Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal...Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal models have led to the identification of twelve aging hallmarks that shared several features:its age-associated manifestation.展开更多
Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expr...Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.展开更多
Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to neurons.In addition to these roles,they play crucial roles in modulating synaptic functions,develo...Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to neurons.In addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).展开更多
The pulse cowpea [Vigna unguiculata (L.) Walp] holds a significant agricultural position in Uganda, ranking fourth among legume crops, following common beans, groundnuts, and soybeans. Known for its versatility, cowpe...The pulse cowpea [Vigna unguiculata (L.) Walp] holds a significant agricultural position in Uganda, ranking fourth among legume crops, following common beans, groundnuts, and soybeans. Known for its versatility, cowpeas are consumable at various developmental stages, from early seedling to maturity. However, the crop faces persistent pest challenges at each stage, leading to substantial yield losses. In Uganda, chemical insecticides are the primary pest control means, but their increased and excessive use raises environmental, health, and economic concerns. This has prompted a quest for alternative and sustainable solutions, prompting an exploration of botanical insecticides. This study, conducted at Makerere University Agricultural Research Institute (MUARIK), aimed to evaluate the effectiveness of three selected botanical insecticides versus four established chemical insecticides for managing cowpea insect pests under field conditions. The treatments included: Carbofuran, Cypermethrin 10% EC, Dimethoate, Pestwin, Pyrethrum ewc , Pyrethrum 5ew, Profenofos 40% Cypermethrin 4% EC mix, and Untreated, arranged in a randomized complete block design with three replications. The significant pests studied were aphids, thrips, pod-sucking bugs, and legume pod borer. Results indicated substantial impacts of the treatments on pest infestation, with Profenofos 40% Cypermethrin 4% EC being the most effective against most pests. The plant parameter, plant height, was significantly affected by treatments in 2016B, while the number of pods was impacted in 2017A. Pestwin, a botanical insecticide blend (containing Azadirachtin indica, Pongamia pinnata, and Ricinus communis extracts) demonstrated superior efficacy against cowpea aphids. Moreover, it positively influenced plant height, number of pods, and pod biomass, surpassing many chemical insecticides. Pestwin’s environmental friendliness positions it as a potential contributor to reducing environmental pollution, making it a promising candidate for inclusion in IPM programs. Overall, the study underscores the importance of exploring botanical alternatives to chemical insecticides for sustainable pest management in cowpea cultivation.展开更多
Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods...Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.展开更多
Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with ...Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.展开更多
Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial in...Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.展开更多
Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression....Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression. Early introduction of immunosuppression forms the mainstay of medical IBD management. Large inter-individual variability in drug responses, in terms of both efficacy and toxicity, leads to high rates of therapeutic failure in the management of IBD. Better patient stratification is needed to maximize patient benefit and minimize the harm caused by adverse events. Pre-treatment pharmacogenetic testing has the potential to optimize drug selection and dose, and to minimize harm caused by adverse drug reactions. In addition, optimizing the use of cheap conventional drugs, and avoiding expensive ineffective drugs, will lead to a significant reduction in costs. Genetic variation in both TPMT and NUDT15, genes involved in thiopurine metabolism, is associated to an increased risk of thiopurine-induced myelosuppression. Moreover, specific HLA haplotypes confer risk to thiopurine-induced pancreatitis and to immunogenicity to tumor necrosis factor-antagonists, respectively. Falling costs and increased availability of genetic tests allow for the incorporation of pre-treatment genetic tests into clinical IBD management guidelines. In this paper, we review clinically useful pharmacogenetic associations for individualized treatment of patients with IBD and discuss the path from identification of a predictive pharmacogenetic marker to implementation into IBD clinical care.展开更多
AIM To investigate the regulation of Myopalladin(Mypn) and identify its gene network involved in restrictive cardiomyopathy(RCM).METHODS Gene expression values were measured in the heart of a large family of BXD recom...AIM To investigate the regulation of Myopalladin(Mypn) and identify its gene network involved in restrictive cardiomyopathy(RCM).METHODS Gene expression values were measured in the heart of a large family of BXD recombinant inbred(RI) mice derived from C57BL/6J and DBA/2J. The proteomics data were collected from Mypn knock-in and knock-out mice. Expression quantitative trait locus(eQ TL) mapping methods and gene enrichment analysis were used to identify Mypn regulation,gene pathway and co-expression networks.RESULTS A wide range of variation was found in expression of Mypn among BXD strains. We identified upstream genetic loci at chromosome 1 and 5 that modulate the expression of Mypn. Candidate genes within these loci include Ncoa2,Vcpip1,Sgk3,and Lgi2. We also identified 15 sarcomeric genes interacting with Mypn and constructed the gene network. Two novel members of this network(Syne1 and Myom1) have been confirmed at the protein level. Several members in this network are already known to relate to cardiomyopathy with some novel genes candidates that could be involved in RCM. CONCLUSION Using systematic genetics approach,we constructed Mypn co-expression networks that define the biological process categories within which similarly regulated genes function. Through this strategy we have found several novel genes that interact with Mypn that may play an important role in the development of RCM.展开更多
Understanding the level of genetic diversity in any population is an important requisite towards strategizing measures for conservation and improvement of stocks. This study focused on the assessment of phylogenetics ...Understanding the level of genetic diversity in any population is an important requisite towards strategizing measures for conservation and improvement of stocks. This study focused on the assessment of phylogenetics and molecular divergence of tilapia fish species obtained from two populations (Domita in South-South and Odeda in South-West, Nigeria) using the displacement loop (D-loop) and cytochrome b region of the mitochondrial deoxyribonucleic acid (mtDNA). A total of 28 samples (15 from South-South and 13 from South-West) were used for the genetic analysis. DNA was extracted from the tissue of all the samples using Quik-gDNATM miniPrep kit. The D-loop containing the hypervariable region was sequenced for all samples from the two populations, while cytochrome b (Cyt b) region of mtDNA was only sequenced for samples from South-South population. Chromatograms of the sequences were viewed and edited using Bioedit software. Multiple sequence alignment was carried out using molecular evolutionary genetic analysis (MEGA) software before subsequent genetic analyses. Phylogenetic analysis grouped the samples into two clusters based on population. Also, when the two mitochondrial regions were pooled together, they clustered into two major groups based on mitochondrial regions. Analysis of molecular variance (AMOVA) revealed 37.32% variation within population and 62.68% variation among population with a significant fixation index of 0.627 (p 0.05). The genetic distance inferred between D-loop regions of South-South and South-West populations was 0.243. Maternal lineage analysis revealed that the origin of tilapia fish from both populations could be traced to Oreochromis spirilus and Oreochromis leucostictus based on mitochondrial D-loop region. The findings of this study revealed molecular divergence among the tilapia populations and may serve as pivot information for the genetic improvement of this important species.展开更多
Stearyl coenzyme A desaturase(SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids.In mammals, depletion or inhibition of SCD activity generally lead...Stearyl coenzyme A desaturase(SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids.In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant(scd-/-) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry(GC-MS) showed that the scd-/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd-/ -mammals, the scd-/- zebrafish showed significantly increased fat accumulation in the whole body,especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis.Mechanistically, srebf1, a gene encoding a transcriptional activator related to adipogenesis,acc1 and acaca, genes involved in fatty acid synthesis, and dgat2, a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd-/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd-/- mutants could be rescued by ubiquitous transgenic overexpression of scd. In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.展开更多
Columbianetin acetate(CE)is one of the effective components of Angelica pubescens.So far,the specific role and molecular mechanism of CE in pancreatic cancer are not clear.Thus,this study aimed to explore the specific...Columbianetin acetate(CE)is one of the effective components of Angelica pubescens.So far,the specific role and molecular mechanism of CE in pancreatic cancer are not clear.Thus,this study aimed to explore the specific mechanism of CE on pancreatic cancer.The target genes combined with CE were predicted through the PharmMapper database and the 3D molecular structure of CE.Then,the Cancer Genome Atlas(TCGA)and Cistrome data browser(DB)databases were used to screen Meiotic nuclear divisions 1(MND1)-related genes,transcription factors,and transcription factor data sets,and the intersection of the above data sets.The“limma”package in the R and gene expression profiling interactive analysis(GEPIA)databases were used to analyze the correlation and survival difference between the target genes and MND1 to predict the degree of association between CE and MND1.Western blotting and RT-PCR experiments revealed the regulatory relationship among CE,E2F1,and MND1 at the cellular level.The specific effects of CE on pancreatic cancer cells were explored through CCK8,wound healing,migration,and flow cycle experiments.E2F1,also the predictive transcription factor of MND1,was also the predictive target protein of CE.At the same time,E2F1 and MND1 were closely related in pancreatic tissue.In the cell function experiment,CE and interference with E2F1 expression could reduce the gene and protein expression of MND1,which was closely associated with cell proliferation,migration,and cycle development.Similarly,interfering with the expression of mnd1 can also inhibit the further development of tumor cells.CE may inhibit the development of pancreatic cancer cells by reducing the expression of MND1.This implies that CE may be a potential novel agent for the treatment of pancreatic cancer.展开更多
Salinity is one of the major abiotic factors that limit the growth and productivity of plants.Foliar application of plant growth regulators(PGRs)may help plants ameliorate the negative impacts of salinity.Thus,a field...Salinity is one of the major abiotic factors that limit the growth and productivity of plants.Foliar application of plant growth regulators(PGRs)may help plants ameliorate the negative impacts of salinity.Thus,a field experiment was conducted at the Botanical Garden University of Balochistan,Quetta,to explore the potential role of PGRs,i.e.,moringa leaf extract(MLE;10%),proline(PRO;1μM),salicylic acid(SA;250μM),and thiourea(TU;10 mM)in ameliorating the impacts of salinity(120 mM)on Plantago ovata,an important medicinal plant.Salinity hampered plant photosynthetic pigments and metabolites but elevated oxidative parameters.However,foliar application of PGRs enhanced photosynthetic pigments,including Chl b(21.11%),carotenoids(57.87%)except Chl a,activated the defense mechanisms by restoring and enhancing the metabolites,i.e.,soluble sugars(49.68%),soluble phenolics(33.34%),and proline(31.47%),significantly under salinity stress.Furthermore,foliar supplementation of PGRs under salt stress led to a decrease of about 43.02%and 43.27%in hydrogen peroxide and malondialdehyde content,respectively.Thus,PGRs can be recommended for improved photosynthetic efficiency and metabolite content that can help to get better yield under salt stress,with the best and most effective treatments being those of PRO and MLE to predominately ameliorate the harsh impacts of salinity.展开更多
Potato is a plant that can be influenced by early blight disease. Early blight is one of the most destructive plant diseases, especially in the members of solanaceae family. This disease can reduce yield. Experiment d...Potato is a plant that can be influenced by early blight disease. Early blight is one of the most destructive plant diseases, especially in the members of solanaceae family. This disease can reduce yield. Experiment design was a factorial randomized complete design to evaluate the isolate pathogenic Alternaria solani in National Plant Gene Bank of Iran, during 2008-2009. This experiment was conducted with three replications, and the factors include test methods and three lines 9506, 10908-05 and 10908-18 with genotypes of Agria, Casmos and Desiree (susceptible) and Delta (resistant control). Analysis of variance table was based on the area under the disease progress curve, indicating the effects of the experimental methods;genotype and their interactions are significant at the 1% level. In greenhouse evaluation, the symptoms appeared on, the first day. In this method the area under the curve progression was noted in 10 times, but in vitro method, the symptoms of this evaluation appeared on the first or second day. The Evaluation was carried out after inoculation, and was noted 6 times. The results indicate that genotypes and lines are located in four different groups. In this case, line 9506 and Cosmos were quite sensitive to the surface, and Desiree, is located in a sensitive area. Line 10908-18 and Agria, located approximately at the level of resistance, and line 10908-05 and Delta, have been resistant surface.展开更多
BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive...BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.展开更多
Congenital anomalies of the hand are malformations occurring during the development of the human limb,and present as isolated disorders or as a part of a syndrome.During the last years,molecular analysis techniques ha...Congenital anomalies of the hand are malformations occurring during the development of the human limb,and present as isolated disorders or as a part of a syndrome.During the last years,molecular analysis techniques have offered increasing knowledge about the molecular basis of hand malformations.Disturbances in the signaling pathways during the development of the upper limb result in malformations of the upper extremity.At present,several genes have been identified as responsible for hand anomalies and other have been recognized as suspect genes related to them.Different and new high throughput methods have been introduced for the identification of the gene mutations.In the current editorial,we summarize concisely the current molecular status of isolated hand genetic disorders and the recent progress in molecular genetics,including the genes related to the disorder.This progress improves the knowledge of these disorders and has implications on genetic counselling and prenatal diagnosis.展开更多
Maize is cultivated extensively throughout the world and has the highest production among cereals.However,Northern corn leaf blight(NCLB)disease caused by Exherohilum turcicum,is the most devastating limiting factor o...Maize is cultivated extensively throughout the world and has the highest production among cereals.However,Northern corn leaf blight(NCLB)disease caused by Exherohilum turcicum,is the most devastating limiting factor of maize production.The disease causes immense losses to corn yield if it develops prior or during the tasseling and silking stages of crop development.It has a worldwide distribution and its development is favoured by cool to moderate temperatures with high relative humidity.The prevalence of the disease has increased in recent years and new races of the pathogen have been reported worldwide.The fungus E.turcicum is highly variable in nature.Though different management strategies have proved effective to reduce economic losses from NCLB,the development of varieties with resistance to E.turcicum is the most efficient and inexpensive way for disease management.Qualitative resistance for NCLB governed by Ht genes is a race-specific resistance which leads to a higher level of resistance.However,some Ht genes can easily become ineffective under the high pressure of virulent strains of the pathogen.Hence,it is imperative to understand and examine the consistency of the genomic locations of quantitative trait loci for resistance to NCLB in diverse maize populations.The breeding approaches for pyramiding resistant genes against E.turcicum in maize can impart NCLB resistance under high disease pressure environments.Furthermore,the genome editing approaches like CRISPR-cas9 and RNAi can also prove vital for developing NCLB resistant maize cultivars.As such this review delivers emphasis on the importance and current status of the disease,racial spectrum of the pathogen,genetic nature and breeding approaches for resistance and management strategies of the disease in a sustainable manner.展开更多
Cancer stands as a prominent public health concern in China, with elusive intervention targets due to unidentified high-risk causal factors for most cancers. Consequently, emphasis has shifted towards screening, diagn...Cancer stands as a prominent public health concern in China, with elusive intervention targets due to unidentified high-risk causal factors for most cancers. Consequently, emphasis has shifted towards screening, diagnosing, and treating early cancer cases within the general population. However, China faces considerable obstacles in its cancer prevention and control efforts, attributing to the complexity and heterogeneity of the occurrence, progression, and prognosis of malignant tumors across populations, time, and regions. Taking esophageal cancer screening practices as an example, this review outlines the importance and assessment of cancer screening, delineating major challenges in China's cancer prevention and control: 1) limited comprehension of cancer's natural history;2) lack of “China Evidence” supporting screening effectiveness and value;3) compromised efficiency and accuracy in current screening modality;and 4) insufficient sustainability of the current screening practices and translation of relevant scientific research achievements. To address these challenges, we propose potential coping strategies: 1)establishing tailored technologies and pathways for cancer prevention and control based on population-based and clinical epidemiological studies using high-quality designs;2) breaking conventional constraints to establish a novel cancer screening strategy aligned with real-world needs;and 3) establishing enhanced communication platforms among scientific research teams, policymakers, and industrial institutions to foster collaboration and innovation.展开更多
Objective:To investigate whether human short interspersed nuclear element antisense RNA(Alu antisense RNA;Alu asRNA)could delay human fibroblast senescence and explore the underlying mechanisms.Methods:We transfected ...Objective:To investigate whether human short interspersed nuclear element antisense RNA(Alu antisense RNA;Alu asRNA)could delay human fibroblast senescence and explore the underlying mechanisms.Methods:We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8(CCK-8),reactive oxygen species(ROS),and senescence-associated beta-galactosidase(SA-β-gal)staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts.We also used an RNA-sequencing(RNA-seq)method to investigate the Alu asRNA-specific mechanisms of anti-aging.We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA.We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts.Results:The CCK-8,ROS and SA-β-gal results showed that Alu asRNA could delay fibroblast aging.RNA-seq showed 183 differentially expressed genes(DEGs)in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection(CPT)reagent.The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent.Notably,Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway.Conclusion:Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.展开更多
Rice is sensitive to salinity stress at both the seedling and reproductive stages.The present study used 145 rice genotypes comprising of 100 landraces and 45 advanced breeding lines collected from different regions o...Rice is sensitive to salinity stress at both the seedling and reproductive stages.The present study used 145 rice genotypes comprising of 100 landraces and 45 advanced breeding lines collected from different regions of India.These genotypes were evaluated in hydroponics under control[electrical conductivity(ECe)~1.2 dS/m]and saline(ECe~10.0 dS/m)environments along with susceptible(IR29)and tolerant(FL478)checks.The stress susceptibility index for eight morphophysiological traits was estimated.Analysis of variance showed significant differences among the genotypes for all the parameters studied in control,stress and relative stress conditions.We identified 3 landraces(Kuttimanja,Tulasimog and IET-13713I)as tolerant and 14 lines as moderately tolerant to salt stress.Strong correlations in the morphological(root and shoot lengths)and physiological traits(shoot Na^(+),Ca^(2+)and Mg^(2+)contents,and Na^(+)/K^(+)ratio)were observed under all the conditions.The hierarchical cluster analysis grouped the genotypes into five clusters,among which cluster Ⅱ comprised salt-tolerant lines.Haplotyping of Saltol region using 11 simple sequence repeat markers on 17 saline tolerant and moderately tolerant lines was conducted.Markers AP3206F,RM10793 and RM3412b,located close to SKC1 gene(11.23‒12.55 Mb),displayed diverse allelic variations and they were not related to the FL478 type.In this region,tolerant lines like Kuttimanja,IET-13713I and Tulasimog have new alleles.As a result,these lines may be suitable candidates for novel genomic regions governing rice salinity tolerance.Salt-tolerance ability of Kuttimanja,Tulasimog and IET-13713I was validated in two years in three salinity stress environments.These promising lines can be used in breeding programs to broaden the genetic base of salinity tolerance in rice,and it may help to dissect key genomic regions responsible for salinity tolerance.展开更多
基金supported by core funding provided by Temasek Life Sciences Laboratory (to CTO)。
文摘Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal models have led to the identification of twelve aging hallmarks that shared several features:its age-associated manifestation.
文摘Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.
基金supported in part by the R21AG077643,R01NS123571,1U19NS130607,and 5T U24 HG012070(to GZ)in part by Alzheimer Association Fellowship Award 23AARFD-1029969(to IOS).
文摘Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to neurons.In addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).
文摘The pulse cowpea [Vigna unguiculata (L.) Walp] holds a significant agricultural position in Uganda, ranking fourth among legume crops, following common beans, groundnuts, and soybeans. Known for its versatility, cowpeas are consumable at various developmental stages, from early seedling to maturity. However, the crop faces persistent pest challenges at each stage, leading to substantial yield losses. In Uganda, chemical insecticides are the primary pest control means, but their increased and excessive use raises environmental, health, and economic concerns. This has prompted a quest for alternative and sustainable solutions, prompting an exploration of botanical insecticides. This study, conducted at Makerere University Agricultural Research Institute (MUARIK), aimed to evaluate the effectiveness of three selected botanical insecticides versus four established chemical insecticides for managing cowpea insect pests under field conditions. The treatments included: Carbofuran, Cypermethrin 10% EC, Dimethoate, Pestwin, Pyrethrum ewc , Pyrethrum 5ew, Profenofos 40% Cypermethrin 4% EC mix, and Untreated, arranged in a randomized complete block design with three replications. The significant pests studied were aphids, thrips, pod-sucking bugs, and legume pod borer. Results indicated substantial impacts of the treatments on pest infestation, with Profenofos 40% Cypermethrin 4% EC being the most effective against most pests. The plant parameter, plant height, was significantly affected by treatments in 2016B, while the number of pods was impacted in 2017A. Pestwin, a botanical insecticide blend (containing Azadirachtin indica, Pongamia pinnata, and Ricinus communis extracts) demonstrated superior efficacy against cowpea aphids. Moreover, it positively influenced plant height, number of pods, and pod biomass, surpassing many chemical insecticides. Pestwin’s environmental friendliness positions it as a potential contributor to reducing environmental pollution, making it a promising candidate for inclusion in IPM programs. Overall, the study underscores the importance of exploring botanical alternatives to chemical insecticides for sustainable pest management in cowpea cultivation.
基金supported by grants from National Innovation Program for College Students(202210367076)Graduate Student Research Innovation Program of Bengbu Medical College(Byycxz22016)the National Natural Science Foundation of China(82072585),and the Key Research Project of Bengbu Medical College(No.2020byzd029).
文摘Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.
基金Supported by The European Union-NextGenerationEU,Through The National Recov-ery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.
基金NC TraC S to Dai XNo.550KR91403+1 种基金NIH T32 to Wiernek SNo.HL083828-04
文摘Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.
文摘Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression. Early introduction of immunosuppression forms the mainstay of medical IBD management. Large inter-individual variability in drug responses, in terms of both efficacy and toxicity, leads to high rates of therapeutic failure in the management of IBD. Better patient stratification is needed to maximize patient benefit and minimize the harm caused by adverse events. Pre-treatment pharmacogenetic testing has the potential to optimize drug selection and dose, and to minimize harm caused by adverse drug reactions. In addition, optimizing the use of cheap conventional drugs, and avoiding expensive ineffective drugs, will lead to a significant reduction in costs. Genetic variation in both TPMT and NUDT15, genes involved in thiopurine metabolism, is associated to an increased risk of thiopurine-induced myelosuppression. Moreover, specific HLA haplotypes confer risk to thiopurine-induced pancreatitis and to immunogenicity to tumor necrosis factor-antagonists, respectively. Falling costs and increased availability of genetic tests allow for the incorporation of pre-treatment genetic tests into clinical IBD management guidelines. In this paper, we review clinically useful pharmacogenetic associations for individualized treatment of patients with IBD and discuss the path from identification of a predictive pharmacogenetic marker to implementation into IBD clinical care.
基金Supported by National Institutes of Health,Nos.R01 HL128350(LL),R01 HL53392 and R01 HL087000(JAT)
文摘AIM To investigate the regulation of Myopalladin(Mypn) and identify its gene network involved in restrictive cardiomyopathy(RCM).METHODS Gene expression values were measured in the heart of a large family of BXD recombinant inbred(RI) mice derived from C57BL/6J and DBA/2J. The proteomics data were collected from Mypn knock-in and knock-out mice. Expression quantitative trait locus(eQ TL) mapping methods and gene enrichment analysis were used to identify Mypn regulation,gene pathway and co-expression networks.RESULTS A wide range of variation was found in expression of Mypn among BXD strains. We identified upstream genetic loci at chromosome 1 and 5 that modulate the expression of Mypn. Candidate genes within these loci include Ncoa2,Vcpip1,Sgk3,and Lgi2. We also identified 15 sarcomeric genes interacting with Mypn and constructed the gene network. Two novel members of this network(Syne1 and Myom1) have been confirmed at the protein level. Several members in this network are already known to relate to cardiomyopathy with some novel genes candidates that could be involved in RCM. CONCLUSION Using systematic genetics approach,we constructed Mypn co-expression networks that define the biological process categories within which similarly regulated genes function. Through this strategy we have found several novel genes that interact with Mypn that may play an important role in the development of RCM.
文摘Understanding the level of genetic diversity in any population is an important requisite towards strategizing measures for conservation and improvement of stocks. This study focused on the assessment of phylogenetics and molecular divergence of tilapia fish species obtained from two populations (Domita in South-South and Odeda in South-West, Nigeria) using the displacement loop (D-loop) and cytochrome b region of the mitochondrial deoxyribonucleic acid (mtDNA). A total of 28 samples (15 from South-South and 13 from South-West) were used for the genetic analysis. DNA was extracted from the tissue of all the samples using Quik-gDNATM miniPrep kit. The D-loop containing the hypervariable region was sequenced for all samples from the two populations, while cytochrome b (Cyt b) region of mtDNA was only sequenced for samples from South-South population. Chromatograms of the sequences were viewed and edited using Bioedit software. Multiple sequence alignment was carried out using molecular evolutionary genetic analysis (MEGA) software before subsequent genetic analyses. Phylogenetic analysis grouped the samples into two clusters based on population. Also, when the two mitochondrial regions were pooled together, they clustered into two major groups based on mitochondrial regions. Analysis of molecular variance (AMOVA) revealed 37.32% variation within population and 62.68% variation among population with a significant fixation index of 0.627 (p 0.05). The genetic distance inferred between D-loop regions of South-South and South-West populations was 0.243. Maternal lineage analysis revealed that the origin of tilapia fish from both populations could be traced to Oreochromis spirilus and Oreochromis leucostictus based on mitochondrial D-loop region. The findings of this study revealed molecular divergence among the tilapia populations and may serve as pivot information for the genetic improvement of this important species.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24010108)National Natural Science Foundation of China(31872554,32172952)Project from the State Key Laboratory of Freshwater Ecology and Biotechnology(2019FBZ05)。
文摘Stearyl coenzyme A desaturase(SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids.In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of scd in teleost fish remains unknown. Here, we generated a zebrafish scd mutant(scd-/-) to elucidate the role of scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry(GC-MS) showed that the scd-/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike Scd-/ -mammals, the scd-/- zebrafish showed significantly increased fat accumulation in the whole body,especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis.Mechanistically, srebf1, a gene encoding a transcriptional activator related to adipogenesis,acc1 and acaca, genes involved in fatty acid synthesis, and dgat2, a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The scd-/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the scd-/- mutants could be rescued by ubiquitous transgenic overexpression of scd. In conclusion, our study demonstrates that scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.
基金supported by grants from the Key Natural Science Project of Anhui Provincial Education Department(Nos.KJ2018A0221,KJ2020A0578 and KJ2021A0773)National Innovation Program for College Students(No.202010367046)Anhui Provincial Undergraduate Innovative Training Program(Nos.S202010367008,S202110367030 and S202110367112).
文摘Columbianetin acetate(CE)is one of the effective components of Angelica pubescens.So far,the specific role and molecular mechanism of CE in pancreatic cancer are not clear.Thus,this study aimed to explore the specific mechanism of CE on pancreatic cancer.The target genes combined with CE were predicted through the PharmMapper database and the 3D molecular structure of CE.Then,the Cancer Genome Atlas(TCGA)and Cistrome data browser(DB)databases were used to screen Meiotic nuclear divisions 1(MND1)-related genes,transcription factors,and transcription factor data sets,and the intersection of the above data sets.The“limma”package in the R and gene expression profiling interactive analysis(GEPIA)databases were used to analyze the correlation and survival difference between the target genes and MND1 to predict the degree of association between CE and MND1.Western blotting and RT-PCR experiments revealed the regulatory relationship among CE,E2F1,and MND1 at the cellular level.The specific effects of CE on pancreatic cancer cells were explored through CCK8,wound healing,migration,and flow cycle experiments.E2F1,also the predictive transcription factor of MND1,was also the predictive target protein of CE.At the same time,E2F1 and MND1 were closely related in pancreatic tissue.In the cell function experiment,CE and interference with E2F1 expression could reduce the gene and protein expression of MND1,which was closely associated with cell proliferation,migration,and cycle development.Similarly,interfering with the expression of mnd1 can also inhibit the further development of tumor cells.CE may inhibit the development of pancreatic cancer cells by reducing the expression of MND1.This implies that CE may be a potential novel agent for the treatment of pancreatic cancer.
基金supported by the Ministry of Education,Science and Technological Development of the Republic of Serbia,Grant No.451–03–68/2022–124/200032.
文摘Salinity is one of the major abiotic factors that limit the growth and productivity of plants.Foliar application of plant growth regulators(PGRs)may help plants ameliorate the negative impacts of salinity.Thus,a field experiment was conducted at the Botanical Garden University of Balochistan,Quetta,to explore the potential role of PGRs,i.e.,moringa leaf extract(MLE;10%),proline(PRO;1μM),salicylic acid(SA;250μM),and thiourea(TU;10 mM)in ameliorating the impacts of salinity(120 mM)on Plantago ovata,an important medicinal plant.Salinity hampered plant photosynthetic pigments and metabolites but elevated oxidative parameters.However,foliar application of PGRs enhanced photosynthetic pigments,including Chl b(21.11%),carotenoids(57.87%)except Chl a,activated the defense mechanisms by restoring and enhancing the metabolites,i.e.,soluble sugars(49.68%),soluble phenolics(33.34%),and proline(31.47%),significantly under salinity stress.Furthermore,foliar supplementation of PGRs under salt stress led to a decrease of about 43.02%and 43.27%in hydrogen peroxide and malondialdehyde content,respectively.Thus,PGRs can be recommended for improved photosynthetic efficiency and metabolite content that can help to get better yield under salt stress,with the best and most effective treatments being those of PRO and MLE to predominately ameliorate the harsh impacts of salinity.
文摘Potato is a plant that can be influenced by early blight disease. Early blight is one of the most destructive plant diseases, especially in the members of solanaceae family. This disease can reduce yield. Experiment design was a factorial randomized complete design to evaluate the isolate pathogenic Alternaria solani in National Plant Gene Bank of Iran, during 2008-2009. This experiment was conducted with three replications, and the factors include test methods and three lines 9506, 10908-05 and 10908-18 with genotypes of Agria, Casmos and Desiree (susceptible) and Delta (resistant control). Analysis of variance table was based on the area under the disease progress curve, indicating the effects of the experimental methods;genotype and their interactions are significant at the 1% level. In greenhouse evaluation, the symptoms appeared on, the first day. In this method the area under the curve progression was noted in 10 times, but in vitro method, the symptoms of this evaluation appeared on the first or second day. The Evaluation was carried out after inoculation, and was noted 6 times. The results indicate that genotypes and lines are located in four different groups. In this case, line 9506 and Cosmos were quite sensitive to the surface, and Desiree, is located in a sensitive area. Line 10908-18 and Agria, located approximately at the level of resistance, and line 10908-05 and Delta, have been resistant surface.
基金Supported by the Key-Area Research and Development Program of Guangdong Province,No.2022B1111070006the Guangdong Innovation Research Team for Higher Education,No.2021KCXTD025.
文摘BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.
文摘Congenital anomalies of the hand are malformations occurring during the development of the human limb,and present as isolated disorders or as a part of a syndrome.During the last years,molecular analysis techniques have offered increasing knowledge about the molecular basis of hand malformations.Disturbances in the signaling pathways during the development of the upper limb result in malformations of the upper extremity.At present,several genes have been identified as responsible for hand anomalies and other have been recognized as suspect genes related to them.Different and new high throughput methods have been introduced for the identification of the gene mutations.In the current editorial,we summarize concisely the current molecular status of isolated hand genetic disorders and the recent progress in molecular genetics,including the genes related to the disorder.This progress improves the knowledge of these disorders and has implications on genetic counselling and prenatal diagnosis.
文摘Maize is cultivated extensively throughout the world and has the highest production among cereals.However,Northern corn leaf blight(NCLB)disease caused by Exherohilum turcicum,is the most devastating limiting factor of maize production.The disease causes immense losses to corn yield if it develops prior or during the tasseling and silking stages of crop development.It has a worldwide distribution and its development is favoured by cool to moderate temperatures with high relative humidity.The prevalence of the disease has increased in recent years and new races of the pathogen have been reported worldwide.The fungus E.turcicum is highly variable in nature.Though different management strategies have proved effective to reduce economic losses from NCLB,the development of varieties with resistance to E.turcicum is the most efficient and inexpensive way for disease management.Qualitative resistance for NCLB governed by Ht genes is a race-specific resistance which leads to a higher level of resistance.However,some Ht genes can easily become ineffective under the high pressure of virulent strains of the pathogen.Hence,it is imperative to understand and examine the consistency of the genomic locations of quantitative trait loci for resistance to NCLB in diverse maize populations.The breeding approaches for pyramiding resistant genes against E.turcicum in maize can impart NCLB resistance under high disease pressure environments.Furthermore,the genome editing approaches like CRISPR-cas9 and RNAi can also prove vital for developing NCLB resistant maize cultivars.As such this review delivers emphasis on the importance and current status of the disease,racial spectrum of the pathogen,genetic nature and breeding approaches for resistance and management strategies of the disease in a sustainable manner.
基金supported by the National Key R&D Program of China (No. 2021YFC2500405)。
文摘Cancer stands as a prominent public health concern in China, with elusive intervention targets due to unidentified high-risk causal factors for most cancers. Consequently, emphasis has shifted towards screening, diagnosing, and treating early cancer cases within the general population. However, China faces considerable obstacles in its cancer prevention and control efforts, attributing to the complexity and heterogeneity of the occurrence, progression, and prognosis of malignant tumors across populations, time, and regions. Taking esophageal cancer screening practices as an example, this review outlines the importance and assessment of cancer screening, delineating major challenges in China's cancer prevention and control: 1) limited comprehension of cancer's natural history;2) lack of “China Evidence” supporting screening effectiveness and value;3) compromised efficiency and accuracy in current screening modality;and 4) insufficient sustainability of the current screening practices and translation of relevant scientific research achievements. To address these challenges, we propose potential coping strategies: 1)establishing tailored technologies and pathways for cancer prevention and control based on population-based and clinical epidemiological studies using high-quality designs;2) breaking conventional constraints to establish a novel cancer screening strategy aligned with real-world needs;and 3) establishing enhanced communication platforms among scientific research teams, policymakers, and industrial institutions to foster collaboration and innovation.
基金supported by grants from the National Natural Science Foundation of China(No.81771499)and the Natural Science Foundation of Hebei Province,China(No.H2018206099 and No.H2021206460).
文摘Objective:To investigate whether human short interspersed nuclear element antisense RNA(Alu antisense RNA;Alu asRNA)could delay human fibroblast senescence and explore the underlying mechanisms.Methods:We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8(CCK-8),reactive oxygen species(ROS),and senescence-associated beta-galactosidase(SA-β-gal)staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts.We also used an RNA-sequencing(RNA-seq)method to investigate the Alu asRNA-specific mechanisms of anti-aging.We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA.We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts.Results:The CCK-8,ROS and SA-β-gal results showed that Alu asRNA could delay fibroblast aging.RNA-seq showed 183 differentially expressed genes(DEGs)in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection(CPT)reagent.The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent.Notably,Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway.Conclusion:Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.
基金the Department of Science and Technology,Government of India(Grant No.CRG/2020/003078).
文摘Rice is sensitive to salinity stress at both the seedling and reproductive stages.The present study used 145 rice genotypes comprising of 100 landraces and 45 advanced breeding lines collected from different regions of India.These genotypes were evaluated in hydroponics under control[electrical conductivity(ECe)~1.2 dS/m]and saline(ECe~10.0 dS/m)environments along with susceptible(IR29)and tolerant(FL478)checks.The stress susceptibility index for eight morphophysiological traits was estimated.Analysis of variance showed significant differences among the genotypes for all the parameters studied in control,stress and relative stress conditions.We identified 3 landraces(Kuttimanja,Tulasimog and IET-13713I)as tolerant and 14 lines as moderately tolerant to salt stress.Strong correlations in the morphological(root and shoot lengths)and physiological traits(shoot Na^(+),Ca^(2+)and Mg^(2+)contents,and Na^(+)/K^(+)ratio)were observed under all the conditions.The hierarchical cluster analysis grouped the genotypes into five clusters,among which cluster Ⅱ comprised salt-tolerant lines.Haplotyping of Saltol region using 11 simple sequence repeat markers on 17 saline tolerant and moderately tolerant lines was conducted.Markers AP3206F,RM10793 and RM3412b,located close to SKC1 gene(11.23‒12.55 Mb),displayed diverse allelic variations and they were not related to the FL478 type.In this region,tolerant lines like Kuttimanja,IET-13713I and Tulasimog have new alleles.As a result,these lines may be suitable candidates for novel genomic regions governing rice salinity tolerance.Salt-tolerance ability of Kuttimanja,Tulasimog and IET-13713I was validated in two years in three salinity stress environments.These promising lines can be used in breeding programs to broaden the genetic base of salinity tolerance in rice,and it may help to dissect key genomic regions responsible for salinity tolerance.
