Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

科宝500和AA白羽肉鸡生产性能比较分析

文章旨在探讨科宝500和爱拔益加(AA)白羽肉鸡生产性能的差异。试验以科宝500和爱拔益加(AA)白羽肉鸡为研究对象,测定1~6周龄两个品种的平均采食量、平均体重、平均日增重、料重比、死淘率以及欧洲效益指数,分析比较两品种间生产性能的差异变化。结果表明:(1)科宝500肉鸡平均采食量前期变化较大,2周龄时显著高于AA肉鸡(P<0.05),但3周龄显著低于AA白羽肉鸡(P<0.05),整个试验期(1~6周龄),科宝500肉鸡平均采食量高于AA肉鸡,但差异不显著(P>0.05);(2)7和35日龄时,科宝500肉鸡平均体重显著大于AA肉鸡(P<0.05),5周龄时,科宝500肉鸡平均日增重显著高于AA肉鸡(P<0.05),而其他周龄及整个试验期(1~6周龄),科宝500肉鸡平均体重和平均日增重均高于AA肉鸡,但差异均不显著(P>0.05);(3)各周龄及整个试验期(1~6周龄)科宝500肉鸡料重比均低于AA肉鸡,但差异均不显著(P>0.05);(4)4周龄时,科宝500肉鸡死淘率显著高于AA肉鸡(P<0.05),而其他周龄及整个试验期(1~6周龄),科宝500肉鸡死淘率高于AA肉鸡,但差异均不显著(P>0.05);(5)欧洲效益指数(EPI)方面,科宝500肉鸡高于AA肉鸡,但差异不显著(P>0.05)。综合分析,科宝500肉鸡生产性能及养殖效益优于AA肉鸡。

土壤游离铁CS AAS测定方法的验证

为提高游离铁的检测效率,本研究对游离铁(Fed)的测定(DCB法)提取液在原子吸收光谱仪上的检测进行验证。使用CS AAS上机时对特征参数包括标准曲线、检出限、检出下限、精密度、准确度进行验证及确认。确定线性范围为0~7.0 mg/L,非线性拟合回归方程相关系数0.999 8、检出限0.005 3 g/kg、检出下限0.021 g/kg。普通土壤样品检测精密度相对相差小于10%,相对标准偏差小于1.9%,满足方法中平行测定质量控制要求和《化学分析方法验证确认和内部质量控制要求》。对高、中、低3个有证标准物质进行6次测定,相对误差小于10%,满足正确度的要求,上机测试数据稳定可靠。

AA抑制率和ADP抑制率对脑出血后再出血及预后的预测价值分析

目的 本研究的目的是评估血栓弹力图(thrombelasto graphy,TEG)测试中AA抑制率和ADP抑制率在预测脑出血(ICH)后再出血和不良功能预后方面的有效性。方法 选取苏州市立医院2019年4月至2022年6月之间114例出现症状6 h内接受CT检查的原发性脑出血患者作为研究对象,评估两组患者入院后TEG指标中花生四烯酸(AA)抑制率、二磷酸腺苷(ADP)抑制率等与脑出血后再出血及病残率、病死率等结局的关系,以及与格拉斯哥昏迷量表评分的相关性。结果 未再出血组AA抑制率和ADP抑制率均明显低于再出血组(P<0.05);再出血组中死亡患者AA抑制率和ADP抑制率均明显高于康复组及病残组(P<0.05);AA抑制率和ADP抑制率与GCS评分呈负相关(r=-0.702,P=0.008)。结论在脑出血后再出血及预后的评估中,AA抑制率和ADP抑制率具有较好的预测价值,值得临床推广。

汉日语言AA式名词叠词与数字的搭配考察

汉日语言中都存在大量AA式名词叠词,但有所不同的是像“年年”这样的同形同义词在汉语中可以和数字“一”共起,在日语中却不行。文章通过词典收集语料后,再将语料逐一输入语料库对汉日AA式名词叠词与数字的搭配见考察,发现汉语AA式名词叠词有“只能与数字‘一’搭配”和“可以和所有数字搭配”两种类型,日语AA式与数字搭配的名词叠词有“不能与数字‘一’搭配”和“可以和所有数字搭配”两种类型。并且汉语AA式名词叠词与数字搭配情况更为普遍,搭配上也更具灵活性。

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.

circMYO9A_006通过翻译蛋白MYO9A-208aa发挥抑制心肌细胞肥大的作用

目的:研究环状RNA MYO9A_006(circMYO9A_006)对心肌细胞肥大表型的调控作用及可能机制。方法:利用腺病毒介导在乳小鼠心室肌细胞(NMVCs)中过表达circMYO9A_006,并以腺病毒介导过表达同样带有绿色荧光蛋白标签的空载体为对照,检测NMVCs中心肌肥大相关蛋白β-肌球蛋白重链(β-MHC)、骨骼肌肌动蛋白α1(ACTA1)和心房钠尿肽(ANP)的表达。建立去氧肾上腺素(PE)诱导的乳大鼠心室肌细胞(NRVCs)肥大模型,通过鬼笔环肽染色检测过表达circMYO9A_006对NRVCs表面积的影响。双萤光素酶报告基因实验检测circMYO9A_006包含的潜在内部核糖体进入位点(IRES)的活性。通过Western blot实验检测circMYO9A_006翻译蛋白MYO9A-208aa及其在细胞内分布情况。分别制备circMYO9A_006-ORF(直接表达MYO9A-208aa)和circMYO9A_006-ATG-mut(不能表达MYO9A-208aa)重组病毒,以空载体病毒和circMYO9A_006重组病毒分别感染NRVCs,检测circMYO9A_006翻译蛋白MYO9A-208aa对心肌细胞肥大表型的特异调节作用。结果:利用腺病毒可在NMVCs中有效介导circMYO9A_006过表达。过表达circMYO9A_006可显著抑制NMVCs中心肌肥大相关蛋白的表达(P<0.01),并显著抑制PE诱导的NRVCs中心肌肥大相关蛋白的表达和细胞表面积的增加(P<0.05)。双萤光素酶报告基因实验结果提示,circMYO9A_006包含的2个IRES均具有活性。Western blot检测结果显示,在NRVCs中过表达circMYO9A_006可翻译预期大小为28 kD的MYO9A-208aa蛋白,并主要分布于细胞质中。过表达MYO9A-208aa和circMYO9A_006可一致地抑制NRVCs心肌肥大相关蛋白表达(P<0.01),并可逆转PE诱导的NRVCs肥大反应(P<0.05);而过表达circMYO9A_006-ATG-mut没有抑制NRVCs肥大的作用。结论:circMYO9A_006通过翻译蛋白MYO9A-208aa发挥抑制心肌细胞肥大的作用。

构式语法框架下清涧方言“圪AA的”状态形容词研究

陕北晋语清涧方言中“圪AA的”状态形容词有180多个且在日常生活中使用频繁,按照构式语法属于四字格构式。形态上,该构式中A可以是形容词、动词和拟声词。“圪AA的”表达式一部分是通过其对应的“A”式“圪A”式、“AA的”式经重叠、加缀等形态变化生成,一部分是通过给“圪AA的”构式填充A后再将其重叠的结果。句法上,该构式可以在句中作谓语、定语、补语和状语,不受单音节否定词修饰,但可以用在“不/没说”含有对比的否定句中。该构式的基本义为描绘性,其语义和语用内涵包括“极致性”语义量值、“消极/负面性”立场态度偏向和“口语性”语体色彩。

Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy

Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.

日粮中添加琥珀酸对AA肉鸡生产性能和肠道健康的影响

试验旨在探究日粮中添加琥珀酸对AA肉鸡生产性能和肠道健康的影响。选用1日龄健康AA肉鸡240羽,根据体重随机分为4组,每组5个重复,每个重复12羽。对照组饲喂基础日粮,抗生素组在基础日粮中添加15 mg/kg维吉尼亚霉素,低剂量和高剂量琥珀酸组分别在基础日粮中添加1 g/kg和2 g/kg琥珀酸。试验期为42 d(1~21 d和22~42 d)。结果表明:与对照组相比,高剂量琥珀酸能够提高肉鸡全净膛率(P<0.05);与抗生素组相比,低剂量琥珀酸能够提高肉鸡血清尿酸和尿素氮水平(P<0.05);日粮中添加琥珀酸对肉鸡肠道形态结构和盲肠微生物组成影响较小,但与对照组相比,添加低剂量和高剂量琥珀酸具有下调肠道炎症因子基因IL-4 mRNA表达的趋势(P=0.0992和P=0.0728),添加高剂量琥珀酸还上调了IFN-γ mRNA的表达(P<0.05),提示日粮中添加琥珀酸有利于缓解肉鸡肠道炎症,调节免疫力。由此可见,日粮中添加高剂量(2 g/kg)琥珀酸能够促进肉鸡生长发育、缓解肠道炎症、调节免疫力,而添加低剂量(1 g/kg)琥珀酸则可以改善机体氨氮代谢水平。

Adenosine cyclic phosphate with ultrasonic-assisted pectinase extraction alleviated allergic reactions in RBL-2H3 through inhibiting the influx of intracellular Ca^(2+)

Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was applied to evaluate the effects of 4 variables by UAPE on cAMP yield.The results showed that the optimal cAMP yield(783.0μg/g)was derived at ratio of liquid to solid 5 mL/g,ratio of pectinase to raw material 1.5%,time 60 min and temperature 40℃.Moreover,the effect of cAMP on the anti-allergic function of action induced by immunoglobulin E(IgE)and its meschanism was investigated through establishing the sensitized cell model in rat basophilic leukemia(RBL-2 H3)cells using dinitrophenylated(DNP)-bovine serum albumin(BSA)-IgE.The results showed that cAMP interfered with sensitized cells,effectively inhibited the occurrence of basophil degranulation in dose dependence,and significantly reduced the activity ofβ-hexosamindase(β-hex),at the optimal concentration of 50μg/mL.The level of anti-inflammatory factor interleukin-10(IL-10)was promoted and the content of pro-inflammatory factor tumor necrosis factor-α(TNF-α)was suppressed by cAMP.In addition,influx of intracellular Ca^(2+) was repressed effectively.Our results demonstrate that jujube cAMP regulated the cytokine balance in the allergy pathway through blocking the influx of extracellular Ca^(2+),with the prevention of allergy symptoms.

Adenosine 2A receptor contributes to the facilitation of postinfectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway

BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.

AA7075-T6铝合金电阻点焊工艺参数优化研究

轻量化结构设计在保证了结构强度的前提下降低了整车质量,减少了能量消耗,成为汽车工业和航空航天的研究重点。本工作通过建立正交实验获取AA7075-T6铝合金的最佳焊接工艺参数。对接头进行拉伸剪切实验、金相观察和显微硬度测试,并对最优参数组合进行数值模拟,以研究焊接工艺参数对接头质量的影响。结果表明:当焊接时间为60 ms、焊接电流为17 kA、电极压力为0.22 MPa时,点焊接头的综合力学性能最好;焊接参数对电阻点焊接头力学性能的影响顺序为焊接时间>焊接电流>电极压力。焊接过程数值模拟得到的熔核尺寸与实验结果一致。焊接过程发生飞溅和熔核存在缩孔缺陷,导致接头的力学性能较差,失效模式为界面断裂。由于焊接过程接头显微组织发生变化,接头显微硬度变化呈“W”形。

Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth

BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

玉米和小麦在AA肉鸡和黄羽肉鸡中的能值及养分代谢率评定

试验旨在比较玉米和小麦在AA肉鸡和黄羽肉鸡中的代谢能值及营养物质的表观代谢率,为玉米和小麦饲粮在家禽养殖生产上的应用提供理论基础。试验通过选择同日龄和相近体重的AA肉鸡和黄羽肉鸡分别进行两个代谢试验。同日龄试验:AA肉鸡和黄羽肉鸡在18日龄时分别各选择96羽,共192羽,AA肉鸡和黄羽肉鸡均随机分为玉米日粮和小麦日粮2个处理组,每个处理组8个重复,每个重复6羽。同体重试验;在试验鸡体重均达到600 g左右时分别在AA肉鸡和黄羽肉鸡中各选择96羽,试验设计分组与同日龄试验一致。试验结果表明,玉米在AA肉鸡中的表观代谢能(AME)、氮校正表观代谢能(AMEn)、粗蛋白和粗脂肪的表观代谢率显著高于同体重的黄羽肉鸡(P<0.05),与同日龄黄羽肉鸡相比没有显著差异;小麦在AA肉鸡中的AME、AMEn、粗蛋白和粗脂肪的表观消化率与同日龄和同体重的黄羽肉鸡相比均有提高,其中AME差异显著(P<0.05);AA肉鸡和黄羽肉鸡对玉米和小麦中淀粉的表观消化率没有显著差异(P>0.05)。综上所述,玉米在AA肉鸡中的能值和养分代谢率高于同体重黄羽肉鸡,小麦在AA肉鸡中的能值和养分表观代谢率高于同日龄和同体重的黄羽肉鸡。

基于AA-UNet的肝硬化辅助诊断系统

为准确地提取高频肝脏超声图像中的肝包膜,本文采用注意力门和空洞空间金字塔池化UNet(Attention gates and Atrous spatial pyramidal pooling UNet,AA-UNet)分割算法,对高频肝脏超声图像中的肝包膜进行识别,并根据肝包膜的物理形状判断肝硬化程度。首先,将数据增强后的高频肝脏超声图像送入网络模型进行训练;其次,将训练好的模型部署到肝硬化辅助诊断系统。实验结果表明,肝硬化辅助诊断系统能有效识别肝包膜区域并判断肝硬化程度。

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.

AA2024铝合金板料敲击式渐进成形性能研究

为了探究合适的数控渐进成形工艺参数范围,确定更优的敲击式渐进成形性能方案,通过单因素试验法研究振幅、频率、工具头直径和层进给量4个因素对AA2024铝合金板料成形性能的影响规律。试验结果表明:与传统的增量成形方式相比,敲击式渐进成形方式会降低板料的成形极限角,板料的成形性能会有所降低;当振幅为5 mm时,成形极限角随着频率的增大而增大;当振幅为10 mm时,成形极限角随着频率的增大而减小,成形随层进给量增大而增大,随层工具头直径增大先减小后增大。

Ywhab通过靶向Hsp90aa1抑制小鼠B细胞淋巴瘤38B9细胞生长

目的:研究Ywhab在小鼠B细胞淋巴瘤发生发展中的作用,并探讨其可能的分子机制。方法:使用生物信息学分析Ywhab与弥漫性大B细胞淋巴瘤(DLBCL)的相关性。在小鼠B细胞淋巴瘤38B9细胞中感染逆转录病毒构建Ywhab基因过表达细胞系,并采用RT-qPCR和Western blot验证Ywhab的mRNA及蛋白(14-3-3β)水平;通过细胞计数法、CCK-8法和小鼠皮下成瘤实验检测Ywhab过表达对38B9细胞在体内外生长的影响;RT-qPCR和Western blot检测细胞凋亡相关蛋白的表达;应用蛋白质免疫共沉淀联合蛋白质谱(CoIP-MS)筛选与14-3-3β特异性结合的蛋白并采用Western blot及分子对接分析进行验证。结果:Ywhab基因在DLBCL中低表达,其低表达预示DLBCL患者的临床预后较差。与正常小鼠骨髓B细胞相比,Ywhab在38B9细胞中低表达。Ywhab过表达能在体内外诱导38B9细胞凋亡,促进凋亡蛋白Puma、Noxa和Bax的mRNA及蛋白表达,抑制抗凋亡蛋白Bcl2的mRNA及蛋白表达(P<0.05)。14-3-3β蛋白能特异性结合Hsp90aa1蛋白并抑制其表达,从而促进38B9细胞凋亡。结论:Ywhab能够显著诱导小鼠B细胞淋巴瘤38B9细胞凋亡,其机制可能是通过靶向抑制Hsp90aa1蛋白表达来实现的。