Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively investigated.However,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and pyroptosis.The direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific inhibitors.We thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific conditions.This editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent models.Only clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

基于改进DeepLabv3+的轻量化作物杂草识别方法

为在存储资源与计算能力有限的设备上实现田间作物和杂草的识别,本文提出一种基于改进DeepLabv3+的轻量化语义分割网络。首先,以MobileNet v2作为DeepLabv3+的特征提取骨干网络,提出双分支残差模块替换倒残差模块,并删除后两层卷积以降低模型参数量。其次,在空洞空间金字塔池化(Atrous Spatial Pyramid Pooling,ASPP)模块中引入分组逐点卷积,使用深度扩张卷积替换标准卷积,并将卷积后的特征图进行多尺度特征融合增强对作物和杂草深层特征的提取能力。最后,将原有的非线性激活函数替换为Leaky ReLU激活函数来提升分割精度。实验结果表明:改进后网络的mIOU达到86.75%,参数量仅为0.69M,FPS达到了98,与原始DeepLabv3+以及3个典型轻量化语义分割网络的相比,参数量最小,在对比的轻量化网络中具有最高的分割精度。

罗汉果皂苷V对RSL3诱导的SH-SY5Y细胞铁死亡的抑制作用及其机制

目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光探针FerroFarRed检测细胞内亚铁离子含量;线粒体红色荧光探针MitoTracker Red CMXRos检测线粒体膜电位(MMP);超氧化物阴离子荧光探针二氢乙啶和线粒体超氧化物红色荧光探针MitoSoX Red分别检测细胞内和线粒体内活性氧(ROS)。微板法检测细胞谷胱甘肽(GSH)和丙二醛(MDA)水平。Western blot检测脂酰辅酶A合成酶长链家族成员4(ACSL4)、环加氧酶2(COX-2、)谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)蛋白表达水平。分子对接技术预测MV与ACSL4、COX-2、GPX4和SLC7A11的靶向关系。结果:与control组相比,RSL3组SH-SY5Y细胞活力显著降低(P<0.01),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著升高(P<0.05或P<0.01),MMP和GSH水平显著降低(P<0.01),ACSL4和COX-2蛋白表达水平显著升高,而GPX4和SLC7A11蛋白表达水平显著降低(P<0.01),提示成功建立了细胞铁死亡模型。MV处理使细胞活力显著升高(P<0.05),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著降低(P<0.01),MMP和GSH水平显著升高(P<0.05或P<0.01);ACSL4和COX-2蛋白水平显著降低,而GPX4和SLC7A11蛋白水平显著升高(P<0.05或P<0.01)。分子对接结果显示,MV与铁死亡核心蛋白ACSL4、COX-2、GPX4和SLC7A11存在结合位点。结论:MV可抑制RSL3诱导的SH-SY5Y细胞铁死亡的发生,其机制可能与激活SLC7A11/GPX4和抑制ACSL4/COX-2有关。

改进DeepLab v3+模型下的梯田遥感提取研究

[目的与意义]梯田作为农业生产的关键要素之一,其面积估算对于农业政策制定、土地规划和资源管理至关重要。为解决复杂的地形条件、种植环境导致传统遥感数据和监测方法难以开展梯田自动化提取问题,探索一种利用深度学习技术在高分辨率遥感影像中精准提取梯田面积的方法。[方法]以休耕期梯田高分六号影像构建语义分割数据集,同时提出一种改进的DeepLab v3+模型。该模型使用轻量级网络MobileNet v2作为骨干网络,为了同时兼顾局部细节和全局语境,使用多尺度特征融合(Multi-scale Feature Fusion module,MSFF)模块代替空洞空间金字塔池化(Atrous Spatial Pyramid Pooling,ASPP)模块,利用扩张率依次增大的空洞卷积级联模式改善信息丢失的问题。此外,对浅层特征和深层特征使用坐标注意力机制以加强网络对于目标的学习。[结果与讨论]利用红、绿和近红外波段组合方式在梯田提取的精度和效果上表现最佳。相比于原始DeepLab v3+网络,精确率、召回率、F_(1)评分和交并比指标分别提升4.62%、2.61%、3.81%和2.81%。此外,与UNet和原始DeepLab v3+相比,改进的DeepLab v3+在参数量上和浮点运算数有着更为优越的性能,其参数量仅为UNet的28.6%和原始DeepLab v3+的19.5%,同时浮点运算数仅为UNet和DeepLab v3+的1/5。这不仅提高了计算效率,也使得改进后的模型更适用于资源有限或计算能力较低的环境中。[结论]深度学习在高分辨率遥感影像梯田识别中具有较高的精度,有利于为梯田精细化监测和管理提供参考依据。

NLRP3炎性小体激活对VCI海马组织凋亡及自噬的影响研究

目的 探究NOD样受体蛋白3 (NLRP3)炎性小体激活对血管性认知功能障碍(VCI)海马组织凋亡及自噬的影响。方法 SPF级SD大鼠采用四血管阻断法复制VCI模型构建,根据研究目的分为正常对照组、假手术组、模型组、雷帕霉素靶蛋白(mTOR)组。分别在造模前、造模后、给药后进行Morris水迷宫实验;同时取海马组织进行苏木精-伊红染色、TUNEL细胞凋亡、qRT-PCR检测磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B (Akt)、mTOR、NLRP3的表达水平、Western blot检测凋亡蛋白表达水平。结果 大鼠迷宫实验鉴定结果显示,造模后迷宫逃逸时间显著大于造模前,给药后模型组迷宫逃逸时间显著高于mTOR组和假手术组,差异有统计学意义(P<0.05)。苏木精-伊红染色结果显示,空白对照组无明显病变、假手术组稍有水肿,模型组海马组织局部有坏死灶,mTOR组仅有水肿。TUNEL染色结果显示,模型组海马组织中细胞凋亡相比其他组相对多,假手术组和mTOR组组织中细胞凋亡不明显,但各组间比较,差异无统计学意义(P> 0.05)。qRT-PCR结果显示,模型组Akt、mTOR、NLRP3表达水平与正常对照组相比均有上升趋势,PI3K有降低趋势,但差异均无统计学意义(P>0.05)。Western blot检测结果显示,p62、caspase-1、LC3-B、Bax蛋白在模型组与正常对照组、假手术组相比有上升趋势,与mTOR组相比有下降趋势;其中mTOR组LC3-B蛋白表达量与模型组相比,差异有统计学意义(P<0.05)。结论NLRP3可能通过调控降低PI3K、升高Akt和mTOR水平促进海马神经元的凋亡而导致VCI的发生。

基于NGF/PI3K/TRPV1信号通路探究参苓白术散对腹泻型肠易激综合征小鼠的干预机制

目的研究基于神经生长因子/磷脂酰肌醇3-激酶/瞬时受体电位香草酸受体1(NGF/PI3K/TRPV1)信号通路探究参苓白术散对腹泻型肠易激综合征小鼠的干预机制。方法选取40只SPF级SD雄性大鼠,其中空白组10只,模型组13只、研究1组7只、研究2组9只。对照组、模型组只进行生理盐水灌胃,不做其他任何处理。研究1组给予匹维溴铵片20mg/kg水溶液进行灌胃,研究2组给予参苓白术散4g/kg进行灌胃。评估Bristol评分情况;分析脾脏系数、胸腺系数情况;检测IgA、IgG、IgM、IL-1β、IL-6、TNF-α表达水平及NGF/PI3K/TRPV1蛋白表达情况。结果相比于空白组,模型组、研究1组、研究2组Bristol评分、脾脏系数、胸腺系数、IgA、IgG、IgM、IL-1β、IL-6、TNF-α水平及NGF、PI3K、TRPV1蛋白表达均上升(P<0.05);相比于模型组、研究1组,研究2组Bristol评分、脾脏系数、胸腺系数、IgA、IgG、IgM、IL-1β、IL-6、TNF-α水平及NGF、PI3K、TRPV1蛋白表达均下降(P<0.05)。结论参苓白术散抑制NGF/PI3K/TRPV1通路,改善大鼠胃肠功能及大便状态,减轻炎症反应,提高免疫功能稳态情况,干预效果显著。

基于NOD样受体3炎性小体通路对利拉鲁肽在氧化低密度脂蛋白诱导内皮细胞损伤的作用机制研究

背景动脉粥样硬化是世界范围内引起心脑血管疾病最主要的原因,炎症是目前研究热点,其中NOD样受体3(NLRP3)是研究最为深入的炎症小体。胰高糖素样肽1(GLP-1)受体激动剂有抗动脉粥样硬化作用,具体机制尚不明确。目的研究利拉鲁肽通过拮抗氧化低密度脂蛋白(ox-LDL)诱导的内皮细胞损伤的作用机制。方法2022-03-25—05-19培养人脐静脉内皮细胞(HUVEC),取HUVEC加空白血清作为对照组,100μg/mL的ox-LDL干预HUVEC 48 h作为模型组,100μg/mL的ox-LDL干预HUVEC 24 h后分别加入100、200、400 nmol/L利拉鲁肽处理24 h作为利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组。CCK-8法计算细胞增殖率。通过扫描电镜观察焦亡细胞形态。检测乳酸脱氢酶(LDH)活力。酶联免疫吸附试验(ELISA)检测白介素(IL)-1β、IL-18表达水平。蛋白质免疫印迹试验(Western blot)检测NLRP3、接头蛋白凋亡相关斑点样蛋白(ASC)、天冬氨酸蛋白水解酶1(Caspase-1)、焦亡执行蛋白(GSDMD)、N端结构域的焦亡执行蛋白(N-GSDMD)表达水平。结果模型组、利拉鲁肽低浓度组和利拉鲁肽中浓度组细胞增殖率低于对照组,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组细胞增殖率高于模型组(P<0.05)。细胞扫描电镜结果示模型组细胞焦亡明显,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组细胞焦亡情况明显改善。模型组、利拉鲁肽低浓度组LDH活力高于对照组,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组低于模型组(P<0.05)。模型组、利拉鲁肽低浓度组IL-1β表达水平高于对照组,利拉鲁肽中浓度组、利拉鲁肽高浓度组IL-1β表达水平低于模型组(P<0.05);模型组IL-18表达水平高于对照组,利拉鲁肽低浓度组、利拉鲁肽中浓度组、利拉鲁肽高浓度组IL-18表达水平低于模型组(P<0.05)。模型组NLRP3、ASC、Caspase-1、GSDMD、N-GSDMD表达水平高于对照组,利拉鲁肽低浓度组ASC、Caspase-1表达水平高于对照组,利拉鲁肽中浓度组NLRP3、ASC表达水平低于模型组,利拉鲁肽高浓度组NLRP3、ASC、Caspase-1表达水平低于模型组(P<0.05)。结论利拉鲁肽显著抑制ox-LDL诱导的内皮细胞NLRP3炎性小体活化,并且能够抑制内皮细胞的焦亡,具有抗动脉粥样硬化作用。

2型糖尿病下肢血管病变患者介入治疗后血清NLRP3及sVCAM-1水平对再狭窄的意义

目的探讨2型糖尿病下肢血管病变患者介入治疗后血清NOD样受体蛋白3(NLRP3)及可溶性血管细胞黏附分子-1(sVCAM-1)水平对再狭窄的意义。方法回顾性分析2022年1月~2023年1月于河北省邯郸市中心医院血管介入科104例成功行血管介入治疗的2型糖尿病下肢血管病变患者的临床资料。根据介入后再狭窄发生情况分为再狭窄组(n=20)和无再狭窄组(n=84),比较两组患者一般资料及介入后24 h血清NLRP3、sVCAM-1水平,采用多因素Logistic回归模型分析再狭窄发生的影响因素;创建受试者工作特征(ROC)曲线,分析血清NLRP3、sVCAM-1检测对再狭窄的预测价值。结果与无再狭窄组相比,再狭窄组患者2型糖尿病病程、下肢动脉病变长度更长,Fontaine分期Ⅳ期占比、下肢动脉完全闭塞占比及血清糖化血红蛋白(HbA1c)、超敏C反应蛋白(hs-CRP)、NLRP3、sVCAM-1水平更高(P<0.05);多因素Logistic回归分析显示,下肢动脉完全闭塞、下肢动脉病变长度、HbA1c、NLRP3及sVCAM-1是2型糖尿病下肢血管病变患者介入后再狭窄发生的影响因素(P<0.05);ROC曲线显示,血清NLRP3、sVCAM-1联合检测对2型糖尿病下肢血管病变患者介入后再狭窄发生的预测价值较高,敏感度为95.00%,特异度为71.43%,ROC曲线下面积为0.929。结论血清NLRP3、sVCAM-1水平高表达均是2型糖尿病下肢血管病变患者介入治疗后再狭窄发生的危险因素,二者联合检测能提高2型糖尿病下肢血管病变患者介入治疗后再狭窄预测的准确性。

改进Deeplabv3+的双注意力融合作物分类方法

近年来,卷积神经网络(convolutional neural networks,CNN)在农作物分类研究中不断取得新进展,但在建模长期依赖关系方面表现出一定的局限性,对农作物全局特征的捕获存在不足。针对以上问题,将Transformer引入Deeplab v3+模型,提出了一种用于无人机影像农作物分类的并行分支结构--DeepTrans(Deeplab v3+with Trans-former)模型。DeepTrans以一种并行的方式将Transformer和CNN结合在一起,利于全局特征与局部特征的有效捕获。通过引入Transformer来增强图像中信息的远距离依赖关系,提高了作物全局信息的提取能力;加入通道注意力机制和空间注意力机制加强Transformer对通道信息的敏感度及ASPP(atrous spatial pyramid pooling)对作物空间信息捕获能力。实验结果表明,DeepTrans模型在MIoU指标上可达0.812,相较于Deeplab v3+模型提高了3.9%,该模型在五类作物的分类中精度均有提升,对于容易错分的甘蔗、玉米和香蕉三种作物,其IoU分别提高了2.9%、4.7%、13%。由此可见,DeepTrans模型在农作物分类图像的内部填充和全局预测方面有着更好的分割效果,有助于更准确地监测农田作物的种植结构及规模。

基于v3洋葱域名的比特币地址威胁程度分析

比特币可以在不透露使用者身份的情况下进行交换,导致其成为不法分子在暗网上进行违法活动的主要方式。为了追踪比特币非法交易,传统方法根据比特币的伪匿名性,在整个区块链上进行启发式地址聚类,没有充分利用比特币地址在暗网上的信息。2021年Tor官方全面启用v3洋葱域名,使得以往的v2洋葱域名数据无法再作为分析的依据。设计并实现基于v3洋葱域名的比特币地址威胁程度的一体化分析框架TLAFDB。信息收集模块使用境外服务器解决地域限制并设置socks5h代理以支持暗网爬虫运行,使用洋葱种子地址在暗网中爬行收集最新的v3洋葱域名数据,信息清洗模块采用可同时覆盖Base58和Bech32编码的正则表达式以提取v3洋葱域名网页中的比特币地址,通过区块链搜索引擎Blockchain.com筛选存在真实交易的比特币地址,并建立其和所在v3洋葱域名的关联关系,信息分析模块采用人工分析和关键词匹配相结合的方法分类v3洋葱域名,赋予其关联的比特币地址类别和流行度并判定威胁程度。实验结果表明,TLAFDB收集了23627个v3洋葱域名网页,提取并分析1141个存在真实交易的比特币地址的类别、流行度和威胁程度,发现在暗网中同一个比特币地址常出现在大量的镜像洋葱域名网页上,超过95%的比特币地址被恶意使用,并且庞氏骗局交易量占高危比特币地址总交易量的99%。

基于改进MobileNet v3的苹果叶片病害识别研究

为解决移动端和嵌入式设备中苹果叶片病害识别准确率不高、效率低下的问题,提出了一种新的基于MobileNet v3网络的分类模型,以实现更加高效和准确的苹果叶片病害识别。首先通过数据增广方法增强数据集,按照9∶1的比例划分训练集和验证集;然后在MobileNet v3网络核心倒残差结构的升维部分引入全维动态卷积,以加强对不同维度注意力权重的学习,从而增强网络的拟合能力;最后在降维部分引入修改后的ConvNext Block模块,减少信息损失并增加全局感受野。采用PyTorch作为分类网络的深度学习框架,使用交叉熵损失函数作为分类任务的损失函数,Adam作为优化器,通过多组对比试验可知,MobileNet v1、MobileNet v2、ResNet34、MobileNet v3以及改进后的MobileNet v3 ODConvNext网络的准确率分别为94.5%、95.7%、97.2%、96.9%及97.5%。可见,MobileNet v3 ODConvNet网络拥有最高的Top-1准确率,相较于MobileNet v3网络和结构更为复杂的ResNet34网络分别提升了0.6、0.3百分点;在运算频率方面,相对于MobileNet v3网络仅增加了1.00×10^(6)次/s,并且仅为ResNet34网络参数量的11.84%。因此,该试验结果证明了改进后的MobileNet v3 ODConvNext模型具有更加轻量级和更高准确率的优点,满足在移动端真实场景下进行苹果叶片病害识别的要求,有助于苹果叶片病害的防治工作。

LAIR-1通过阻断JAK2 V617F突变的人HEL细胞JAK/STAT和PI3K/AKT/mTOR信号通路抑制其增殖并促进其凋亡

目的研究人白细胞相关免疫球蛋白样受体1(LAIR-1)对Janus激酶2(JAK2)V617F突变的人急性髓系白血病HEL细胞JAK/信号转导子与转录激活子(STAT)和磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)信号通路的调节作用,以及对细胞增殖和凋亡的影响。方法采用反转录PCR和基因测序鉴定JAK2 V617F突变;应用免疫共沉淀和Western blot法鉴定LAIR-1募集的蛋白酪氨酸磷酸酶(PTP)种类;采用CCK-8法检测HEL细胞的增殖;采用异硫氰酸荧光素标记的膜联素Ⅴ/碘化丙啶(annexinⅤ-FITC/PI)双标记结合流式细胞术检测HEL细胞的凋亡率;采用Western blot法检测JAK/STAT和PI3K/AKT/mTOR通路蛋白酪氨酸磷酸化水平及细胞周期蛋白D1(cyclin D1)、Bcl2相关X蛋白(BAX)和B细胞淋巴瘤因子2(Bcl2)的蛋白表达。结果在JAK2 V617F突变的HEL细胞中,LAIR-1与其配体胶原蛋白结合后可募集含Src同源域2磷酸酶2(SHP-2);LAIR-1可以下调HEL细胞JAK2、STAT1、STAT3、STAT5、AKT和mTOR的蛋白酪氨酸磷酸化水平,并能够显著抑制cyclin D1和Bcl2的表达,而对BAX的表达水平未见显著影响;LAIR-1能够明显抑制HEL细胞的增殖,促进HEL细胞凋亡。结论在JAK2 V617F突变的人白血病HEL细胞中,LAIR-1可通过募集SHP-2抑制JAK/STAT和PI3K/AKT/mTOR信号通路的活化,进而抑制HEL细胞的增殖,促进细胞凋亡。

STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

基于DeepLab v3+的综放工作面含矸率预测研究

针对综放工作面真实煤矸堆叠状态下的体积含矸率很难获取的问题,提出一种基于DeepLab v3+的综放工作面含矸率预测方法。构建了煤矸堆积体图像数据集,采用半自动的数据标注方法和限制对比度自适应直方图均衡化法对煤矸图像进行预处理。运用DeepLab v3+模型进行煤矸图像语义分割,进而计算煤矸图像的投影面积含矸率。利用PFC3D数值模拟软件,基于重建的三维煤矸块体建立数值模型,模拟顶煤放落和刮板输送机运煤过程,通过fish语言读取每个矸石或煤的体积,计算得到煤矸堆积体体积含矸率。通过分析不同顶煤厚度条件下刮板输送机上煤矸堆积体的投影面积含矸率与体积含矸率的量化关系,建立了煤流的体积含矸率预测模型。实验结果表明:DeepLab v3+模型的准确率、平均像素准确率和平均交并比分别为97.68%,97.72%,95.33%,均高于经典语义分割模型FCN8s和PSPNet,实现了煤矸堆积体投影面积含矸率的精准快速识别;体积含矸率预测模型的决定系数R^(2)为0.9828,预测效果较好。

基于改进MobileNet v3的苹果叶片病害识别方法及移动端应用

准确识别苹果叶片病害种类以进行及时防治对于苹果增量增产具有重要的意义,为实现在移动设备实时对苹果叶片进行病害识别,提高苹果的产量,减少种植者的损失。首先收集了黑星病、斑点落叶病、锈病、白粉病、混合病、褐斑病等6种苹果叶部病害和健康叶片的图像,并使用Retinex算法对图像进行数据增强,以提高数据集质量,然后将数据集按照8∶1∶1的比例划分为训练集、验证集和测试集;其次对MobileNet v3网络模型进行改进优化调整,在精简网络结构的同时减少冗余参数,并在非线性激活层后加入批归一化层,以提高网络的特征提取能力;同时,为了提升在低精度移动设备上的准确性和模型运行效率,将全连接层中的激活函数替换为ReLU6函数;最后,在模型训练时使用动量随机梯度下降优化器来进行模型权重系数的寻优,以减少训练时间和达到更高的分类准确率。试验结果表明,改进后的MobileNet v3-A3网络对苹果叶片病害图像的识别准确率为96.48%,模型权重为2.98 MB,识别速率为8.82 ms/幅图片,与其他同量级卷积神经网络相比识别精度更高、模型更小、识别速度更快。本研究使用Android Studio将权重模型封装到安卓软件中,实现了移动设备对苹果叶片病害的准确快速识别。