:The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target.We aimed to study whether NEDD8(neural precursor cell expressed,developmentally down-regulated 8)might serve as a therapeutic target in esophageal squamous cell carcinoma(ESCC).Methods:The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas(TCGA)database and tissue arrays.NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms.Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways.The cell cycle and apoptosis were assessed with fluorescence activated cell sorting.A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing in vivo.Results:NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC,and NEDD8 overexpression was associated with poorer overall patient survival(mRNA level:P=0.028,protein level:P=0.026,log-rank test).Downregulation of NEDD8 significantly suppressed tumor growth both in vitro and in vivo.Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest,DNA damage,and apoptosis in ESCC cells.Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases(CRLs)substrates through inactivation of CRLs,thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC.Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.Conclusions:Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown,and validated NEDD8 as a potential target for ESCC therapy.
基金financially supported by the National Key Research and Development Program of China (2021YFD1200605)the National Natural Science Foundation of China (32171961)。
文摘Wide hybridization is a strategy for broadening the genetic basis of wheat. Because an efficient method for inducing wheat–alien chromosome translocations will allow producing useful germplasm, it is desirable to discover new genes that induce chromosomal variation. In this study, chromosome 5P from A.cristatum was shown to induce many types of chromosomal structural variation in a common wheat background, including nonhomoeologous chromosome translocations, as revealed by genomic in situ hybridization, fluorescence in situ hybridization, and DNA marker analysis. Aberrant meiosis was associated with chromosomal structural variation, and aberrant meiotic behavior was observed in wheat–A.cristatum 5P monosomic and disomic addition lines, suggesting that the effect of chromosome 5P was independent of the number of chromosome 5P copies. Chromosome 5P disturbed homologous chromosome pairing at pachytene stage in a common wheat background, resulting in a high frequency of univalent formation and reduced crossing over. Thirteen genes involved in DNA repair or chromatin remodeling, including RAD52-like and MSH6 genes, were differentially expressed(upregulated) in wheat–A. cristatum 5P addition lines according to transcriptome analysis, implicating chromosome 5P in the process of meiotic double-strand break repair. These findings provide a new, efficient tool for inducing wheat–alien chromosome translocations and producing new germplasm.
基金the National Natural Science Foundation of China (Nos.51525202, 51772084, 61574054, 61635001, and 51802089)Innovation platform and talent plan of Hunan Province (No.2017RS3027)+1 种基金the Program for Youth Leading Talent and Science and Technology Innovation of Ministry of Science and Technology of Chinathe Foundation for Innovative Research Groups of NSFC (No.21521063).
文摘Lead halide perovskites have received tremendous attentions recently for their excellent properties such as high light absorption coefficient and long charge carrier diffusion length. However, the stability issues and the existence of toxic lead cations have largely limited their applications in optoelectronic area. Herein, we report the synthesis and investigation of highly stable and lead-free Cs3Bi2I9 perovskite nanoplates for visible light photodetection applications. The Cs3Bi2I9 nanoplates were synthesized through a facile solution-processed method, which is also applicable to various substrates. The achieved nanoplates present very good crystal quality and exhibit excellent long-term stability even exposed in moist air for several months. Photodetectors were constructed based on these high-quality perovskite nanoplates for the first time, and display a maximum photoresponsivity of 33.1 mA/W under the illumination of 450 nm laser, which is six times higher than the solution-synthesized CH3NH3PbI3 nanowire photodetectors. The specific detectivity of these devices can reach up to 10^10 Jones. Additionally, the devices exhibit fast rise and decay time of 10.2 and 37.2 ms, respectively, and highly stable photoswitching behavior with their photoresponse well retaining under alternating light and darkness. This work opens up a new opportunity for stable and low-toxic perovskite-based optoelectronic applications.
基金We thank Prof.Feng Lin for his efforts on FDTD simulations.This work is supported by the National Natural Science Foundation of China(Nos.92163135,11904098,51972105,U19A2090,and 62090035)Hunan Provincial Natural Science Foundation of China(No.2019JJ30004)+1 种基金Key Program of the Hunan Provincial Science and Technology Department(Nos.2019XK2001 and 2020XK2001)This work is also supported by State Key Laboratory of Artificial Microstructure&Mesoscopic Physics.
文摘Optoelectronic synaptic elements are emerging functional devices for the vigorous development of advanced neuromorphic computing technology in the post-Moore era.However,optoelectronic devices based on transition metal dichalcogenides(TMDs)are limited to their poor mobilities and weak light-matter interactions,which still hardly exhibit superior device performances in the application of artificial synapses.Here,we demonstrate the successful fabrication of Au nanoparticle-coupled MoS_(2)heterostructures via chemical vapor deposition(CVD),where the light absorption of MoS_(2)is greatly enhanced and engineered by plasmonic effects.Hot electrons are excited from Au nanoparticles,and then injected into MoS_(2)semiconductors under the light illumination.The plasmonically-engineered photo-gating effect at the metal-semiconductor junction is demonstrated to create optoelectronic devices with excellent synaptic behaviors,especially in ultra-sensitive excitatory postsynaptic current(EPSC,9.6×10^(-3)nA@3.4 nW·cm^(-2)),ultralow energy consumption(34.7 pJ),long-state retention time(>1,000 s),and tunable synaptic plasticity transitions.The material system of Au-nanoparticles coupled TMDs presents unique advantages for building artificial synapses,which may lead the future development of neuromorphic electronics in optical information sensing and learning.
基金funded by grants from the National Key Research and Development Program of China(2018YFD1000702/2018YFD1000700)the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS),China.
文摘Barley is a diploid species with a genome smaller than those of other members of the Triticeae tribe,making it an attractive model for genetic studies in Triticeae crops.The recent development of barley genomics has created a need for a high-throughput platform to identify genetically uniform mutants for gene function investigations.In this study,we report an ethyl methanesulfonate(EMS)-mutagenized population consisting of 8525M_(3) lines in the barley landrace“Hatiexi”(HTX),which we complement with a high-quality de novo assembly of a reference genome for this genotype.The mutation rate within the population ranged from 1.51 to 4.09 mutations per megabase,depending on the treatment dosage of EMS and the mutation discrimination platform used for genotype analysis.We implemented a three-dimensional DNA pooling strategy combined with multiplexed amplicon sequencing to create a highly efficient and cost-effective TILLING(targeting induced locus lesion in genomes)platform in barley.Mutations were successfully identified from 72 mixed amplicons within a DNA pool containing 64 individual mutants and from 56 mixed amplicons within a pool containing 144 individuals.We discovered abundant allelic mutants for dozens of genes,including the barley Green Revolution contributor gene Brassinosteroid insensitive 1(BRI1).As a proof of concept,we rapidly determined the causal gene responsible for a chlorotic mutant by following the MutMap strategy,demonstrating the value of this resource to support forward and reverse genetic studies in barley.
基金The Chinese Minister of Science and Technology grant(2016YFA0501800)the National Natural Science Foundation of China(grant Nos.81625018,81820108022,81772470,81572340,81602072,81772459)+3 种基金the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-10-E00056)the Program of Shanghai Academic/Technology Research Leader(18XD1403800)the National Thirteenth Five-Year Science and Technology Major Special Project for New Drug and Development(2017ZX09304001)the“Shuguang Program”supported by Shanghai Education Development Foundation(14SG07)supported this work.
文摘Tumor necrosis factor alpha-induced protein 1(TNFAIP1)modulates a plethora of important biological processes,including tumorigenesis and cancer cell migration.However,the regulatory mechanism of TNFAIP1 degradation remains largely elusive.In the present study,with a label-free quantitative proteomic approach,TNFAIP1 was identified as a novel ubiquitin target of the Cullin-RING E3 ubiquitin ligase(CRL)complex.More importantly,Cul3-ROC1(CRL3),a subfamily of CRLs,was identified to specifically interact with TNFAIP1 and promote its polyubiquitination and degradation.Mechanistically,BTBD9,a specific adaptor component of CRL3 complex,was further defined to bind and promote the ubiquitination and degradation of TNFAIP1 in cells.As such,downregulation of BTBD9 promoted lung cancer cell migration by upregulating the expression of TNFAIP1,whereas TNFAIP1 deletion abrogated this effect.Finally,bioinformatics and clinical sample analyses revealed that BTBD9 was downregulated while TNFAIP1 was overexpressed in human lung cancer,which was associated with poor overall survival of patients.Taken together,these findings reveal a previously unrecognized mechanism by which the CRL3^(BTBD9) ubiquitin ligase controls TNFAIP1 degradation to regulate cancer cell migration.
基金funded by the National Natural Science Foundation of China(32222078,32272810,32130096,and 31972493)supported by the Innovation Program of Chinese Academy of Agricultural Sciences。
文摘Inorganic phosphate(Pi)availability is an important factor which affects the growth and yield of crops,thus an appropriate and effective response to Pi fluctuation is critical.However,how crops orchestrate Pi signaling and growth under Pi starvation conditions to optimize the growth defense tradeoff remains unclear.Here we show that a Pi starvationinduced transcription factor NIGT1(NITRATE-INDUCIBLE GARP-TYPE TRANSCRIPTIONAL REPRESSOR 1)controls plant growth and prevents a hyper-response to Pi starvation by directly repressing the expression of growth-related and Pisignaling genes to achieve a balance between growth and response under a varying Pi environment.NIGT1 directly binds to the promoters of Pi starvation signaling marker genes,like IPS1,mi R827,and SPX2,under Pi-deficient conditions to mitigate the Pi-starvation responsive(PSR).It also directly represses the expression of vacuolar Pi efflux transporter genes VPE1/2 to regulate plant Pi homeostasis.We further demonstrate that NIGT1 constrains shoot growth by repressing the expression of growth-related regulatory genes,including brassinolide signal transduction master regulator BZR1,cell division regulator CYCB1;1,and DNA replication regulator PSF3.Our findings reveal the function of NIGT1 in orchestrating plant growth and Pi starvation signaling,and also provide evidence that NIGT1 acts as a safeguard to avoid hyper-response during Pi starvation stress in rice.
基金This work was supported by the following funds:The Chinese Minister of Science and Technology grant(2016YFA0501800)National Natural Science Foundation of China(Grants 81625018,81802743,and 81820108022)+2 种基金Program of Shanghai Academic/Technology Research Leader(18XD1403800)Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-10-E00056)National Thirteenth Five-Year Science and Technology Major Special Project for New Drug and Development(2017ZX09304001).
文摘Dear Editor,S phase kinase-associated protein 2(SKP2),a substrate recognition component of the SCFSKP2 ubiquitin ligase complex,plays an oncogenic role in tumorigenesis by targeting a variety of tumor suppressors(e.g.,p21,p27,and p130)for ubiquitina-tion and subsequent degradation.1 As a well-characterized oncoprotein,the aberrant expression and dysregulation of SKP2 are frequently observed in different human cancers.Given its critical role in governing tumorigenesis and progression,SKP2 has emerged as a potential pharmacological target for anticancer therapy.
基金supported by grants from the Taishan Scholar Foundation of Shandong Province(tsqn202103161)the Natural Science Foundation of Shandong Province(ZR202103010405)+3 种基金the Key R&D Program of Shandong Province,China(ZR202211070163)the Foundation of President of the Peking University Institute of Advanced Agricultural Sciences(ZR202211070163)the Peanut Seed Industry Project in Shandong Province,China(2022LZGC007)to X.LIt was also funded by the National Natural Science Foundation of China(NSFC)Key Program(32230006)to X.W.D.
文摘Peanut(Arachis hypogaea L.)is an important leguminous oil and economic crop that produces flowers aboveground and fruits belowground.Subterranean fruit-pod development,which significantly affects peanut production,involves complex molecular mechanisms that likely require the coordinated regulation of multiple genes in different tissues.To investigate the molecular mechanisms that underlie peanut fruitpod development,we characterized the anatomical features of early fruit-pod development and integrated single-nucleus RNA-sequencing(snRNA-seq)and single-nucleus assay for transposase-accessible chromatin with sequencing(snATAC-seq)data at the single-cell level.We identified distinct cell types,such as meristem,embryo,vascular tissue,cuticular layer,and stele cells within the shell wall.These specific cell types were used to examine potential molecular changes unique to each cell type during pivotal stages of fruit-pod development.snRNA-seq analyses of differentially expressed genes revealed cell-type-specific insights that were not previously obtainable from transcriptome analyses of bulk RNA.For instance,we identified MADS-box genes that contributes to the formation of parenchyma cells and gravity-related genes that are present in the vascular cells,indicating an essential role for the vascular cells in peg gravitropism.Overall,our single-nucleus analysis provides comprehensive and novel information on specific cell types,gene expression,and chromatin accessibility during the early stages of fruit-pod development.This information will enhance our understanding of the mechanisms that underlie fruit-pod development in peanut and contribute to efforts aimed at improving peanut production.
基金supported by the National Natural Science Foundation of China(No.81602072,No.81902380,No.81820108022,No.81625018)National High Technology Research and Development Program of China(No.2015AA021107-019)+5 种基金Scientific Research Project of Shanghai Science and Technology Commission(No.18411960600)Program of Shanghai Academic/Technology Research Leader(No.18XD1403800)Innovation Program of Shanghai Municipal Education Commission(No.2019-01-07-00-10-E00056)Shanghai Technological Innovation Action Projects(No.18411950800)Shanghai Sailing Program(No.2017YF1405000)Shanghai‘Rising Stars of Medical Talent’Youth Development Program,Outstanding Youth Medical Talents,2018.
文摘Dear Editor,Esophageal squamous cell carcinoma(ESCC)is the major histologic subtype of esophageal cancer with high incidence and mortality.1 However,few achievements have been made in the development of targeted drugs.2 Neddylation,a reversible post-translational modification,attaches ubiquitin-like molecule NEDD8 to substrates in a three-step enzymatic reaction catalyzed by NEDD8-activating enzyme E1(NAE,NAE1 and UBA3 heterodimer),NEDD8-conjugating enzyme E2s(UBE2M/UBC12 or UBE2F)and substrate-specific NEDD8-E3 ligases.3 The best-characterized substrates of neddylation are cullin family proteins,the essential components of multiunit Cullin-RING ubiquitin ligases(CRLs).4 Currently,the inhibition of cullin neddylation by targeting overactivated neddylation pathway has emerged as an attractive approach for anticancer therapy.5,6 Our previous study reported that MLN4924,a specific inhibitor of NAE,significantly inhibited the tumor growth of ESCC by blocking cullin neddylation and inactivating CRLs activity.7 However,recent studies found that MLN4924 treatment-emergent NAE mutations would confer the drug resistance.8,9 Therefore,it is urgent to identify other neddylation enzymes(E2s or E3s)as alternative anticancer targets and develop novel anti-ESCC strategies.
基金The authors would like to thank financial supports from the National Natural Science Foundation of China(Grant Nos.42272122 and 40902088).
文摘Five complete caverns were discovered in Longyou in 1992.They were manually caved in argillaceous siltstone at shallow depths more than 2000 years ago.When they were un-watered,their integrity was maintained completely,and their interior rock surfaces were free of old cracks.Since then,however,the rock's interior faces have initiated and propagated more and more cracks.This paper attempts to address the question of why the rock interior faces were free of old cracks once they were unearthed.To address this question,this paper proposes a hypothesis that the argillaceous siltstone has the ability of self-healing its cracks over a short period of time under weak acid water environment.Data and evidence are presented herewith to prove the hypothesis.They include observations and measurements in the field and test results in the laboratory.Specifically,a three-point bending test is used to form a tensile crack in a rectangular rock specimen and a deadload test for the specimen immersed in initially weak acid water is used for self-healing its crack.The results have shown that the argillaceous siltstone is in a state of weak alkalinity and the rain water at the site is in a state of weak acidity.Therefore,when it is immersed in weak acid water for some time,the argillaceous siltstone would be able to make chemical reactions to generate new minerals such as calcite.The new minerals would be able to infill the cracks and then heal the crack within a few years.Once the crack is self-healed,the rock can regain its strength and integrity.Consequently,the rock interior surfaces could be free of old cracks when the water was pumped out of the caverns.