A Temporary Frequency Response Strategy Using a Voltage Source-Based PermanentMagnet Synchronous Generator and Energy Storage Systems

Energy storage systems(ESS)and permanent magnet synchronous generators(PMSG)are speculated to be able to exhibit frequency regulation capabilities by adding differential and proportional control loops with different control objectives.The available PMSG kinetic energy and charging/discharging capacities of the ESS were restricted.To improve the inertia response and frequency control capability,we propose a short-term frequency support strategy for the ESS and PMSG.To this end,the weights were embedded in the control loops to adjust the participation of the differential and proportional controls based on the system frequency excursion.The effectiveness of the proposed control strategy was verified using PSCAD/EMTDC.The simulations revealed that the proposed strategy could improve the maximum rate of change of the frequency nadir and maximum frequency excursion.Therefore,it provides a promising solution of ancillary services for frequency regulation of PMSG and ESS.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

Rumen microbial degradation of bromoform from red seaweed(Asparagopsis taxiformis)and the impact on rumen fermentation and methanogenic archaea

Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degradation process of CHBr3 from A taxiformis in the rumen and whether this process is diet-dependent.An in vitro batch culture system was used according to a 2×2 factorial design,assessing two A taxiformis inclusion rates[0(CTL)and 2%DM diet(AT)]and two diets[high-concentrate(HC)and high-forage diet(HF)].Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0,0.5,1,3,6,8,12,16,24,48 and 72 h to assess the pattern of degradation of CHBr_(3) into dibromomethane(CH_(2)Br_(2))and fermentation parameters.Additionally,an in vitro experiment with pure cultures of seven methanogens strains(Methanobrevibacter smithii,Methanobrevibacter ruminantium,Methanosphaera stadtmanae,Methanosarcina barkeri,Methanobrevibacter millerae,Methanorhermobacter wolfei and Methanobacterium mobile)was conducted to test the effects of increasing concentrations of CHBr3(0.4,2,10and 50μmol/L).Results The addition of AT significantly decreased CH_(4) production(P=0.002)and the acetate:propionate ratio(P=0.003)during a 72-h incubation.The concentrations of CHBr_(3) showed a rapid decrease with nearly 90%degraded within the first 3 h of incubation.On the contrary,CH_(2)Br_(2) concentration quickly increased during the first 6 h and then gradually decreased towards the end of the incubation.Neither CHBr_(3) degradation nor CH_(2)Br_(2) synthesis were affected by the type of diet used as substrate,suggesting that the fermentation rate is not a driving factor involved in CHBr_(3)degradation.The in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of M.smithii,M.ruminantium,M.stadtmanae,M.barkeri,M.millerae,M.wolfei,and M.mobile.Conclusions The present work demonstrated that CHBr_(3) from A.taxiformis is quickly degraded to CH_(2)Br_(2)in the rumen and that the fermentation rate promoted by different diets is not a driving factor involved in CHBr_(3)degradation.

Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short distances.Biodiversity research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be considered.For first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary causes.This investigation covered four transects(traversing ca.2200 m a.s.l.) encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10°).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill orders.The exception was a slight increase in phylogenetic diversity when dominant species were over-weighted.The decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional strategies.Besides,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional diversity.For phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate lineages.This could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.

Glial regenerative response in the imaginal discs of Drosophila melanogaster

Glial cells play a key role during nervous system development and actively participate in all the cellular processes involved in maintaining its structural robustness and functional plasticity.In response to neuronal damage,glial cells proliferate,migrate to the injured region and change their morphology,function,and behavior(Gallo and Deneen,2014;Kato et al.,2018).This glial regenerative response is associated with the repairing function of these cells and is found across species,suggesting that it may reflect a common underlying genetic mechanism(Kato et al.,2018).

Ecological stoichiometric comparison of plant-litter-soil system in mixed-species and monoculture plantations of Robinia pseudoacacia,Amygdalus davidiana,and Armeniaca sibirica in the Loess Hilly Region of China

We examined how afforestation patterns impact carbon(C),nitrogen(N),and phosphorus(P)stoichiometry in the plant-litter-soil system.Plant leaf,branch,stem,and root,litter,and soil samples were collected from mixedspecies plantations of Robinia pseudoacacia with Amygdalus davidiana(RPAD),R.pseudoacacia with Armeniaca sibirica(RPAS),and monocultures of R.pseudoacacia(RP),A.davidiana(AD),and A.sibirica(AS)in the Loess Hilly Region.The results showed that in mixed-species plantations,R.pseudoacacia had lower leaf N and P concentrations than in monocultures,while both A.davidiana and A.sibirica had higher leaf N and P concentrations.Soil P limited tree growth in both afforestation models.Mixing R.pseudoacacia with A.davidiana or A.sibirica reduced N-limitation during litter decomposition.Average soil total N and P concentrations were higher in RPAS than in RPAD,and both were higher than the corresponding monocultures.The average soil C:N ratio was the smallest in RPAS,while the average soil C:P ratio was larger in RPAS than in RP.A positive correlation between N and P concentrations,and between C:N and C:P ratios,was found in litter and all plant organs of mono-and mixedstands.Alternatively,for N concentration and C:N ratio,the correlations between plant(i.e.,leaf,branch,root)and litter and between plant and soil were inverse between plantation types.RPAD has an increased litter decomposition rate to release N and P,while RPAS has a faster rate of soil N mineralization.RPAD was the best plantation(mixed)to improve biogeochemical cycling,as soil nutrient restrictions,particularly for P-limitation,on trees growth were alleviated.This study thus provides insights into suitable tree selection and management by revealing C:N:P stoichiometry in the plant-litter-soil system under different afforestation patterns.

Fungal diversity and community composition responses to the reintroduction of fire in a non-managed Mediterranean shrubland ecosystem

Background:More than a decade of fire suppression has changed the structure of fire-adapted shrubland ecosystems in Spain’s National Parks,which are now at extreme risk of uncontrolled wildfires.Prescribed burning can mitigate the risk of wildfires by reducing the fuel load but prescribed burning may also alter the soil properties and reduce microbial and fungal activity,causing changes in the availability of nutrients deep in the soil layer.Although fungal communities are a vital part of post-fire restoration,some fire effects remain unclear.To examine the short-term effects of prescribed burning on soil fungal communities in Doñana Biological Reserve(SW Spain),we collected soil samples pre-burn and 1 day,6 and 12 months post-burn from burned plots to perform physicochemical and metabarcode DNA analyses.Results:Prescribed burning had no significant effect on the total fungal operational taxonomic unit richness and abundance.However,changes in soil pH,nitrogen and potassium content post-burn affected fungal community composition.Small non-significant changes in pH and phosphorous affected the composition of ectomycorrhizal fungi.Conclusions:The ectomycorrhizal fungal community appears to be resilient to the effects of low-to moderate-intensity fires and saprotrophic taxa may benefit from this kind of fire.This finding revealed that prescribed burning is a potentially valuable management tool for reducing fire hazards in shrublands that has little effect on the total richness and abundance of fungal communities.

泥河湾盆地中更新世气候转型期人类的适应行为

中更新世气候转型期(1.25-0.7 MaBP)是晚新生代最重要的气候变化时段之一。该时期大陆内部干旱化加剧,北半球冬季温度迅速下降,动植物群发生变化,对古人类的环境适应能力提出新的挑战。泥河湾盆地发育我国北方第四纪典型的河湖相沉积体系,其间富集众多早-中更新世旧石器时代遗址,是探讨更新世环境变化与人类适应行为的关键区域。本文选取盆地内岑家湾台地飞梁、麻地沟、岑家湾和东谷坨等重要遗址,通过多指标的统计分析,解读中更新世气候转型期古人类的适应策略。研究结果显示,因地制宜、就地取材是古人类获取石器原料的途径,不同遗址利用者对不同原料的选择和利用主要和遗址距离原料的远近有直接关系,而针对不同原料类型采取的差异化开发策略,预示着古人类认知能力的提高。尽管锤击法是古人类常用的剥片技术,但是砸击技术可能与本地原料质量具有更直接的关系;作为锤击法的有效补充,砸击技术的运用或许与古人类的认知水平提高存在关联。石核和石片的特征表明,该时期古人类对石核开发利用程度显著提高,剥片技术多样化,灵活性增强,展示了计划性和认知能力的提高。对优质燧石原料的青睐一直是古人类制作石器的主要策略,该时期修理类产品不仅种类增多,加工方式多样化程度也相对较高,加工精细的小型刮削器、钻、尖状器、凹缺器、齿状器和多边修理工具等产品增多指示对多种功能的适应,暗示古人类对区域生态景观多元化的积极响应。古人类灵活的技术多样化策略可能与其认知水平的提高存在关联,而气候与环境波动造成的生存压力等多方面叠加因素,可能共同作用于古人类的认知行为上,促使人类调整技术,适应多变的区域环境。本研究对探讨泥河湾盆地更新世古人类生存行为演化与环境关系、人类对东亚高纬度半干旱区适应策略具有重要意义。

Single atom Cu-N-C catalysts for the electro-reduction of CO_(2) to CO assessed by rotating ring-disc electrode

The electrochemical CO_(2) reduction reaction(CO_(2)RR) to controllable chemicals is considered as a promising pathway to store intermittent renewable energy. Herein, a set of catalysts based on copper-nitrogendoped carbon xerogel(Cu-N-C) are successfully developed varying the copper amount and the nature of the copper precursor, for the efficient CO_(2)RR. The electrocatalytic performance of Cu-N-C materials is assessed by a rotating ring-disc electrode(RRDE), technique still rarely explored for CO_(2)RR. For comparison, products are also characterized by online gas chromatography in a H-cell. The as-synthesized Cu-NC catalysts are found to be active and highly CO selective at low overpotentials(from -0.6 to -0.8 V vs.RHE) in 0.1 M KHCO_(3), while H_(2) from the competitive water reduction appears at larger overpotentials(-0.9 V vs. RHE). The optimum copper acetate-derived catalyst containing Cu-N_(4) moieties exhibits a CO_(2)-to-CO turnover frequency of 997 h^(-1) at -0.9 V vs. RHE with a H_(2)/CO ratio of 1.8. These results demonstrate that RRDE configuration can be used as a feasible approach for identifying electrolysis products from CO_(2)RR.

Prevalence and ecological factors affecting the distribution of plant-parasitic nematodes in Prunus groves in Spain

A wide survey was conducted to study plant-parasitic nematodes(PPNs)associated with Prunus groves in Spain.This research aimed to determine the prevalence and distribution of PPNs in Prunus groves,as well as the influence of explanatory variables describing soil,climate and agricultural management in structuring the variation of PPNs community composition.A total of 218 sampling sites were surveyed and 84 PPN species belonging to 32 genera were identified based of an integrative taxonomic approach.PPN species considered as potential limiting factors in Prunus production,such as Meloidogyne arenaria,M.incognita,M.javanica,Pratylenchus penetrans and P.vulnus,were identified in this survey.Seven soil physico-chemical(C,Mg,N,Na,OM,P,pH and clay,loamy sand and sandy loam texture classes),four climate(Bio04,Bio05,Bio13 and Bio14)and four agricultural management variables(grove-use history less than 10 years,irrigation,apricot seedling rootstock,and Montclar rootstock)were identified as the most influential variables driving spatial patterns of PPNs communities.In particular,younger plantations showed higher values for species richness and diversity indices than groves cultivated for more than 20 years with Prunus spp.Our study increases the knowledge of the distribution and prevalence of PPNs associated with Prunus rhizosphere,as well as on the influence of explanatory variables driving the spatial structure PPNs communities,which has important implications for the successful design of sustainable management strategies in the future in this agricultural system.

碳基固体氧化物燃料电池研究进展

随着人们对绿色能源和环境友好型社会需求的日益增长,先进能量转换装置或系统的研发亟待加速,而燃料电池系统被认为是最有希望的未来发电装置。在不同种类的燃料电池中,固体氧化物燃料电池(SOFCs)是一种清洁环保的发电装置,因其独特的多燃料运行能力及能量转化效率高等优点而前景广阔。然而,传统使用镍-金属陶瓷阳极的SOFCs,在碳氢化合物燃料下运行时,由于燃料的不完全氧化会使阳极产生积碳,从而导致电池性能下降。讨论了碳基SOFC中碳沉积机理和解决阳极积碳的策略,重点介绍了目前广泛研究的具有混合离子-电子导体的双金属-金属陶瓷材料的种类以及研究进展,并总结了双金属-金属陶瓷材料的抗积碳机理,主要表现为降低阳极表面的碳沉积速率以及加速积碳的去除。还介绍了在还原性气氛中,钙钛矿材料中纳米粒子原位偏析的原理,并讨论了原位偏析所形成的纳米颗粒以及其与钙钛矿主体所形成的金属氧化物异质结构在抗积碳阳极中的应用。此外,还探究了多层阳极和单原子催化剂阳极在中温SOFCs中的应用。在燃料电池技术巨大进步的推动下,人们对可用于固定式发电的集成煤气化的燃料电池发电系统(IGFCs)产生了新的兴趣,该系统对于实现煤炭的清洁高效利用具有重要意义,该技术的关键依托于SOFCs的成熟度。最后,总结并指出了碳基SOFCs未来的一些研究方向。

Presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

Hereditary spastic paraplegia(HSP)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower limbs.Pat ients can also experience peripheral neuropathy,cognitive impairment,and other neurological symptoms.To date,more than 80 genes have been implicated in HSP,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(Parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSP.

Twenty years of population dynamics in European beech-oak forest at their rear range margin anticipate changes in its structure and composition

There is an increasing interest in restoring degraded forests,which occupy half of the forest areas.Among the forms of restoration,passive restoration,which involves the elimination of degrading factors and the free evolution of natural dynamics by applying minimal or no management,is gaining attention.Natural dynamics is difficult to predict due to the influence of multiple interacting factors such as climatic and edaphic conditions,composition and abundance of species,and the successional character of these species.Here,we study the natural dynamics of a mixed forest located in central Spain,which maintained an open forest structure,due to intensive use,until grazing and cutting were banned in the 1960s.The most frequent woody species in this forest are Fagus sylvatica,Quercus petraea,Quercus pyrenaica,Ilex aquifolium,Sorbus aucuparia,Sorbus aria and Prunus avium,with contrasting shade and drought tolerance.These species are common in temperate European deciduous forest and are found here near their southern distribution limit,except for Q.pyrenaica.In order to analyze forest dynamics and composition,three inventories were carried out in 1994,2005 and 2015.Our results show that,despite the Mediterranean influence,the natural dynamics of this forest has been mainly determined by different levels of shade tolerance.After the abandonment of grazing and cutting,Q.pyrenaica expanded rapidly due to its lower shade tolerance,whereas after canopy closure and forest densification,shade-tolerant species gained ground,particularly F.sylvatica,despite its lower drought and late-frost tolerance.If the current dynamics continue,F.sylvatica will overtake the rest of the species,which will be relegated to sites with shallow soils and steep slopes.Simultaneously,all the multi-centennial beech trees,which are undergoing a rapid mortality and decline process,will disappear.

Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of 65years.According to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 years.In 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

小胶质细胞在卒中中的作用

小胶质细胞在缺血后的炎症反应和受损组织的清除中扮演关键角色,它们对缺血引起的干扰反应迅速,致力于恢复失去的稳态。然而,被修改的环境,包括离子失衡、关键的神经元-小胶质细胞相互作用的中断、去极化传播以及来自坏死神经元的危险信号的产生,诱导了小胶质细胞的形态和表型转变。这导致它们表现为促炎表型并增加吞噬活动。从缺血后的第3天开始,巨噬细胞渗透到坏死组织核心,而小胶质细胞则在病灶周边聚集。此外,炎症促使代谢转向有利于糖酵解、戊糖磷酸途径和脂质合成。这些转变与吞噬脂质的摄入相结合,促进了脂滴生成、合成代谢,并使小胶质细胞增殖。增殖的小胶质细胞释放营养因子,有助于神经保护和修复。然而,一些小胶质细胞持续积累脂质,并转变为功能失调且可能有害的泡沫细胞。研究还表明,有些小胶质细胞要么清除凋亡细胞能力的受损,要么消除突触、活神经元或内皮细胞。然而,阐明被吞噬细胞的生存能力、局部环境特征、组织损伤程度和时间序列将是至关重要的。缺血为小胶质细胞提供了丰富多样的、依赖于区域和损伤的刺激,随着时间演变导致出现不同的小胶质细胞表型,包括表现为促炎性或功能失调特征的细胞,以及显示出促进修复功能的细胞。准确分析小胶质细胞表型,以及更精确地了解相关的缺血后组织条件,是对卒中进行针对性干预的必要步骤。

Exploring multifaceted factors in chronic kidney disease risk: A comprehensive analysis of biochemistry, lifestyle, and inflammation in elderly Chinese individuals

This letter praises a recent article in the World Journal of Clinical Cases(Roles of biochemistry data,lifestyle,and inflammation in identifying abnormal renal function in old Chinese),examining factors affecting abnormal renal function in elderly Chinese using advanced machine learning.It highlights the importance of uric acid,age,hemoglobin,body mass index,sport hours,and systolic blood pressure.The study's holistic approach,integrating lifestyle and inflammation,offers a nuanced understanding of chronic kidney disease risk factors.The letter suggests exploring mechanistic pathways of hyperuricemia,the link between anemia and renal function,and the connection between body mass index and estimated glomerular filtration rate.It advocates investigating physical activity's impact on renal health and the independent effects of blood pressure.The study significantly contributes to chronic kidney disease understanding,proposing avenues for further exploration and interventions.Commendations are extended to the authors and the journal.

Assessing the Performance of a Dynamical Downscaling Simulation Driven by a Bias-Corrected CMIP6 Dataset for Asian Climate

In this study,we aim to assess dynamical downscaling simulations by utilizing a novel bias-corrected global climate model(GCM)data to drive a regional climate model(RCM)over the Asia-western North Pacific region.Three simulations were conducted with a 25-km grid spacing for the period 1980–2014.The first simulation(WRF_ERA5)was driven by the European Centre for Medium-Range Weather Forecasts Reanalysis 5(ERA5)dataset and served as the validation dataset.The original GCM dataset(MPI-ESM1-2-HR model)was used to drive the second simulation(WRF_GCM),while the third simulation(WRF_GCMbc)was driven by the bias-corrected GCM dataset.The bias-corrected GCM data has an ERA5-based mean and interannual variance and long-term trends derived from the ensemble mean of 18 CMIP6 models.Results demonstrate that the WRF_GCMbc significantly reduced the root-mean-square errors(RMSEs)of the climatological mean of downscaled variables,including temperature,precipitation,snow,wind,relative humidity,and planetary boundary layer height by 50%–90%compared to the WRF_GCM.Similarly,the RMSEs of interannual-tointerdecadal variances of downscaled variables were reduced by 30%–60%.Furthermore,the WRF_GCMbc better captured the annual cycle of the monsoon circulation and intraseasonal and day-to-day variabilities.The leading empirical orthogonal function(EOF)shows a monopole precipitation mode in the WRF_GCM.In contrast,the WRF_GCMbc successfully reproduced the observed tri-pole mode of summer precipitation over eastern China.This improvement could be attributed to a better-simulated location of the western North Pacific subtropical high in the WRF_GCMbc after GCM bias correction.

Evolutionary history shapes variation of wood density of tree species across the world

The effect of evolutionary history on wood density variation may play an important role in shaping variation in wood density,but this has largely not been tested.Using a comprehensive global dataset including 27,297 measurements of wood density from 2621 tree species worldwide,we test the hypothesis that the legacy of evolutionary history plays an important role in driving the variation of wood density among tree species.We assessed phylogenetic signal in different taxonomic(e.g.,angiosperms and gymnosperms)and ecological(e.g.,tropical,temperate,and boreal)groups of tree species,explored the biogeographical and phylogenetic patterns of wood density,and quantified the relative importance of current environmental factors(e.g.,climatic and soil variables)and evolutionary history(i.e.,phylogenetic relatedness among species and lineages)in driving global wood density variation.We found that wood density displayed a significant phylogenetic signal.Wood density differed among different biomes and climatic zones,with higher mean values of wood density in relatively drier regions(highest in subtropical desert).Our study revealed that at a global scale,for angiosperms and gymnosperms combined,phylogeny and species(representing the variance explained by taxonomy and not direct explained by long-term evolution process)explained 84.3%and 7.7%of total wood density variation,respectively,whereas current environment explained 2.7%of total wood density variation when phylogeny and species were taken into account.When angiosperms and gymnosperms were considered separately,the three proportions of explained variation are,respectively,84.2%,7.5%and 6.7%for angiosperms,and 45.7%,21.3%and 18.6%for gymnosperms.Our study shows that evolutionary history outpaced current environmental factors in shaping global variation in wood density.

A novel motion tracking system for evaluation of functional rehabilitation of the upper limbs

Upper limb function impairment is one of the most common sequelae of central nervous system in jury, especially in stroke patients and when spinal cord injury produces tetraplegia. Conventional assessment methods cannot provide objective evaluation of patient performance and the effec tiveness of therapies. The most common assessment tools are based on rating scales, which are inefficient when measuring small changes and can yield subjective bias. In this study, we designed an inertial sensorbased monitoring system composed of five sensors to measure and analyze the complex movements of the upper limbs, which are common in activities of daily living. We devel oped a kinematic model with nine degrees of freedom to analyze upper limb and head movements in three dimensions. This system was then validated using a commercial optoelectronic system. These findings suggest that an inertial sensorbased motion tracking system can be used in patients who have upper limb impairment through data integration with a virtual realitybased neurorehabili tation system.

Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer’s disease therapy

There is no effective treatment to face Alzheimer’s disease complexity.Multitarget molecules are a good approach against the multiple physiopathological events associated with its development and progression.In this context,N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine(ASS234)has been tested achieving promising results.ASS234 has demonstrated to cross the blood-brain barrier in vivo,and a good in silico safety profile being less toxic than donepezil.Besides,ASS234 reversibly inhibits human acetyl-and butyryl-cholinesterase,and irreversibly inhibits human monoamine oxidase A and B.Moreover,this multitarget molecule has antioxidant and neuroprotective properties,and inhibitsΑβ1–42 andΑβ1–40 self-aggregation.Inquiring about the mechanism of action,several signaling pathways related to Alzheimer’s disease had been explored showing that ASS234 induces the wingless-type MMTV integration site(Wnt)family and several members of the heat shock proteins family and moreover counteracts neuroinflammatory and oxidative stress-related genes promoting the induction of several key antioxidant genes.Finally,in vivo experiments with ASS234 in C57BL/6J mice displayed its ability to reduce amyloid plaque burden and gliosis in the cortex and hippocampus,ameliorating scopolamine-induced learning deficits.Here we gather the information regarding ASS234 evaluated so far,showing its ability to face different targets,necessary to counteract a neurodegenerative disease as complex as the Alzheimer’s disease.