Origin of the presence/absence variation of the LTIA1/LTIA2 mini-ribonucleaseⅢgenes required for low-temperature growth in rice

A rice low temperature-induced albino variant was determined by the recessive ltia1 and ltia2 genes.LTIA1 and LTIA2 encode highly conserved mini-ribonucleasesⅢlocated in chloroplasts and expressed in aerial parts of the plant.At low temperature,LTIA1 and LTIA2 redundantly affect chlorophyll levels,non-photochemical quenching,photosynthetic quantum yield of PSⅡand seedling growth.LTIA1 and LTIA2 proteins are involved in splicing of atp F and the biogenesis of 16S and 23S rRNA in chloroplasts.Presence/absence variation of LTIA1,the ancestral copy,was found only in japonica but that of LTIA2 in all rice subgroups.Accessions with LTIA2 presence tended to be distributed more remote from the equator compared to those with LTIA2 absence.LTIA2 duplicated from LTIA1 at the early stage of divergence of the AA genome Oryza species but deleted againin O.nivara.In cultivated rice,absence of LTIA2 is derived from O.nivara.LTIA1 absence occurred more recently in japonica.

An allelic variation in the promoter of the LRR-RLK gene,qSS6.1,is associated with melon seed size

Seed size is an important agronomic trait in melons that directly affects seed germination and subsequent seedling growth.However,the genetic mechanism underlying seed size in melon remains unclear.In the present study,we employed Bulked-Segregant Analysis sequencing(BSA-seq)to identify a candidate region(~1.35 Mb)on chromosome 6 that corresponds to seed size.This interval was confirmed by QTL mapping of three seed size-related traits from an F2 population across three environments.This mapping region represented nine QTLs that shared an overlapping region on chromosome 6,collectively referred to as qSS6.1.New InDel markers were developed in the qSS6.1 region,narrowing it down to a 68.35 kb interval that contains eight annotated genes.Sequence variation analysis of the eight genes identified a SNP with a C to T transition mutation in the promoter region of MELO3C014002,a leucine-rich repeat receptor-like kinase(LRR-RLK)gene.This mutation affected the promoter activity of the MELO3C014002 gene and was successfully used to differentiate the large-seeded accessions(C-allele)from the small-seeded accessions(T-allele).qRT-PCR revealed differential expression of MELO3C014002 between the two parental lines.Its predicted protein has typical LRR-RLK family domains,and phylogenetic analyses reveled its similarity with the homologs in several plant species.Altogether,these findings suggest MELO3C014002 as the most likely candidate gene involved in melon seed size regulation.Our results will be helpful for better understanding the genetic mechanism regulating seed size in melons and for genetically improving this important trait through molecular breeding pathways.

A Study to Observe Pulse Pressure Variation after Induction with Propofol for General Anesthesia

Background and Aims: Pulse pressure variation (PPV) is a reliable and predictive dynamic parameter presently being utilized for fluid responsiveness. In the operating room, fluid administration based on PPV monitoring helps the physician in deciding whether to volume resuscitate or use interventions in patients undergoing surgery. Propofol is an intravenous induction agent which lowers blood pressure. There are multiple causes such as depression in cardiac output, and peripheral vasodilatation for hypotension. We undertook this study to observe the utility of PPV as a guide to fluid therapy after propofol induction. Primary outcome of our study was to monitor PPV as a marker of fluid responsiveness for the hypotension caused by propofol induction. Secondary outcome included the correlation of PPV with other hemodynamic parameters like heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP);after induction with propofol at regular interval of time. Methods: A total number of 90 patients were recruited. Either of the radial artery was then cannulated under local anaesthesia with 20G VygonLeadercath arterial cannula and invasive monitoring transduced. A baseline recording of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and PPV was then recorded. Patients were then induced with predetermined doses of propofol (2 mg/kg) and recordings of HR, SBP, DBP, and PPV were taken at 5, 10 and 15 minutes. Results: Intraoperatively, PPV was significantly higher at 5 minutes and significantly lower at 15 minutes after induction. It was observed that there were no statistically significant correlations between PPV and SBP or DBP. PPV was strongly and directly associated with HR. Conclusion: We were able to establish that PPV predicts fluid responsiveness in hypotension caused by propofol induction;and can be used to administer fluid therapy in managing such hypotension. However, PPV was not directly correlated with hypotension subsequent to propofol administration.

Temperature is a cryptic factor shaping the geographical pattern of genetic variation in Ceratophyllum demersum across a subtropical freshwater lake

Macrophyte habitats exhibit remarkable heterogeneity,encompassing the spatial variation of abiotic and biotic components such as changes in water conditions and weather as well as anthropogenic stressors.Environmental factors are thought to be important drivers shaping the genetic and epigenetic variation of aquatic plants.However,the links among genetic diversity,epigenetic variation,and environmental variables remain largely unclear,especially for clonal aquatic plants.Here,we performed population genetic and epigenetic analyses in conjunction with habitat discrimination to elucidate the environmental factors driving intraspecies genetic and epigenetic variation in hornwort(Ceratophyllum demersum)in a subtropical lake.Environmental factors were highly correlated with the genetic and epigenetic variation of C.demersum,with temperature being a key driver of the genetic variation.Lower temperature was detected to be correlated with greater genetic and epigenetic variation.Genetic and epigenetic variation were positively driven by water temperature,but were negatively affected by ambient air temperature.These findings indicate that the genetic and epigenetic variation of this clonal aquatic herb is not related to the geographic feature but is instead driven by environmental conditions,and demonstrate the effects of temperature on local genetic and epigenetic variation in aquatic systems.

Genetic mechanism of body size variation in groupers:Insights from phylotranscriptomics

Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely unknown.Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size,providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates.Herein,we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea.Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size,respectively.A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups.Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups.These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks.Based on our results,we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection,leading to genetic variations in metabolic patterns,organ development,and lifespan,resulting in body size divergence between the two locally adapted populations.These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.

Insights into genetic diversity and phenotypic variations in domestic geese through comprehensive population and pan-genome analysis

Background Domestic goose breeds are descended from either the Swan goose(Anser cygnoides)or the Greylag goose(Anser anser),exhibiting variations in body size,reproductive performance,egg production,feather color,and other phenotypic traits.Constructing a pan-genome facilitates a thorough identification of genetic variations,thereby deepening our comprehension of the molecular mechanisms underlying genetic diversity and phenotypic variability.Results To comprehensively facilitate population genomic and pan-genomic analyses in geese,we embarked on the task of 659 geese whole genome resequencing data and compiling a database of 155 RNA-seq samples.By constructing the pan-genome for geese,we generated non-reference contigs totaling 612 Mb,unveiling a collection of 2,813 novel genes and pinpointing 15,567 core genes,1,324 softcore genes,2,734 shell genes,and 878 cloud genes in goose genomes.Furthermore,we detected an 81.97 Mb genomic region showing signs of genome selection,encompassing the TGFBR2 gene correlated with variations in body weight among geese.Genome-wide association studies utilizing single nucleotide polymorphisms(SNPs)and presence-absence variation revealed significant genomic associations with various goose meat quality,reproductive,and body composition traits.For instance,a gene encoding the SVEP1 protein was linked to carcass oblique length,and a distinct gene-CDS haplotype of the SVEP1 gene exhibited an association with carcass oblique length.Notably,the pan-genome analysis revealed enrichment of variable genes in the“hair follicle maturation”Gene Ontology term,potentially linked to the selection of feather-related traits in geese.A gene presence-absence variation analysis suggested a reduced frequency of genes associated with“regulation of heart contraction”in domesticated geese compared to their wild counterparts.Our study provided novel insights into gene expression features and functions by integrating gene expression patterns across multiple organs and tissues in geese and analyzing population variation.Conclusion This accomplishment originates from the discernment of a multitude of selection signals and candidate genes associated with a wide array of traits,thereby markedly enhancing our understanding of the processes underlying domestication and breeding in geese.Moreover,assembling the pan-genome for geese has yielded a comprehensive apprehension of the goose genome,establishing it as an indispensable asset poised to offer innovative viewpoints and make substantial contributions to future geese breeding initiatives.

An efficient parallel algorithm of variational nodal method for heterogeneous neutron transport problems

The heterogeneous variational nodal method(HVNM)has emerged as a potential approach for solving high-fidelity neutron transport problems.However,achieving accurate results with HVNM in large-scale problems using high-fidelity models has been challenging due to the prohibitive computational costs.This paper presents an efficient parallel algorithm tailored for HVNM based on the Message Passing Interface standard.The algorithm evenly distributes the response matrix sets among processors during the matrix formation process,thus enabling independent construction without communication.Once the formation tasks are completed,a collective operation merges and shares the matrix sets among the processors.For the solution process,the problem domain is decomposed into subdomains assigned to specific processors,and the red-black Gauss-Seidel iteration is employed within each subdomain to solve the response matrix equation.Point-to-point communication is conducted between adjacent subdomains to exchange data along the boundaries.The accuracy and efficiency of the parallel algorithm are verified using the KAIST and JRR-3 test cases.Numerical results obtained with multiple processors agree well with those obtained from Monte Carlo calculations.The parallelization of HVNM results in eigenvalue errors of 31 pcm/-90 pcm and fission rate RMS errors of 1.22%/0.66%,respectively,for the 3D KAIST problem and the 3D JRR-3 problem.In addition,the parallel algorithm significantly reduces computation time,with an efficiency of 68.51% using 36 processors in the KAIST problem and 77.14% using 144 processors in the JRR-3 problem.

Genetic variation and selection of 10-year-old Eucalyptus camaldulensis based on wind damage index and wood properties

Typhoons are becoming frequent and intense with ongoing climate change,threatening ecological security and healthy forest development in coastal areas.Eucalyptus of a predominant introduced species in southern China,faces significant growth challenges because of typhoon.Therefore,it is vital to investigate the variation of related traits and select superior breeding materials for genetic improvement.Variance,genetic parameter,and correlation analyses were carried out on wind damage indices and eight wood proper-ties in 88 families from 11 provenances of 10-year-old Euca-lyptus camaldulensis.The selection index equation was used for evaluating multiple traits and selecting superior prov-enances and family lines as future breeding material.The results show that all traits were highly significantly differ-ent at provenance and family levels,with the wind damage index having the highest coefficient of genetic variation.The heritability of each trait ranged from 0.48 to 0.87,with the wind damage index,lignin and hemicellulose contents,and microfibril angle having the highest heritabilities.The wind damage index had a positive genetic correlation with wood density,a negative correlation with lignin content,a negative phenotypic correlation and a negative genetic correlation with microfibril angle.Wind damage index and genetic progress in the selection of eight wood traits varied from 7.2%to 614.8%.Three provenances and 12 superior families were selected.The genetic gains of the wind damage index were 10.2%and 33.9%for provenances and families,and these may be starting material for genetic modification for wind resistance in eucalyptus and for their dissemination to typhoon-prone coastal areas of southern China.

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on electrooculogram.The potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and photoreceptor.In this study,the complete clinical characteristics of two Chinese ARB families were summarized.Methods:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family members.Results:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB families.The novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1.Another novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators.Conclusion:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes.The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

Genetic variation features of neonatal hyperbilirubinemia caused by inherited diseases

BACKGROUND Genetic factors play an important role in neonatal hyperbilirubinemia(NH)caused by genetic diseases.AIM To explore the characteristics of genetic mutations associated with NH and analyze the correlation with genetic diseases.METHODS This was a retrospective cohort study.One hundred and five newborn patients diagnosed with NH caused by genetic diseases were enrolled in this study between September 2020 and June 2023 at the Second Affiliated Hospital of Xiamen Medical College.A 24-gene panel was used for gene sequencing to analyze gene mutations in patients.The data were analyzed via Statistical Package for the Social Sciences 20.0 software.RESULTS Seventeen frequently mutated genes were found in the 105 patients.Uridine 5'-diphospho-glucuronosyltransferase 1A1(UGT1A1)variants were identified among the 68 cases of neonatal Gilbert syndrome.In patients with sodium taurocholate cotransporting polypeptide deficiency,the primary mutation identified was Na+/taurocholate cotransporting polypeptide Ntcp(SLC10A1).Adenosine triphosphatase 7B(ATP7B)mutations primarily occur in patients with hepatolenticular degeneration(Wilson's disease).In addition,we found that UGT1A1 and glucose-6-phosphate dehydrogenase mutations were more common in the high-risk group than in the low-risk group,whereas mutations in SLC10A1,ATP7B,and heterozygous 851del4 mutation were more common in the low-risk group.CONCLUSION Genetic mutations are associated with NH and significantly increase the risk of disease in affected newborns.

Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Genetic variation in ZmSO contributes to ABA response and drought tolerance in maize seedlings

Water scarcity impairs maize growth and yield.Identification and deployment of superior droughttolerance alleles is desirable for the genetic improvement of stress tolerance in maize.Our previous study revealed that maize sulfite oxidase(SO) catalyzes the oxidation of sulfite to sulfate and may be involved in drought response.But it was unclear whether the natural variation in Zm SO is directly associated with the drought resistance of maize.In the present study,we showed that Zm SO was associated with drought tolerance in maize seedlings,using gene association analysis and a transgene approach.A 14-bp insertion variation,containing two ABA-responsive elements,in the promoter region of Zm SO conferred ABAinducible expression,leading to increased drought tolerance.Genetic selection of this favorable allele increased drought tolerance.This study has identified elite alleles associated with sulfur metabolism for improving maize drought resistance.

Genome-wide association studies reveal the genetic basis of amino acid content variation in tea plants

Tea is one of the most popular non-alcoholic beverages in the world,and free amino acids,especially theanine,make a major contribution to the umami taste of tea.However,the genetic basis of the variation in amino acid content in tea plants remains largely unknown.Here,we measured the free amino acid content in fresh leaves of 174 tea accessions over two years using a targeted metabolomics approach and obtained genotype data via RNA sequencing.Genome-wide association studies were conducted to investigate loci affecting the content of free amino acids.A total of 69 quantitative trait loci(–log10(P-value)>5)were identified.Functional annotation revealed that branched-chain amino acid aminotransferase,glutamine synthetase,nitrate transporter,and glutamate decarboxylase might be important for amino acid metabolism.Two significant loci,glutamine synthetase(Glu1,P=3.71×10^(−4);Arg1,P=4.61×10^(−5))and branched-chain amino acid aminotransferase(Val1,P=4.67×10^(−5);I_Leu1,P=3.56×10^(−6)),were identified,respectively.Based on the genotyping result,two alleles of CsGS(CsGS-L and CsGS-H)and CsBCAT(CsBCAT-L and CsBCAT-H)were selected to perform function verification.Overexpression of CsGS-L and CsGS-H enhanced the contents of glutamate and arginine in transgenic plants,and overexpression of CsBCAT-L and CsBCAT-H promoted the accumulation of valine,isoleucine and leucine.Enzyme activity assay uncovered that SNP1054 is important for CsGS catalyzing glutamate into glutamine.Furthermore,CsGS-L and CsGS-H differentially regulated the accumulation of glutamine,and CsBCAT-L and CsBCAT-H differentially regulated the accumulation of branched-chain amino acids.In summary,the findings in our study would provide new insights into the genetic basis of amino acids contents variation in tea plants and facilitate the identification of elite genes to enhance amino acids content.

Whole-genome methylation analysis reveals epigenetic variation between wild-type and nontransgenic cloned,ASMT transgenic cloned dairy goats generated by the somatic cell nuclear transfer

Background:SCNT(somatic cell nuclear transfer)is of great significance to biological research and also to the livestock breeding.However,the survival rate of the SCNT cloned animals is relatively low compared to other transgenic methods.This indicates the potential epigenetic variations between them.DNA methylation is a key marker of mammalian epigenetics and its alterations will lead to phenotypic differences.In this study,ASMT(acetylserotonin-Omethyltransferase)ovarian overexpression transgenic goat was produced by using SCNT.To investigate whether there are epigenetic differences between cloned and WT(wild type)goats,WGBS(whole-genome bisulfite sequencing)was used to measure the whole-genome methylation of these animals.Results:It is observed that the different m Cp G sites are mainly present in the intergenic and intronic regions between cloned and WT animals,and their CG-type methylation sites are strongly correlated.DMR(differentially methylated region)lengths are located around 1000 bp,mainly distributed in the exonic,intergenic and intronic functional domains.A total of 56 and 36 DMGs(differentially methylated genes)were identified by GO and KEGG databases,respectively.Functional annotation showed that DMGs were enriched in biological-process,cellularcomponent,molecular-function and other signaling pathways.A total of 10 identical genes related to growth and development were identified in GO and KEGG databases.Conclusion:The differences in methylation genes among the tested animals have been identified.A total of 10 DMGs associated with growth and development were identified between cloned and WT animals.The results indicate that the differential patterns of DNA methylation between the cloned and WT goats are probably caused by the SCNT.These novel observations will help us to further identify the unveiled mechanisms of somatic cell cloning technology,particularly in goats.

RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation

BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.

Genetic dissection and validation of a major QTL for grain weight on chromosome 3B in bread wheat(Triticum aestivum L.)

Grain weight is one of the key components of wheat(Triticum aestivum L.)yield.Genetic manipulation of grain weight is an efficient approach for improving yield potential in breeding programs.A recombinant inbred line(RIL)population derived from a cross between W7268 and Chuanyu 12(CY12)was employed to detect quantitative trait loci(QTLs)for thousand-grain weight(TGW),grain length(GL),grain width(GW),and the ratio of grain length to width(GLW)in six environments.Seven major QTLs,QGl.cib-2D,QGw.cib-2D,QGw.cib-3B,QGw.cib-4B.1,QGlw.cib-2D.1,QTgw.cib-2D.1 and QTgw.cib-3B.1,were consistently identified in at least four environments and the best linear unbiased estimation(BLUE)datasets,and they explained 2.61 to 34.85%of the phenotypic variance.Significant interactions were detected between the two major TGW QTLs and three major GW loci.In addition,QTgw.cib-3B.1 and QGw.cib-3B were co-located,and the improved TGW at this locus was contributed by GW.Unlike other loci,QTgw.cib-3B.1/QGw.cib-3B had no effect on grain number per spike(GNS).They were further validated in advanced lines using Kompetitive Allele Specific PCR(KASP)markers,and a comparison analysis indicated that QTgw.cib-3B.1/QGw.cib-3B is likely a novel locus.Six haplotypes were identified in the region of this QTL and their distribution frequencies varied between the landraces and cultivars.According to gene annotation,spatial expression patterns,ortholog analysis and sequence variation,the candidate gene of QTgw.cib-3B.1/QGw.cib-3B was predicted.Collectively,the major QTLs and KASP markers reported here provide valuable information for elucidating the genetic architecture of grain weight and for molecular marker-assisted breeding in grain yield improvement.

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。