Tea plant genomics:achievements,challenges and perspectives

Tea is among the world’s most widely consumed non-alcoholic beverages and possesses enormous economic,health,and cultural values.It is produced from the cured leaves of tea plants,which are important evergreen crops globally cultivated in over 50 countries.Along with recent innovations and advances in biotechnologies,great progress in tea plant genomics and genetics has been achieved,which has facilitated our understanding of the molecular mechanisms of tea quality and the evolution of the tea plant genome.In this review,we briefly summarize the achievements of the past two decades,which primarily include diverse genome and transcriptome sequencing projects,gene discovery and regulation studies,investigation of the epigenetics and noncoding RNAs,origin and domestication,phylogenetics and germplasm utilization of tea plant as well as newly developed tools/platforms.We also present perspectives and possible challenges for future functional genomic studies that will contribute to the acceleration of breeding programs in tea plants.

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.

Impairment of liver regeneration by the histone deacetylase inhibitor valproic acid in mice

Background and objective:Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors.A variety of genetic factors have been reported,whereas few investigations have focused on epigenetic regulation during liver regeneration.In the present study,valproic acid(VPA),a histone deacetylase(HDAC) inhibitor,was used to investigate the effect of HDAC on liver regeneration.Methods:VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration.The mice were sacrificed,and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment.DNA synthesis was detected via a BrdU assay,and cell proliferation was tested using Ki-67.The expressions of cyclin D1,cyclin E,cyclin dependent kinase 2(CDK2),and CDK4 were detected by Western blot analysis.Chromatin immunoprecipitation(ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot.Results:Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased,and the peak of BrdU was delayed in the VPA-administered mice.Consistently,cyclin D1 expression was also delayed.We identified B-myc as a target gene of HDACs by complementary DNA(cDNA) microarray.The expression of B-myc increased in the VPA-administered mice after hepatectomy(PH).The ChIP assay confirmed the presence of HDACs at the B-myc promoter.Conclusions:HDAC activities are essential for liver regeneration.Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest,thereby causing an anti-proliferative effect on liver regeneration.