The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage

Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.

Utilizing hybrid faradaic mechanism via catalytic and surface interactions for high-performance flexible energy storage system

Improving the capacitance and energy density is a significant challenge while developing practical and flexible energy storage system(ESS).Redox mediators(RMs),as redox-active electrolyte additives,can provide additional energy storing capability via electrochemical faradaic contribution on electrodes for high-performance flexible ESSs.Particularly,determining effective material combinations between electrodes and RMs is essential for maximizing surface faradaic redox reactions for energy-storage performance.In this study,an electrode-RM system comprising heterostructured hybrid(carbon fiber(CF)/MnO_(2)) faradaic electrodes and iodine RMs(I-RMs) in a redox-active electrolyte is investigated.The CF/MnO_(2)with the 1-RMs(CF/MnO_(2)-I) induces dominant catalytic faradaic interaction with the I-RMs,significantly enhancing the surface faradaic kinetics and increasing the overall energy-storage performance.The CF/MnO_(2)-I ESSs show a 12.6-fold(or higher) increased volumetric energy density of 793.81 mWh L^(-1)at a current of 10 μA relative to ESSs using CF/MnO_(2)without I-RMs(CF/MnO_(2)).Moreover,the CF/MnO_(2)-I retains 93.1% of its initial capacitance after 10,000 cycles,validating the excellent cyclability.Finally,the flexibility of the ESSs is tested at different bending angles(180° to 0°),demonstrating its feasibility for flexible and high-wear environments.Therefore,CF/MnO_(2)electrodes present a practical material combination for high-performance flexible energy-storage devices owing to the catalytic faradaic interaction with I-RMs.

Supplementary Material: Stepping Stone Mechanism: Carrier-Free Long-Range Magnetism Mediated by Magnetized Cation States in Quintuple Layer

The long-range magnetism observed in group-V tellurides quintuple layers is the only working example of carrierfree dilute magnetic semiconductors（DMS）, whereas the physical mechanism is unclear, except the speculation on the band topology enhanced van Vleck paramagnetism. Based on DFT calculations, we find a stable longrange ferromagnetic order in a single quintuple layer of Cr-doped Bi_2Te_3 or Sb_2Te_3, with the dopant separation more than 9 ？. This configuration is the global energy minimum among all configurations. Different from the conventional super exchange theory, the magnetism is facilitated by the lone pair derived anti-bonding states near the cations. Such anti-bonding states work as stepping stones merged in the electron sea and conduct magnetism.Further, spin orbit coupling induced band inversion is found to be insignificant in the magnetism. Therefore, our findings directly dismiss the common misbelief that band topology is the only factor that enhances the magnetism.We further demonstrate that removal of the lone pair derived states destroys the long-range magnetism. This novel mechanism sheds light on the fundamental understanding of long-range magnetism and may lead to discoveries of new classes of DMS.

Enhancing CO_(2)capture of an aminoethylethanolamine-based non-aqueous absorbent by using tertiary amine as a proton-transfer mediator:From performance to mechanism

Non-aqueous absorbents(NAAs)have attracted increasing attention for CO_(2)capture because of their great energy-saving potential.Primary diamines which can provide high CO_(2)absorption loading are promising candidates for formulating NAAs but suffer disadvantages in regenerability.In this study,a promising strategy that using tertiary amines(TAs)as proton-transfer mediators was proposed to enhance the regenerability of an aminoethylethanolamine(AEEA,diamine)/dimethyl sulfoxide(DMSO)(A/D)NAA.Surprisingly,some employed TAs such as N,N-diethylaminoethanol(DEEA),N,N,N’,N’’,N’’-pentamethyldiethylenetriamine(PMDETA),3-dimethylamino-1-propanol(3DMA1P),and N,N-dimethylethanolamine(DMEA)enhanced not only the regenerability of the A/D NAA but also the CO_(2)absorption performance.Specifically,the CO_(2)absorption loading and cyclic loading were increased by about 12.7%and 15.5%-22.7%,respectively.The TA-enhanced CO_(2)capture mechanism was comprehensively explored via nuclear magnetic resonance technique and quantum chemical calculations.During CO_(2)absorption,the TA acted as an ultimate proton acceptor for AEEA-zwitterion and enabled more AEEA to form carbamate species(AEEACOO-)to store CO_(2),thus enhancing CO_(2)absorption.For CO_(2)desorption,the TA first provided protons directly to AEEACOO-as a proton donor;moreover,it functioned as a proton carrier and facilitated the low-energy step-wise proton transfer from protonated AEEA to AEEACOO-.Consequently,the presence of TA made it easier for AEEACOO-to obtain protons to decompose,resulting in enhanced CO_(2)desorption.In a word,introducing the TA as a proton-transfer mediator into the A/D NAA enhanced both the CO_(2)absorption performance and the regenerability,which was an efficient way to“kill two birds with one stone”.

In vivo evidence of IGF-I–estrogen crosstalk in mediating the cortical bone response to mechanical strain

Although insulin-like growth factor-I （IGF-I） and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading. To test this, at 5 weeks of age, partial ovariectomy （pOVX） or a sham operation was performed on heterozygous IGF-I conditional knockout （H IGF-I KO） and control mice generated using a Cre-loxP approach. At 10 weeks of age, a 10 N axial load was applied on the right tibia of these mice for a period of 2 weeks and the left tibia was used as an internal non-non-loaded control. At the cortical site, partial estrogen loss reduced total volumetric bone mineral density （BMD） by 5% in control pOVX mice （P=0.05, one-way ANOVA）, but not in the H IGF-I KO pOVX mice. At the trabecular site, bone volume/total volume （BV/TV） was reduced by 5%-6% in both control pOVX （P〈0.05） and H IGF-I KO pOVX （P=0.05） mice. Two weeks of mechanical loading caused a 7 %-8% and an 11%-13% （P〈0.05 vs. non-loaded bones） increase in cortical BMD and cortical thickness （Ct.Th）, respectively, in the control sham, control pOVX and H IGF-I KO sham groups. By contrast, the magnitude of cortical BMD （4%, P=0.13） and Ct.Th （6%, P〈0.05） responses were reduced by 50% in the H IGF-I KO pOVX mice compared to the other three groups. The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant （P〈0.05） by two-way ANOVA. Two weeks of axial loading caused similar increases in trabecular BV/TV （13%-17%） and thickness （17%-23%） in all four groups of mice. In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.

Pain-related mediators underlie incision-induced mechanical nociception in the dorsal root ganglia

Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in- terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no- ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery （n = 32） and sham surgery （n = 8） groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re- ceived anesthesia, but not an incision. Yon Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord （L3-5） showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons （diameter 〈 20 pm and 20-40 pm） and satellite cells in the dorsal root ganglia of the spinal cord （L3-5） in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons （diameter 〉 40 pm） at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci- sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me- chanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by in- cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.

Application of Fast Radical Rearrangement in the Mechanistic Investigation of Intramolecular C-H Insertion by Rh(Ⅱ)-Mediated Carbenoids

In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclopropyl)ethyl diazoacetoacetate 8a and methyl 2-diazo-3oxo-6-(2-phenylcyclopropyl) hexanoate 8b have been synthesized. Preliminary investigation of the intramolecular C-H insertion with Rh2(OAc)4 as catalyst supports a concerted insertion process.

数字化转型对纺织业升级的影响研究

纺织业是传统产业中的支柱产业,用数字技术推动中国纺织产业升级具有重要意义。本文基于2012—2020年中国A股上市公司数据,构建纺织企业升级的指标,考察数字化转型对纺织业升级的影响。实证结果表明,数字化转型主要通过推动企业流程升级和功能升级两种途径,显著促进纺织业升级。本文采用工具变量法弱化由于遗漏变量等因素导致的内生性问题,通过替换变量和滞后变量法进行稳健性检验,得到一致的检验结果。机制检验表明,数字化转型主要通过营运效应、市场效应和成本效应促进纺织产业升级。本文的研究结果为促进企业数字化转型、推动纺织业升级和通过数字化转型促进纺织业产业升级提供了政策启示。

Activin-Directed Differentiation of Human Embryonic Stem Cells Differentially Modulates Alveolar Epithelial Wound Repair via Paracrine Mechanism

Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.

高等教育、区域创新能力与数字经济发展

在加快建设数字中国的时代背景下,对高等教育与数字经济之间的关系进行探索有助于优化高等教育的定位和资源配置,并赋能经济社会高质量发展。本研究基于2011—2020年我国各省份的面板数据,实证探究高等教育对区域数字经济发展的影响效应、作用机制和异质性特征。研究发现,高等教育是区域数字经济发展的重要推动力量,其正向影响效应在使用工具变量缓解内生性问题后仍然稳健;区域创新能力是高等教育驱动数字经济增长的有效机制;高等教育对数字经济的贡献具有明显的时序动态性和区域异质性。基于研究结果,未来我国应彰显数字经济发展中的高校力量,通过探索数字创新人才培养体系、实施差异化产学研融合策略以及优化高等教育资源配置等举措,加快构建高等教育与数字经济协同发展的新格局。

论公证调解的实践困境、理论基础与优化路径

作为多元化纠纷解决机制的组成部分,公证调解体现了公证制度由“纠纷预防”向“纠纷解决”的功能扩张。其制度发展大致沿循中国式法治现代化道路,经历了小调解、大调解以及司法辅助事务参与三个阶段,但实践中存在的运行无序性、发展依附性与功能模糊性三重困境阻碍了其解纷效能的发挥。在理论层面,多中心社会治理模式、“案多人少”困境下公民合法权益保障,构成公证调解的外部正当性基础,功能扩张的公证改革总趋势、评价型调解、多元公证业务衔接的比较优势,构成公证调解的内部正当性基础;来源于公证权的调解权与定性为社会调解的制度属性,使得公证调解独立于人民调解和司法权。在制度层面,应当以规范化逻辑为指引,确立完善公证调解制度的“三步走”总体方案,以社会化逻辑为导向明确多元化调解类型与调解模式,以专业化逻辑为牵引发挥衔接多元公证业务结案方式的调解协议执行优势。可采用“一般涵盖+重点突出+负面清单”的基本思路确定调解范围,同时适用单一“认证调解员”制度,并采用“规定上限+弹性计费”方式确定调解费用。

高职院校教育质量内部交互影响机制研究——基于S学院CCSS调查数据的中介效应分析

基于S学院CCSS调查的3177个样本数据,通过效度检验、模型拟合度检验、路径分析、中介效应检验等,验证包括学生动机、课程学习投入、向学/厌学的学生因素,支持性校园环境、课程质量的院校因素,以及生师互动、生生互动、学生权力三个中介变量对教育质量的影响程度及作用机制。研究结果表明:高职院校教育质量受到内部多重因素交互作用及影响;生师互动对教育质量的中介影响呈现类型化差异;教育收获和就业力对生生互动影响最为敏感;教育质量受学生权力中介效应影响不容忽视。

论强制调解于“一带一路”投资争端解决的适用

“一带一路”倡议实施十年间,沿线国直接投资数额显著增加、投资结构持续多元化,但也有若干项目由于投资者和当地政府矛盾而被迫中断。“一带一路”是和平之路、合作共赢之路,可以效仿国内法中的强制调解制度,通过引入程序上的强制性来扩大调解在投资者-东道国投资争端解决中的适用,发挥其比投资仲裁更为经济、灵活、有助于合作关系修复的优势。强制调解制度并不会改变调解作为ADR自愿性的本质特征,和解协议的达成仍取决于双方同意。“一带一路”投资争端解决引入强制调解制度时,应该选择适当的路径,明确适用范围,综合考虑磋商、仲裁、东道国法院诉讼等其他争端解决方式的优劣,通过程序规则衔接,着眼于一整套高效、灵活争端解决机制的构建。

高速铁路对城市空间结构的影响及机制研究

为探索高速铁路在城市空间格局演化中的作用,利用夜间灯光数据和LandScan人口分布数据构造了表征城市空间结构的城市蔓延指数,运用多期DID模型和工具变量法实证检验了高速铁路对城市空间结构的影响及作用机制。研究发现:高速铁路开通显著促进了城市空间结构的分散化,在考虑内生性问题及一系列稳健性检验后该结论依然成立。异质性分析表明,高速铁路对城市空间结构的重塑作用在中小规模城市和位于三大城市群以外的城市中更显著。机制分析发现,高速铁路能够通过推动产业结构高级化和建成区面积扩张导致城市空间结构趋于分散化,劳动力集聚则在高速铁路与城市空间结构之间起到遮掩效应。研究对于更好地推进高速铁路建设和引导城市空间结构有序发展具有重要意义。

基于调解机制的医疗投诉解决研究

文章旨在探讨基于调解机制的医疗投诉纠纷解决方法,并分析其应用效果。首先综述了医疗投诉纠纷的定义、分类和原因,发现其对患者、医生和医疗机构都有负面影响。调解机制作为一种快速、灵活且与当事人合作的争议解决方式受到关注。研究系统概述了调解机制的理论和实践,并揭示了它在其他领域的成功应用案例。随后构建基于调解机制的医疗投诉纠纷解决模式,并通过案例分析和效果评估验证了该模式的可行性和有效性。进一步探讨调解机构和人员建设的关键问题,例如机构建立、组织架构和调解人员的选拔与培训。通过实证研究方法,对该模式进行实证研究,并评估患者和医生的满意度。最后,讨论基于调解机制的医疗投诉纠纷解决模式的优势、问题以及未来的应用前景,并提出结论和进一步研究建议。本研究的结果有望为医疗投诉纠纷解决提供新的思路和方法,促进医患双方的有效沟通与合作,提升医疗服务质量和患者满意度。

理论研究Cu@C_(2)N催化剂表面上水分子对电催化CO_(2)还原反应机理的影响

电催化CO_(2)还原反应(CO_(2)RR)的反应途径涉及多个质子-电子对转移,在水溶剂条件下,质子的来源是水分子,考虑水分子对质子-电子对的转移机制十分必要。本研究提出水辅助氢穿梭模型,与常用的以氢原子作为氢源的直接加氢模型对比,研究水分子在CO_(2)RR中对质子-电子对转移的影响。采用密度泛函理论,系统地研究了铜原子嵌入C_(2)N单层催化剂(Cu@C_(2)N)和石墨烯作为衬底的Cu@C_(2)N/石墨烯复合催化剂(Cu@C_(2)N/G)表面上不同加氢模型的CO_(2)RR反应机理。在水辅助氢穿梭模型中,氢原子与水分子结合形成水合质子,水合质子将自身的氢原子转移到催化剂表面的反应物上形成反应中间体,增强了中间体与催化剂之间的相互作用。此外,在Cu@C_(2)N/G催化剂中,石墨烯将电子转移到表面的Cu@C_(2)N上,提高了催化剂的CO_(2)RR催化活性。进一步,计算了Cu@C_(2)N和Cu@C_(2)N/G催化剂上CO_(2)RR和析氢反应的极限电位,讨论催化剂的活性和选择性。结果表明CO_(2)在低电位下容易生成HCOOH,施加高电位时可以生成CO、CH3OH和CH4并伴随着H2的生成。

高性能TEMPO功能化木粉-聚乙烯醇/锂铝水滑石复合材料的制备及性能

【目的】探究聚乙烯醇/锂铝水滑石(PVA/LDH)分散液对巴沙木加工剩余物理化性能的影响,为构建高性能木质复合材料提供理论依据,实现木材加工剩余物的高值化利用。【方法】受天然贝壳“砖-泥”有序结构启发,以巴沙木加工剩余物(木粉)为主要原料,经脱木素和氧化改性,获得2,2,6,6-四甲基哌啶-1-氧自由基(TEMPO)功能化改性木粉(T-WP),向其中加入不同比例PVA/LDH分散液,通过真空抽滤自组装过程将无机纳米片水滑石插层,构建天然有机聚合物与无机纳米片复合的高性能新型木质层状复合材料,基于FTIR、XPS、Zeta电位、力学性能等测试与分析,探究各组分间的相互作用及机械性能协同增强机制。【结果】1)木粉粒径100目时,纯T-WP薄膜的力学拉伸强度和韧性最大,分别为(225.25±0.82)MPa和(5.18±0.36)MJ·m^(-3)。2)PVA/LDH纳米片体系在T-WP上成功插层,并与T-WP分子链上的含氧官能团形成氢键、静电相互作用以及共价交联作用。3)对不同PVA/LDH添加量的T-WP-PVA/LDH复合材料进行力学性能分析,PVA/LDH添加量为20 wt%时,T-WP-PVA/LDH复合材料的拉伸强度和杨氏模量最大,分别为(287.29±4.91)MPa和(14.21±2.60)GPa,是纯T-WP的1.28和2.40倍。4)在相对湿度90%、温度25℃条件下放置16 h,T-WP-PVA/LDH复合材料的吸湿率为45.43%,力学拉伸强度为105.40 MPa;在湿润土壤中,T-WP-PVA/LDH复合材料表现出较好的可生物降解特性。【结论】T-WP-PVA/LDH仿生层状复合材料中,T-WP分子链上的活性含氧基团与PVA/LDH体系形成氢键、静电相互作用以及Al—O—C共价交联作用,构建协同增强体系,赋予T-WP-PVA/LDH复合材料优异的力学性能。木质层状复合材料优异的特性使其在包装、地膜、一次性餐盒等领域具有广泛应用前景,有望替代部分聚乙烯、聚丙烯等石油基产品。

创新驱动绿色经济增长的理论分析与实证检验

为了研究创新如何赋能绿色经济增长,首先从理论上解析了创新驱动绿色经济增长的直接作用机制和传导机制,提出研究假说;其次构建直接效应模型和中介效应模型,运用2005—2020年中国省级面板数据实证检验理论假说。研究发现创新驱动存在正向赋能绿色经济增长的直接效应,并且创新驱动绿色经济增长的正向赋能在经济发展水平较高的地区作用效果更强。创新也能够通过人力资本、产业升级、金融发展和政府干预等中介传导机制间接赋能绿色经济增长。各中介变量作用强度按照“人力资本>产业升级>政府中介>金融发展”的大小排序,人力资本的中介作用最为强劲,金融发展作用强度最小。为了更好地实现创新驱动绿色经济增长,不仅应积极发挥创新驱动的直接赋能效应,还应该高度重视各种间接赋能机制。

数字经济驱动体育产业高质量发展的影响机制研究

数字经济是促进经济高质量发展的新动能,是驱动体育产业高质量发展的新引擎。文章基于2013—2020年中国20个省(市)面板数据,实证检验了数字经济对体育产业高质量发展的影响效应及作用机制。结果表明:(1)数字经济能显著驱动体育产业高质量发展,这一结论在采用工具变量、替换变量等稳健性检验后依然成立;(2)作用机制结果表明,数字经济可通过扩大互联网应用驱动体育产业高质量发展;(3)异质性分析表明,数字经济对东、中部地区体育产业高质量发展均有正向驱动作用,进一步分析发现东部地区驱动效应强于中部地区。基于上述结果,提出以下建议:(1)持续深化数字化建设,全面释放数字经济发展红利;(2)大力推广互联网应用,营造体育产业高质量发展的科技环境;(3)提升技术创新水平,开辟体育产业高质量发展创新之道;(4)因地制宜推进数字经济建设,消除区域间数字经济极化效应。