Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

气动升力协同列车升力翼优化设计研究

气动升力协同列车是一种新型高速列车的概念模型,旨在提高运行速度的同时兼顾列车整体耗能与寿命周期成本。其通过加装升力翼,提高列车的气动升力,从而减少列车轮毂磨损。为设计出适合现有高铁限界约束的升力翼,本文采用Hicks-Henne翼型参数化方法和遗传算法,建立了考虑列车外型与高铁限界约束的气动优化方法,并利用此方法开展了翼型优化设计,以优化翼型为基础设计了加装翼梢小翼的三维升力翼模型。研究表明:采用本文优化设计方法得到的优化翼型,相比基础翼型,升力系数提升13%,阻力系数几乎不变。加装翼梢小翼可以有效的减小升力翼的气动阻力,通过对比不同外倾角和后掠角的小翼气动特性,设计出了一种外倾角为15°、后掠角为30°的较优升力翼模型,其最大升力系数可达到1.8247。

Highly Thermally Conductive and Structurally Ultra‑Stable Graphitic Films with Seamless Heterointerfaces for Extreme Thermal Management

Highly thermally conductive graphitic film(GF)materials have become a competitive solution for the thermal management of high-power electronic devices.However,their catastrophic structural failure under extreme alternating thermal/cold shock poses a significant challenge to reliability and safety.Here,we present the first investigation into the structural failure mechanism of GF during cyclic liquid nitrogen shocks(LNS),which reveals a bubbling process characterized by“permeation-diffusion-deformation”phenomenon.To overcome this long-standing structural weakness,a novel metal-nanoarmor strategy is proposed to construct a Cu-modified graphitic film(GF@Cu)with seamless heterointerface.This well-designed interface ensures superior structural stability for GF@Cu after hundreds of LNS cycles from 77 to 300 K.Moreover,GF@Cu maintains high thermal conductivity up to 1088 W m^(−1)K^(−1)with degradation of less than 5%even after 150 LNS cycles,superior to that of pure GF(50%degradation).Our work not only offers an opportunity to improve the robustness of graphitic films by the rational structural design but also facilitates the applications of thermally conductive carbon-based materials for future extreme thermal management in complex aerospace electronics.

Spatial diversion and coordination of flood water for an urban flood control project in Suzhou, China

Suzhou City,located in the Yangtze River Delta in China,is prone to flooding due to a complex combination of natural factors,including its monsoon climate,low elevation,and tidally influenced position,as well as intensive human activities.The Large Encirclement Flood Control Project(LEFCP)was launched to cope with serious floods in the urban area.This project changed the spatiotemporal pattern of flood processes and caused spatial diversion of floods from the urban area to the outskirts of the city.Therefore,this study developed a distributed flood simulation model in order to understand this transition of flood processes.The results revealed that the LEFCP effectively protected the urban areas from floods,but the present scheduling schemes resulted in the spatial diversion of floods to the outskirts of the city.With rainstorm frequencies of 10.0%to 0.5%,the water level differences between two representative water level stations(Miduqiao(MDQ)and Fengqiao(FQ))located inside and outside the LEFCP area,ranged from 0.75 m to 0.24 m and from 1.80 m to 1.58 m,respectively.In addition,the flood safety margin at MDQ and the duration with the water level exceeding the warning water level at FQ ranged from 0.95 m to 0.43 m and from 4 h to 22 h,respectively.Rational scheduling schemes for the hydraulic facilities of the LEFCP in extreme precipitation cases were developed ac-cording to food simulations under seven scheduling scenarios.This helps to regulate the spatial flood diversion caused by the LEFCP during extreme precipitation.

Synergistic effect of Zr and Mo on precipitation and high-temperature properties of Al-Si-Cu-Mg alloys

This study focuses on finding a solution to the sharp decline in mechanical properties of Al-Si-Cu-Mg alloys due to rapid coarsening of traditional intermediate phases at high temperature.A new type of modified al oy,to be used in automobile engines at high temperatures,was prepared by adding Zr and Mo into Al-Si-Cu-Mg alloy.The synergistic effects of Zr and Mo on the microstructure evolution and high-temperature mechanical properties were studied.Results show that the addition of Zr and Mo generates a series of intermetallic phases dispersed in the alloy.They can improve the strength of the alloy by hindering dislocation movement and crack propagation.In addition,some nano-strengthened phases show coherent interfaces with the matrix and improve grain refinement.The addition of Mo greatly improves the heat resistance of the alloy.The extremely low diffusivity of Mo enables it to improve the thermal stability of the intermetallic phases,inhibit precipitation during aging,reduce the size of the precipitates,and improve the heat resistance of the alloy.

MACS-W:A modified optical clearing agent for imaging 3D cell cultures

Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness.While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D,they often have limitations,such as being too harsh for fragile 3D cell cultures,requiring complex handling protocols,or inducing tissue deformation with shrinkage or expansion.To address this issue,we proposed a modified optical clearing method for 3D cell cultures,called MACS-W,which is simple,highly efficient,and morphology-preserving.In our evaluation of MACS-W,we found that it exhibits excellent clearing capability in just 10 min,with minimal deformation,and helps drug evaluation on tumor spheroids.In summary,MACS-W is a fast,minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.

Enhanced reversible hydrogen storage properties of wrinkled graphene microflowers confined LiBH_(4) system with high volumetric hydrogen storage capacity

LiBH_(4)with high hydrogen storage density,is regarded as one of the most promising hydrogen storage materials.Nevertheless,it suffers from high dehydrogenation temperature and poor reversibility for practical use.Nanoconfinement is effective in achieving low dehydrogenation temperature and favorable reversibility.Besides,graphene can serve as supporting materials for LiBH_(4)catalysts and also destabilize LiBH_(4)via interfacial reaction.However,graphene has never been used alone as a frame material for nanoconfining LiBH_(4).In this study,graphene microflowers with large pore volumes were prepared and used as nanoconfinement framework material for LiBH_(4),and the nanoconfinement effect of graphene was revealed.After loading 70 wt%of LiBH_(4) and mechanically compressed at 350 MPa,8.0 wt% of H2 can be released within 100 min at 320C,corresponding to the highest volumetric hydrogen storage density of 94.9 g H2 L^(-1)ever reported.Thanks to the nanoconfinement of graphene,the rate-limiting step of dehydrogenation of nanoconfined LiBH_(4) was changed and its apparent activation energy of the dehydrogenation(107.3 kJ mol^(-1))was 42%lower than that of pure LiBH_(4).Moreover,the formation of the intermediate Li_(2)B_(12)H_(12) was effectively inhibited,and the stable nanoconfined structure enhanced the reversibility of LiBH_(4).This work widens the understanding of graphene's nanoconfinement effect and provides new insights for developing high-density hydrogen storage materials.

Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease:a phaseⅠ/Ⅱclinical trial

Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until now.Growing preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure AD.Aims The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate AD.Methods The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and 48.Results No adverse events were reported.In the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive function.Moreover,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36.There were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some extent.Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.

Flexible Large-Area Graphene Films of 50-600 nm Thickness with High Carrier Mobility

Bulk graphene nanofilms feature fast electronic and phonon transport in combination with strong light-matter interaction and thus have great potential for versatile applications,spanning from photonic,electronic,and optoelectronic devices to charge-stripping and electromagnetic shielding,etc.However,large-area flexible close-stacked graphene nanofilms with a wide thickness range have yet to be reported.Here,we report a polyacrylonitrile-assisted’substrate replacement’strategy to fabricate large-area free-standing graphene oxide/polyacrylonitrile nanofilms(lateral size~20 cm).Linear polyacrylonitrile chains-derived nanochannels promote the escape of gases and enable macro-assembled graphene nanofilms(nMAGs)of 50-600 nm thickness following heat treatment at 3,000℃.The uniform nMAGs exhibit 802-1,540 cm^(2)V-1s-1carrier mobility,4.3-4.7 ps carrier lifetime,and>1,581 W m^(-1)K^(-1)thermal conductivity(n MAG-assembled 10μm-thick films,mMAGs).nMAGs are highly flexible and show no structure damage even after 1.0×10^(5)cycles of folding-unfolding.Furthermore,n MAGs broaden the detection region of graphene/silicon heterojunction from near-infrared to mid-infrared and demonstrate higher absolute electromagnetic interference(EMI)shielding effectiveness than state-of-the-art EMI materials of the same thickness.These results are expected to lead to the broad applications of such bulk nanofilms,especially as micro/nanoelectronic and optoelectronic platforms.

Green‑Solvent Processed Blade‑Coating Organic Solar Cells with an Efficiency Approaching 19%Enabled by Alkyl‑Tailored Acceptors

Power-conversion-efficiencies(PCEs)of organic solar cells(OSCs)in laboratory,normally processed by spin-coating technology with toxic halogenated solvents,have reached over 19%.However,there is usually a marked PCE drop when the bladecoating and/or green-solvents toward large-scale printing are used instead,which hampers the practical development of OSCs.Here,a new series of N-alkyl-tailored small molecule acceptors named YR-SeNF with a same molecular main backbone are developed by combining selenium-fused central-core and naphthalene-fused endgroup.Thanks to the N-alkyl engineering,NIR-absorbing YR-SeNF series show different crystallinity,packing patterns,and miscibility with polymeric donor.The studies exhibit that the molecular packing,crystallinity,and vertical distribution of active layer morphologies are well optimized by introducing newly designed guest acceptor associated with tailored N-alkyl chains,providing the improved charge transfer dynamics and stability for the PM6:L8-BO:YRSeNF-based OSCs.As a result,a record-high PCE approaching 19%is achieved in the blade-coating OSCs fabricated from a greensolvent o-xylene with high-boiling point.Notably,ternary OSCs offer robust operating stability under maximum-power-point tracking and well-keep>80%of the initial PCEs for even over 400 h.Our alkyl-tailored guest acceptor strategy provides a unique approach to develop green-solvent and blade-coating processed high-efficiency and operating stable OSCs,which paves a way for industrial development.

Quantum color image scaling based on bilinear interpolation

As a part of quantum image processing, quantum image scaling is a significant technology for the development of quantum computation. At present, most of the quantum image scaling schemes are based on grayscale images, with relatively little processing for color images. This paper proposes a quantum color image scaling scheme based on bilinear interpolation, which realizes the 2^(n_(1)) × 2^(n_(2)) quantum color image scaling. Firstly, the improved novel quantum representation of color digital images(INCQI) is employed to represent a 2^(n_(1)) × 2^(n_(2)) quantum color image, and the bilinear interpolation method for calculating pixel values of the interpolated image is presented. Then the quantum color image scaling-up and scaling-down circuits are designed by utilizing a series of quantum modules, and the complexity of the circuits is analyzed.Finally, the experimental simulation results of MATLAB based on the classical computer are given. The ultimate results demonstrate that the complexities of the scaling-up and scaling-down schemes are quadratic and linear, respectively, which are much lower than the cubic function and exponential function of other bilinear interpolation schemes.

Maize-soybean relay cropping increases soybean yield synergistically by extending the post-anthesis leaf stay-green period and accelerating grain filling

Relay cropping of Poaceae and Fabaceae promotes high yield and land-use efficiency by allowing a double harvest.However,it is difficult to increase yield synergistically because of the reduced photosynthetic abilities of legume leaves under the shade of graminoids.Leaf photosynthetic capacity in relay cropping systems is associated with ecological niche differentiation and photosynthetic compensation after restoration of normal light.We conducted a field experiment in southwest China in 2020–2021 to evaluate the effects of three cropping patterns:maize–soybean relay cropping(IMS),monoculture maize(MM),and monoculture soybean(SS),and N application levels:no N application(NN:0 kg N ha^(−1)),reduced N(RN:180 kg N ha^(−1)),and conventional N(CN:240 kg N ha^(−1)).Compared to monocropping,relay cropping increased the stay-green traits of maize and soybean by 13%and 89%,respectively.Relay cropping prolonged the leaf stay-green duration in the maize and soybean lag phase by almost 4 and 8 days,respectively.Relay cropping maize(IM)increased the leaf area index(LAI)by 79.4%to 88.5%under NN and 55.5%to 148%under RN.Relay cropping soybean(IS)increased the LAI from 115%to 437%at days 40 to 50 after anthesis.IM increased yield by 65.6%.IS increased yield by 9.7%.HI and system yield were at their highest values under RN.In the relay cropping system,reduced N application extended green leaf duration,increased photosynthesis inside the canopy at multiple levels,ultimately increases soybean yield synergistically.

一种翼型风洞试验数据的不确定度分析方法

对风力机翼型进行气动分析、优化设计以及风洞试验研究等工作,对提高叶片的风能捕获能力、减小叶片的质量和相应的系统载荷具有重要的意义。风洞试验数据分析是试验研究的重要环节,试验数据的不确定度分析对试验结果的可靠性有着重要的影响。风洞试验是一个多环节的复杂过程,如何有效地分析各类误差源的影响对获取真实可靠的风洞试验数据至关重要。本文给出了一种翼型风洞试验数据不确定度的分析方法,运用该方法对OA309标准模型翼型在马赫数0.4,0.8时,风洞试验得到的升力系数,阻力系数,俯仰力矩系数不确定度进行了分析,得到了实验误差范围,通过对结果进行分析发现:压力传感器的准确度对试验结果影响较大。Ma=0.4时,升力系数的不确定度相对自身而言较小,仅为1.4%,阻力系数的不确定度相对自身而言较大,最大为8.1%,俯仰力矩系数的不确定度为6.41%。

载脂蛋白E基因型与阿尔茨海默病锥体外系症状的相关性研究

目的:锥体外系症状(EPS)在阿尔茨海默病(AD)中并不少见。载脂蛋白E(APOE)ε4等位基因是迟发性AD的主要危险因素,既往国外研究有报告其与AD的EPS有关,本研究旨在探讨阿尔茨海默病患者载脂蛋白E基因型与AD是否合并EPS的关系。方法:纳入瑞金医院记忆门诊2012~2022年间130例临床诊断AD患者,男女比例为0.78:1,平均年龄70.51±11.65岁。回顾分析APOE基因型及有无合并锥体外系症状以确定APOE基因型与EPS的关系。结果:所有患者中,26例患者(20.00%)合并有EPS,其中多在AD发病的2年以后出现EPS症状(64.71%)。合并有EPS的患者(n=18)APOE基因型分布:ε3/ε3、ε2/ε3、ε3/ε4、ε2/ε4、ε4/ε4型分别为61.11%、5.56%、22.22%、5.56%、5.56%。调整年龄、性别、基线临床痴呆评级后,携带APOE ε4等位基因的AD患者与EPS合并症状的发生无相关性(OR:0.658,P=0.474)。结论:本研究表明APOE ε4等位基因与AD患者的EPS发生无明显相关性。

A transient model integrating the nanoconfinement effect and pore structure characteristics of oil transport through nanopores

Understanding the integrated transport behavior of oil in shale nanopores is critical to efficient shale oil development. In this paper, based on the time-dependent Poiseuille flow momentum equation, we present a novel transient model to describe oil transport in unsteady and steady states. The model incorporates the effect of the critical shift density, apparent viscosity, slip length, and alkane property, as well as pore tortuosity and surface roughness. We evaluated our model through a comparison with other models, experiments, and molecular dynamics simulations. The results show that the development rates of the volume flows of C_(6)–C_(12) alkane confined in inorganic nanopores and C_(12) alkane confined in organic nanopores were faster than that of the corresponding bulk alkane. In addition, the critical drift density positively promoted the volume flow development rate in the unsteady state and negatively inhibited the mass flow rate in the steady state. This effect was clearest in pores with a smaller radius and lower-energy wall and in alkane with shorter chain lengths. Furthermore, both the nanoconfinement effect and pore structure determined whether the volume flow enhancement rate was greater than or less than 1. The rate increased or decreased with time and was controlled mainly by the nanoconfinement effect. Moreover, as the wall energy increased, the flow inhibition effect increased;as the carbon number of alkane increased, the flow promotion effect increased. The results indicate that the proposed model can accurately describe oil transport in shale nanopores.

Experimental investigation of dynamic stall flow control using a microsecond-pulsed plasma actuator

To alleviate the performance deterioration caused by dynamic stall of a wind turbine airfoil,the flow control by a microsecond-pulsed dielectric barrier discharge(MP-DBD) actuator on the dynamic stall of a periodically pitching NACA0012 airfoil was investigated experimentally.Unsteady pressure measurements with high temporal accuracy were employed in this study,and the unsteady characteristics of the boundary layer were investigated by wavelet packet analysis and the moving root mean square method based on the acquired pressure.The experimental Mach number was 0.2,and the chord-based Reynolds number was 870 000.The dimensionless actuation frequencies F+ were chosen to be 0.5,1,2,and 3,respectively.For the light dynamic regime,the MP-DBD plasma actuator plays the role of suppressing flow separation from the trial edge and accelerating the flow reattachment due to the high-momentum freestream flow being entrained into the boundary layer.Meanwhile,actuation effects were promoted with the increasing dimensionless actuation frequency F+.The control effects of the deep dynamic stall were to delay the onset and reduce the strength of the dynamic stall vortex due to the accumulating vorticity near the leading edge being removed by the induced coherent vortex structures.The laminar fluctuation and Kelvin-Helmholtz(K-H) instabilities of transition and relaminarization were also mitigated by the MP-DBD actuation,and the alleviated K-H rolls led to the delay of the transition onset and earlier laminar reattachment,which improved the hysteresis effect of the dynamic stall.For the controlled cases of F+=2,and F+=3,the laminar fluctuation was replaced by relatively low frequency band disturbances corresponding to the harmonic responses of the MP-DBD actuation frequency.

Promoting CO_(2) and H_(2)O activation on O-vacancy regulated In-Ti dual-sites for enhanced CH_(4) photo-production

Engineering the specific active sites of photocatalysts for simultaneously promoting CO_(2)and H_(2)O activation is important to achieve the efficient conversion of CO_(2)to hydrocarbon with H_(2)O as a proton source under sunlight.Herein,we delicately design the In/TiO_(2)-VOphotocatalyst by engineering In single atoms(SAs)and oxygen vacancies(VOs)on porous TiO_(2).The relation between structure and performance of the photocatalyst is clarified by both experimental and theoretical analyses at the atomic levels.The In/TiO_(2)-VOphotocatalyst furnish a high CH_(4)production rate up to 35.49μmol g^(-1)h^(-1)with a high selectivity of 91.3%under simulated sunlight,while only CO is sluggishly generated on TiO_(2)-VO.The combination of in situ spectroscopic analyses with theoretical calculations reveal that the VOsites accelerate H_(2)O dissociation and increase proton feeding for CO_(2)reduction.Furthermore,the VOregulated In-Ti dual sites enable the formation of a stable adsorption conformation of In-C-O-Ti intermediate,which is responsible for the highly selective reduction of CO_(2)to CH_(4).This work demonstrates a new strategy for the development of effective photocatalysts by coupling metal SA sites with the adjacent metal sites of support to synergistically enhance the activity and selectivity of CO_(2)photoreduction.

Combined effect of subsurface dam and layered heterogeneity on groundwater flow and salinity distribution in stratified coastal aquifers

In this paper,for the first time,we investigated the combined effect of subsurface dams and a typical stratified aquifer(two high-permeability layers with a low-permeability layer between them)on groundwater flow and salinity distribution in a tidally influenced coastal unconfined aquifer.Subsurface dams can inhibit the invasion of saltwater,and the low-permeability layer(LPL)and tide action can increase the effect of subsurface dams and the removal rate of residual saltwater.Through sensitivity analysis,it was discovered that shifting the dam location towards the inland resulted in a reduction in the effective heights of the dam.The upper saline plume contracted with increasing dam height,and the upper boundary of LPL was moved to shallower regions.And the natural removal time increased significantly with increasing dam height and the bottom boundary of LPL was moved to deeper regions.In addition,if the dam location was close to the sea boundary and the bottom boundary of LPL was moved to deeper regions,we could increase the subsurface dam height to reduce the risks of control of saltwater intrusion.This study provides us a comprehensive understanding of the complex hydrodynamics of saltwater intrusion and provides guides for the design of subsurface dams aimed at saltwater intrusion control in stratified coastal aquifers.

Correction:Monodomain Liquid Crystals of Two‑Dimensional Sheets by Boundary‑Free Sheargraphy

In this article Florian Puchtler at affiliation‘University of Bayreuth’,Josef Breu at affiliation‘University of Bayreuth’,and Ziliang Wu at affiliation‘Zhejiang University’was missing from the author Min Cao,Senping Liu,Qingli Zhu,Ya Wang,Jingyu Ma,Zeshen Li,Dan Chang,Enhui Zhu,Xin Ming,Florian Puchtler,Josef Breu,Ziliang Wu,Yingjun Liu,Yanqiu Jiang,Zhen Xu,Chao Gao list.

Turbulent boundary layer control with DBD plasma actuators

The flat-plate turbulent boundary layer at Reτ=1140 is manipulated using a spanwise array of bidirectional dielectric barrier discharge(DBD)plasma actuators.Based on the features of no moving mechanical parts in the DBD plasma control technology and hot-wire anemometer velocity measurements,a novel convenient method of local drag reduction(DR)measurement is proposed by measuring the single-point velocity within the linear region of the viscous sublayer.We analyze the premise of using the method,and the maximum effective measurement range of-73.1%<DR<42.2%is obtained according to the experimental environment in this work.The local drag decreases downstream of the center of two adjacent upper electrodes and increases downstream of the upper electrodes.The magnitude of the local DR increases with increasing voltage and decreases as it moves away from the actuators.For the spanwise position in between,the streamwise distribution of the local DR is very dependent on the voltage.The variable-interval time-average detection results reveal that all bursting intensities are reduced compared to the baseline,and the amount of reduction is comparable to the absolute values of the local DR.Compared with previous results,we infer that the control mechanism is that many meandering streaks are combined together into single stabilized streaks.