Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, trans...Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.展开更多
AIM To determine the association of human antigen R(HuR) and inhibitors of apoptosis proteins(IAP1, IAP2) and prognosis in pancreatic cancer.METHODS Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreat...AIM To determine the association of human antigen R(HuR) and inhibitors of apoptosis proteins(IAP1, IAP2) and prognosis in pancreatic cancer.METHODS Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma(PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction(RT-PCR), western blot analysis was carried out.RESULTS RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas(P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression(P < 0.05, r = 0.783). Western blot analysis confirmed RTPCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients(P < 0.05).Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased.CONCLUSION HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.展开更多
There is a continuing need for novel antivirals to treat hepatitis B virus (HBV) infection, as it remains a major health problem worldwide. Ideally new classes of antivirals would target multiple steps in the viral li...There is a continuing need for novel antivirals to treat hepatitis B virus (HBV) infection, as it remains a major health problem worldwide. Ideally new classes of antivirals would target multiple steps in the viral lifecycle. In this review, we consider the steps in which HBV RNAs are processed, exported from the nucleus and translated. These are often overlooked steps in the HBV life-cycle. HBV, like retroviruses, incorporates a number of unusual steps in these processes, which use a combination of viral and host cellular machinery. Some of these unusual steps deserve a closer scrutiny. They may provide alternative targets to existing antiviral therapies, which are associated with increasing drug resistance. The RNA post-transcriptional regulatory element identified 20 years ago promotes nucleocytoplasmic export of all unspliced HBV RNAs. There is evidence that inhibition of this step is part of the antiviral action of interferon. Similarly, the structured RNA epsilon element situated at the 5’ end of the polycistronic HBV pregenomic RNA also performs key roles during HBV replication. The pregenomic RNA, which is the template for translation of both the viral core and polymerase proteins, is also encapsidated and used in replication. This complex process, regulated at the epsilon element, also presents an attractive antiviral target. These RNA elements that mediate and regulate gene expression are highly conserved and could be targeted using novel strategies employing RNAi, miRNAs or aptamers. Such approaches targeting these functionally constrained genomic regions should avoid escape mutations. Therefore understanding these regulatory elements, along with providing potential targets, may also facilitate the development of other new classes of antiviral drugs.展开更多
Objective: To investigate the post-transcriptional regulation of p21WAF1/CIP1 by p53. Methods: The MDA-MB-468 cells have endogenous mutant p53 and the MCF7 cells lines have wtp53. Recombinant p53 expression and p21WAF...Objective: To investigate the post-transcriptional regulation of p21WAF1/CIP1 by p53. Methods: The MDA-MB-468 cells have endogenous mutant p53 and the MCF7 cells lines have wtp53. Recombinant p53 expression and p21WAF1/CIP1 induction were detected by Western blot analysis. Northern blot analysis was carried out to examine whether changes in p21WAF1/CIP1 protein levels in MCF7 cells treated with AdCMVp53 are reflected at the mRNA level. Flow cytometric analysis of MCF7 cells following overexpression of recombination. Results: The ratio of p53: p21WAF1/CIP1 was below 1 at the early stages of AdCMVp53 infection, but increased to 1.6 by day 3 and to 9.7 by day 5 post-infection. As expected, p21WAF1/CIP1 expression was not detectable in MDA-MB-468 cells despite the presence of high levels of mutant p53 protein. The G1/S ratios in untreated controls and AdCMVβgal infected MCF7 cells were 1.10 and 1.35, respectively. By Northern blot analyzing the p21WAF1/CIP1: GAPDH ratios at different time points against the ratio at time point 0, a maximum 3-fold induction of p21WAF1/CIP1 mRNA expression relative to untreated control was observed on day 1 post-infection. The flow cytometric analysis indicated that MCF7 cells infected with AdCMVp53 undergo G1 arrest at both time points studied, with G1/S ratios ranging from 5.54 at day 1 to 5.65 at day 7. The G1/S ratios in untreated controls and AdCMVβgal infected MCF7 cells were 1.10 and 1.35, respectively. Conclusion: This study demonstrated that p53 could regulate p21WAF1/CIP1 gene expression at both the transcriptional and post-transcriptional levels in MCF7 cells. The latter mechanism may be involved in or be responsible for, the induction of cell cycle arrest by transcription-defective mutants of p53.展开更多
Hematopoiesis represents a meticulously regulated and dynamic biological process.Genetic aberrations affecting blood cells,induced by various factors,frequently give rise to hematological tumors.These instances are of...Hematopoiesis represents a meticulously regulated and dynamic biological process.Genetic aberrations affecting blood cells,induced by various factors,frequently give rise to hematological tumors.These instances are often accompanied by a multitude of abnormal post-transcriptional regulatory events,including RNA alternative splicing,RNA localization,RNA degradation,and storage.Notably,post-transcriptional regulation plays a pivotal role in preserving hematopoietic homeostasis.The DEAD-Box RNA helicase genes emerge as crucial post-transcriptional regulatory factors,intricately involved in sustaining normal hematopoiesis through diverse mechanisms such as RNA alternative splicing,RNA modification,and ribosome assembly.This review consolidates the existing knowledge on the role of DEAD-box RNA helicases in regulating normal hematopoiesis and underscores the pathogenicity of mutant DEADBox RNA helicases in malignant hematopoiesis.Emphasis is placed on elucidating both the positive and negative contributions of DEAD-box RNA helicases within the hematopoietic system.展开更多
RNA-binding proteins(RBPs)are components of the post-transcriptional regulatory system,but their regulatory effects on complex traits remain unknown.Using an integrated strategy involving map-based cloning,functional ...RNA-binding proteins(RBPs)are components of the post-transcriptional regulatory system,but their regulatory effects on complex traits remain unknown.Using an integrated strategy involving map-based cloning,functional characterizations,and transcriptomic and population genomic analyses,we revealed that RBP-K(LOC_Os08g23120),RBP-A(LOC_Os11g41890),and RBP-J(LOC_Os10g33230)encode proteins that form an RBP-A-J-K complex that negatively regulates rice yield-related traits.Examinations of the RBP-A-J-K complex indicated RBP-K functions as a relatively non-specific RBP chaperone that enables RBP-A and RBP-J to function normally.Additionally,RBP-J most likely affects GA pathways,resulting in considerable increases in grain and panicle lengths,but decreases in grain width and thickness.In contrast,RBP-A negatively regulates the expression of genes most likely involved in auxin-regulated pathways controlling cell wall elongation and carbohydrate transport,with substantial effects on the rice grain filling process as well as grain length and weight.Evolutionarily,RBP-K is relatively ancient and highly conserved,whereas RBP-J and RBP-A are more diverse.Thus,the RBP-A-J-K complex may represent a typical functional model for many RBPs and protein complexes that function at transcriptional and post-transcriptional levels in plants and animals for increased functional consistency,efficiency,and versatility,as well as increased evolutionary potential.Our results clearly demonstrate the importance of RBP-mediated post-transcriptional regulation for the diversity of complex traits.Furthermore,rice grain yield and quality may be enhanced by introducing various complete or partial loss-of-function mutations to specific RBP genes using clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9 technology and by exploiting desirable natural tri-genic allelic combinations at the loci encoding the components of the RBP-A-J-K complex through marker-assisted selection.展开更多
Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is preci...Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic modifications.In recent years,research on posttranscriptional levels in erythropoiesis has expanded significantly.The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis.RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation efficiency.Noncoding RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination.This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis.These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.展开更多
Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells ...Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on the interplay of specific RNA binding proteins with neurogenic microRNAs.Taking under consideration that the molecular mechanisms of neurogenesis exert high similarity to the ones driving direct neuronal reprogramming,we also discuss the current advances in in vitro and in vivo direct neuronal reprogramming approaches that have employed microRNAs or RNA binding proteins as reprogramming factors,highlighting the so far known mechanisms of their reprogramming action.展开更多
Background:N6-methyladenosine(m^(6)A)and DNA 5-methylcytosine(5mC)methylation plays crucial roles in diverse biological processes,including skeletal muscle development and growth.Recent studies unveiled a potential li...Background:N6-methyladenosine(m^(6)A)and DNA 5-methylcytosine(5mC)methylation plays crucial roles in diverse biological processes,including skeletal muscle development and growth.Recent studies unveiled a potential link between these two systems,implicating the potential mechanism of coordinated transcriptional and post-transcrip-tional regulation in porcine prenatal myogenesis and postnatal skeletal muscle growth.Methods:Immunofluorescence and co-IP assays were carried out between the 5mC writers and m^(6)A writers to investigate the molecular basis underneath.Large-scale in-house transcriptomic data were compiled for applying weighted correlation network analysis(WGCNA)to identify the co-expression patterns of m^(6)A and 5mC regulators and their potential role in pig myogenesis.Whole-genome bisulfite sequencing(WGBS)and methylated RNA immu-noprecipitation sequencing(MeRIP-seq)were performed on the skeletal muscle samples from Landrace pigs at four postnatal growth stages(days 30,60,120 and 180).Results:Significantly correlated expression between 5mC writers and m^(6)A writers and co-occurrence of 5mC and m^(6)A modification were revealed from public datasets of C2C12 myoblasts.The protein-protein interactions between the DNA methylase and the m^(6)A methylase were observed in mouse myoblast cells.Further,by analyzing tran-scriptome data comprising 81 pig skeletal muscle samples across 27 developmental stages,we identified a 5mC/m^(6)A epigenetic module eigengene and decoded its potential functions in pre-or post-transcriptional regulation in postnatal skeletal muscle development and growth of pigs.Following integrative multi-omics analyses on the WGBS methylome data and MeRIP-seq data for both m^(6)A and gene expression profiles revealed a genome/transcriptome-wide correlated dynamics and co-occurrence of 5mC and m^(6)A modifications as a consequence of 5mC/m^(6)A crosstalk in the postnatal myogenesis progress of pigs.Last,we identified a group of myogenesis-related genes collaboratively regulated by both 5mC and m^(6)A modifications in postnatal skeletal muscle growth in pigs.Conclusions:Our study discloses a potential epigenetic mechanism in skeletal muscle development and provides a novel direction for animal breeding and drug development of related human muscle-related diseases.展开更多
Liquid-liquid phase separation,a novel biochemical phenomenon,has been increasingly studied for its medical applications.It underlies the formation of membrane-less organelles and is involved in many cellular and biol...Liquid-liquid phase separation,a novel biochemical phenomenon,has been increasingly studied for its medical applications.It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes.During transcriptional regulation,dynamic condensates are formed through interactions between transcriptional elements,such as transcription factors,coactivators,and mediators.Cancer is a disease characterized by uncontrolled cell proliferation,but the precise mechanisms underlying tumorigenesis often remain to be elucidated.Emerging evidence has linked abnormal transcriptional condensates to several diseases,especially cancer,implying that phase separation plays an important role in tumorigenesis.Condensates formed by phase separation may have an effect on gene transcription in tumors.In the present review,we focus on the correlation between phase separation and transcriptional regulation,as well as how this phenomenon contributes to cancer development.展开更多
Typical application scenarios,such as vehicle to grid(V2G)and frequency regulation,have imposed significant long-life demands on lithium-ion batteries.Herein,we propose an advanced battery life-extension method employ...Typical application scenarios,such as vehicle to grid(V2G)and frequency regulation,have imposed significant long-life demands on lithium-ion batteries.Herein,we propose an advanced battery life-extension method employing bidirectional pulse charging(BPC)strategy.Unlike traditional constant current charging methods,BPC strategy not only achieves comparable charging speeds but also facilitates V2G frequency regulation simultaneously.It significantly enhances battery cycle ampere-hour throughput and demonstrates remarkable life extension capabilities.For this interesting conclusion,adopting model identification and postmortem characterization to reveal the life regulation mechanism of BPC:it mitigates battery capacity loss attributed to loss of lithium-ion inventory(LLI)in graphite anodes by intermittently regulating the overall battery voltage and anode potential using a negative charging current.Then,from the perspective of internal side reaction,the life extension mechanism is further revealed as inhibition of solid electrolyte interphase(SEI)and lithium dendrite growth by regulating voltage with a bidirectional pulse current,and a semi-empirical life degradation model combining SEI and lithium dendrite growth is developed for BPC scenarios health management,the model parameters are identified by genetic algorithm with the life simulation exhibiting an accuracy exceeding 99%.This finding indicates that under typical rate conditions,adaptable BPC strategies can extend the service life of LFP battery by approximately 123%.Consequently,the developed advanced BPC strategy offers innovative perspectives and insights for the development of long-life battery applications in the future.展开更多
Inhomogeneous lithium-ion(Li^(+))deposition is one of the most crucial problems,which severely deteriorates the performance of solid-state lithium metal batteries(LMBs).Herein,we discovered that covalent organic frame...Inhomogeneous lithium-ion(Li^(+))deposition is one of the most crucial problems,which severely deteriorates the performance of solid-state lithium metal batteries(LMBs).Herein,we discovered that covalent organic framework(COF-1)with periodically arranged boron-oxygen dipole lithiophilic sites could directionally guide Li^(+)even deposition in asymmetric solid polymer electrolytes.This in situ prepared 3D cross-linked network Poly(ACMO-MBA)hybrid electrolyte simultaneously delivers outstanding ionic conductivity(1.02×10^(-3)S cm^(-1)at 30°C)and excellent mechanical property(3.5 MPa).The defined nanosized channel in COF-1 selectively conducts Li^(+)increasing Li^(+)transference number to 0.67.Besides,The COF-1 layer and Poly(ACMO-MBA)also participate in forming a boron-rich and nitrogen-rich solid electrolyte interface to further improve the interfacial stability.The Li‖Li symmetric cell exhibits remarkable cyclic stability over 1000 h.The Li‖NCM523 full cell also delivers an outstanding lifespan over 400 cycles.Moreover,the Li‖LiFePO_(4)full cell stably cycles with a capacity retention of 85%after 500 cycles.the Li‖LiFePO_(4)pouch full exhibits excellent safety performance under pierced and cut conditions.This work thereby further broadens and complements the application of COF materials in polymer electrolyte for dendrite-free and high-energy-density solid-state LMBs.展开更多
Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord...Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.展开更多
MicroRNAs(miRNAs)are a highly conserved class of small(18–24 nucleotides)non-coding RNAs that regulate a broad spectrum of biological processes.Aberrations or corruptions of miRNA functions may lead to deregulated ce...MicroRNAs(miRNAs)are a highly conserved class of small(18–24 nucleotides)non-coding RNAs that regulate a broad spectrum of biological processes.Aberrations or corruptions of miRNA functions may lead to deregulated cell proliferation,tumorigenesis,and ultimately,cancer.Increasing evidences suggested that a large fraction of miRNAs is regulated at the posttranscriptional stage,which impacts on the level and function of miRNAs during cell development and human diseases.Recently,several distinct mechanisms are emerging to regulate the biogenesis,stability and function of miRNAs at post-transcriptional level,such as specific binding to terminal loops of miRNA precursors(primiRNAs or pre-miRNAs)by RNA-binding proteins and 3’-terminal modifications by particular enzymes.Signaling cascades and post-translational modifications of the core components of RNA machinery also take part in the posttranscriptional regulation of miRNAs.展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of trea...The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.展开更多
Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water sh...Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water shortages and the overuse of fertilizers.The field experiment had twelve treatments and a control(CK)trial including two irrigation amounts(I1,100%ETm;I2,60%ETm;where ETm is the maximum evapotranspiration),two nitrogen applications(N1,360 kg ha^(−1);N2,120 kg ha^(−1))and three biochar application levels(B1,60 t ha^(−1);B_(2),30 t ha^(−1)and B3,0 t ha^(−1)).A multi-objective synergistic irrigation-nitrogen-biochar application system for improving tomato yield,quality,water and nitrogen use efficiency,and greenhouse emissions was developed by integrating the techniques of experimentation and optimization.First,a coupled irrigation-nitrogen-biochar plot experiment was arranged.Then,tomato yield and fruit quality parameters were determined experimentally to establish the response relationships between irrigation-nitrogen-biochar dosage and yield,comprehensive quality of tomatoes(TCQ),irrigation water use efficiency(IWUE),partial factor productivity of nitrogen(PFPN),and net greenhouse gas emissions(NGE).Finally,a multi-objective dynamic optimization regulation model of irrigation-nitrogen-biochar resource allocation at different growth stages of tomato was constructed which was solved by the fuzzy programming method.The results showed that the application of irrigation and nitrogen to biochar promoted increase in yield,IWUE and PFPN,while it had an inhibitory effect on NGE.In addition,the optimal allocation amounts of water and fertilizer were different under different scenarios.The yield of the S1 scenario increased by 8.31%compared to the B_(1)I_(1)N_(2) treatment;TCQ of the S2 scenario increased by 5.14%compared to the B_(2)I_(2)N_(1) treatment;IWUE of the S3 scenario increased by 10.01%compared to the B1I2N2 treatment;PFPN of the S4 scenario increased by 9.35%compared to the B_(1)I_(1)N_(2) treatment;and NGE of the S5 scenario decreased by 11.23%compared to the B_(2)I1N1 treatment.The optimization model showed that the coordination of multiple objectives considering yield,TCQ,IWUE,PFPN,and NGE increased on average from 4.44 to 69.02%compared to each treatment when the irrigation-nitrogen-biochar dosage was 205.18 mm,186 kg ha^(−1)and 43.31 t ha^(−1),respectively.This study provides a guiding basis for the sustainable management of water and fertilizer in greenhouse tomato production under drip irrigation fertilization conditions.展开更多
Lead iodide(PbI2) is a vital raw material for preparing perovskite solar cells(PSCs),and it not only takes part in forming the light absorption layer but also remains in the grain boundary as a passivator.In other wor...Lead iodide(PbI2) is a vital raw material for preparing perovskite solar cells(PSCs),and it not only takes part in forming the light absorption layer but also remains in the grain boundary as a passivator.In other words,the PbI2 content in the precursor and as formed film will affect the efficiency and stability of the PSCs.With moderate residual PbI2,it passivates the bulk/surface defects of perovskite,reduces the interfacial recombination,promotes the perovskite stability,minimizes the device hysteresis,and so on.Deficient PbI2 residue will reduce the interfacial passivation effect and device performance.In addition to facilitating the non-radiative recombination,over PbI2 residue can also lead to electronic insulation in the grain boundary and deteriorate the device performance.However,the impact and regulation of PbI2 residue on the device performance and stability is still not fully understood.Herein,a comprehensive and detailed review is presented by discussing the PbI2 residue impact and its regulation strategies(i.e., elimination,facilitation and conversion of the residue PbI2) to manipulate the PbI2 content,distribution and forms.Finally,we also show future outlooks in this field,with an aim to help further the progression of high-efficiency and stable PSCs.展开更多
In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogr...In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.展开更多
By virtue of a 3∶1 complementary coordination strategy,a chiral heteroleptic metal-organic cage that con-tains divergent functional units,Pd‑R(Zn),was precisely constructed via self-assembly of monodentate variationa...By virtue of a 3∶1 complementary coordination strategy,a chiral heteroleptic metal-organic cage that con-tains divergent functional units,Pd‑R(Zn),was precisely constructed via self-assembly of monodentate variational Zn-salen ligands RZn and NADH(reduced nicotinamide adenine dinucleotide)mimic modified tridentate ligands with square-planar Pd ions.UV-Vis and luminescence spectra experiments reveal that different anions could selec-tively interact with different sites of Zn-salen modified metal-organic cages to achieve the structural regulation of cage compound,by using the differentiated host-guest electrostatic interactions of counter ions with metal-organic hosts.Compared to other anions,the presence of chloride ions caused the most significant fluorescence emission enhancement of Pd‑R(Zn),meanwhile,the UV-Vis absorption band attributed to the salen aromatic backbone showed an absorption decrease,and the metal-to-ligand induced peak displayed a blue shift effect.Circular dichro-ism and ^(1)H NMR spectra further demonstrate that the introduction of chloride anions is beneficial to keeping a more rigid scaffold.展开更多
文摘Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis. Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms. Recent advances in our understanding of post-transcriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA. Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses. RNA interference (RNAi) technology is being used in vitro and in animal models with promising results. Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.
文摘AIM To determine the association of human antigen R(HuR) and inhibitors of apoptosis proteins(IAP1, IAP2) and prognosis in pancreatic cancer.METHODS Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma(PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction(RT-PCR), western blot analysis was carried out.RESULTS RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas(P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression(P < 0.05, r = 0.783). Western blot analysis confirmed RTPCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients(P < 0.05).Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased.CONCLUSION HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.
基金Supported by Thailand Research Fundthe Commission on Higher Education Fund grant(to Nattanan Panjaworayan T-Thienprasert),No.MRG5680051and NZ Health Research Council Grant 05/195(to Augustine Chen and Chris M Brown)
文摘There is a continuing need for novel antivirals to treat hepatitis B virus (HBV) infection, as it remains a major health problem worldwide. Ideally new classes of antivirals would target multiple steps in the viral lifecycle. In this review, we consider the steps in which HBV RNAs are processed, exported from the nucleus and translated. These are often overlooked steps in the HBV life-cycle. HBV, like retroviruses, incorporates a number of unusual steps in these processes, which use a combination of viral and host cellular machinery. Some of these unusual steps deserve a closer scrutiny. They may provide alternative targets to existing antiviral therapies, which are associated with increasing drug resistance. The RNA post-transcriptional regulatory element identified 20 years ago promotes nucleocytoplasmic export of all unspliced HBV RNAs. There is evidence that inhibition of this step is part of the antiviral action of interferon. Similarly, the structured RNA epsilon element situated at the 5’ end of the polycistronic HBV pregenomic RNA also performs key roles during HBV replication. The pregenomic RNA, which is the template for translation of both the viral core and polymerase proteins, is also encapsidated and used in replication. This complex process, regulated at the epsilon element, also presents an attractive antiviral target. These RNA elements that mediate and regulate gene expression are highly conserved and could be targeted using novel strategies employing RNAi, miRNAs or aptamers. Such approaches targeting these functionally constrained genomic regions should avoid escape mutations. Therefore understanding these regulatory elements, along with providing potential targets, may also facilitate the development of other new classes of antiviral drugs.
文摘Objective: To investigate the post-transcriptional regulation of p21WAF1/CIP1 by p53. Methods: The MDA-MB-468 cells have endogenous mutant p53 and the MCF7 cells lines have wtp53. Recombinant p53 expression and p21WAF1/CIP1 induction were detected by Western blot analysis. Northern blot analysis was carried out to examine whether changes in p21WAF1/CIP1 protein levels in MCF7 cells treated with AdCMVp53 are reflected at the mRNA level. Flow cytometric analysis of MCF7 cells following overexpression of recombination. Results: The ratio of p53: p21WAF1/CIP1 was below 1 at the early stages of AdCMVp53 infection, but increased to 1.6 by day 3 and to 9.7 by day 5 post-infection. As expected, p21WAF1/CIP1 expression was not detectable in MDA-MB-468 cells despite the presence of high levels of mutant p53 protein. The G1/S ratios in untreated controls and AdCMVβgal infected MCF7 cells were 1.10 and 1.35, respectively. By Northern blot analyzing the p21WAF1/CIP1: GAPDH ratios at different time points against the ratio at time point 0, a maximum 3-fold induction of p21WAF1/CIP1 mRNA expression relative to untreated control was observed on day 1 post-infection. The flow cytometric analysis indicated that MCF7 cells infected with AdCMVp53 undergo G1 arrest at both time points studied, with G1/S ratios ranging from 5.54 at day 1 to 5.65 at day 7. The G1/S ratios in untreated controls and AdCMVβgal infected MCF7 cells were 1.10 and 1.35, respectively. Conclusion: This study demonstrated that p53 could regulate p21WAF1/CIP1 gene expression at both the transcriptional and post-transcriptional levels in MCF7 cells. The latter mechanism may be involved in or be responsible for, the induction of cell cycle arrest by transcription-defective mutants of p53.
基金Chongqing Science Fund for Distinguished Young Scholars(No.CSTB2022NSCQJQX0032)Chongqing University Innovation Research Group Project(No.CXQT21011)+2 种基金Chongqing Medical University Youth Innovation in Future Medicine(No.W0156)the National Natural Science Foundation of China(No.82200123)Natural Science Foundation of Chongqing,China,(No.CSTB2023NSCQ-MSX0280).
文摘Hematopoiesis represents a meticulously regulated and dynamic biological process.Genetic aberrations affecting blood cells,induced by various factors,frequently give rise to hematological tumors.These instances are often accompanied by a multitude of abnormal post-transcriptional regulatory events,including RNA alternative splicing,RNA localization,RNA degradation,and storage.Notably,post-transcriptional regulation plays a pivotal role in preserving hematopoietic homeostasis.The DEAD-Box RNA helicase genes emerge as crucial post-transcriptional regulatory factors,intricately involved in sustaining normal hematopoiesis through diverse mechanisms such as RNA alternative splicing,RNA modification,and ribosome assembly.This review consolidates the existing knowledge on the role of DEAD-box RNA helicases in regulating normal hematopoiesis and underscores the pathogenicity of mutant DEADBox RNA helicases in malignant hematopoiesis.Emphasis is placed on elucidating both the positive and negative contributions of DEAD-box RNA helicases within the hematopoietic system.
基金supported by the Innovation Program of Shanghai Municipal Education Commission(2023ZKZD05)the National Natural Science Foundation of China(32172043,31971918 and 32170356)+2 种基金the Shanghai Science and Technology Innovation Action Plan Project(22N11900200)the Innovation Program of Chinese Academy of Agricultural Sciencesthe grant from the National Key Research and Development Program of China(2021YFA1300401).
文摘RNA-binding proteins(RBPs)are components of the post-transcriptional regulatory system,but their regulatory effects on complex traits remain unknown.Using an integrated strategy involving map-based cloning,functional characterizations,and transcriptomic and population genomic analyses,we revealed that RBP-K(LOC_Os08g23120),RBP-A(LOC_Os11g41890),and RBP-J(LOC_Os10g33230)encode proteins that form an RBP-A-J-K complex that negatively regulates rice yield-related traits.Examinations of the RBP-A-J-K complex indicated RBP-K functions as a relatively non-specific RBP chaperone that enables RBP-A and RBP-J to function normally.Additionally,RBP-J most likely affects GA pathways,resulting in considerable increases in grain and panicle lengths,but decreases in grain width and thickness.In contrast,RBP-A negatively regulates the expression of genes most likely involved in auxin-regulated pathways controlling cell wall elongation and carbohydrate transport,with substantial effects on the rice grain filling process as well as grain length and weight.Evolutionarily,RBP-K is relatively ancient and highly conserved,whereas RBP-J and RBP-A are more diverse.Thus,the RBP-A-J-K complex may represent a typical functional model for many RBPs and protein complexes that function at transcriptional and post-transcriptional levels in plants and animals for increased functional consistency,efficiency,and versatility,as well as increased evolutionary potential.Our results clearly demonstrate the importance of RBP-mediated post-transcriptional regulation for the diversity of complex traits.Furthermore,rice grain yield and quality may be enhanced by introducing various complete or partial loss-of-function mutations to specific RBP genes using clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9 technology and by exploiting desirable natural tri-genic allelic combinations at the loci encoding the components of the RBP-A-J-K complex through marker-assisted selection.
基金supported by grants from the National Natural Science Foundation of China(Grant numbers 81920108004 and 82270127)the Fundamental Research Funds of the Central Universities of Central South University(Grant number 2021zzts0562)the Fundamental Research Funds for the Scientific Research Innovation Project of Hunan Province(Grant number CX20210182).
文摘Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic modifications.In recent years,research on posttranscriptional levels in erythropoiesis has expanded significantly.The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis.RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation efficiency.Noncoding RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination.This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis.These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.
基金supported by Stavros Niarhos FoundationGreek‘Flagship Action for the Study of Neurodegenerative Diseases on the Basis of Precision Medicine’(to DT).
文摘Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on the interplay of specific RNA binding proteins with neurogenic microRNAs.Taking under consideration that the molecular mechanisms of neurogenesis exert high similarity to the ones driving direct neuronal reprogramming,we also discuss the current advances in in vitro and in vivo direct neuronal reprogramming approaches that have employed microRNAs or RNA binding proteins as reprogramming factors,highlighting the so far known mechanisms of their reprogramming action.
基金supported by the Agricultural Science and Technology Innovation Program and The Elite Young Scientists Program of CAAS.ZT was supported by the National Natural Science Foundation of China(31830090)the Basic and Applied Basic Research Foundation of Guangdong province(2019B1515120059)+1 种基金the Shenzhen Dapeng New District Special Fund for Industry Development(KY20180114)the Agricultural Science and Technology Innovation Program(CAAS-ZDRW202006).
文摘Background:N6-methyladenosine(m^(6)A)and DNA 5-methylcytosine(5mC)methylation plays crucial roles in diverse biological processes,including skeletal muscle development and growth.Recent studies unveiled a potential link between these two systems,implicating the potential mechanism of coordinated transcriptional and post-transcrip-tional regulation in porcine prenatal myogenesis and postnatal skeletal muscle growth.Methods:Immunofluorescence and co-IP assays were carried out between the 5mC writers and m^(6)A writers to investigate the molecular basis underneath.Large-scale in-house transcriptomic data were compiled for applying weighted correlation network analysis(WGCNA)to identify the co-expression patterns of m^(6)A and 5mC regulators and their potential role in pig myogenesis.Whole-genome bisulfite sequencing(WGBS)and methylated RNA immu-noprecipitation sequencing(MeRIP-seq)were performed on the skeletal muscle samples from Landrace pigs at four postnatal growth stages(days 30,60,120 and 180).Results:Significantly correlated expression between 5mC writers and m^(6)A writers and co-occurrence of 5mC and m^(6)A modification were revealed from public datasets of C2C12 myoblasts.The protein-protein interactions between the DNA methylase and the m^(6)A methylase were observed in mouse myoblast cells.Further,by analyzing tran-scriptome data comprising 81 pig skeletal muscle samples across 27 developmental stages,we identified a 5mC/m^(6)A epigenetic module eigengene and decoded its potential functions in pre-or post-transcriptional regulation in postnatal skeletal muscle development and growth of pigs.Following integrative multi-omics analyses on the WGBS methylome data and MeRIP-seq data for both m^(6)A and gene expression profiles revealed a genome/transcriptome-wide correlated dynamics and co-occurrence of 5mC and m^(6)A modifications as a consequence of 5mC/m^(6)A crosstalk in the postnatal myogenesis progress of pigs.Last,we identified a group of myogenesis-related genes collaboratively regulated by both 5mC and m^(6)A modifications in postnatal skeletal muscle growth in pigs.Conclusions:Our study discloses a potential epigenetic mechanism in skeletal muscle development and provides a novel direction for animal breeding and drug development of related human muscle-related diseases.
基金supported by the Jiangsu Province Natural Science Foundation(Grant No.BK20201492)the Key Medical Research Project of Jiangsu Provincial Health Commission(Grant No.K2019002)the Clinical Capacity Improvement Project of Jiangsu Province People's Hospital(Grant No.JSPH-MA-2021-8).
文摘Liquid-liquid phase separation,a novel biochemical phenomenon,has been increasingly studied for its medical applications.It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes.During transcriptional regulation,dynamic condensates are formed through interactions between transcriptional elements,such as transcription factors,coactivators,and mediators.Cancer is a disease characterized by uncontrolled cell proliferation,but the precise mechanisms underlying tumorigenesis often remain to be elucidated.Emerging evidence has linked abnormal transcriptional condensates to several diseases,especially cancer,implying that phase separation plays an important role in tumorigenesis.Condensates formed by phase separation may have an effect on gene transcription in tumors.In the present review,we focus on the correlation between phase separation and transcriptional regulation,as well as how this phenomenon contributes to cancer development.
基金supported by the National Natural Science Foundation of China(52177217)。
文摘Typical application scenarios,such as vehicle to grid(V2G)and frequency regulation,have imposed significant long-life demands on lithium-ion batteries.Herein,we propose an advanced battery life-extension method employing bidirectional pulse charging(BPC)strategy.Unlike traditional constant current charging methods,BPC strategy not only achieves comparable charging speeds but also facilitates V2G frequency regulation simultaneously.It significantly enhances battery cycle ampere-hour throughput and demonstrates remarkable life extension capabilities.For this interesting conclusion,adopting model identification and postmortem characterization to reveal the life regulation mechanism of BPC:it mitigates battery capacity loss attributed to loss of lithium-ion inventory(LLI)in graphite anodes by intermittently regulating the overall battery voltage and anode potential using a negative charging current.Then,from the perspective of internal side reaction,the life extension mechanism is further revealed as inhibition of solid electrolyte interphase(SEI)and lithium dendrite growth by regulating voltage with a bidirectional pulse current,and a semi-empirical life degradation model combining SEI and lithium dendrite growth is developed for BPC scenarios health management,the model parameters are identified by genetic algorithm with the life simulation exhibiting an accuracy exceeding 99%.This finding indicates that under typical rate conditions,adaptable BPC strategies can extend the service life of LFP battery by approximately 123%.Consequently,the developed advanced BPC strategy offers innovative perspectives and insights for the development of long-life battery applications in the future.
基金financially supported by the National Natural Science Foundation of China(No.52273081,No.22278329)Young Talent Support Plan of Xi’an Jiaotong University+2 种基金Natural Science Basic Research Program of Shaanxi(No.2022TD-27,No.2020-JC-09)the financial support from Swedish Research Council Grant(2021-05839)the“Young Talent Support Plan”of Xi’an Jiaotong University
文摘Inhomogeneous lithium-ion(Li^(+))deposition is one of the most crucial problems,which severely deteriorates the performance of solid-state lithium metal batteries(LMBs).Herein,we discovered that covalent organic framework(COF-1)with periodically arranged boron-oxygen dipole lithiophilic sites could directionally guide Li^(+)even deposition in asymmetric solid polymer electrolytes.This in situ prepared 3D cross-linked network Poly(ACMO-MBA)hybrid electrolyte simultaneously delivers outstanding ionic conductivity(1.02×10^(-3)S cm^(-1)at 30°C)and excellent mechanical property(3.5 MPa).The defined nanosized channel in COF-1 selectively conducts Li^(+)increasing Li^(+)transference number to 0.67.Besides,The COF-1 layer and Poly(ACMO-MBA)also participate in forming a boron-rich and nitrogen-rich solid electrolyte interface to further improve the interfacial stability.The Li‖Li symmetric cell exhibits remarkable cyclic stability over 1000 h.The Li‖NCM523 full cell also delivers an outstanding lifespan over 400 cycles.Moreover,the Li‖LiFePO_(4)full cell stably cycles with a capacity retention of 85%after 500 cycles.the Li‖LiFePO_(4)pouch full exhibits excellent safety performance under pierced and cut conditions.This work thereby further broadens and complements the application of COF materials in polymer electrolyte for dendrite-free and high-energy-density solid-state LMBs.
基金supported by Guangdong Provincial Basic and Applied Basic Research Fund,No.2021A1515011299(to KT)。
文摘Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.
文摘MicroRNAs(miRNAs)are a highly conserved class of small(18–24 nucleotides)non-coding RNAs that regulate a broad spectrum of biological processes.Aberrations or corruptions of miRNA functions may lead to deregulated cell proliferation,tumorigenesis,and ultimately,cancer.Increasing evidences suggested that a large fraction of miRNAs is regulated at the posttranscriptional stage,which impacts on the level and function of miRNAs during cell development and human diseases.Recently,several distinct mechanisms are emerging to regulate the biogenesis,stability and function of miRNAs at post-transcriptional level,such as specific binding to terminal loops of miRNA precursors(primiRNAs or pre-miRNAs)by RNA-binding proteins and 3’-terminal modifications by particular enzymes.Signaling cascades and post-translational modifications of the core components of RNA machinery also take part in the posttranscriptional regulation of miRNAs.
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).
文摘The small and scattered enterprise pattern in the county economy has formed numerous sporadic pollution sources, hindering the centralized treatment of the water environment, increasing the cost and difficulty of treatment. How enterprises can make reasonable decisions on their water environment behavior based on the external environment and their own factors is of great significance for scientifically and effectively designing water environment regulation mechanisms. Based on optimal control theory, this study investigates the design of contractual mechanisms for water environmental regulation for small and medium-sized enterprises. The enterprise is regarded as an independent economic entity that can adopt optimal control strategies to maximize its own interests. Based on the participation of multiple subjects including the government, enterprises, and the public, an optimal control strategy model for enterprises under contractual water environmental regulation is constructed using optimal control theory, and a method for calculating the amount of unit pollutant penalties is derived. The water pollutant treatment cost data of a paper company is selected to conduct empirical numerical analysis on the model. The results show that the increase in the probability of government regulation and public participation, as well as the decrease in local government protection for enterprises, can achieve the same regulatory effect while reducing the number of administrative penalties per unit. Finally, the implementation process of contractual water environmental regulation for small and medium-sized enterprises is designed.
基金supported by the National Natural Science Foundation of China(52222902 and 52079029)。
文摘Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water shortages and the overuse of fertilizers.The field experiment had twelve treatments and a control(CK)trial including two irrigation amounts(I1,100%ETm;I2,60%ETm;where ETm is the maximum evapotranspiration),two nitrogen applications(N1,360 kg ha^(−1);N2,120 kg ha^(−1))and three biochar application levels(B1,60 t ha^(−1);B_(2),30 t ha^(−1)and B3,0 t ha^(−1)).A multi-objective synergistic irrigation-nitrogen-biochar application system for improving tomato yield,quality,water and nitrogen use efficiency,and greenhouse emissions was developed by integrating the techniques of experimentation and optimization.First,a coupled irrigation-nitrogen-biochar plot experiment was arranged.Then,tomato yield and fruit quality parameters were determined experimentally to establish the response relationships between irrigation-nitrogen-biochar dosage and yield,comprehensive quality of tomatoes(TCQ),irrigation water use efficiency(IWUE),partial factor productivity of nitrogen(PFPN),and net greenhouse gas emissions(NGE).Finally,a multi-objective dynamic optimization regulation model of irrigation-nitrogen-biochar resource allocation at different growth stages of tomato was constructed which was solved by the fuzzy programming method.The results showed that the application of irrigation and nitrogen to biochar promoted increase in yield,IWUE and PFPN,while it had an inhibitory effect on NGE.In addition,the optimal allocation amounts of water and fertilizer were different under different scenarios.The yield of the S1 scenario increased by 8.31%compared to the B_(1)I_(1)N_(2) treatment;TCQ of the S2 scenario increased by 5.14%compared to the B_(2)I_(2)N_(1) treatment;IWUE of the S3 scenario increased by 10.01%compared to the B1I2N2 treatment;PFPN of the S4 scenario increased by 9.35%compared to the B_(1)I_(1)N_(2) treatment;and NGE of the S5 scenario decreased by 11.23%compared to the B_(2)I1N1 treatment.The optimization model showed that the coordination of multiple objectives considering yield,TCQ,IWUE,PFPN,and NGE increased on average from 4.44 to 69.02%compared to each treatment when the irrigation-nitrogen-biochar dosage was 205.18 mm,186 kg ha^(−1)and 43.31 t ha^(−1),respectively.This study provides a guiding basis for the sustainable management of water and fertilizer in greenhouse tomato production under drip irrigation fertilization conditions.
基金financially supported by the National Natural Science Foundation of China(U21A2078,22179042,and 12104170)the Natural Science Foundation of Fujian Province(2020J06021 and 2020J01064)Scientific Research Funds of Huaqiao University(23BS109)。
文摘Lead iodide(PbI2) is a vital raw material for preparing perovskite solar cells(PSCs),and it not only takes part in forming the light absorption layer but also remains in the grain boundary as a passivator.In other words,the PbI2 content in the precursor and as formed film will affect the efficiency and stability of the PSCs.With moderate residual PbI2,it passivates the bulk/surface defects of perovskite,reduces the interfacial recombination,promotes the perovskite stability,minimizes the device hysteresis,and so on.Deficient PbI2 residue will reduce the interfacial passivation effect and device performance.In addition to facilitating the non-radiative recombination,over PbI2 residue can also lead to electronic insulation in the grain boundary and deteriorate the device performance.However,the impact and regulation of PbI2 residue on the device performance and stability is still not fully understood.Herein,a comprehensive and detailed review is presented by discussing the PbI2 residue impact and its regulation strategies(i.e., elimination,facilitation and conversion of the residue PbI2) to manipulate the PbI2 content,distribution and forms.Finally,we also show future outlooks in this field,with an aim to help further the progression of high-efficiency and stable PSCs.
基金supported by the National Natural Science Foundation of China(32100448,32070558,32061143030,32170636)Natural Science Foundation of Jiangsu Province(BK20210799)+2 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the Seed Industry Revitalization Project of Jiangsu Province(JBGS[2021]009)the Shanghai Science and Technology Agriculture Project([2022]No.1–6)the Project of Zhongshan Biological Breeding Laboratory(BM2022008-029)。
文摘In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.
文摘By virtue of a 3∶1 complementary coordination strategy,a chiral heteroleptic metal-organic cage that con-tains divergent functional units,Pd‑R(Zn),was precisely constructed via self-assembly of monodentate variational Zn-salen ligands RZn and NADH(reduced nicotinamide adenine dinucleotide)mimic modified tridentate ligands with square-planar Pd ions.UV-Vis and luminescence spectra experiments reveal that different anions could selec-tively interact with different sites of Zn-salen modified metal-organic cages to achieve the structural regulation of cage compound,by using the differentiated host-guest electrostatic interactions of counter ions with metal-organic hosts.Compared to other anions,the presence of chloride ions caused the most significant fluorescence emission enhancement of Pd‑R(Zn),meanwhile,the UV-Vis absorption band attributed to the salen aromatic backbone showed an absorption decrease,and the metal-to-ligand induced peak displayed a blue shift effect.Circular dichro-ism and ^(1)H NMR spectra further demonstrate that the introduction of chloride anions is beneficial to keeping a more rigid scaffold.