Maresin 1 alleviates neuroinflammation and cognitive decline in a mouse model of cecal ligation and puncture

Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Association between Serum Uric Acid and the Early Marker of Kidney Function Decline among Chinese Middle-Aged and Older Population:Evidence from the China Health and Retirement Longitudinal Study

Objective To evaluate the association between serum uric acid(SUA)and kidney function decline.Methods Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis.The kidney function decline was defined as an annual estimated glomerular filtration rate(e GFR)decrease by>3 mL/min per 1.73 m^(2).Multivariable logistic regression was applied to determine the association between SUA and kidney function decline.The shape of the association was investigated by restricted cubic splines.Results A total of 7,346 participants were included,of which 1,004 individuals(13.67%)developed kidney function decline during the follow-up of 4 years.A significant dose-response relation was recorded between SUA and the kidney function decline(OR 1.14,95%CI 1.03-1.27),as the risk of kidney function decline increased by 14%per 1 mg/d L increase in SUA.In the subgroup analyses,such a relation was only recorded among women(OR 1.22,95%CI 1.03-1.45),those aged<60 years(OR 1.22,95%CI 1.05-1.42),and those without hypertension and without diabetes(OR 1.22,95%CI 1.06-1.41).Although the dose-response relation was not observed in men,the high level of SUA was related to kidney function decline(OR 1.83,95%CI 1.05-3.17).The restricted cubic spline analysis indicated that SUA>5 mg/dL was associated with a significantly higher risk of kidney function decline.Conclusion The SUA level was associated with kidney function decline.An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.

Reasons and effects of the decline of willing related potential living kidney donors

BACKGROUND Although the availability of related living donors(LDs)provides a better chance for receiving kidney transplantation(KT),the evaluation protocols for LD selection remain a safeguard for the LD’s safety.These protocols are variable from one center to another,resulting in variable rates of decline of the potential LDs(PLDs).The decline of willing PLDs may occur at any stage of evaluation,starting from the initial contact and counseling to the day of operation.AIM To identify the causes of the decline of PLDs,the predictors of PLD candidacy,and the effect on achieving LDKT.METHODS A retrospective study was performed on the willing PLDs who attended our outpatient clinic for kidney donation to their related potential recipients between October 2015 and December 2022.The variables influencing their candidacy rate and the fate of their potential recipients were studied.Two groups of PLDs were compared:Candidate PLDs after a completed evaluation vs non-candidate PLDs with a complete or incomplete evaluation.A multivariate logistic regression was performed to assess the factors contributing to the achievement of PLD candidacy.RESULTS Of 321 willing PLDs,257 PLDs(80.1%)accessed the evaluation to variable extents for 212 potential recipients,with a mean age(range)of 40.5±10.4(18-65)years,including 169 females(65.8%).The remaining 64 PLDs(19.9%)did not access the evaluation.Only 58 PLDs(18.1%)succeeded in donating,but 199 PDLs(62.0%)were declined;exclusion occurred in 144 PLDs(56.0%)for immunological causes(37.5%),medical causes(54.9%),combined causes(9.7%),and financial causes(2.1%).Regression and release occurred in 55 PLDs(17.1%).The potential recipients with candidate PLDs were not significantly different from those with non-candidate PLDs,except in age(P=0.041),rates of completed evaluation,and exclusion of PLDs(P<0.001).There were no factors that independently influenced the rate of PLD candidacy.Most patients who failed to have KT after the decline of their PLDs remained on hemodialysis for 6 mo to 6 years.CONCLUSION The rate of decline of willing related PLDs was high due to medical or immunological contraindications,release,or regression of PLDs.It reduced the chances of high percentages of potential recipients in LDKT.

Heterosis of Vine Decline Disease Resistance Caused by the Fungus Monosporascus cannonballus in Melons (Cucumis melo L)

Vine decline disease (VDD) constitutes a menace to melons worldwide. Especially, the one caused by the fungus Monosporascus cannonballus. Thus, resistant plant material must be released to help growers. Hence, our goal was to develop resistant plant material to VDD. More than 600 melon accessions are expected to be tested for disease resistance in M. cannonballus infested soil in Weslaco, Texas, USA, to identify resistance to VDD, and other important traits. So far, at most 7 lines were found to be resistant to VDD and some of them were used to develop elite, muskmelon inbred lines by pedigree breeding following single or double backcrosses. These elite parents were crossed to each other to develop the hybrids M3 and M4. They were also tested in the same infested field in Weslaco. The hybrids were grown using standard commercial practices followed by growers and when their fruits were ready, their roots were sampled as well as scored for disease severity to estimate high and mid-parent heterosis Our results indicate the existence of heterosis regarding resistance to VDD. Thus, resistant plant material can be developed and selection for resistance can be accomplished.

Diabetes and cognitive decline:Challenges and future direction

There is growing evidence that diabetes can induce cognitive decline and dementia.It is a slow,progressive cognitive decline that can occur in any age group,but is seen more frequently in older individuals.Symptoms related to cognitive decline are worsened by chronic metabolic syndrome.Animal models are frequently utilized to elucidate the mechanisms of cognitive decline in diabetes and to assess potential drugs for therapy and prevention.This review addresses the common factors and pathophysiology involved in diabetes-related cognitive decline and outlines the various animal models used to study this condition.

Analysis of the relationship between blood pressure variability and subtle cognitive decline in older adults

BACKGROUND Blood pressure variability(BPV)has been shown to be related to mild cognitive impairment and Alzheimer's disease in a number of studies.However,the relationship between BPV and subtle cognitive decline(SCD)has received minimal attention in this field of research to date and has rarely been reported.AIM To examine whether SCD is independently associated with changes in BPV in older adults.METHODS Participants were selected based on having participated in cognitive function evaluation and ambulatory blood pressure measurement at the Shanghai Sixth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine between June 2020 and August 2022.The participants included 182 individuals with SCD as the experimental group and 237 with normal cognitive function as the control group.The basic data,laboratory examinations,scale tests,and ambulatory blood pressure test results of the two groups were analyzed retrospectively,and the relationship between SCD and BPV was subsequently evaluated.RESULTS Significant differences were observed between the two groups of participants(P<0.05)in terms of age,education level,prevalence rate of diabetes,fasting blood glucose level,24-h systolic blood pressure standard deviation and coefficient of variation,24-h diastolic blood pressure standard deviation and coefficient of variation.The scale monitoring results showed significant differences in the scores for memory,attention,and visual space between the experimental and control groups.Logistic regression analysis indicated that age,education level,blood sugar level,and BPV were factors influencing cognitive decline.Linear regression analysis showed that there was an independent correlation between blood pressure variation and SCD,even after adjusting for related factors.Each of the above differences was still significant.CONCLUSION This study suggests that increased BPV is associated with SCD.

衰退企业“临危受命”CEO如何实现业绩反转——基于模糊集定性比较分析

面临衰退威胁的企业往往期望变更C E O以摆脱困境,然而何种战略能帮助继任CEO实现企业业绩反转,现有研究未能给出解答。基于此,本文将权力理论引入研究框架,运用模糊集定性比较分析方法,以2006—2016年变更CEO的民营制造类衰退企业为研究对象,探索了衰退企业继任CEO、董事会之间的权力制衡关系与反转战略的组合匹配对业绩反转的影响,归纳出“董事会主导×防御型”“外部CEO主导×探索型”“内部CEO主导×防御型”三种反转模式,发现了“董事会为主、CEO为辅”和“CEO为主、董事会监督和咨询为辅”两类制衡关系中主导者动机和能力与战略的匹配,是实现业绩反转的关键,支持了新战略领导层之间的互动关系与企业战略导向的匹配会影响反转战略有效性的命题,丰富了衰退企业业绩反转研究的理论视角和研究方法。

霸权衰落与“泛安全化”:基于美国的个案分析

衰落是霸权的宿命,但霸权国既不会主动放弃国际政治中的主导地位,也不会静待霸权体系崩溃。处于衰落阶段的霸权国期待维持与崛起国之间的权力差距,以延长霸权的寿命。然而,权力转移等国际关系结构性因素的变化导致离岸平衡和军事打击等传统手段难以在衰落阶段奏效。相比之下,“安全化”为霸权国家的霸权护持行动与选择——如领域撤退或强制惩罚——提供了合法性依据。同时,由于霸权的同心圆特性,核心利益被触动会引发霸权国在核心和外围领域的全方位的打压,进而泛化议题和对象。衰落中的霸权国通过“危机感知”—“构建并接受安全化诉求”—“泛安全化”的传导路径,将维持霸权地位的诉求以泛安全化的形式展现出来。然而,美国霸权衰落的经验事实表明,泛安全化作为衰落阶段的霸权护持手段不仅与理论预期相反,而且成效也不尽人意。面对美国霸权的泛安全化,中国应当保持战略定力,坚守并贯彻总体国家安全观。

人口老龄化与少子化趋势下税收政策的应对策略

人口老龄化和少子化是当前我国经济社会发展面临的基本国情,对我国社会经济发展既有挑战和冲击,也有机遇。一方面,老龄化、少子化会带来人口红利的消失,与养老相关的财政支出压力增大,并通过影响消费需求、劳动参与率、劳动力成本等因素对税基产生影响。另一方面,人口老龄化会也会带来新的发展机遇,如用工成本增加倒逼企业进行技术创新、老年人口增加助力银发经济崛起等,为税收征收开辟新的增长点。为此,我国税收政策要积极适应老龄化、少子化带来的新变化,积极应对挑战,抓住机遇,调整完善有利于促进生育、促进企业技术创新、助推银色经济发展、促进低龄老年人再就业的税收政策,以促进老龄化进程中的经济发展和社会稳定,为未来的可持续发展奠定基础。

英国中小学课间休息时间锐减现状、原因与思考

近年来,英国中小学课间休息时间不断锐减成为社会公众讨论的焦点话题,备受国际社会关注。英国中小学课间休息时间锐减主要表现为总时长方面呈阶梯式递减趋势,分时段的中午和下午休息时长是主要被削减时段。研究发现,效率至上教育质量观的抑制、学校相关活动对课间休息时间的挤占、教师基于“合理性理由”取消课间休息以及认知层面对课间休息定位模糊是造成英国中小学课间休息时间锐减的主要原因。英国的中小学课间休息锐减并非一国现象,具有普遍的启示意义。中小学课间休息总时长多少为宜、休息方式隔段还是整段、能否基于“合理性理由”取消课间休息、如何组织课间休息等基本问题仍需深思与探讨。

老年主观认知下降/轻度认知障碍病人身体活动促进的研究进展

对目前国内外老年主观认知下降/轻度认知障碍病人身体活动促进现状进行综述,提出目前我国缺少高质量的针对老年轻度认知障碍或主观认知下降病人身体活动的干预研究和针对性指南以及提高该群体的身体活动促进策略,提示未来应进行高质量的老年轻度认知障碍或主观认知下降病人身体活动的干预研究,从而为本土政策的制定提供可信的理论基础。

青年强则国强:青年人口学前瞻与优化青年人口发展

从当年梁启超发出历史呼号“少年强则国强”、李大钊提出“青春中华之创造”到如今党的二十大报告发出时代强音“青年强,则国家强”,显示了一脉相承的青少年与国家发展联系紧密的认识逻辑。本文回顾和界定了青年及青年人口学的内涵,认为青年可定义为“风险型人口”和“资源型人口”两大类,继而讨论了“青年强”的三重含义,即青年人口储备充足、青年人口素质卓越和青年人口红利丰厚,充分诠释了“青年强,则国家强”时代命题的深刻内涵。概言之,人尽其才则“青年强”,才尽其用则“国家强”。本文从国际比较的视角阐述了我国青年人口发展面临的问题和挑战,突出表现为:中国未来青年人口数量将长期处于缩减状态;青年人口的科学文化素质、身体健康素质和思想素质都有待“提质增效”;就业不充分,青年人口红利没有被充分释放。因此,要优化青年人口发展、进一步增强青年力量,采取相应的对策来强化青年人口储备、优化青年人口素质、极化青年人口红利、激发全人口活力。在人口负增长时代,建设适宜青年生存与发展的青年友好型社会极为必要,把解决青年问题作为解决低生育率等社会人口问题的重要突破口迫在眉睫。

老年医源性功能下降预防与管理的证据总结

目的:系统检索、评价并整合老年医源性功能下降的相关证据,为临床医护人员预防并管理老年人医源性功能下降提供循证依据。方法:遵循“6S”模型依次检索计算机决策系统、指南、专业学会网站以及数据库中有关老年医源性功能下降的相关证据,包括指南、临床决策、最佳实践、专家共识、证据总结、系统评价和随机对照试验,检索时限为建库至2024年3月10日。由2名研究者独立进行文献筛选及质量评价,结合主题及专业判断提取证据。结果:共纳入15篇文献,包括1篇临床决策、10篇系统评价、4篇随机对照试验,最终形成评估、风险识别、运动、营养、老年专用病房5个方面18条证据。结论:该研究总结了老年医源性功能下降预防与管理的证据,为临床实践提供了循证依据,医护人员可结合临床情景、证据的促进或阻碍因素以及患者意愿,有针对性地选择证据,尽量避免老年医源性功能下降。

层层加码与层层递减:不同类型公共政策自上而下执行的权变逻辑

公共政策自上而下执行中层层加码的现象由来已久且较为普遍。基于不同类型公共政策主要直接功能存在的差异,对规范性、分配性、导向性等3类公共政策自上而下执行中对政策目标、政策工具、政策监控层层加码或层层递减的表现和结果展开分析,从利益逻辑、行为逻辑、制度逻辑探寻行为背后的逻辑动因。要消解政策执行中的层层加码或层层递减现象,应制定明确的政策目标并运用有效的政策工具,健全公共政策执行者激励相容机制,积极践行全过程人民民主,增强目标群体的民主法治监督能力和公共舆论客观理性,在减少政策执行层级的同时加强跨层级治理。

企业战略变化、垄断地位与投资效率——基于企业生命周期的视角

以2002-2021年沪深A股上市公司数据为研究样本,实证分析企业在不同生命周期阶段下的战略变化与投资效率之间的关系。研究发现:成长期企业采取积极的战略变化有助于提高其投资效率;成熟期企业的战略变化与投资效率之间存在倒“U”形关系;衰退期企业的战略变化对投资效率的影响并不显著,但在进一步研究中发现,进攻型战略变化有助于企业扭亏为盈;企业的垄断地位会弱化战略变化与投资效率之间的关系;相较于非国有控股企业,国有控股企业的战略变化对投资效率的影响更为显著。成长期企业应积极主动地调整战略以适应市场需求的变化;成熟期企业应避免过度的战略变化,以免损害已经积累的核心竞争力;衰退期企业要勇于尝试新的战略方向,重新进行品牌定位;企业在制定战略时要充分考虑企业垄断地位和企业性质等因素,以实现企业可持续发展。

口咽拭子样品在小鼠肺炎病毒病原检测中的应用

目的评价分子病原学及血清学检测方法在小鼠肺炎病毒(PVM)检测中的适用性。方法3周龄BALB/c和C57BL/6J小鼠雌雄各半,滴鼻感染PVM,在感染后1、2、3周,1、2、3月采集各实验鼠口咽拭子及尾尖血,分别应用PCR和ELISA方法进行检测。结果两品系小鼠感染PVM病毒1周后,口咽拭子PVM核酸检出率为70%~100%,随后2周和3周检出率降低,CT值增高,1个月后无检出;外周血PVM抗体1周无检出,随后2、3周检出率为80%~100%,1至3月全部检出,且PVM抗体ELISA检测吸光度持续增高,2月和3月仍维持较高的抗体水平。结论小鼠口咽拭子样品的PCR检测结合血清学检测技术,可应用于小鼠PVM的质量控制。

补贴退坡会对中国新能源汽车需求产生影响吗?——基于西安的实证

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甘肃天水苹果黑星病年消长动态调查及防治药剂筛选

为明确苹果黑星病在甘肃天水的年消长动态、发病规律及筛选高效防治药剂,2023年在苹果生长季持续对苹果黑星病的病叶率和病情指数进行了调查,同时选用10种农药制剂进行田间药剂筛选试验。结果表明,天水地区苹果黑星病在5月中旬开始侵染,7月底达到第一次发病高峰,之后进入病情发展缓慢期,8月下旬至9月下旬,病菌又一次侵染秋梢,达到第二次发病高峰,之后进入病菌越冬预备期。田间防治试验表明,25%苯甲·吡唑酯SC 1000倍液、25%戊唑·异菌脲SC 2500倍液、40%氟硅唑EC 1500倍液和20%烯肟·戊唑醇SC 1000倍液的防效达83.56%~93.12%,可作为首选药剂;12.5%烯唑醇WP 1500倍液、25%吡唑醚菌酯SC 800倍液、12.5%腈菌唑EC 1000倍液和40%咪鲜胺EW 800倍液,防效次之,可作为辅助药剂,与首选药剂交替使用。综上所述,本试验明确了苹果黑星病的年消长动态、发病规律,筛选出了高效防治药剂,为苹果黑星病的有效防控提供了理论依据和技术支撑。

基于递减分析的页岩油气可采量评估

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