Multi-omics analysis reveals the pivotal role of phytohormone homeostasis in regulating maize grain water content

Grain water content(GWC)is a key determinant for mechanical harvesting of maize(Zea mays).In our previous research,we identified a quantitative trait locus,qGWC1,associated with GWC in maize.Here,we examined near-isogenic lines(NILs)NILL and NILH that differed at the qGWC1 locus.Lower GWC in NILL was primarily attributed to reduced grain water weight(GWW)and smaller fresh grain size,rather than the accumulation of dry matter.The difference in GWC between the NILs became more pronounced approximately 35 d after pollination(DAP),arising from a faster dehydration rate in NILL.Through an integrated analysis of the transcriptome,proteome,and metabolome,coupled with an examination of hormones and their derivatives,we detected a marked decrease in JA,along with an increase in cytokinin,storage forms of IAA(IAA-Glu,IAA-ASP),and IAA precursor IPA in immature NILL kernels.During kernel development,genes associated with sucrose synthases,starch biosynthesis,and zein production in NILL,exhibited an initial up-regulation followed by a gradual down-regulation,compared to those in NILH.This discovery highlights the crucial role of phytohormone homeostasis and genes related to kernel development in balancing GWC and dry matter accumulation in maize kernels.

Anew wave of innovations within the DNA damagee response

Genome instability has been identified as one of the enabling hallmarks in cancer.DNA damage response(DDR)network is responsible for maintenance of genome integrity in cells.As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress,targeting DDR processes could induce excessive DNA damages(or unrepaired DNA)that eventually lead to cell death.Poly(ADP-ribose)polymerase(PARP)inhibitors have brought impressive benefit to patients with breast cancer gene(BRCA)mutation or homologous recombination deficiency(HRD),which proves the concept of synthetic lethality in cancer treatment.Moreover,the other two scenarios of DDR inhibitor application,replication stress and combination with chemo-or radio-therapy,are under active clinical exploration.In this review,we revisited the progress of DDR targeting therapy beyond the launched firstgeneration PARP inhibitors.Next generation PARP1 selective inhibitors,which could maintain the efficacy while mitigating side effects,may diversify the application scenarios of PARP inhibitor in clinic.Albeit with unavoidable on-mechanism toxicities,several small molecules targeting DNA damage checkpoints(gatekeepers)have shown great promise in preliminary clinical results,which may warrant further evaluations.In addition,inhibitors for other DNA repair pathways(caretakers)are also under active preclinical or clinical development.With these progresses and efforts,we envision that a new wave of innovations within DDR has come of age.