PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

Tackling the proton limit under industrial electrochemical CO_(2)reduction by a local proton shuttle

Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In this work,an ion‐polymer‐modified gas‐diffusion electrode is used to tackle this proton limit.It is found that gas diffusion electrode‐Nafion shows an impressive performance of 75.2%Faradaic efficiency in multicarbon products at an industrial current density of 1.16 A/cm^(2).Significantly,in‐depth electrochemical characterizations combined with in situ Raman have been used to determine the full workflow of protons,and it is found that HCO_(3)^(−)acts as a proton pool near the reaction environment,and HCO_(3)^(−)and H_(3)O^(+)are local proton donors that interact with the proton shuttle−SO_(3)^(−)from Nafion.With rich proton hopping sites that decrease the activation energy,a“Grotthuss”mechanism for proton transport in the above system has been identified rather than the“Vehicle”mechanism with a higher energy barrier.Therefore,this work could be very useful in terms of the achievement of industrial CO_(2)reduction fundamentally and practically.

Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma

Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.

例谈ICL植入术治疗高度近视的围手术期护理

随着现代医疗技术的不断进步,有晶体眼人工晶体植入术(ICL植入术)已成为治疗高度近视的一种有效手段。该手术通过植入人工晶体来矫正高度近视患者的视力问题,具有手术风险低、恢复时间短、视觉质量高等优点。然而,手术的成功不仅依赖于医生的精湛技艺,围手术期的护理工作同样至关重要。围手术期护理涵盖了从术前准备到术后康复的整个过程,其目的在于确保手术的顺利进行,减少术后并发症的发生,同时帮助患者尽快恢复健康。对于高度近视患者而言,由于手术涉及眼部敏感区域,围手术期的护理更需细致入微。因此,本文通过分析,深入探讨了ICL植入术治疗高度近视的围手术期护理要点,旨在为临床护理工作提供借鉴与指导,共同推动眼科护理水平的提升。

Asymmetric acidic/alkaline N_(2)electrofixation accelerated by high-entropy metal-organic framework derivatives

High-entropy materials are composed of five or more metal elements with equimolar or near-equimolar concentrations within one crystal structure,which offer remarkable structural properties for many applications.Despite previously reported entropy-driven stabilization mechanisms,many high-entropy materials still tend to decompose to produce a variety of derivatives under operating conditions.In this study,we use transition-metal(Ni,Co,Ni,Zn,V)-based high-entropy metal-organic frameworks(HE-MOFs)as the precursors to produce different derivatives under acidic/alkaline treatment.We have shown that HE-MOFs and derivatives have shown favorable kinetics for N_(2)electrofixation in different pH electrolytes,specifically cathodic nitrogen reduction reaction in acidic media and anodic oxygen evolution reaction in alkaline media.To buffer the pH mismatch,we have further constructed an asymmetric acidic/alkaline device prototype by using bipolar membranes.As expected,the prototype showed remarkable activities,with an NH_(3)yield rate of 42.76μg h^(−1)mg^(−1),and Faradaic efficiency of 14.75%and energy efficiency of 2.59%,which are 14.4 and 4.4 times larger than those of its symmetric acidic and alkaline counterparts,respectively.

EHF通过抑制Wnt/β-catenin通路活性下调胰腺癌细胞的干性

目的:探索E26转化特异性同源因子(E26 transformation-specific homologous factor,EHF)调控胰腺癌细胞干性的机制。方法:通过生信分析寻找介导EHF调控胰腺癌干性的信号通路。利用Western blot及RT-qPCR技术验证胰腺癌细胞中EHF表达与目标干性通路活性的相关性。利用ChIP及双荧光素酶实验验证EHF对靶基因的调控作用。阻断通路活性后,利用功能学实验分析目标通路在EHF调控胰腺癌细胞干性过程中的作用。结果:生信分析发现Wnt/β-catenin通路参与EHF对胰腺癌干性的调控。构建EHF稳定过表达及稳定降表达的胰腺癌细胞系,通过Western blot及RT-qPCR技术证实胰腺癌细胞EHF的表达与Wnt/β-catenin通路的活性呈负相关,差异均具有统计学意义(均P<0.01)。EHF可通过结合β-catenin的启动子区直接抑制β-catenin的转录。通过流式细胞术、悬浮成球及软琼脂克隆形成实验证明,在利用XAV939阻断Wnt/β-catenin通路的活性后,由EHF敲低所引起的胰腺癌细胞干性上调可被有效抑制,差异均具有统计学差异(均P<0.01)。结论:EHF通过抑制Wnt/β-catenin通路活性下调胰腺癌细胞的干性,靶向Wnt/β-catenin通路的小分子抑制剂有潜力成为治疗胰腺癌的药物。

Significant suppression of residual nitrogen incorporation in diamond film with a novel susceptor geometry employed in MPCVD

This work proposed to change the structure of the sample susceptor of the microwave plasma chemical vapor deposition(MPCVD)reaction chamber,that is,to introduce a small hole in the center of the susceptor to study its suppression effect on the incorporation of residual nitrogen in the MPCVD diamond film.By using COMSOL multiphysics software simulation,the plasma characteristics and the concentration of chemical reactants in the cylindrical cavity of MPCVD system were studied,including electric field intensity,electron number density,electron temperature,the concentrations of atomic hydrogen,methyl,and nitrogenous substances,etc.After introducing a small hole in the center of the molybdenum support susceptor,we found that no significant changes were found in the center area of the plasma,but the electron state in the plasma changed greatly on the surface above the susceptor.The electron number density was reduced by about 40%,while the electron temperature was reduced by about 0.02 eV,and the concentration of atomic nitrogen was decreased by about an order of magnitude.Moreover,we found that if a specific lower microwave input power is used,and a susceptor structure without the small hole is introduced,the change results similar to those in the surface area of the susceptor will be obtained,but the spatial distribution of electromagnetic field and reactant concentration will be changed.

中国现代化自主性逻辑确立及其世界历史意义——从“现代化在中国”到“中国式现代化”

中国式现代化道路是以中华民族为主体,在世界历史进程中探索社会主义现代化的伟大创造,彰显了中华民族的主体性和创造性。回顾中国式现代化道路的生成历程,一个重大变化就是实现了从“现代化在中国”到“中国式现代化”的历史跃迁,完成了从“外源”到“内生”、从“简单模仿”到“自主创新”的转变与升华,从而使“中国式”具有了更为根本的实质内容,也因而具有了更为深远的世界历史意义。

NMDARs regulate the excitatory-inhibitory balance within neural circuits

Excitatory-inhibitory(E/I)balance is essential for normal neural development,behavior and cognition.E/I imbalance leads to a variety of neurological disorders,such as autism and schizophrenia.NMDA receptors(NMDARs)regulate AMPAR-mediated excitatory and GABAAR-mediated inhibitory synaptic transmission,suggesting that NMDARs play an important role in the establishment and maintenance of the E/I balance.In this review,we briefly introduced NMDARs,AMPARs and GABAARs,summarized the current studies on E/I balance mediated by NMDARs,and discussed the current advances in NMDAR-mediated AMPAR and GABAAR development.Specifically,we analyzed the role of NMDAR subunits in the establishment and maintenance of E/I balance,which may provide new therapeutic strategies for the recovery of E/I imbalance in neurological disorders.

电化学还原高压CO_(2)捕集溶液制太阳能燃料

本文突破单一考虑CO_(2)转化的局限,从CO_(2)捕集-转化-利用集成的角度提出了直接光/电化学还原高压CO_(2)捕集溶液制太阳能燃料,在捕集端避免高温条件气相CO_(2)再生步骤;在产无端利用CO_(2)和CO溶解度的巨大差异,实现零能耗气体产物分离;在转化过程中,本文建立了考虑压力的光/电化学CO_(2)还原多尺度方法.本文建立了微观第一性原理计算-介观动力学模拟-宏观输运模型耦合的多尺度模型,以基元反应参数、分电流密度作为跨接参数,以电极表面CO_(2)浓度、pH作为迭代参数,实现了多尺度模拟计算;研究了宏观压力变化对界面微环境(电极表面分子覆盖度和局域pH)的作用机制,发现分子覆盖度对CO_(2)还原反应的促进作用与局域pH对析氢反应的抑制作用相协同,实现了CO_(2)高效、高选择性转化.本文研制了直接光/电化学还原高压CO_(2)捕集溶液制太阳能燃料原理样机,太阳能制燃料效率达到16.8%,超过了文献报道的饱和CO_(2)溶液供给的太阳能制燃料系统.

FULL TIME-SPACE GOVERNANCE STRATEGY AND TECHNOLOGY FOR CROPLAND NON-POINT POLLUTION CONTROL IN CHINA

Ensuring food safety while reducing agricultural non-point source pollution is quite challenging,especially in developing and underdeveloped countries.Effective systematic strategies and comprehensive technologies need to be developed for agricultural non-point source pollution control at the watershed scale to improve surface water quality.In this review,a proposal is made for a full time-space governance strategy that prioritizes source management followed by endpoint water pollution control.The 4R chain technology system is specifically reviewed,including source reduction,process retention,nutrient reuse and water restoration.The 4R chain technology system with the full time-space governance strategy was applied at the scale of an administrative village and proved to be a feasible solution for reducing agricultural non-point source pollution in China.In the future,a monitoring system needs to be established to trace N and P transport.Additionally,new smart fertilizer and intelligent equipment need to be developed,and relevant governance standards and supportive policies need to be set to enhance the efficacy of agricultural non-point source pollution control.

构建人类命运共同体的几个基础性问题

构建人类命运共同体是以习近平总书记为核心的中国共产党人为解决当今世界发展难题贡献的中国智慧和中国方案。深刻理解和把握这一方案的逻辑,前提是要充分阐明以下三个基础性问题:一是如何理解人类命运共同体思想的科学合理性;二是现阶段构建人类命运共同体是否具有现实可行性;三是如何把握构建人类命运共同体的世界意义。对这三个基础性问题的研究和回答,直接影响着对构建人类命运共同体的必然性、可行性、时代性的认识和相关实践。

Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR- 24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3＇UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.

Crystal structure of SARS-CoV-2 main protease in complex with the natural product inhibitor shikonin illuminates a unique binding mode

Almost everyone is susceptible to the severe acute respiratorysyndrome coronavirus 2(SARS-CoV-2),an RNA virus,which cancause many symptoms and even death among high-risk individu-als[1,2].The main protease(M^(Pro),also known as 3CL^(Pro))is a cys-teine protease essential for producing infectious virions and thusan attractive target for drug development.Up to now,many studiesusing either in silico ligand docking or drug discovery based onavailable structures have been performed to discover new MPTO.inhibiting agents[3.4].

“双一流”背景下本科实验教学仪器开放共享管理模式及管理系统的探索与实践

为了探索本科教学仪器开放共享管理模式(Opening and sharing management mode,OSMM)在"双一流"背景下高校人才培养过程中所发挥的作用,结合厦门大学环境与生态学院实验教学中心本科教学仪器开放共享管理模式及管理系统的建设经验和不足,探讨了实验室信息管理系统(Laboratory information management system,LIMS)在开放共享模式中发挥的重要作用,进而提出促进高校教学仪器设备开放共享建设、提高教学仪器使用率的几点措施,以便能充分发挥仪器设备的功效,保证教学与科研的正常进行,促进高校的可持续健康发展和国家"双一流"建设的稳步推进。

Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer＇s disease （AD）. Although amyloid-β （Aβ） aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons （PNs） in the olfactory lobe of the fruit fly. Methods Cholinergic spontaneous and miniature excitatory postsynaptic current （mEPSC） were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue. Results In fly pupae （2 days before eclosion）, overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc. Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.

Nitrogen slow-release behavior of oxamide granules in two different types of paddy soils

Oxamide is a potential slow-release nitrogen(N)fertilizer,especially under waterlogged conditions,due to its low solubility in water and the slow-release of ammonium by soil amidases.To investigate the effects of oxamide granules(2.00-2.38 mm in diameter)as a single basal fertilizer(180 or 144 kg N ha^(-1))on rice growth,soil properties,and N use efficiency in terms of N recovery efficiency(NRE),we conducted field experiments on two different types of paddy soils over two rice-growing seasons.Results showed that the fertilization effects of oxamide granules varied between the two types of paddy soils.In the red clayey paddy soil,the grain yields for both rice-growing seasons were high with a significantly higher NRE in the oxamide treatment than in the urea treatment.However,in the alluvial sandy paddy soil,the grain yields in the oxamide treatment were slightly lower than those in the urea treatment.Furthermore,oxamide produced little improvement in NRE in the alluvial sandy paddy soil.Soil incubation experiments over 98 d were also carried out to evaluate the factors affecting the N release behavior of oxamide granules in the two types of paddy soils.We found that the amidase activity was higher and,therefore,the oxamide hydrolysis rate was faster in the alluvial sandy paddy soil,which had a higher soil pH value and organic matter content,compared to the red clayey paddy soil.The faster N release and the longer growth period resulted in a mismatch between N supply by oxamide and rice demand,which,in turn,led to little improvement in NRE and a decreased grain yield in the alluvial sandy paddy soil,especially in the reduced oxamide treatment.These results could help select the appropriate size of oxamide granules for use as a slow-release N fertilizer depending on the soil properties and growth period of rice.

Structure of SARS-CoV-2 main protease in the apo state

Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has been a global pandemic that severely threatens global health with concordant economic damage.However,there is currently no clinically approved vaccines or drugs against COVID-19(Lu et al.,2020).

Efficient solar fuel production with a high-pressure CO_(2)-captured liquid feed

We demonstrated an efficient solar photovoltaic-powered electrochemical CO_(2) reduction device with a high-pressure CO_(2)-captured liquid feed.In an“air-to-barrel”picture,this device holds promise to avoid both high-temperature gaseous CO_(2) regeneration and high energy-cost gas product separation steps,while these steps are necessary for devices with a gaseous CO_(2) feed.To date,solar fuel production with a CO_(2)-saturated liquid feed suffers from high over-potential to suppress the hydrogen evolution reaction and consequently,low solar-to-chemical(STC)energy conversion efficiency.Here,we presented a distinct high-pressure operando strategy,i.e.,we took extra advantage of the high pressure in catalyst synthesis besides in the period of the CO_(2) reduction reaction(CO_(2)RR).The power of this strategy was demonstrated by a proof-of-concept device in which a representative copper catalyst was first synthesized in operando in a high-pressure(50 bar)CO_(2)-saturated KHCO3 solution,and then this high-pressure CO_(2)-captured liquid was converted to solar fuel using the operando synthesized Cu catalyst.This Cu catalyst achieved 95%CO_(2)RR selectivity at the recorded low potential of−0.3 V vs.RHE enabled by the combination of operando facet engineering and oxide derivation.Furthermore,this device achieved a record-high STC efficiency of 21.6%under outdoor illumination,superior to other CO_(2)-saturated liquid-fed devices,and compared favorably to gaseous CO_(2)-fed devices.