BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability

Multiple myeloma(MM)is an incurable plasma cell malignancy in the bone marrow characterized by chromosome instability(CIN),which contributes to the acquisition of heterogeneity,along with MM progression,drug resistance,and relapse.In this study,we elucidated that the expression of BUB1B increased strikingly in MM patients and was closely correlated with poor outcomes.Overexpression of BUB1B facilitated cellular proliferation and induced drug resistance in vitro and in vivo,while genetic targeting BUB1B abrogated this effect.Mechanistic studies unveiled that enforced expression of BUB1B evoked CIN resulting in MM poor outcomes mainly through phosphorylating CEP170.Interestingly,we discovered the existence of circBUB1B_544aa containing the kinase catalytic center of BUB1B,which was translated by a circular RNA of BUB1B.The circBUB1B_544aa elevated in MM peripheral blood samples was closely associated with MM poor outcomes and played a synergistic effect with BUB1B on evoking CIN.In addition,MM cells could secrete circBUB1B_544aa and interfere the MM microenvironmental cells in the same manner as BUB1B full-length protein.Intriguingly,BUB1B siRNA,targeting the kinase catalytic center of both BUB1B and circBUB1B_544aa,significantly inhibited MM malignancy in vitro and in vivo.Collectively,BUB1B and circBUB1B_544aa are promising prognostic and therapeutic targets of MM.

Coalescence of Al_(0.3)CoCrFeNi polycrystalline high-entropy alloy in hot-pressed sintering: a molecular dynamics and phase- field study

Existing hot sintering models based on molecular dynamics focus on single-crystal alloys.This work proposes a new multiparticle model based on molecular dynamics to investigate coalescence kinetics during the hot-pressed sintering of a polycrystalline Al_(0.3)CoCrFeNi high-entropy alloy.The accuracy and effectiveness of the multiparticle model are verified by a phase-field model.Using this model,it is found that when the particle contact zones undergo pressure-induced evolution into exponential power creep zones,the occurrences of phenomena,such as necking,pore formation/filling,dislocation accumulation/decomposition,and particle rotation/rearrangement are accelerated.Based on tensile test results,Young’s modulus of the as-sintered Al_(0.3)CoCrFeNi high-entropy alloy is calculated to be 214.11±1.03 GPa,which deviates only 0.82%from the experimental value,thus further validating the feasibility and accuracy of the multiparticle model.