Resistant starch formation in rice:Genetic regulation and beyond

Resistant starch(RS),a healthy dietary fiber,is a particular type of starch that has attracted much research attention in recent years.RS has important roles in reducing glycemic index,postprandial blood glucose levels,and serum cholesterol levels,thereby improving and preventing many diseases,such as diabetes,obesity,and cardiovascular disease.The formation of RS is influenced by intrinsic properties of starch(e.g.,starch granule structure,starch crystal structure,and amylose-to-amylopectin ratio)and non-starch components(e.g.,proteins,lipids,and sugars),aswell as storage and processing conditions.Recent studies have revealed that several starch-synthesis-related genes(SSRGs)are crucial for the formation of RS during seed development.Several transcription factors and mRNA splicing factors have been shown to affect the expression or splicing of SSRGs that regulate RS content,suggesting their potential roles in RS formation.This review focuses mainly on recent research progress on the genetic regulation of RS content and discusses the emerging genetic and molecular mechanisms of RS formation in rice.

Epigenetic Regulation of a Powdery Mildew Resistance Gene in Medicago truncatula

Dear Editor, Medicago truncatula is a model legume that is conge- neric with alfalfa （Medicago sativa）, a forage crop of global importance. Over the last decade, tremendous genetic and genomic tools have been developed for this model system, which has greatly facilitated the study of various aspects of legume genomics and biology. From an applied perspective, genomic information gained from M. truncatula is particu- larly useful for genetic improvement of cultivated alfalfa, a crop that is not amenable to genetic analysis because of its allogamous and autotetraploid nature （Yang et al., 2008）. For instance, M. truncatula can be used to clone the orthologs of many economically important genes in alfalfa,

Advances in studies on the physiological and molecular regulation of barley tillering

Tillering is a crucial trait closely associated with yield potential and environmental adaptation in cereal crops,regulated by the synergy of endogenous(genetic)and exogenous(environmental)factors.The physiological and molecular regulation of tillering has been intensively studied in rice and wheat.However,tillering research on barley is scarce.This review used the recent advances in bioinformatics to map all known and potential barley tiller development genes with their chromosomal genetic and physical positions.Many of them were mapped for the first time.We also discussed tillering regulation at genetic,physiological,and environmental levels.Moreover,we established a novel link between the genetic control of phytohormones and sugars with tillering.We provided evidence of how environmental cues and cropping systems help optimize the tiller number.This comprehensive review enhances the understanding of barley’s physiological and genetic mechanisms controlling tillering and other developmental traits.

Nonlinear Mathematical Simulation and Analysis of Dha Regulon for Glycerol Metabolism in Klebsiella pneumoniae

Glycerol may be converted to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae under anaerobic conditions and glycerol dismutation involves two parallel pathways controlled by the dha regulon. In this study, a fourteen-dimensional nonlinear dynamic system is presented to describe the continuous culture and multiplicity analysis, in which two regulated negative-feedback mechanisms of repression and enzyme inhibition are investigated. The model describing the expression of gene-mRNA-enzyme-product was established according to the repression of the dha regulon by 3-hydroxypropionaldehy (3-HPA). Comparisons between simulated and experimental results indicate that the model can be used to describe the production of 1,3-PD under continuous fermentation. The new model is translated into the corresponding S-system version. The robustness of this model is discussed by using the S-system model and the sensitivity analysis shows that the model is sufficiently robust. The influences of initial glycerol concentration and dilution rate on the biosynthesis of 1,3-PD and the stability of the dha regulon model are investigated. The intracellular concentrations of glycerol, 1,3-PD, 3-HPA, repressor mRNA, repressor, mRNA and protein levels of glycerol dehydratase (GDHt) and 1,3-PD oxydoreductase (PDOR) can be predicted for continuous cultivation. The results of simulation and analysis indicate that 3-HPA accumulation will repress the expression of the dha regulon at the transcriptional level. This model gives new insights into the regulation of glycerol metabolism in K. pneumoniae and explain some of the experimental observations.

Genetic and epigenetic regulators of retinal Müller glial cell reprogramming

Background:Retinal diseases characterized with irreversible loss of retinal nerve cells,such as optic atrophy and retinal degeneration,are the main causes of blindness.Current treatments for these diseases are very limited.An emerging treatment strategy is to induce the reprogramming of Müller glial cells to generate new retinal nerve cells,which could potentially restore vision.Main text:Müller glial cells are the predominant glial cells in retinae and play multiple roles to maintain retinal homeostasis.In lower vertebrates,such as in zebrafish,Müller glial cells can undergo cell reprogramming to regenerate new retinal neurons in response to various damage factors,while in mammals,this ability is limited.Interestingly,with proper treatments,Müller glial cells can display the potential for regeneration of retinal neurons in mammalian retinae.Recent studies have revealed that dozens of genetic and epigenetic regulators play a vital role in inducing the reprogramming of Müller glial cells in vivo.This review summarizes these critical regulators for Müller glial cell reprogramming and highlights their differences between zebrafish and mammals.Conclusions:A number of factors have been identified as the important regulators in Müller glial cell reprogramming.The early response of Müller glial cells upon acute retinal injury,such as the regulation in the exit from quiescent state,the initiation of reactive gliosis,and the re-entry of cell cycle of Müller glial cells,displays significant difference between mouse and zebrafish,which may be mediated by the diverse regulation of Notch and TGFβ(transforming growth factor-β)isoforms and different chromatin accessibility.

Regulators of liver cancer stem cells

Hepatocellular carcinoma(HCC)is a leading cause of cancer deaths.It is often detected at a stage when there are few therapeutic options.Liver cancer stem cells(LCSCs)are highly tumorigenic and resistant to chemotherapy and radiation therapy.Their presence in HCC is a major reason why HCC is difficult to treat.The development of LCSCs is regulated by a variety of factors.This review summarizes recent advances on the factors that regulate the development of LCSCs.Due to the importance of LCSCs in the development of HCC,a better understanding of how LCSCs are regulated will help to improve the treatments for HCC patients.

Macrophage senescence in health and diseases

Macrophage senescence,manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype,has long been consid-ered harmful.Persistent senescence of macrophages may lead to maladaptation,immune dysfunction,and finally the development of age-related diseases,infections,autoimmune diseases,and malignancies.However,it is a ubiquitous,multi-factorial,and dynamic complex phenomenon that also plays roles in remodeled processes,including wound repair and embryogenesis.In this review,we summarize some general molecular changes and several specific biomarkers during macrophage senescence,which may bring new sight to recognize senescent macrophages in different conditions.Also,we take an in-depth look at the functional changes in senescent macrophages,including metabolism,autophagy,polarization,phagocytosis,antigen presentation,and infiltration or recruitment.Furthermore,some degenerations and diseases associated with senescent macrophages as well as the mechanisms or relevant genetic regulations of senescent macrophages are integrated,not only emphasizing the possibility of regulating macrophage senescence to benefit age-associated diseases but also has an implication on the finding of potential tar-gets ordrugs clinically.

The genetic and epigenetic alterations in human hepatocellular carcinoma： a recent update

Hepatocellular carcinoma （HCC） is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-poptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and IncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.

Understanding the mechanistic regulation of ferroptosis in cancer:the gene matters

Ferroptosis has emerged as a crucial regulated cell death involved in a variety of physiological processes or pathological diseases,such as tumor suppression.Though initially being found from anticancer drug screening and considered not essential as apoptosis for growth and development,numerous studies have demonstrated that ferroptosis is tightly regulated by key genetic pathways and/or genes,including several tumor suppressors and oncogenes.In this review,we introduce the basic concepts of ferroptosis,characterized by the features of non-apoptotic,iron-dependent,and overwhelmed accumulation of lipid peroxides,and the underlying regulated circuits are considered to be pro-ferroptotic pathways.Then,we discuss several established lipid peroxidation defending systems within cells,including SLC7A11/GPX4,FSP1/CoQ,GCH1/BH4,and mitochondria DHODH/CoQ,all of which serve as anti-ferroptotic pathways to prevent ferroptosis.Moreover,we provide a comprehensive summary of the genetic regulation of ferroptosis via targeting the above-mentioned pro-ferroptotic or anti-ferroptotic pathways.The regulation of proand anti-ferroptotic pathways gives rise to more specific responses to the tumor cells in a contextdependent manner,highlighting the unceasing study and deeper understanding of mechanistic regulation of ferroptosis for the purpose of applying ferroptosis induction in cancer therapy.

Deciphering spike architecture formation towards yield improvement in wheat

Wheat is the most widely grown crop globally,providing 20%of the daily consumed calories and protein content around the world.With the growing global population and frequent occurrence of extreme weather caused by climate change,ensuring adequate wheat production is essential for food security.The archi-tecture of the inflorescence plays a crucial role in determining the grain number and size,which is a key trait for improving yield.Recent advances in wheat genomics and gene cloning techniques have improved our understanding of wheat spike development and its applications in breeding practices.Here,we summarize the genetic regulation network governing wheat spike formation,the strategies used for identifying and studying the key factors affecting spike architecture,and the progress made in breeding applications.Additionally,we highlight future directions that will aid in the regulatory mechanistic study of wheat spike determination and targeted breeding for grain yield improvement.

Profiling proteomic responses to hexokinase-II depletion in terpene-producing Saccharomyces cerevisiae

Hexokinase II(Hxk2)is a master protein in glucose-mediated transcriptional repression signaling pathway.De-grading Hxk2 through an auxin-inducible protein degradation previously doubled sesquiterpene(nerolidol)pro-duction at gram-per-liter levels in Saccharomyces cerevisiae.Global transcriptomics/proteomics profiles in Hxk2-deficient background are important to understanding genetic and molecular mechanisms for improved nerolidol production and guiding further strain optimization.Here,proteomic responses to Hxk2 depletion are investi-gated in the yeast strains harboring a GAL promoters-controlled nerolidol synthetic pathway,at the exponential and ethanol growth phases and in GAL80-wildtype and gal80Δbackgrounds.Carbon metabolic pathways and amino acid metabolic pathways show diversified responses to Hxk2 depletion and growth on ethanol,including upregulation of alternative carbon catabolism and respiration as well as downregulation of amino acid synthesis.De-repression of GAL genes may contribute to improved nerolidol production in Hxk2-depleted strains.Seven-teen transcription factors associated with upregulated genes are enriched.Validating Ash1-mediated repression on the RIM4 promoter shows the variation on the regulatory effects of different Ash1-binding sites and the syner-gistic effect of Ash1 and Hxk2-mediated repression.Further validation of individual promoters shows that HXT1 promoter activities are glucose-dependent in hxk2Δbackground,but much weaker than those in HXK2-wildtype background.In summary,inactivating HXK2 may relieve glucose repression on respiration and GAL promoters for improved bioproduction under aerobic conditions in S.cerevisiae.The proteomics profiles provide a better genetics overview for a better metabolic engineering design in Hxk2-deficient backgrounds.