Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is cruci...Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is crucial to advancing rice breeding program and supporting smallholder farmers.Transcription Activator-Like effectors(TALes)are key virulence factors in Xoo,with some targeting the susceptibility(S)genes such as the sugar transporter SWEET genes in rice.Among these,SWEET14 is an important S gene,with its promoter bound by the TALe TalC which exists across all sequenced African Xoo isolates.In the present study,we utilized CRISPR/Cas9-based cytidine and adenine base editors to alter the effector binding element(EBE)of TalC in the promoter of SWEET14 in rice cultivars Kitaake,IR24,and Zhonghua 11.Mutations with C to T changes in EBE led to reduced SWEET14 induction by TalC-containing Xoo strains,resulting in resistance to African Xoo isolates reliant on TalC for virulence.Conversely,A to G changes retained SWEET14 inducibility and susceptibility to Xoo in edited lines.Importantly,no off-target mutations were detected at predicted sites,and the edited lines exhibited no obvious defects in major agronomic traits in Kitaake.These results underscore the effectiveness of base editing systems for both molecular biology research and crop improvement endeavors.展开更多
Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide.The predominant type of primary liver cancer is hepatocellular carcinoma(HCC).Tumor vascular endothelial cells(VECs),a...Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide.The predominant type of primary liver cancer is hepatocellular carcinoma(HCC).Tumor vascular endothelial cells(VECs),a major component of cells in the microenvironment of HCC,play multifaceted roles in contributing to tumor angiogenesis,proliferation,and migration,as well as therapeutic resistance by attracting myeloid-derived suppressor cells and suppressing cytotoxic CD8 T cell differentiation and function.Recently,Wu et al reported that apatinib,an inhibitor of vascular endothelial growth factor receptor 2,can inhibit tumor VEC glycolysis by regulating phosphatidylinositol 3-kinase/protein kinase B/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 signaling pathway to suppress HCC progression.With great interest,this editorial paper aims to review the function and key molecular signaling pathways of tumor VECs in HCC initiation and progression and summarize potential treatment options in clinical trials.展开更多
The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation...The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctio...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctionassociated steatohepatitis(MASH)can progress to liver cirrhosis and hepatocellular carcinoma.Despite its growing burden,effective therapies for MASLD and MASH remain limited.Accumulating evidence indicates that short-chain fatty acids(SCFAs)modulate the activation of hepatic innate and adaptive immune cells,influencing liver inflammation and fibrosis.Moreover,SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity,affecting MASLD progression.This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation,fibrosis,and energy metabolism.Several key molecular signaling pathways are discussed.Clinical trials aiming to modulate SCFA production through different treatments are reviewed.Collectively,emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is featured by the accumulation of excessive fat in the liver.It is caused by many factors,such as overweight,obesity,diabetes,and high plasma levels of s...Metabolic dysfunction-associated steatotic liver disease(MASLD)is featured by the accumulation of excessive fat in the liver.It is caused by many factors,such as overweight,obesity,diabetes,and high plasma levels of sugar,cholesterol,and triglycerides.MASLD is commonly associated with type 2 diabetes(T2D),which is characterized by a pathophysiological deficiency of insulin secretion due to impaired function of pancreatic βcells and insulin resistance.T2D has become a global pandemic that influences more than 21.7 million people worldwide.Preclinical and clinical studies have been performed to investigate molecular crosslinks between T2D and MASLD and their therapeutic strategies.Accumulating evidence has demonstrated that macrophages are cellular mediators that contribute to the progression of MASLD and T2D by impacting the resolution of inflammation.Different types of macrophages are involved in the pathogenesis of MASLD and T2D,including liver-resident macrophages or Kupffer cells,monocyte-derived macrophages,and adipose tissue macrophages.These macrophages secrete enzymes,chemokines,cytokines,as well as exosomes,to induce metabolic inflammation and insulin resistance,immune cell infiltration,and tissue injury.In this review,we provide a comprehensive summary of the molecular and cellular interactions between MASLD and T2D with a specific discussion of the critical roles of macrophages and inflammation.The underlying molecular mechanisms and the associated therapeutic targets and strategies are also reviewed.展开更多
Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ...Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic rats.Its effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were measured.Results:Significant increase in activities of SOD.CAT, GST while,a decrease in LPO content was observed.Whereas,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAK,40.5 mg/g of QEK and 12.12 mg/g of QE,respectively.On the other hand.FRAP assay results of M.oleifera leaves was(85.00±5.00)μM of Fe^+/g of extract powder.Conclusions:The significant antioxidant activities of M.oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.展开更多
Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies,such as hepatitis viral infection,alcohol consumption,and metabolicassociated fatty liver disease.It is commonly associate...Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies,such as hepatitis viral infection,alcohol consumption,and metabolicassociated fatty liver disease.It is commonly associated with liver injury,inflammation,and cell death.Liver fibrosis is characterized by abnormal accumulation of extracellular matrix components that are expressed by liver myofibroblasts such as collagens and alpha-smooth actin proteins.Activated hepatic stellate cells contribute to the major population of myofibroblasts.Many treatments for liver fibrosis have been investigated in clinical trials,including dietary supplementation(e.g.,vitamin C),biological treatment(e.g.,simtuzumab),drug(e.g.,pegbelfermin and natural herbs),genetic regulation(e.g.,non-coding RNAs),and transplantation of stem cells(e.g.,hematopoietic stem cells).However,none of these treatments has been approved by Food and Drug Administration.The treatment efficacy can be evaluated by histological staining methods,imaging methods,and serum biomarkers,as well as fibrosis scoring systems,such as fibrosis-4 index,aspartate aminotransferase to platelet ratio,and non-alcoholic fatty liver disease fibrosis score.Furthermore,the reverse of liver fibrosis is slowly and frequently impossible for advanced fibrosis or cirrhosis.To avoid the lifethreatening stage of liver fibrosis,anti-fibrotic treatments,especially for combined behavior prevention,biological treatment,drugs or herb medicines,and dietary regulation are needed.This review summarizes the past studies and current and future treatments for liver fibrosis.展开更多
Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's dis...Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.展开更多
Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,...Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.展开更多
Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral...Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral infection,and autoimmune hepatitis,which can lead to liver fibrosis,cirrhosis,and cancer.Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD.Molecular signaling pathways such as AMPactivated protein kinase(AMPK),C-Jun N-terminal kinase,and peroxisome proliferator-activated receptors(PPARs)are implicated in the pathogenesis of CLD.Therefore,antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD,NAFLD,and hepatocellular carcinoma(HCC).In this review,we summarize some powerful products that can be potential applied in all the stages of CLD,from ALD/NAFLD to HCC.The selected agents such asβ-sitosterol,curcumin,genistein,and silymarin can regulate the activation of several important molecules,including AMPK,Farnesoid X receptor,nuclear factor erythroid 2-related factor-2,PPARs,phosphatidylinositol-3-kinase,and lysyl oxidase-like proteins.In addition,clinical trials are undergoing to evaluate their efficacy and safety.展开更多
Pancreatic cancer(PC)is the third-leading cause of cancer deaths.The overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold b...Pancreatic cancer(PC)is the third-leading cause of cancer deaths.The overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold by 2060.Many factors such as genetic and environmental factors and metabolic diseases can drive PC development and progression.The most common type of PC in the clinic is pancreatic ductal adenocarcinoma,comprising approximately 90%of PC cases.Multiple pathogenic processes including but not limited to inflammation,fibrosis,angiogenesis,epithelial-mesenchymal transition,and proliferation of cancer stem cells are involved in the initiation and progression of PC.Early diagnosis is essential for curable therapy,for which a combined panel of serum markers is very helpful.Although some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment,current therapies have not shown promising outcomes.Fortunately,the development of novel immunotherapies,such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells,combined with therapies such as neoadjuvant therapy plus surgery,and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC patients.Herein,the pathogenesis,molecular signaling pathways,diagnostic markers,prognosis,and potential treatments in completed,ongoing,and recruiting clinical trials for PC were reviewed.展开更多
Retrotransposons,a type of DNA fragment that can mobilize itself on genome,can generate genetic variations and develop for molecular markers based on the insertion polymorphism.Zinc finger proteins(ZNFs)are among the ...Retrotransposons,a type of DNA fragment that can mobilize itself on genome,can generate genetic variations and develop for molecular markers based on the insertion polymorphism.Zinc finger proteins(ZNFs)are among the most abundant proteins in eukaryotic animals,and their functions are extraordinarily diverse and particularly important in gene regulation.In the current study,bioinformatic prediction was performed to screen for retrotransposon insertion polymorphisms(RIPs)in six ZNF genes(ZNF2,ZNF3,ZNF7,ZNF8,ZNF10 and ZNF12).Six RIPs in these ZNFs,including one short interspersed nuclear element(SINE)RIP in intron 1 and one long interspersed nuclear element 1(L1)RIP in intron 3 of ZNF2,one SINE RIP in 5′flanking region and one SINE RIP in intron 2 of ZNF3,one SINE RIP in 3′UTR of ZNF7 and one L1 RIP in intron 2 of ZNF12,were discovered and their presence was confirmed by PCR.The impact of the SINE RIP in the first intron of ZNF2,which is close to the core promoter of ZNF2,on the gene activity was investigated by dual-luciferase assay in three cell lines.Our results showed that the SINE insertion in the intron 1 of ZNF2 repressed the core promoter activity extremely significantly(P<0.01)in cervical cancer cells and porcine primary embryonic fibroblasts(HeLa and PEF),thus SINE may act as a repressor.This SINE RIP also significantly(P<0.05)affected the corrected back fat thickness in Yorkshire pigs.The corrected back fat thickness of individuals with SINE insertion in the first intron of ZNF2 was significantly(P<0.05)higher than that of individuals without SINE insertion.In summary,our data suggested that RIPs play important roles in the genetic variations of these ZNF genes and SINE RIP in the intron 1 of ZNF2 may provide a useful molecular marker for the screening of fat deposition in the pig breeding.展开更多
Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and ...Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.展开更多
The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight fo...The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19(COVID-19)pandemic.Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms,including fever,cough,fatigue,and loss of smell and taste.However,many individuals develop pneumonia,acute respiratory distress syndrome,septic shock,and multiorgan dysfunction.In addition to these primarily respiratory symptoms,SARS-CoV-2 can also infiltrate the central nervous system,which may damage the blood-brain barrier and the neuron's synapses.Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves,leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions.Additionally,SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier.As a result,this exacerbates pro-inflammatory responses both locally and systemically,resulting in impaired clinical outcomes.Recent evidence has highlighted the complex interactions that mutually modulate respiratory,neurological,and gastrointestinal function.In this review,we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis.We further highlight targeting specific responses to SARS-CoV-2 for the development of novel,urgently needed therapeutic interventions.Finally,we propose a prospective related to the individuals from Low-and Middle-Income countries.Here,the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.展开更多
Metabolite composition is strongly affected by genotype,environment,and interactions between genotype and environment,although the extent of variation caused by these factors may depend upon the type of metabolite.To ...Metabolite composition is strongly affected by genotype,environment,and interactions between genotype and environment,although the extent of variation caused by these factors may depend upon the type of metabolite.To characterize the complexity of genotype,environment,and their interaction in hybrid seeds,50 genetically diverse non-genetically modified(GM) maize hybrids were grown in six geographically diverse locations in North America.Polar metabolites from 553 harvested corn grain samples were isolated and analyzed by gas chromatography–mass spectrometry and 45 metabolites detected in all samples were used to generate a data matrix for statistical analysis.There was moderate variation among biological replicates and across genotypes and test sites.The genotype effects were detected by univariate and Hierarchical clustering analyses(HCA) when environmental effects were excluded.Overall,environment exerted larger effects than genotype,and polar metabolite accumulation showed a geographic effect.We conclude that it is possible to increase seed polar metabolite content in hybrid corn by selection of appropriate inbred lines and growing regions.展开更多
Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic disea...Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.展开更多
Transcription factors(TFs)function as master regulators in multiple signaling pathways and govern diverse developmental and adaptive processes in plants.Some TFs identified in crop plants play critical roles in regula...Transcription factors(TFs)function as master regulators in multiple signaling pathways and govern diverse developmental and adaptive processes in plants.Some TFs identified in crop plants play critical roles in regulating yield through changes in plant architecture,including roots,stems,leaves,flowers,fruits,and grains.Although altering crop architecture can increase yields,the extent of yield enhancement is frequently hampered by diseases.Developing new crop varieties with improved yields and enhanced disease resistance remains challenging because immune system activation often impairs plant growth.Recently,approaches using TF engineering have made substantial progress in elevating both growth performance and disease resistance.However,most of these techniques rely on traditional transgenic methods.This review highlights discoveries in the last decade demonstrating improvements in growth performance,yield and immunity through TF engineering.We focus mainly on changes in plant architecture related to improved yield and disease resistance.We conclude with perspectives on the potential application of these discoveries for generating desirable crop traits by merging the most noteworthy biotechnology approaches,such as clustered regularly interspaced small palindromic repeats(CRISPR)/CRISPR-associated protein 9-mediated genome editing,with canonical molecular biology.展开更多
Human adiponectin receptors(AdipoRs)and membrane progestin receptors(mPRs,members of the progestin and adipoQ receptor[PAQR]family)are seven-transmembrane receptors involved in the regulation of metabolism and cancer ...Human adiponectin receptors(AdipoRs)and membrane progestin receptors(mPRs,members of the progestin and adipoQ receptor[PAQR]family)are seven-transmembrane receptors involved in the regulation of metabolism and cancer development,which share structural similarities with G protein-coupled receptors.Plant PAQR-like sensors(PLSs)are homologous to human PAQRs but their molecular functions remain unclear.In this study,we found that PLSs associate with cell surface receptor-like kinases through KIN7 and positively regulate plant immune responses,stomatal defense,and disease resistance.Moreover,PLSs activate heterotrimeric G proteins(Gαβγ)to transduce immune signals and regulate the exchange of GDP for GTP on GPA1.Further analyses revealed that the immune function of PLSs is conserved in rice and soybean and contributes to resistance against multiple diseases.Notably,heterologous expression of human AdipoRs in Arabidopsis replicates the immune functions of PLSs.Collectively,our findings demonstrate that PLSs are key modulators of plant immunity via the G-protein pathway and highlight the potential application of human genes in enhancing plant disease resistance.展开更多
Pulmonary fibrosis, a progressive chronic disease with a high mortality rate, has limited treatment options. Currently, lung transplantation remains the only effective treatment. Here we report that a small RNA, HJT-s...Pulmonary fibrosis, a progressive chronic disease with a high mortality rate, has limited treatment options. Currently, lung transplantation remains the only effective treatment. Here we report that a small RNA, HJT-sRNA-m7, from a Chinese herbal medicine Hong Jing Tian(HJT, RHODIOHAE CRENULATAE RADIX ET RHIZOMA, Rhodiola crenulata) can effectively reduce the expressions of fibrotic hallmark genes and proteins both in alveolar in vitro and in mouse lung tissues in vivo. We also discovered over one hundred oil-soluble chemicals from HJT decoctions, most of which are found in lipid extracts from other Chinese herbals decoctions, including Pu Gong Ying(PGY, TARAXACI HERBA, Taraxacum mongolicum), Chuan Xin Lian(CXL, changed to "ANDROGRAPHIS HERBA, Andrographis paniculata"), and Jin Yin Hua(JYH, lonicera japonica or Honeysuckle). We identified the active component in these decoctions as two forms of phosphocholines, PC(18:0/18:2) and PC(16:0/18:2). These PCs potentially could form liposomes with small RNAs to enter human alveolar and gastric cells. Our experimental results suggest an unprecendent lipid complex route through which botanic small RNA can enter human bodies.Our results provide an innovative treatment strategy for oral delivery of siRNAs as therapeutic medication.展开更多
A genome-wide screen for mutants showing altered brassinosteroid （BR） sensitivity or bril-like phenotypes resulted in the identification of two new mutant alleles of TWISTED DWARF 1 （TWD1）, twd1-4, and twdl-5. Pre...A genome-wide screen for mutants showing altered brassinosteroid （BR） sensitivity or bril-like phenotypes resulted in the identification of two new mutant alleles of TWISTED DWARF 1 （TWD1）, twd1-4, and twdl-5. Pre- vious studies indicated that TWD1, also named as ULTRACURVATA 2 or FKBP42, associates with auxin efflux transporters and is essential for their biological functions. Although earlier reports showed that BR signaling is downregulated in twdl, how TWD1 is integrated in BR signaling has not been elucidated. Here, we provide ge- netic and biochemical evidence demonstrating that TWD1 interacts with the BR receptor BRI1 in vivo in a BR- independent manner. Further analyses indicated that TWD1 modulates the BR signal transduction not by altering ER quality control or protein abundance of BRI1; instead, TWD1 appears to be critical in BR- induced interaction of BRI1 and its co-receptor BAK1, as well as BR-induced phosphorylation of these two proteins. These results provide better understanding of the early events of the BR signaling pathway.展开更多
基金supported by a sub-award to the University of Missouri from the Heinrich Heine University of Dusseldorf funded by the Bill&Melinda Gates Foundation(OPP1155704)(Bing Yang)and the China Scholar Council(Chenhao Li,as a joint Ph.D.student).
文摘Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is crucial to advancing rice breeding program and supporting smallholder farmers.Transcription Activator-Like effectors(TALes)are key virulence factors in Xoo,with some targeting the susceptibility(S)genes such as the sugar transporter SWEET genes in rice.Among these,SWEET14 is an important S gene,with its promoter bound by the TALe TalC which exists across all sequenced African Xoo isolates.In the present study,we utilized CRISPR/Cas9-based cytidine and adenine base editors to alter the effector binding element(EBE)of TalC in the promoter of SWEET14 in rice cultivars Kitaake,IR24,and Zhonghua 11.Mutations with C to T changes in EBE led to reduced SWEET14 induction by TalC-containing Xoo strains,resulting in resistance to African Xoo isolates reliant on TalC for virulence.Conversely,A to G changes retained SWEET14 inducibility and susceptibility to Xoo in edited lines.Importantly,no off-target mutations were detected at predicted sites,and the edited lines exhibited no obvious defects in major agronomic traits in Kitaake.These results underscore the effectiveness of base editing systems for both molecular biology research and crop improvement endeavors.
文摘Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide.The predominant type of primary liver cancer is hepatocellular carcinoma(HCC).Tumor vascular endothelial cells(VECs),a major component of cells in the microenvironment of HCC,play multifaceted roles in contributing to tumor angiogenesis,proliferation,and migration,as well as therapeutic resistance by attracting myeloid-derived suppressor cells and suppressing cytotoxic CD8 T cell differentiation and function.Recently,Wu et al reported that apatinib,an inhibitor of vascular endothelial growth factor receptor 2,can inhibit tumor VEC glycolysis by regulating phosphatidylinositol 3-kinase/protein kinase B/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 signaling pathway to suppress HCC progression.With great interest,this editorial paper aims to review the function and key molecular signaling pathways of tumor VECs in HCC initiation and progression and summarize potential treatment options in clinical trials.
文摘The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctionassociated steatohepatitis(MASH)can progress to liver cirrhosis and hepatocellular carcinoma.Despite its growing burden,effective therapies for MASLD and MASH remain limited.Accumulating evidence indicates that short-chain fatty acids(SCFAs)modulate the activation of hepatic innate and adaptive immune cells,influencing liver inflammation and fibrosis.Moreover,SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity,affecting MASLD progression.This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation,fibrosis,and energy metabolism.Several key molecular signaling pathways are discussed.Clinical trials aiming to modulate SCFA production through different treatments are reviewed.Collectively,emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is featured by the accumulation of excessive fat in the liver.It is caused by many factors,such as overweight,obesity,diabetes,and high plasma levels of sugar,cholesterol,and triglycerides.MASLD is commonly associated with type 2 diabetes(T2D),which is characterized by a pathophysiological deficiency of insulin secretion due to impaired function of pancreatic βcells and insulin resistance.T2D has become a global pandemic that influences more than 21.7 million people worldwide.Preclinical and clinical studies have been performed to investigate molecular crosslinks between T2D and MASLD and their therapeutic strategies.Accumulating evidence has demonstrated that macrophages are cellular mediators that contribute to the progression of MASLD and T2D by impacting the resolution of inflammation.Different types of macrophages are involved in the pathogenesis of MASLD and T2D,including liver-resident macrophages or Kupffer cells,monocyte-derived macrophages,and adipose tissue macrophages.These macrophages secrete enzymes,chemokines,cytokines,as well as exosomes,to induce metabolic inflammation and insulin resistance,immune cell infiltration,and tissue injury.In this review,we provide a comprehensive summary of the molecular and cellular interactions between MASLD and T2D with a specific discussion of the critical roles of macrophages and inflammation.The underlying molecular mechanisms and the associated therapeutic targets and strategies are also reviewed.
基金National Medicinal Plants Board. Govt,of India,New Delhi,India for providing financial assistance in the form of Senior Research Fellowship to cam' out the present study
文摘Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic rats.Its effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were measured.Results:Significant increase in activities of SOD.CAT, GST while,a decrease in LPO content was observed.Whereas,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAK,40.5 mg/g of QEK and 12.12 mg/g of QE,respectively.On the other hand.FRAP assay results of M.oleifera leaves was(85.00±5.00)μM of Fe^+/g of extract powder.Conclusions:The significant antioxidant activities of M.oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.
文摘Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies,such as hepatitis viral infection,alcohol consumption,and metabolicassociated fatty liver disease.It is commonly associated with liver injury,inflammation,and cell death.Liver fibrosis is characterized by abnormal accumulation of extracellular matrix components that are expressed by liver myofibroblasts such as collagens and alpha-smooth actin proteins.Activated hepatic stellate cells contribute to the major population of myofibroblasts.Many treatments for liver fibrosis have been investigated in clinical trials,including dietary supplementation(e.g.,vitamin C),biological treatment(e.g.,simtuzumab),drug(e.g.,pegbelfermin and natural herbs),genetic regulation(e.g.,non-coding RNAs),and transplantation of stem cells(e.g.,hematopoietic stem cells).However,none of these treatments has been approved by Food and Drug Administration.The treatment efficacy can be evaluated by histological staining methods,imaging methods,and serum biomarkers,as well as fibrosis scoring systems,such as fibrosis-4 index,aspartate aminotransferase to platelet ratio,and non-alcoholic fatty liver disease fibrosis score.Furthermore,the reverse of liver fibrosis is slowly and frequently impossible for advanced fibrosis or cirrhosis.To avoid the lifethreatening stage of liver fibrosis,anti-fibrotic treatments,especially for combined behavior prevention,biological treatment,drugs or herb medicines,and dietary regulation are needed.This review summarizes the past studies and current and future treatments for liver fibrosis.
基金supported by the National Institute on Aging (NIA)National Institutes of Health (NIH)+3 种基金Nos.K99AG065645,R00AG065645R00AG065645-04S1 (to SK)NIH research grants,NINDS,No.R01 NS115834NINDS/NIA,No.R01 NS115834-02S1 (to LG)。
文摘Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.
文摘Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.
文摘Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral infection,and autoimmune hepatitis,which can lead to liver fibrosis,cirrhosis,and cancer.Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD.Molecular signaling pathways such as AMPactivated protein kinase(AMPK),C-Jun N-terminal kinase,and peroxisome proliferator-activated receptors(PPARs)are implicated in the pathogenesis of CLD.Therefore,antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD,NAFLD,and hepatocellular carcinoma(HCC).In this review,we summarize some powerful products that can be potential applied in all the stages of CLD,from ALD/NAFLD to HCC.The selected agents such asβ-sitosterol,curcumin,genistein,and silymarin can regulate the activation of several important molecules,including AMPK,Farnesoid X receptor,nuclear factor erythroid 2-related factor-2,PPARs,phosphatidylinositol-3-kinase,and lysyl oxidase-like proteins.In addition,clinical trials are undergoing to evaluate their efficacy and safety.
文摘Pancreatic cancer(PC)is the third-leading cause of cancer deaths.The overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold by 2060.Many factors such as genetic and environmental factors and metabolic diseases can drive PC development and progression.The most common type of PC in the clinic is pancreatic ductal adenocarcinoma,comprising approximately 90%of PC cases.Multiple pathogenic processes including but not limited to inflammation,fibrosis,angiogenesis,epithelial-mesenchymal transition,and proliferation of cancer stem cells are involved in the initiation and progression of PC.Early diagnosis is essential for curable therapy,for which a combined panel of serum markers is very helpful.Although some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment,current therapies have not shown promising outcomes.Fortunately,the development of novel immunotherapies,such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells,combined with therapies such as neoadjuvant therapy plus surgery,and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC patients.Herein,the pathogenesis,molecular signaling pathways,diagnostic markers,prognosis,and potential treatments in completed,ongoing,and recruiting clinical trials for PC were reviewed.
基金supported by the National Natural Science Foundation of China(32002146 and 31872977)the China Postdoctoral Science Foundation(2020M671630)+3 种基金the Jiangsu Postdoctoral Science Foundation of China(2021K221B)to Chen Caithe Jiangsu Agriculture Science and Technology Innovation Fund,China[CX(19)2016]the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe High-end Talent Support Program of Yangzhou University,China to Song Chengyi。
文摘Retrotransposons,a type of DNA fragment that can mobilize itself on genome,can generate genetic variations and develop for molecular markers based on the insertion polymorphism.Zinc finger proteins(ZNFs)are among the most abundant proteins in eukaryotic animals,and their functions are extraordinarily diverse and particularly important in gene regulation.In the current study,bioinformatic prediction was performed to screen for retrotransposon insertion polymorphisms(RIPs)in six ZNF genes(ZNF2,ZNF3,ZNF7,ZNF8,ZNF10 and ZNF12).Six RIPs in these ZNFs,including one short interspersed nuclear element(SINE)RIP in intron 1 and one long interspersed nuclear element 1(L1)RIP in intron 3 of ZNF2,one SINE RIP in 5′flanking region and one SINE RIP in intron 2 of ZNF3,one SINE RIP in 3′UTR of ZNF7 and one L1 RIP in intron 2 of ZNF12,were discovered and their presence was confirmed by PCR.The impact of the SINE RIP in the first intron of ZNF2,which is close to the core promoter of ZNF2,on the gene activity was investigated by dual-luciferase assay in three cell lines.Our results showed that the SINE insertion in the intron 1 of ZNF2 repressed the core promoter activity extremely significantly(P<0.01)in cervical cancer cells and porcine primary embryonic fibroblasts(HeLa and PEF),thus SINE may act as a repressor.This SINE RIP also significantly(P<0.05)affected the corrected back fat thickness in Yorkshire pigs.The corrected back fat thickness of individuals with SINE insertion in the first intron of ZNF2 was significantly(P<0.05)higher than that of individuals without SINE insertion.In summary,our data suggested that RIPs play important roles in the genetic variations of these ZNF genes and SINE RIP in the intron 1 of ZNF2 may provide a useful molecular marker for the screening of fat deposition in the pig breeding.
文摘Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.
基金Supported by National Institutes of Health grants,No.R01AI129745,No.R21MH113455,No.R01DA052845,and No.R01AI113883(to Byrareddy SN).
文摘The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19(COVID-19)pandemic.Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms,including fever,cough,fatigue,and loss of smell and taste.However,many individuals develop pneumonia,acute respiratory distress syndrome,septic shock,and multiorgan dysfunction.In addition to these primarily respiratory symptoms,SARS-CoV-2 can also infiltrate the central nervous system,which may damage the blood-brain barrier and the neuron's synapses.Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves,leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions.Additionally,SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier.As a result,this exacerbates pro-inflammatory responses both locally and systemically,resulting in impaired clinical outcomes.Recent evidence has highlighted the complex interactions that mutually modulate respiratory,neurological,and gastrointestinal function.In this review,we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis.We further highlight targeting specific responses to SARS-CoV-2 for the development of novel,urgently needed therapeutic interventions.Finally,we propose a prospective related to the individuals from Low-and Middle-Income countries.Here,the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.
基金financially supported by DuP ont–Pioneer HiB red
文摘Metabolite composition is strongly affected by genotype,environment,and interactions between genotype and environment,although the extent of variation caused by these factors may depend upon the type of metabolite.To characterize the complexity of genotype,environment,and their interaction in hybrid seeds,50 genetically diverse non-genetically modified(GM) maize hybrids were grown in six geographically diverse locations in North America.Polar metabolites from 553 harvested corn grain samples were isolated and analyzed by gas chromatography–mass spectrometry and 45 metabolites detected in all samples were used to generate a data matrix for statistical analysis.There was moderate variation among biological replicates and across genotypes and test sites.The genotype effects were detected by univariate and Hierarchical clustering analyses(HCA) when environmental effects were excluded.Overall,environment exerted larger effects than genotype,and polar metabolite accumulation showed a geographic effect.We conclude that it is possible to increase seed polar metabolite content in hybrid corn by selection of appropriate inbred lines and growing regions.
文摘Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.
基金supported by Basic Science Research Program and LAMP Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(Nos.RS-2021-NR065275,RS-2023-00301974)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.RS-2022-NR070837,RS-2025-00559795)+1 种基金grants from the New Breeding Technologies Development Program(RS-2024-00322125)Rural Development Administration,Republic of Korea.
文摘Transcription factors(TFs)function as master regulators in multiple signaling pathways and govern diverse developmental and adaptive processes in plants.Some TFs identified in crop plants play critical roles in regulating yield through changes in plant architecture,including roots,stems,leaves,flowers,fruits,and grains.Although altering crop architecture can increase yields,the extent of yield enhancement is frequently hampered by diseases.Developing new crop varieties with improved yields and enhanced disease resistance remains challenging because immune system activation often impairs plant growth.Recently,approaches using TF engineering have made substantial progress in elevating both growth performance and disease resistance.However,most of these techniques rely on traditional transgenic methods.This review highlights discoveries in the last decade demonstrating improvements in growth performance,yield and immunity through TF engineering.We focus mainly on changes in plant architecture related to improved yield and disease resistance.We conclude with perspectives on the potential application of these discoveries for generating desirable crop traits by merging the most noteworthy biotechnology approaches,such as clustered regularly interspaced small palindromic repeats(CRISPR)/CRISPR-associated protein 9-mediated genome editing,with canonical molecular biology.
基金supported by grants from the Biological Breeding-National Science and Technology Major Project(2023ZD04070)the National Natural Science Foundation of China(32070285 and 32270251)+2 种基金the Chinese Universities Scientific Fund of China Agricultural University(no.2023RC011 to D.C.)the Pinduoduo-China Agricultural University Research Fund(grant no.PC2023A01005)funded by the National Institute of General Medical Sciences of the National Institutes of Health(grant no.R01GM121445).
文摘Human adiponectin receptors(AdipoRs)and membrane progestin receptors(mPRs,members of the progestin and adipoQ receptor[PAQR]family)are seven-transmembrane receptors involved in the regulation of metabolism and cancer development,which share structural similarities with G protein-coupled receptors.Plant PAQR-like sensors(PLSs)are homologous to human PAQRs but their molecular functions remain unclear.In this study,we found that PLSs associate with cell surface receptor-like kinases through KIN7 and positively regulate plant immune responses,stomatal defense,and disease resistance.Moreover,PLSs activate heterotrimeric G proteins(Gαβγ)to transduce immune signals and regulate the exchange of GDP for GTP on GPA1.Further analyses revealed that the immune function of PLSs is conserved in rice and soybean and contributes to resistance against multiple diseases.Notably,heterologous expression of human AdipoRs in Arabidopsis replicates the immune functions of PLSs.Collectively,our findings demonstrate that PLSs are key modulators of plant immunity via the G-protein pathway and highlight the potential application of human genes in enhancing plant disease resistance.
基金supported by the Ministry of Science and Technology of China (2015CB553406)the National Natural Science Foundation of China (81230002, 81490531)the Ministry of Education (IRT1121, B08007)
文摘Pulmonary fibrosis, a progressive chronic disease with a high mortality rate, has limited treatment options. Currently, lung transplantation remains the only effective treatment. Here we report that a small RNA, HJT-sRNA-m7, from a Chinese herbal medicine Hong Jing Tian(HJT, RHODIOHAE CRENULATAE RADIX ET RHIZOMA, Rhodiola crenulata) can effectively reduce the expressions of fibrotic hallmark genes and proteins both in alveolar in vitro and in mouse lung tissues in vivo. We also discovered over one hundred oil-soluble chemicals from HJT decoctions, most of which are found in lipid extracts from other Chinese herbals decoctions, including Pu Gong Ying(PGY, TARAXACI HERBA, Taraxacum mongolicum), Chuan Xin Lian(CXL, changed to "ANDROGRAPHIS HERBA, Andrographis paniculata"), and Jin Yin Hua(JYH, lonicera japonica or Honeysuckle). We identified the active component in these decoctions as two forms of phosphocholines, PC(18:0/18:2) and PC(16:0/18:2). These PCs potentially could form liposomes with small RNAs to enter human alveolar and gastric cells. Our experimental results suggest an unprecendent lipid complex route through which botanic small RNA can enter human bodies.Our results provide an innovative treatment strategy for oral delivery of siRNAs as therapeutic medication.
文摘A genome-wide screen for mutants showing altered brassinosteroid （BR） sensitivity or bril-like phenotypes resulted in the identification of two new mutant alleles of TWISTED DWARF 1 （TWD1）, twd1-4, and twdl-5. Pre- vious studies indicated that TWD1, also named as ULTRACURVATA 2 or FKBP42, associates with auxin efflux transporters and is essential for their biological functions. Although earlier reports showed that BR signaling is downregulated in twdl, how TWD1 is integrated in BR signaling has not been elucidated. Here, we provide ge- netic and biochemical evidence demonstrating that TWD1 interacts with the BR receptor BRI1 in vivo in a BR- independent manner. Further analyses indicated that TWD1 modulates the BR signal transduction not by altering ER quality control or protein abundance of BRI1; instead, TWD1 appears to be critical in BR- induced interaction of BRI1 and its co-receptor BAK1, as well as BR-induced phosphorylation of these two proteins. These results provide better understanding of the early events of the BR signaling pathway.
