Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

大数据如何影响劳动收入份额?——来自国家级大数据综合试验区的证据

推动劳动收入份额的增长是实现共同富裕的重要保障。文章立足于数据已经成为中国经济发展最重要的生产要素之一这一基本事实,以大数据作为研究切入,基于2011—2020年中国A股上市公司数据,利用国家级大数据综合试验区建立这一外生事件,采用多期双重差分方法系统考察了大数据与劳动收入份额的关系。研究结果显示,大数据能够显著提升企业劳动收入份额,且在经过平行趋势检验、安慰剂检验等一系列稳健性检验后,该结论依然成立。机制分析表明,大数据可以通过直接效应和间接效应影响企业劳动收入份额。其中,直接效应表现为新任务创造和自动化扩张效应,且新任务创造效应有助于企业劳动收入份额的增加,而自动化扩张效应会导致企业劳动收入份额降低。间接效应表现为自动化加深和融资约束缓解效应,且两种间接效应均能有效提升企业劳动收入份额。进一步分析发现,大数据的劳动收入份额提升效应仅存在于东部地区和高市场化水平地区的企业、资本密集型企业、非国有企业以及小规模企业。此外,大数据主要通过缓解企业间的工资收入差距,而非企业内部的工资收入差距来改善劳动收入内部分配结构。文章的研究有助于理解数据要素如何改变要素收入分配结构,为政府部门强化大数据在改善收入差距的作用提供了决策参考。

Investigation of Resonator BWO-Based Spectroscopy of the Atmosphere in the THz Region

This paper intends to give a code about atmospheric propagation effects affecting terahertz (THz) communication system. The main focus is on attenuation caused by atmospheric gases with the radiation transmission theory and the empirical continuum absorption based on the HITRAN database. Theoretical aspects about them are presented, emphasizing on those which deserve special attention as frequency increases. Laboratory measurements of the absorption spectra of laboratory air and major atmospheric gases mixed with water vapor in the 250 - 350 GHz frequency range at atmospheric pressure and room temperature on a basis of backward wave oscillators (BWOs) are obtained. The results of experiments are compared with the calculations. It is found that the water vapor transmittance is greater than the calculation. Data of these measurements agree with the results of analysis of atmospheric spectra with in statistical accuracy of experiments. Accurate measurements are also needed for further studies of the physics of the molecules and their interactions. The investigation makes it significant for enhancing accuracy of models of radiation propagation in the atmosphere.

调节性B细胞在乳腺癌免疫微环境中的生物学作用

乳腺癌是全世界范围内女性首位恶性肿瘤,虽然手术、放化疗、靶向治疗、内分泌治疗很大程度提高了肿瘤患者的生存,但有一部分病人仍然预后不佳。免疫微环境在乳腺癌的发生、发展、逃避免疫应答中发挥重要作用。调节性B细胞(Breg)是近年来报道的一类具有免疫抑制功能、维持免疫耐受的B细胞新亚群,其通过表面信号分子及分泌细胞因子抑制免疫应答,协助肿瘤免疫逃逸。目前,调节性B细胞在肿瘤免疫微环境中的作用成为肿瘤免疫研究的新热点,其可能成为未来乳腺癌免疫治疗又一新兴靶点。

Effect of continuous annealing temperature on microstructure and properties of ferritic rolled interstitial-free steel

In this report,the microstructure,mechanical properties,and textures of warm rolled interstitial-free steel annealed at four different temperatures(730,760,790,and 820°C)were studied.The overall structural features of specimens were investigated by optical microscopy,and the textures were measured by X-ray diffraction(XRD).Nano-sized precipitates were then observed by a transmission electron microscope(TEM)on carbon extraction replicas.According to the results,with increased annealing temperatures,the ferrite grains grew;in addition,the sizes of Ti_4C_2S_2 and Ti C precipitates also increased.Additionally,the sizes of Ti N and Ti S precipitates slightly changed.When the annealing temperature increased from 730 to 820°C,the yield strength(YS)and the ultimate tensile strength(UTS)showed a decreasing trend.Meanwhile,elongation and the strain harden exponent(n value)increased to 49.6%and 0.34,respectively.By comparing textures annealed at different temperatures,the intensity of{111}texture annealed at 820°C was the largest,while the difference between the intensity of{111}<110>and{111}<112>was the smallest when the annealing temperature was 820°C.Therefore,the plastic strain ratio(r value)annealed at 820°C was the highest.

Structural, mechanical, and electronic properties of 25 kinds of Ⅲ–Ⅴbinary monolayers: A computational study with first-principles calculation

Using first-principle calculations,we investigate the mechanical,structural,and electronic properties and formation energy of 25 kinds ofⅢ-Ⅴ binary monolayers in detail.A relative radius of the binary compound according to the atomic number in the periodic table is defined,and based on the definition,the 25 kinds ofⅢ-Ⅴ binary compounds are exactly located at a symmetric position in a symmetric matrix.The mechanical properties and band gaps are found to be very dependent on relative radius,while the effective mass of holes and electrons are found to be less dependent.A linear function between Young’s modulus and formation energy is fitted with a linear relation in this paper.The change regularity of physical properties of B-Ⅴ(Ⅴ=P,As,Sb,Bi)andⅢ-N(Ⅲ=Al,Ga,In,Tl)are found to be very different from those of otherⅢ-Ⅴ binary compounds.

抗撞结构桩基承载能力的撞击头部设计方法

为从动态冲击试验中获取毁灭性碰撞时准确的特征参数,考虑动态冲击试验中台车撞击头对试验结果的影响,参考反求凸轮轮廓的设计思想,提出了根据立柱倒伏的路径反求撞击头轮廓的设计方法。此外,成功将台车撞击埋入硬黏土中的单柱有限元仿真模型校准为台车动态冲击试验,并利用校准后的有限元仿真模型对反求出的撞击头轮廓进行仿真分析,验证了反求出的撞击头能够反映桩基真实的承载能力。

Characteristics of Leakage Pollution of Longpan Road Gas Station and Its Enlightenment

Geological penetrating radar combined with drilling and chemical analysis has been applied to investigate leakage pollution of Longpan Road gas station in Nanjing, China. The results indicate that radar images show strong reflection anomalies along the northeast to the gas station, characterized by contaminants or contaminant plumes spreading downstream and below. The drilling results confirmed the contents of monocyclic and polycyclic aromatic hydrocarbons contained in the layers of fine sands ranging from 0.60 m to 6.0 m beneath the surface mostly exceed Chinese standard severely, such as toluene and isobutylbenzene with high content at 2738 μg/kg and 64505 μg/kg, respectively. Therefore, it is considered that geological penetrating radar can be employed to investigate leakage contamination of gas stations, and remediation and administration should be conducted in the polluted soil layers and aquifers.

A method for estimating the fresh water-salt water interface with hydraulic heads in a coastal aquifer and its application

Examining the descriptions of piezometric heads at two points in both the salt water and fresh water zones reveals that when the groundwater flow system is in steady state and satisfies the Dupuit assumption, the location of the fresh water-salt water interface in a homogeneous, isotropic, and unconfined coastal aquifer can be estimated based on a piezometric head of fresh water at a point in the fresh water zone （from the water table to the interface） vertically lined up with a piezometric head of salt water at a point in the salt water zone （from the interface down）. Research shows that the new method is a general relation and that both the Hubbert relation describing the location of the interface and the Ghy- ben--Herzberg relation are special cases of this method. The method requires two piezometric wells to be close to each other and each tapping into a different zone. Measurements of piezometric heads at a well cluster consisting of piezometric wells tapping separately into fresh water and salt water zones near Beihai, China at 5-day intervals for 15 months are used to illustrate the estimation of interface location. The depth of the interface for well H5 ranges from 32 to 72 m below the sea level.

Mechanism of Tingli Dazao Xiefei Decoction in the Treatment of COPD Based on Network Pharmacology and Molecular Docking Technology

[Objectives]The action mechanism of Tingli Dazao Xiefei Decoction in the treatment of COPD was explored by the network pharmacology and molecular docking technology.[Methods]The TCMSP database was used to perform active ingredient screening and target prediction on Chinese medicines contained in Tingli Dazao Xiefei Decoction,and COPD-related targets were searched through disease databases.Common targets of Tingli Dazao Xiefei Decoction and COPD were imported into Metascape database for GO analysis and KEGG pathway enrichment analysis.The STRING database was used to perform PPI analysis on common targets,and core targets were screened through the Cytoscape software.The Pymol,AutoDockTools,Vina and other software were used for molecular docking of some core targets and ingredients.[Results]From Tingli Dazao Xiefei Decoction,26 active ingredients which shared 211 common targets and 22 core targets with COPD,were screened out.Enrichment analysis revealed a total of 1892 biological processes,78 cell components,152 molecular functions,and 164 signal paths.The molecular docking of part of the core targets and corresponding ingredients obtained better results.[Conclusions]Tingli Dazao Xiefei Decoction treats COPD through multiple targets and multiple pathways,revealing its mechanism for treating COPD.

Differential expression profile of circular RNAs in mouse peritoneum with peritoneal fibrosis and the potential regulatory role of novel_circ_0007527

CircRNAs,a novel type of endogenous non-coding RNAs(ncRNAs),are typically produced by back-splicing from exons of protein-coding genes,which are characterized by a covalently closed structure with neither 5'to 3'polarity nor a poly(A)tail.'On the one hand,circRNAs are involved in the regulation of a variety of important biological processes,such as apoptosis,proliferation,migration,and inflammatory responses.'On the other hand,the relationship between circRNAs and several fibrotic diseases has been reported.2 However.

The genomes of medicinal skullcaps reveal the polyphyletic origins of clerodane diterpene biosynthesis in the family Lamiaceae

The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata,although the molecular mechanisms behind clerodane biosynthesis are unknown.Here,we report a high-quality assembly of the 414.98 Mb genome of S.barbata into 13 pseudochromosomes.Using phylogenomic and biochemical data,we mapped the plastidial metabolism of kaurene(gibberellins),abietane,and clerodane diterpenes in three species of the family Lamiaceae(Scutellaria barbata,Scutellaria baicalensis,and Salvia splendens),facilitating the identification of genes involved in the biosynthesis of the clerodanes,kolavenol,and isokolavenol.We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism.Despite the assumed monophyletic origin of clerodane biosynthesis,which is widespread in species of the Lamiaceae,our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae.Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family,Lamiaceae,but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.

Performance Comparison of Computational Methods for the Prediction of the Function and Pathogenicity of Non-coding Variants

Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects.Hence,an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences.However,it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods.To solve this issue,we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets:(1)rare germline variants from clinical relevant sequence variants(ClinVar),(2)rare somatic variants from Catalogue Of Somatic Mutations In Cancer(COSMIC),(3)common regulatory variants from curated expression quantitative trait locus(eQTL)data,and(4)disease-associated common variants from curated genomewide association studies(GWAS).All 24 tested methods performed differently under various conditions,indicating varying strengths and weaknesses under different scenarios.Importantly,the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve(AUROC)of 0.4481–0.8033 and poor for rare somatic variants from COSMIC(AUROC=0.4984–0.7131),common regulatory variants from curated eQTL data(AUROC=0.4837–0.6472),and disease-associated common variants from curated GWAS(AUROC=0.4766–0.5188).We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder,and found that the combined annotation-dependent depletion(CADD)and context-dependent tolerance score(CDTS)methods showed better performance.Summarily,we assessed the performance of 24 computational methods under diverse scenarios,providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants.

Molecular identification of Sporothrix clinical isolates in China

研究目的:明确中国地区孢子丝菌病的致病菌种。创新要点:构建中国地区临床孢子丝菌系统进化树,用分子生物学方法对致病菌种进行重新鉴定。研究方法:多基因测序和系统发育分析。重要结论:球形孢子丝菌可能为中国地区孢子丝菌病的主要病原菌,申克孢子丝菌在中国地区是否存在尚需进一步验证。

Thermodynamic and economic analyses of a coal and biomass indirect coupling power generation system

The coal and biomass coupling power genera-tion technology is considered as a promising technology for energy conservation and emission reduction.In this paper,a novel coal and biomass indirect coupling system is proposed based on the technology of biomass gasification and co-combustion of coal and gasification gas.For the sake of comparison,a coal and biomass direct coupling system is also introduced based on the technology of co-combustion of coal and biomass.The process of the direct and the indirect coupling system is simulated.The thermodynamic and economic performances of two systems are analyzed and compared.The simulation indicates that the thermodynamic performance of the indirect coupling system is slightly worse,but the economic performance is better than that of the direct coupling system.When the blending ratio of biomass is 20%,the energy and exergy fficiencies of the indirect coupling system are 42.70%and 41.14%,the intemal rate of returm(IRR)and discounted payback period(DPP)of the system are 25.68%and 8.56 years.The price fluctuation of fuels and products has a great influence on the economic performance of the indirect coupling system.The environmental impact analysis indicates that the indirect coupling system can inhibit the propagation of NOx and reduce the environmental cost.

Terahertz synthetic aperture in-line holography with intensity correction and sparsity autofocusing reconstruction

We demonstrate high-resolution and high-quality terahertz(THz)in-line digital holography based on the synthetic aperture method.The setup is built on a self-developed THz quantum cascade laser,and a lateral resolution better than 70μm(~λ)is achieved at 4.3 THz.To correct intensity differences between sub-holograms before aperture stitching,a practical algorithm with global optimization is proposed.To address the twin-image problem for in-line holography,a sparsity-based phase retrieval algorithm is applied to perform the high-quality reconstruction.Furthermore,a new autofocusing criterion termed"reconstruction objective function"is introduced to obtain the best in-focus reconstruction distance,so the autofocusing procedure and the reconstruction are unified within the same framework.Both simulation and experiment prove its accuracy and robustness.Note that all the methods proposed here can be applied to other wavebands as well.We demonstrate the success of this THz synthetic aperture in-line holography on biological and semiconductor samples,showing its potential applications in bioimaging and materials analysis.

A MULTIVARIATE MULTIQUADRIC QUASI-INTERPOLATION WITH QUADRIC REPRODUCTION

In this paper, by using multivariate divided differences to approximate the partial derivative and superposition, we extend the multivariate quasi-interpolation scheme based on dimension-splitting technique which can reproduce linear polynomials to the scheme quadric polynomials. Furthermore, we give the approximation error of the modified scheme. Our multivariate multiquadric quasi-interpolation scheme only requires information of lo- cation points but not that of the derivatives of approximated function. Finally, numerical experiments demonstrate that the approximation rate of our scheme is significantly im- proved which is consistent with the theoretical results.

Texture development and properties of Ti-IF steels produced by different hot-rolling processes

Texture is a pivotal factor for the deep drawability of interstitial free steel (IF steel). The evolution of microstructure and recrystallization texture of Ti-IF steel through the processing of hot rolling, cold rolling and annealing have been studied. The mechanical properties including strain hardening index n and plastic strain ratio r are also measured. For comparison, ferrite rolling and austenite rolling are both studied. The results show that the intensity of γ-fiber after ferrite rolling is higher than that after austenite rolling. The great balance between the {111}〈110〉 and {111}〈112〉 leads to low △r value after annealing. The size of precipitates in ferrite rolled sample is generally larger than that in austenite rolled sample. Compared to austenite rolled sample, the ferrite rolled and annealed one has better formability and its r value reaches 2.36. Different from laboratory production, the test steels were acquired from industrial trial, and all the result can be used in industrial production directly.

Influences of flexible defect on the interplay of supercoiling and knotting of circular DNA

Knots are discovered in biophysical systems,such as DNA and proteins.Knotted portions in knotted DNA are significantly bent and their corresponding bending angles are comparable with or larger than the sharp bending angle resulting in flexible defects.The role of flexible defects in the interplay of supercoiling and knotting of circular DNA were predicted by a Monte Carlo simulation.In knotted DNA with a particular knot type,a flexible defect noticeably enhances the supercoiling of the knotted DNA and the decreasing excitation energy makes the knotted portion more compact.A reduction in twist rigidity and unwinding of flexible defects are incorporated into the numerical simulations,so that interplay of supercoiling and knotting of circular DNA is studied under torsional conditions.Increasing unwinding not only results in a wider linking number distribution,but also leads to a drift of the distribution to lower values.A flexible defect has obvious effects on knotting probability.The summation of equilibrium distribution probability for nontrivial knotted DNA with different contour length does not change with excitation energy monotonically and has a maximum at an intermediate value of excitation energy around 5 kBT.In the phase space of knot length and gyration radius of knotted DNA,knot length does not anticorrelate with its gyration radius,which is attributed to the flexible defect in the knotted portion,which leads to the release of bending energy and inhibited the competition between entropy and bending energy.

中国球形孢子丝菌双相cDNA消减文库构建及其差异基因的筛选和验证(英文)

目的:为进一步研究中国球形孢子丝菌的双向转换机制,明确目的差异基因对我国球形孢子丝菌形态和双相转换的影响,探讨可能参与的信号传导通路,以期较全面地探讨孢子丝菌双相转换相关的分子机制,也为筛选抗真菌药物研究提供新的靶位和切入点。创新点:以中国球形孢子丝菌双向转换为立足点,应用抑制性消减文库成功构建的高特异性的中国球形孢子丝菌酵母相(Y)和菌丝相(M)的正反cDNA基础上,对中国球形孢子丝菌双相转换相关基因进行生物信息学分析并对部分有意义的差异表达基因进行验证。方法:本实验通过抑制性消减杂交技术构建中国球形孢子丝菌酵母相和菌丝相的正反cDNA消减文库,并对差异基因进行生物信息学分析,获得部分有意义的差异表达基因,再通过实时荧光聚合酶链反应(PCR)技术验证目的基因在双相中的差异表达。结论:通过抑制性消减杂交技术对中国球形孢子丝菌的正向和反向两个文库进行筛选,获得可能参与球形孢子丝菌细胞壁合成、信号转到、新陈代谢类等相关的片段重叠群(contigs),结果表明中国球形孢子丝菌在双相型转换中存在明显表达差异基因,同时利用相对定量的实时荧光定量技术对其中两个基因(细胞表面分子类基因细胞周期检测点激酶CHK和结构基因类核糖体RNA基因)进行验证,认为它们可能与双相转换有关。