Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)...Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.展开更多
该文报道1个累及3代共9人的Nascimento型X连锁智力障碍(Nascimento form of syndromic X-linked intellectual developmental disorder,MRXSN)大家系的临床特点及基因突变类型并进行文献复习。家系中共9人有相似的智力障碍、特殊面容等...该文报道1个累及3代共9人的Nascimento型X连锁智力障碍(Nascimento form of syndromic X-linked intellectual developmental disorder,MRXSN)大家系的临床特点及基因突变类型并进行文献复习。家系中共9人有相似的智力障碍、特殊面容等,其中4人已去世。基因检测提示先证者UBE2A基因存在2~3号外显子缺失,来自母亲。荧光定量聚合酶链反应显示,先证者和表舅UBE2A基因存在2~3号外显子缺失,先证者之母亲、外婆及表姨奶UBE2A基因存在2~3号外显子杂合缺失;先证者之父亲、姐姐、表姨UBE2A基因2~3号外显子拷贝数均正常。文献报道的34例患者临床表型多样,UBE2A基因突变(22/34,65%)和大片段缺失(12/34,35%)为主要突变类型。中重度智力障碍(34/34,100%)、言语障碍(33/34,97%)、特殊面容(32/34,94%)等是MRXSN患者主要的临床表现。该病具有明显的表型异质性,尽早明确诊断有利于优生优育。展开更多
精确的环境感知是实现自主代客泊车(automated valet parking,AVP)功能的基础,传统的AVP系统主要依赖于单车的感知,但随着场端智能技术的不断发展,车端与场端之间协同交互成为自主代客泊车落地的必然趋势。本文提出了一种基于V2X车场协...精确的环境感知是实现自主代客泊车(automated valet parking,AVP)功能的基础,传统的AVP系统主要依赖于单车的感知,但随着场端智能技术的不断发展,车端与场端之间协同交互成为自主代客泊车落地的必然趋势。本文提出了一种基于V2X车场协同的地下停车场全域感知方法,该方法将地下停车场的全域感知问题转化为大规模图模型的构建与优化问题。通过输入场端激光雷达、摄像头的传感器信息以及智能网联车的感知数据,以车辆位姿为节点,建立多种边约束关系。为了提高感知精度,本文提出了一种融合车道级地图信息的大规模图模型方法,通过将停放车辆作为半静态信息约束,并结合车道级地图信息构建横向约束,在求解过程中引入滑动窗口以减小图模型的规模,最终以地图形式输出感知结果供车端使用。通过仿真实验和在占地面积为2 500 m^(2)以上的地下停车场场景中进行实地实验,结果表明,该方法显著提升了在复杂停车场环境下的感知能力,实现了地下停车场的全域感知。展开更多
基金supported by Guangdong Province Basic and Applied Basic Research Fund Project(2023A1515220104)Open Fund of Key Laboratory of Hepatoaplenic Surgery,Ministry of Education(Award Number:GPKF202407).
文摘Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.
文摘该文报道1个累及3代共9人的Nascimento型X连锁智力障碍(Nascimento form of syndromic X-linked intellectual developmental disorder,MRXSN)大家系的临床特点及基因突变类型并进行文献复习。家系中共9人有相似的智力障碍、特殊面容等,其中4人已去世。基因检测提示先证者UBE2A基因存在2~3号外显子缺失,来自母亲。荧光定量聚合酶链反应显示,先证者和表舅UBE2A基因存在2~3号外显子缺失,先证者之母亲、外婆及表姨奶UBE2A基因存在2~3号外显子杂合缺失;先证者之父亲、姐姐、表姨UBE2A基因2~3号外显子拷贝数均正常。文献报道的34例患者临床表型多样,UBE2A基因突变(22/34,65%)和大片段缺失(12/34,35%)为主要突变类型。中重度智力障碍(34/34,100%)、言语障碍(33/34,97%)、特殊面容(32/34,94%)等是MRXSN患者主要的临床表现。该病具有明显的表型异质性,尽早明确诊断有利于优生优育。
文摘精确的环境感知是实现自主代客泊车(automated valet parking,AVP)功能的基础,传统的AVP系统主要依赖于单车的感知,但随着场端智能技术的不断发展,车端与场端之间协同交互成为自主代客泊车落地的必然趋势。本文提出了一种基于V2X车场协同的地下停车场全域感知方法,该方法将地下停车场的全域感知问题转化为大规模图模型的构建与优化问题。通过输入场端激光雷达、摄像头的传感器信息以及智能网联车的感知数据,以车辆位姿为节点,建立多种边约束关系。为了提高感知精度,本文提出了一种融合车道级地图信息的大规模图模型方法,通过将停放车辆作为半静态信息约束,并结合车道级地图信息构建横向约束,在求解过程中引入滑动窗口以减小图模型的规模,最终以地图形式输出感知结果供车端使用。通过仿真实验和在占地面积为2 500 m^(2)以上的地下停车场场景中进行实地实验,结果表明,该方法显著提升了在复杂停车场环境下的感知能力,实现了地下停车场的全域感知。
