The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves gl...The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.展开更多
Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal ...Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.展开更多
INTRODUCTION.On January 7,2025,at 9:05 AM BJT,a MS6.8 earthquake(CENC epicenter:28.50°N,87.45°E)struck Dingri County,Xizang Province(hereinafter referred to as the Dingri mainshock).The inferred moment magni...INTRODUCTION.On January 7,2025,at 9:05 AM BJT,a MS6.8 earthquake(CENC epicenter:28.50°N,87.45°E)struck Dingri County,Xizang Province(hereinafter referred to as the Dingri mainshock).The inferred moment magnitude,based on regional/teleseismic waveform inversion and back-projection,is approximately MW7.1.Focal mechanism solutions,aftershock distribution,and field surveys indicate that the Dingri mainshock was a normal-faulting event,with a nearly north-south strike and a westward-dipping fault plane.展开更多
为了有效应对玉米地杂草对玉米产量和品质的影响,实现玉米与杂草的快速、准确检测,提出了一种基于改进YOLOv8n(You Only Look Once Version 8 nano)的玉米与杂草检测模型。首先,提出了ACMConv(Accurate and Computationally Minimal Con...为了有效应对玉米地杂草对玉米产量和品质的影响,实现玉米与杂草的快速、准确检测,提出了一种基于改进YOLOv8n(You Only Look Once Version 8 nano)的玉米与杂草检测模型。首先,提出了ACMConv(Accurate and Computationally Minimal Convolution)新型卷积方式,显著减少了模型计算量,使模型更加轻量化;其次,使用SELU激活函数,引入非线性因素,有效缓解了梯度消失问题;最后,引入Focal Loss作为边界框损失函数,使模型更加容易收敛。实验结果表明,相较于原始YOLOv8n模型,改进后的YOLOv8n模型的平均精度均值提升了1.3百分点,计算量降低了7.3%,实现了对玉米与杂草的高效、准确检测。展开更多
基金funded by the Alexander von Humboldt Stiftungsupported by DFG (SCH W534/6-1 to SWS)
文摘The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.
基金supported by grants from the National Natural Science Foundation of China(82372881 to Weiyang He)the Chongqing Biomedicine Key R&D Project(CSTB2021TIAD-KPX0041 to Weiyang He).
文摘Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.
基金supported by the“CUG Scholar”Scientific Research Funds at China University of Geosciences(Wuhan)(No.2021230)supported by the National Natural Science Foundation of China(Nos.41922025,42204062)。
文摘INTRODUCTION.On January 7,2025,at 9:05 AM BJT,a MS6.8 earthquake(CENC epicenter:28.50°N,87.45°E)struck Dingri County,Xizang Province(hereinafter referred to as the Dingri mainshock).The inferred moment magnitude,based on regional/teleseismic waveform inversion and back-projection,is approximately MW7.1.Focal mechanism solutions,aftershock distribution,and field surveys indicate that the Dingri mainshock was a normal-faulting event,with a nearly north-south strike and a westward-dipping fault plane.
文摘为了有效应对玉米地杂草对玉米产量和品质的影响,实现玉米与杂草的快速、准确检测,提出了一种基于改进YOLOv8n(You Only Look Once Version 8 nano)的玉米与杂草检测模型。首先,提出了ACMConv(Accurate and Computationally Minimal Convolution)新型卷积方式,显著减少了模型计算量,使模型更加轻量化;其次,使用SELU激活函数,引入非线性因素,有效缓解了梯度消失问题;最后,引入Focal Loss作为边界框损失函数,使模型更加容易收敛。实验结果表明,相较于原始YOLOv8n模型,改进后的YOLOv8n模型的平均精度均值提升了1.3百分点,计算量降低了7.3%,实现了对玉米与杂草的高效、准确检测。
