NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Modeling monocular form deprivation in rabbits using a simulated-cataract intraocular lens

AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2) thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2) into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2) were successfully constructed.The 0 SiO_(2) PSF was transparent,while the 10%wt SiO_(2) PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2) was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.

IMPACT de la déprivation sociale sur les difficultés psychosociales au décours d’un cancer pédiatrique:uneétude prospective IMPACT of the Social Deprivation on Psychosocial Difficulties of Pediatric Cancer Survivors:A Prospective Study

The posttreatment period is a key part of the management of pediatric cancer.During this time,school and psychological difficulties have been described in childhood cancer survivors(CCS)and can be prognostic for the success of social reintegration.This study estimated the influence of the household’s socioeconomic status(SES)on these psychosocial difficulties.This study is based on a prospective multicentric database and focused on children who received a psychosocial evaluation during their follow-up from 2013 to 2020.We retrieved data on school and psychological difficulties.Household SES was estimated by a social deprivation score.Data from1003 patients were analyzed.School difficulties were noted in 22%of CCS.A greater social deprivation was significantly associated with school difficulty.Tumor relapse,treatment with hematopoietic stem cell transplantation,and central nervous system(CNS)tumors remained significant risk factors.In the subgroup of CNS tumors,school difficulties were increased and associated with greater social deprivation.Psychological difficulties were not associated with the deprivation score.There is a link between SES and school difficulties in CCS.Further investigations should be carried out for children with CNS tumors,which is the population of the greatest concern.

Alterations of sleep deprivation on brain function:A coordinatebased resting-state functional magnetic resonance imaging metaanalysis

BACKGROUND Sleep deprivation is a prevalent issue that impacts cognitive function.Although numerous neuroimaging studies have explored the neural correlates of sleep loss,inconsistencies persist in the reported results,necessitating an investigation into the consistent brain functional changes resulting from sleep loss.AIM To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases.Two metaanalytic methods,signed differential mapping(SDM)and activation likelihood estimation(ALE),were employed to analyze functional magnetic resonance imaging(fMRI)data.METHODS A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29,2023.Studies that met specific inclusion criteria,focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered.A total of 21 studies were selected for SDM and ALE meta-analyses.RESULTS Twenty-one studies,including 23 experiments and 498 subjects,were included.Compared to pre-sleep deprivation,post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule.SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus,left middle frontal gyrus,corpus callosum,and right cuneus.CONCLUSION This meta-analysis consistently identified brain regions affected by sleep deprivation,notably the left medial frontal gyrus and corpus callosum,shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.

Regulatory role of CREB/BDNF signaling pathway in acute sleep deprivation-induced anxiety-like behavior mice

Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.

Neuroprotective effects of neural stem cells pretreated with neuregulin1β on PC12 cells exposed to oxygen-glucose deprivation/reoxygenation

Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function

Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.

Salidroside attenuates oxygen and glucose deprivation-induced neuronal injury by inhibiting ferroptosis

Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 cells into neurons. The effects of salidroside on survival, apoptosis, inflammatory response, and oxidative stress of neurons undergoing OGD were evaluated. Using precursor cells as controls, the effect of salidroside on the differentiation progression of OGDtreated cells was evaluated. In addition, the effect of erastin, a ferroptosis inducer, on NT2 cells was examined to investigate the underlying mechanisms of neuroprotective action of salidroside.Results: Salidroside alleviated the effects of OGD on neuronal survival, apoptosis, inflammation, and oxidative stress, and promoted NT2 cell differentiation. Moreover, salidroside prevented ferroptosis of OGD-treated cells, which was abolished following erastin treatment, indicating that ferroptosis mediated the regulatory pathway of salidroside.Conclusions: Salidroside attenuates OGD-induced neuronal injury by inhibiting ferroptosis and promotes neuronal differentiation.

Local digital lending development and the incidence of deprivation in Kenya

In the developing world,vulnerable communities often lack access to regular income sources to cope with unforeseen events.Recent advancements in financial technology have enabled microcredit to be delivered via digital platforms.Although digital credit may quicken remote access to consumer credit without the need for collateral,little is known about its contribution to the welfare of underserved communities.This study examines the effects of local digital lending development on deprivation and explores the implications of these effects on rural inhabitants.The results show a negative association between local digital lending development and food deprivation on one hand and health deprivation on the other.The evidence suggests that local digital lending development can reduce the probability of food and health deprivation.Furthermore,the evidence reveals that inhabitants of rural communities benefit more from digital lending development.This study recommends the decentralization of financial inclusion policies as a pathway to promote digital lending at the local level.

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway

AIM:To construct an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R)induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion(I/R)injury in 661W cells and the protective effect of ginsenoside Rg1.METHODS:The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro.Apoptosis,intracellular reactive oxygen species(ROS)levels and superoxide dismutase(SOD)levels were measured at different time points during the reperfusion injury process.The injury model was pretreated with graded concentrations of ginsenoside Rg1.Real-time polymerase chain reaction(PCR)was used to measure the expression levels of cytochrome C(cyt C)/B-cell lymphoma-2(Bcl2)/Bcl2 associated protein X(Bax),heme oxygenase-1(HO-1),caspase9,nuclear factor erythroid 2-related factor 2(nrf2),kelch-like ECH-associated protein 1(keap1)and other genes.Western blot was used to detect the expression of nrf2,phosphorylated nrf2(pnrf2)and keap1 protein levels.RESULTS:Compared to the untreated group,the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased(P<0.01).Additionally,the ROS content increased and SOD levels decreased significantly(P<0.01).In contrast,treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na_(2)S_(2)O_(4)treated group(P<0.01).Moreover,Rg1 reduced the levels of caspase3,caspase9,and cyt C,while increasing the Bcl2/Bax level.These differences were all statistically significant(P<0.05).Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment,however,Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na_(2)S_(2)O_(4)treated group(P<0.001).CONCLUSION:The OGD/R process is induced in 661W cells using Na_(2)S_(2)O_(4).Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway.These results suggest a potential protective effect of Rg1 against retinal I/R injury.

Establishment of oxygen glucose deprivation reperfusion model of senescent SH-SY5Y cells

Obejective:To explore the establishment of an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells.Methods:SH-SY5Y cells were randomly divided into control(D-galactose 0 mmol/L group),D-galactose(25 mmol/L,50 mmol/L,100 mmol/L,200 mmol/L,400 mmol/L)groups,and treated with corresponding concentrations of D-galactose for 48 h.The changes of cell morphology,β-galactosidase,the cell morphology,β-galactosidase activity by microscopic observation,cell proliferation rate by EdU kit and cell survival rate by CCK-8 assay were used to determine the decaying concentration of D-galactose and to establish the senescence model.The senescent SH-SY5Y cells were randomly divided into control group(oxygen glucose deprivation without treatment group),oxygen glucose deprivation treatment(0.5 h,1 h,1.5 h,2 h)group,followed by re-glucose reoxygenation for 24 h,and CCK-8 assay for the survival rate of senescent SH-SY5Y cells.Results:There were no significant changes in cell morphology and β-gal activity in the 25 mmol/L and 50 mmol/L groups compared with the control group(P>0.05),cytosolic hypertrophy was seen in the cells of the 100 mmol/L group,chromatin fixation in the cells of the 200 mmol/L group,and massive vacuolization in the cells of the 400 mmol/L group;the positive rate ofβ-galactosidase staining in the cells of the(100-400 mmol/L)group was significantly higher compared with the control group(P<0.05),with little difference between the 100 mmol/L and 200 mmol/L groups(P>0.05);the cell proliferation ability of the(100-400 mmol/L)group was significantly decreased in a concentration-dependent manner(P<0.05);the cell survival rate was decreased in a concentration-dependent manner(P<0.05),with IC_(50) between 100 mmol/L and 200 mmol/L.The survival of senescent SH-SY5Y cells showed a time-dependent decrease in oxygen-glucose deprivation(P<0.05),with an IC_(50) close to 1 h.Conclusion:D-gal concentration of 100 mmoL/L and 48 h of cell action could establish a survival rate of about 50%of senescent SH-SY5Y cells,and oxygen glucose deprivation of senescent SH-SY5Y cells for 1 h and reperfusion for 24 h could establish an oxygen glucose deprivation/reperfusion model of senescent SH-SY5Y cells with a survival rate close to 50%.

天麻素对睡眠剥夺大鼠神经递质的影响及机制研究

目的:研究天麻素对睡眠剥夺大鼠乙酰胆碱酯酶(acetylcholinesterase,AchE)、5-羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)、去甲肾上腺素(norepinephrine,NE)的影响。方法:选取健康雌性SD大鼠24只,采用随机分配法将实验动物分成3组,分别为正常对照组、睡眠剥夺组、睡眠剥夺+天麻素组,每组8只。正常对照组正常饲养,每日腹腔注射生理盐水20mg/kg,睡眠剥夺组睡眠剥夺后腹腔注射生理盐水20mg/kg,睡眠剥夺+天麻素组20mg/kg。ELISA分析大鼠血清中AchE、5-HT、DA、NE含量。结果:与正常对照组相比,睡眠剥夺组AchE,NE显著升高,DA,5-HT降低(P<0.01),与睡眠剥夺组相比,睡眠剥夺+天麻素组AchE降低,与睡眠剥夺组相比,睡眠剥夺+天麻素组5-HT增高(P<0.01),DA,NE无统计学意义。结论:天麻素可以改善大鼠因睡眠剥夺所造成的神经系统损伤。

姜酮通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用

目的:探讨姜酮对氧糖剥夺/复糖复氧(OGD/R)后小鼠海马神经元HT22细胞的保护作用,阐明其相关作用机制。方法:培养HT22细胞,设置不同OGD/R时间梯度,建立OGD/R细胞损伤模型。HT22细胞分为对照组、OGD/R组、OGD/R+1μmol·L^(-1)姜酮组、OGD/R+10μmol·L^(-1)姜酮、OGD/R+100μmol·L^(-1)姜酮组和OGD/R+0.2%二甲亚枫(DMSO)组,CCK-8法检测各组细胞活性并计算各组细胞存活率,确定姜酮最适药物浓度。细胞分为对照组、OGD/R组、OGD/R+姜酮组和OGD/R+姜酮+核因子E2相关因子2(Nrf2)抑制剂(ML385)组,OGD/R+姜酮组细胞经姜酮给药处理4 h后予以OGD 8 h和复糖复氧8 h处理,OGD/R+姜酮+ML385组细胞在姜酮给药前予以10μmol·L^(-1)ML385预处理6 h,CCK-8法检测各组细胞活性,Western blotting法检测各组细胞中Nrf2、血红素加氧酶1(HO-1)、B细胞淋巴瘤2(Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白表达水平,酶联免疫吸附试验(ELISA)法检测各组细胞培养上清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平。结果:与对照组比较,HT22细胞经OGD 8 h和复糖复糖8 h处理后细胞存活率低于50%,以OGD 8 h和复糖复糖8 h建立HT22细胞OGD/R模型。与OGD/R组比较,OGD/R+不同剂量姜酮组细胞存活率均不同程度升高,其中OGD/R+100μmol·L^(-1)姜酮组细胞存活率升高最明显(P<0.01),故选用100μmol·L^(-1)姜酮用于后续实验。与对照组比较,OGD/R组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bax蛋白表达水平明显升高(P<0.01),Bcl-2蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.01);与OGD/R组比较,OGD/R+姜酮组细胞活性明显升高(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显升高(P<0.05或P<0.01),Bax蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显升高(P<0.01),MDA水平明显降低(P<0.01);与OGD/R+姜酮组比较,OGD/R+姜酮+ML385组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显降低(P<0.01),Bax蛋白表达水平明显升高(P<0.01),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.05)。结论:姜酮可通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用。

壳三糖和壳五糖对睡眠剥夺小鼠学习记忆障碍的影响

各种原因引起的睡眠时间减少已成为生活常态,睡眠剥夺会降低机体的学习记忆能力,影响生活质量。该研究对C57BL/6J小鼠进行21 d睡眠剥夺,同时每天对小鼠灌胃壳三糖(chitotriose,COS3)和壳五糖(chitopentaose,COS5),通过体重、新物体识别实验、病理学染色、氧化应激和凋亡相关蛋白表达评估COS3和COS5的保护作用。结果显示,COS3和COS5干预能够缓解小鼠体重下降和海马神经细胞坏死变形,显著提高海马组织中超氧化物歧化酶水平和总抗氧化能力,显著降低海马丙二醛含量。COS3和COS5干预能够显著提升海马p-PI3K(phospho-phosphotylinosital 3 kinase)和p-Akt(phospho-protein kinase B)蛋白的相对表达量,激活PI3K/Akt信号通路,缓解神经细胞凋亡。研究表明,COS3和COS5能够明显改善睡眠剥夺引起的学习记忆能力下降,其机制可能与COS3和COS5能够缓解海马组织氧化应激和神经细胞凋亡有关,其中COS3的效果优于COS5。

鼻腔递送血管活性肠肽对弱视大鼠视皮层脑源性神经营养因子的影响

目的探索血管活性肠肽(VIP)对形觉剥夺性弱视大鼠视皮层脑源性神经营养因子(BDNF)的影响,探讨弱视治疗的神经保护作用机制。方法选取3周龄健康SD大鼠36只,随机分为对照组、模型组、治疗组,各12只。采用前爪触地实验测定大鼠视敏度,图形视觉诱发电位(PVEP)测定客观视觉功能;采用Western blotting检测各组大鼠视皮层BDNF表达水平,采用免疫荧光染色观察胶质纤维酸性蛋白(GFAP)和VIP在视皮层中的表达水平和GFAP表达部位,苏木精-伊红(HE)染色观察大鼠视皮层病理学改变。结果与模型组比较,治疗组视敏度和客观视觉功能均提高(P<0.05),BDNF蛋白表达水平增加(P<0.05),但仍低于对照组(P<0.05)。免疫荧光检测结果显示:GFAP阳性细胞在正常组与弱视组中主要表达在视皮层Ⅰ层和Ⅵ层,且弱视组大鼠视皮层GFAP荧光强度明显低于对照组(P<0.05),治疗组视皮层VIP和GFAP的荧光强度均明显增加(P<0.05)。结论VIP对弱视大鼠有治疗作用,可能与活化视皮层星形胶质细胞释放BDNF有关。这为弱视的治疗提供了新思路。

公共转移支付对家庭消费相对剥夺的影响

本文基于中国家庭追踪调查数据(CFPS),运用双向固定效应模型,实证考察公共转移支付对家庭消费相对剥夺的影响及作用机理。研究发现,公共转移支付可以显著缓解家庭消费相对剥夺。经过一系列稳健性检验并缓解潜在的内生性问题后,研究结论依然成立。异质性分析表明,相比于民生性转移支付,生产性转移支付显著缓解了家庭消费相对剥夺;公共转移支付对贫困县和高抚养比家庭的消费相对剥夺影响更大。机制分析表明,公共转移支付主要通过降低家庭收入相对剥夺、改善收入不确定性和提高社会信任水平来缓解家庭消费相对剥夺。本研究为缓解个体消费相对剥夺、改善居民福利水平,进而实现共同富裕提供了微观证据。

血清白细胞介素-35表达水平与前列腺癌全雄激素阻断治疗预后的相关性分析

目的 探究血清白细胞介素-35(IL-35)表达水平与前列腺癌全雄激素阻断(MAB)患者预后的相关性。方法 收集2017年4月至2020年4月在本院接受MAB治疗的60例前列腺癌患者为研究对象。测定患者治疗前血清IL-35水平。依据随访结果,用受试者工作特征(ROC)曲线确定IL-35最佳截断值,并以此将纳入者分为低IL-35组和高IL-35组。比较2组病理特征,Kaplan-Meier生存曲线和Cox回归模型分析血清IL-35与患者预后的相关性。结果 以3年随访是否死亡为结局绘制ROC曲线,所得IL-35最佳截断值147.73 pg/ml[曲线下面积(95%CI)=0.667(0.517,0.818,P<0.001)],并以此为临界点将患者分为低IL-35组(<147.73 pg/ml)和高IL-35组(≥147.73 pg/ml)。高IL-35组中Gleason评分>7分(58%和29%)、肿瘤T分期中T4期(74%和44%)和伴淋巴结转移(68%和39%)者占比均显著高于低IL-35组(P<0.05)。KaplanMeier生存曲线显示,低IL-35组患者无进展生存(PFS)[(32±4)个月和(23±4)个月]和总生存[(32±3)个月和(24±4)个月]情况均优于高IL-35组患者(χ^(2)=11.988、8.617,P<0.05);单因素和多因素Cox回归模型分析显示,血清IL-35水平[HR值(95%CI)=1.044 (1.017,1.073)]、[HR值(95%CI)=1.035(1.006,1.064)];Gleason评分[HR值(95%CI)=2.218 (1.449,6.307)]、[HR值(95%CI)=3.056 (1.649,9.447)];临床T分期[HR值(95%CI)=2.056(1.553,5.984)]、[HR值(95%CI)=1.900(1.237,11.622)]和伴淋巴结转移[HR值(95%CI)=2.415(2.084,7.445)]、[HR值(95%CI)=4.147(1.081,15.910)]均是影响MAB治疗的前列腺癌患者无进展生存期(PFS)和总生存情况的独立危险因素(P<0.05)。结论 治疗前血清IL-35水平异常升高是影响前列腺癌患者MAB治疗预后的独立危险因素。

rh-CSF1改善缺糖缺氧损伤神经元线粒体功能和细胞凋亡

目的探讨集落刺激因子-1(colony stimulating factor-1,CSF1)抑制氧糖剥夺(oxygen-glucose deprivation,OGD)神经元凋亡的作用机制。方法采用大鼠原代大脑皮质神经元,分为OGD损伤神经元模型组(OGD组,n=3)、重组人CSF1(recombined human CSF1,rh-CSF1)干预组(rh-CSF1组,n=3)、对照组(n=3)。测定3组神经元凋亡率和其中三磷酸腺苷(adenosine triphosphate,ATP)含量,活性氧簇水平、线粒体膜电位和线粒体脱氧核糖核酸(deoxyribonucleic acid,DNA)拷贝数,检测线粒体内丙二醛含量和超氧化物歧化酶活性。结果OGD组模型进行基线评估,结果示神经元凋亡率、活性氧簇、线粒体内丙二醛水平、线粒体膜电位、线粒体DNA拷贝数、ATP含量、线粒体内超氧化物歧化酶活性与对照组有统计学差异(P<0.01)。rh-CSF1干预可提高OGD损伤后神经元的线粒体膜电位(0.55±0.03 vs.0.43±0.06,P<0.01)、线粒体DNA拷贝数(0.88±0.05 vs.0.72±0.06,P<0.05)、ATP含量([15.70±0.99)mmol/mg vs(.11.70±1.00)mmol/mg,P<0.01)]和线粒体内超氧化物歧化酶活性([18.47±1.38)U/mg vs.14.78±1.81)U/mg,P<0.05)],降低活性氧簇(3.64±0.21 vs.4.45±0.33,P<0.05)和线粒体内丙二醛水平([2.13±0.19)mmol/mg vs(.2.78±0.20)mmol/mg,P<0.05)],减轻神经元凋亡率。结论rh-CSF1可能通过改善线粒体功能、减轻氧化应激及抑制细胞凋亡,从而改善OGD诱导损伤神经元的受损程度。

肌醇需求酶1信号通路在自噬改善大鼠冠心病心肌缺血损伤中的作用

目的:基于探讨肌醇需求酶1(IRE1)信号通路在自噬改善大鼠冠心病心肌缺血损伤中的作用。方法:将H9c2细胞分为对照组、IRE1组、缺氧缺糖(OGD)/复氧(OGD/R)组、OGD/R+IRE1组、氯喹组、IRE1+氯喹组、OGD/R+氯喹组、OGD/R+IRE1+氯喹组、OGD组、OGD+氯喹组、OGD/R+IRE1+敲低X盒结合蛋白1(si-XBP1)组、OGD/R+IRE1+过表达X盒结合蛋白1(XBP1-OE)组。通过自噬双标腺病毒(Adv-RFP-GFP-LC3)评估各组细胞的自噬通量。通过免疫荧光和免疫印迹分析X盒结合蛋白1(XBP1)的核转位。另将32只成年雄性C57BL/6 J小鼠随机分为假手术组、缺血/再灌注(I/R)组、IRE1组和I/R+IRE1组,每组8只。通过超声心动图评估大鼠心功能。通过定量免疫印迹分析自噬相关蛋白。结果:(1)细胞试验:与OGD/R组比,OGD/R+IRE1组H9c2细胞中IRE1蛋白表达水平显著增加(P<0.001),微管相关蛋白轻链3蛋白Ⅱ(LC3Ⅱ)和泛素结合蛋白(p62)蛋白表达均显著降低(P均<0.05)。与OGD/R+氯喹组比,OGD/R+IRE1+氯喹组H9c2细胞中LC3Ⅱ和p62蛋白表达均显著增加(P均<0.05)。与对照组比,OGD/R组H9c2细胞中IRE1细胞核/细胞质荧光强度比显著增加(P<0.001);与OGD/R组比,OGD/R+IRE1组IRE1细胞核/细胞质荧光强度增加(P<0.001)。与OGD/R组比,OGD/R+IRE1组核蛋白中的XBP1水平增加(P<0.05)。与OGD/R+IRE1组比,OGD/R+IRE1+si-XBP1组黄色点状体显著减少(P<0.01),OGD/R+IRE1+XBP1-OE组黄色点状体显著增加(P<0.05)。(2)大鼠体内实验:与假手术组比,I/R组左心室射血分数和短轴缩短率均显著降低(P均<0.05)。与I/R组比,I/R+IRE1组心功能障碍改善(P均<0.05)。与假手术组比,I/R组心肌自噬空泡的数量、IRE1、LC3Ⅱ和p62表达均显著增加(P均<0.05)。与I/R组比,I/R+IRE1组心肌自噬空泡的数量、p62表达均显著降低(P均<0.05),心肌组织中IRE1、LC3Ⅱ的表达均增加(P均<0.05)。结论:IRE1通过促进XBP1的核转位恢复了OGD/R和I/R诱导的自噬通量阻断,自噬通量的恢复有助于保护心功能。

睡眠剥夺大鼠脑肠肽改变在大鼠咽喉反流中的作用

目的研究睡眠剥夺大鼠血清中脑肠肽改变在大鼠咽喉反流发病中的作用。方法选取40只健康成年雄性SD大鼠,分为实验组和对照组,对照组正常睡眠,实验组分为三组,每组10只,用改良多平台水环境法剥夺8 h的白天睡眠,分别持续1、2、3个月,用ELISA法检测各组外周血中胃泌素(MTL)和生长抑素(SS)浓度,放射免疫法检测外周血中胃动素(GAS)浓度,比较各组结果。结果睡眠剥夺2月组GAS浓度明显低于对照组,睡眠剥夺3月组GAS浓度明显高于1月组和2月组(P<0.05)。三个实验组与对照组之间比较MTL浓度差异均无统计学意义(P>0.05),睡眠剥夺2月组MTL浓度明显高于3月组(P<0.01)。各实验组与对照组之间、三个实验组之间SS浓度均无统计学差异。结论睡眠剥夺可能通过影响GAS和MTL的分泌与大鼠咽喉反流的发生相关。