Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

A likely paleo-autotetraploidization event shaped the high conservation of Nyssaceae genome

Scientific knowledge about the ancestral genome of core eudicot plant kingdom can potentially have profound impacts on both basic and applied research,including evolution,genetics,genomics,ecology,agriculture,forestry,and global climate.To investigate which plant conserves best the core eudicots common ancestor genome,we compared Arcto-Tertiary relict Nyssaceae and 30 other eudicot plant families.The genomes of Davidia involucrata(a known living fossil),Camptotheca acuminata and Nyssa sinensis,one per existent genus of Nyssaceae,were performed comparative genomic analysis.We found that Nyssaceae originated from a single Nyssaceae common tetraploidization event(NCT)-autotetraploidization 28-31 Mya after the core eudicot common hexaploidization(ECH).We identified Nyssaceae orthologous and paralogous genes,determined its chromosomal evolutionary trajectory,and reconstructed the Nyssaceae most recent ancestor genome.D.involucrata genome contained the entire seven paleochromosomes and 17 ECH-generated eudicot common ancestor chromosomes and was the slowest in mutation among the analyzed 42 species of 31 plant families.Combing both its high retention of paleochromosomes and its low mutation rate,D.involucrata provides the best case in conservation of the core eudicot paleogenome.

Allotetraploidization event of Coptis chinensis shared by all Ranunculales

Coptis chinensis Franch.,also named Chinese goldthread is a member of Ranunculaceae in the order Ranunculales and represents an important lineage of early eudicots with traditional medicinal value.In our study,by using syntenic analysis combined with phylogenomic analysis of C.chinensis and four other representative genomes from basal and core eudicots,we confirmed that the WGD event in C.chinensis was shared by Aquilegia coerulea and Papaver somniferum L.and quickly occurred after Ranunculales diverged from other eudicots,likely a Ranunculales common tetraploidization(RCT).The synonymous nucleotide substitutions at synonymous sites distribution of syntenic blocks across these genomes showed that the evolutionary rate of the P.somniferum genome is faster than that of the C.chinensis genome by approximately 13.7%,possibly due to Papaveraceaes having an additional special tetraploidization event(PST).After Ks correction,the RCT dated to 115—130 million years ago(MYA),which was close to the divergence of Ranunculaceaes and Papaveraceaes approximately115.45—130.51 MYA.Moreover,we identified homologous genes related to polyploidization and speciation and constructed multiple sequence alignments with different reference genomes.Notably,the event-related subgenomes in the basal genomes all showed genomic fractionation bias,suggesting a likely allopolyploid nature of the RCT,PST and T-Alpha and T-Beta events in Tetracentron sinense.In addition,we detected that the sixteen P450 subfamilies were markedly expanded in the genomes of Ranunculales,and most of them were related to the RCT and PST events.We constructed a new platform for Early Eudicot Comparative Genomic Research(http://www.cgrpoee.top/index.html)to store more information.In summary,our findings support the WGD of C.chinensis shared by Ranunculales,which is likely an allotetraploidization event.This present effort offered new insights into the evolution of key polyploidization events and the genes related to secondary metabolites during the diversification of early eudicots.

Molecular hallmarks of long non-coding RNAs in aging and its significant effect on aging-associated diseases

Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.

Telomere-to-telomere and gap-free reference genome assembly of the kiwifruit Actinidia chinensis

Kiwifruit is an economically and nutritionally important fruit crop with extremely high contents of vitamin C.However,the previously released versions of kiwifruit genomes all have a mass of unanchored or missing regions.Here,we report a highly continuous and completely gap-free reference genome of Actinidia chinensis cv.‘Hongyang’,named Hongyang v4.0,which is the first to achieve two de novo haploid-resolved haplotypes,HY4P and HY4A.HY4P and HY4A have a total length of 606.1 and 599.6 Mb,respectively,with almost the entire telomeres and centromeres assembled in each haplotype.In comparison with Hongyang v3.0,the integrity and contiguity of Hongyang v4.0 is markedly improved by filling all unclosed gaps and correcting some misoriented regions,resulting in∼38.6–39.5 Mb extra sequences,which might affect 4263 and 4244 protein-coding genes in HY4P and HY4A,respectively.Furthermore,our gap-free genome assembly provides the first clue for inspecting the structure and function of centromeres.Globally,centromeric regions are characterized by higher-order repeats that mainly consist of a 153-bp conserved centromere-specific monomer(Ach-CEN153)with different copy numbers among chromosomes.Functional enrichment analysis of the genes located within centromeric regions demonstrates that chromosome centromeres may not only play physical roles for linking a pair of sister chromatids,but also have genetic features for participation in the regulation of cell division.The availability of the telomere-to-telomere and gap-free Hongyang v4.0 reference genome lays a solid foundation not only for illustrating genome structure and functional genomics studies but also for facilitating kiwifruit breeding and improvement.

Gapless genome assembly of azalea and multi-omics investigation into divergence between two species with distinct f lower color

The genus Rhododendron(Ericaceae),with more than 1000 species highly diverse in f lower color,is providing distinct ornamental values and a model system for f lower color studies.Here,we investigated the divergence between two parental species with different f lower color widely used for azalea breeding.Gapless genome assembly was generated for the yellow-f lowered azalea,Rhododendron molle.Comparative genomics found recent proliferation of long terminal repeat retrotransposons(LTR-RTs),especially Gypsy,has resulted in a 125 Mb(19%)genome size increase in species-specific regions,and a significant amount of dispersed gene duplicates(13402)and pseudogenes(17437).Metabolomic assessment revealed that yellow f lower coloration is attributed to the dynamic changes of carotenoids/f lavonols biosynthesis and chlorophyll degradation.Time-ordered gene co-expression networks(TO-GCNs)and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct f lower pigmentation.B3 and ERF TFs were found dominating the gene regulation of carotenoids/f lavonols characterized pigmentation in R.molle,while WRKY,ERF,WD40,C2H2,and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-f lowered R simsii.This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.

Role of foliar spray of plant growth regulators in improving photosynthetic pigments and metabolites in Plantago ovata (Psyllium) under salt stress–A field appraisal

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.

Natural isothiocyanates of the genus Capparis as potential agonists of apoptosis and antitumor drugs

BACKGROUND Using gas chromatography-mass spectrometry(GC/MS)analysis,we examined the composition of volatile components present in the yellow and green fruits,seeds,and jam of the scrambling shrub Capparis cartilaginea(C.cartilaginea).These plant samples were collected from Kibbutz Yotvata in Israel.In all the tested samples,isothiocyanates were identified.Utilizing the PASS program,we ascertained the biological activity of these isothiocyanates present in the Capparis genus.The study results highlighted that all isothiocyanates could potentially act as apoptosis agonists,making them strong candidates for antitumor drugs.This information holds significant value for the fields of medicinal chemistry,pharmacology,and practical medicine.AIM To investigate the volatile components present in the yellow and green fruits,seeds,and jam of the C.cartilaginea shrub using GC/MS analysis,to detect isothiocyanates in all the analyzed plant samples,and to assess the biological activity of these isothiocyanates utilizing the PASS program.METHODS We utilized two primary methods to analyze the volatile compounds present in the yellow and green fruits,seeds,and jams of the C.cartilaginea,native to Israel.We identified biologically active isothiocyanates in these samples.Their anticipated biological activities were determined using the PASS program,with the most dominant activities being apoptosis agonist,anticarcinogenic,and antineoplastic specifically for genitourinary cancer.RESULTS Fruits,seeds,and jams containing isothiocyanates,which exhibit antineoplastic and anticarcinogenic activities,could be suggested for cancer prevention and management.Specific isothiocyanates,with therapeutic potential in this realm,could be recommended as potent anticancer agents in practical medicine following clinical trials.CONCLUSION The discovery that isothiocyanates exhibit potent antineoplastic and anticarcinogenic activities was unexpected.Additionally,certain isothiocyanates demonstrated antifungal,antiviral(specifically against arbovirus),and antiparasitic properties.

Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis:A randomized controlled trial

BACKGROUND Fecal microbial transplantation(FMT)is a promising new method for treating active ulcerative colitis(UC),but knowledge regarding FMT for quiescent UC is scarce.AIM To investigate FMT for the maintenance of remission in UC patients.METHODS Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy.The primary endpoint was set to the maintenance of remission,a fecal calprotectin level below 200μg/g,and a clinical Mayo score below three throughout the 12-mo follow-up.As secondary endpoints,we recorded the patient’s quality of life,fecal calprotectin,blood chemistry,and endoscopic findings at 12 mo.RESULTS The main endpoint was achieved by 13 out of 24(54%)patients in the FMT group and by 10 out of 24(41%)patients in the placebo group(log-rank test,P=0.660).Four months after FMT,the quality-of-life scores decreased in the FMT group compared to the placebo group(P=0.017).In addition,the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point(P=0.003).There were no differences in blood chemistry,fecal calprotectin,or endoscopic findings among the study groups at 12 mo.The adverse events were infrequent,mild,and distributed equally between the groups.CONCLUSION There were no differences in the number of relapses between the study groups at the 12-mo follow-up.Thus,our results do not support the use of a single-dose FMT for the maintenance of remission in UC.

Two-step model of paleohexaploidy, ancestral genome reshuffling and plasticity of heat shock response in Asteraceae

An ancient hexaploidization event in the most but not all Asteraceae plants,may have been responsible for shaping the genomes of many horticultural,ornamental,and medicinal plants that promoting the prosperity of the largest angiosperm family on the earth.However,the duplication process of this hexaploidy,as well as the genomic and phenotypic diversity of extant Asteraceae plants caused by paleogenome reorganization,are still poorly understood.We analyzed 11 genomes from 10 genera in Asteraceae,and redated the Asteraceae common hexaploidization(ACH)event∼70.7–78.6 million years ago(Mya)and the Asteroideae specific tetraploidization(AST)event∼41.6–46.2 Mya.Moreover,we identified the genomic homologies generated from the ACH,AST and speciation events,and constructed a multiple genome alignment framework for Asteraceae.Subsequently,we revealed biased fractionations between the paleopolyploidization produced subgenomes,suggesting the ACH and AST both are allopolyplodization events.Interestingly,the paleochromosome reshuffling traces provided clear evidence for the two-step duplications of ACH event in Asteraceae.Furthermore,we reconstructed ancestral Asteraceae karyotype(AAK)that has 9 paleochromosomes,and revealed a highly flexible reshuffling of Asteraceae paleogenome.Of specific significance,we explored the genetic diversity of Heat Shock Transcription Factors(Hsfs)associated with recursive whole-genome polyploidizations,gene duplications,and paleogenome reshuffling,and revealed that the expansion of Hsfs gene families enable heat shock plasticity during the genome evolution of Asteraceae.Our study provides insights on polyploidy and paleogenome remodeling for the successful establishment of Asteraceae,and is helpful for further communication and exploration of the diversification of plant families and phenotypes.

Evolutionary relationships of mitogenomes in a recently radiated Old World avian family

Environmentally heterogeneous mountains provide opportunities for rapid diversification and speciation.The family Prunellidae(accentors)is a group of birds comprising primarily mountain specialists that have recently radiated across the Palearctic region.This rapid diversification poses challenges to resolving their phylogeny.Herein we sequenced the complete mitogenomes and estimated the phylogeny using all 12(including 28 individuals)currently recognized species of Prunellidae.We reconstructed the mitochondrial genome phylogeny using 13 protein-coding genes of 12 species and 2 Eurasian Tree Sparrows(Passer montanus).Phylogenetic relationships were estimated using a suite of analyses:maximum likelihood,maximum parsimony and the coalescent-based SVDquartets.Divergence times were estimated by implementing a Bayesian relaxed clock model in BEAST2.Based on the BEAST time-calibrated tree,we implemented an ancestral area reconstruction using RASP v.4.3.Our phylogenies based on the maximum likelihood,maximum parsimony and SVDquartets approaches support a clade of large-sized accentors(subgenus Laiscopus)to be sister to all other accentors with small size(subgenus Prunella).In addition,the trees also support the sister relationship of P.immaculata and P.rubeculoides+P.atrogularis with 100%bootstrap support,but the relationships among the remaining eight species in the Prunella clade are poorly resolved.These species cluster in different positions in the three phylogenetic trees and the nodes are often poorly supported.The five nodes separating the seven species diverged simultaneously within less than half million years(i.e.,between 2.71 and 3.15 million years ago),suggesting that the recent radiation is likely responsible for rampant incomplete lineage sorting and gene tree conflicts.Ancestral area reconstruction indicates a central Palearctic region origin for Prunellidae.Our study highlights that whole mitochondrial genome phylogeny can resolve major lineages within Prunellidae but is not sufficient to fully resolve the relationship among the species in the Prunella clade that almost simultaneously diversify during a short time period.Our results emphasize the challenge to reconstruct reliable phylogenetic relationship in a group of recently radiated species.

Prospects of DNA microarray application in management of chronic obstructive pulmonary disease:A systematic review

Chronic obstructive pulmonary disease(COPD)is incurable chronic disease which kills 3.3 million each year worldwide.Number of global cases of COPD is steadily rising alongside with life expectancy,disproportionally hitting middle-income countries like Russia and China,in such conditions,new approaches to the COPD management are desperately needed.DNA microarray technology is a powerful genomic tool that has the potential to uncover underlying COPD biological alteration and brings up revolutionized treatment option to clinicians.We executed systematic review studies of studies published in last 10 years regarding DNA microarray application in COPD management,with complacence to PRISMA criteria and using PubMed and Medline data bases as data source.Out of 920 identified papers,39 were included in the final analysis.We concluded that Genome-wide expression profiling using DNA microarray technology has great potential in enhancing COPD management.Current studied proofed this method is reliable and possesses many potential applications such as individual at risk of COPD development recognition,early diagnosis of disease,COPD phenotype identification,exacerbation prediction,personalized treatment optioning and prospect of oncogenesis evaluation in patients with COPD.Despite all the proofed benefits of this technology,researchers are still in the early stage of exploring it’s potential.Therefore,large clinical trials are still needed to set up standard for DNA microarray techniques usage implementation in COPD management guidelines,subsequently giving opportunity to clinicians for controlling or even eliminating COPD entirely.

A Comprehensive View on the Progress of Organoid Research with an Emphasis on its Relevance to Disease Characterization

INTRODUCTION Organoids are primary tissue or stem cells derived cell aggregates that have the capacity for self-organization,self-renewal,and the capacity to mimic cellular and tissue level functions.Organoids can overcome the shortcomings of traditional 2D cell culture models and closely mimic 3D primary tissue composition.

Systematics of the avian family Alaudidae using multilocus and genomic data

The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.

Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

MicroRNAs modulation in lung cancer: exploring dual mechanisms and clinical prospects

The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.

Haplotype-resolved and chromosome-scale genomes provide insights into co-adaptation between the Amur tiger and Amur leopard

DEAR EDITOR,Big cats,such as Amur tigers(Panthera tigris altaica)and Amur leopards(P.pardus orientalis),are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al.,2022),thus playing a crucial role in maintaining biodiversity and ecosystem integrity by regulating prey-predator dynamics.However,human-induced pressures,habitat fragmentation,and environmental alterations have restricted these species in small and isolated populations.Currently,all extant big cats are categorized as endangered or threatened according to their conservation status.Amur tigers and Amur leopards share overlapping geographic ranges,habitats,and certain prey species in the forests of Northeast Asia(Jiang et al.,2015).To reduce interspecies conflict,these carnivores exhibit differentiated dietary and temporal niches.Amur tigers predominantly prey on large ungulates,while Amur leopards hunt small to medium-sized animals(Sugimoto et al.,2016).Additionally,they occupy different temporal niches,with tigers being active at night and leopards more active during the day.Despite spatial and temporal niche partitioning,interspecific competition between these two species is inevitable.Tigers,benefiting from their greater size,have a competitive advantage over leopards,which can manifest in occasional leopard predation by tigers and declines in leopard populations with increasing tiger density(Jiang et al.,2015).Tigers also displace leopards from marginal habitats in nature reserves where they coexist.