Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain

A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine （0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion） and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine （receptor internalization/endocytosis）. The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.

Biogenic Amine Neurotransmitter Response to Morphine in the Anterior Cingulate Cortex Predicts Propensity for Acquiring Self-Administration and the Intensity of the Withdrawal Syndrome

Individual differences in behavioral characteristics or initial responses to abused drugs had been recently demonstrated to have predictive value in the propensity of later abuse. The research described here was initiated to determine the initial response of rats to administration of morphine if the physiological response has predictive value for the propensity of the animals to later self-administration. The initial response of extracellular fluid levels of the biogenic monoamine neurotransmitters in the anterior cingulate cortex (aCC) was assessed in drug rats with in vivo microdialysis following administration of morphine. Rats that did not acquire morphine self-administration (NSA) had higher baseline levels of aCC extracellular fluid levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) than animals that developed stable morphine self-administration (SA). However, the response independent administration of morphine resulted in a dramatic increase in (DA) in aCC in the SA group, while the morphine injection in the NSA rats increased extracellular fluid levels of noradrenaline (NA). It is possible that these differences might be related to the development of physical dependence. Therefore, the development of physical dependence was observed in these animals. There was no relationship between the propensity to self-administration morphine and the development of physical dependence. Rats that showed the highest withdrawal scores had lower extracellular fluid levels of serotonin (5-HT) compared to rats showing low withdrawal scores. Thus, monoamine neuronal innervations of the aCC respond to an initial dose of morphine that is predictive of the later propensity to self-administration and the resistance and predisposition to the formation of opiate dependence, but there is no relationship between these two indices in individual animals. These data add to a growing body of evidence for the involvement of neuronal systems in the aCC in the actions of opiates.

Bottom-up holistic carrier management strategy induced synergistically by multiple chemical bonds to minimize energy losses for efficient and stable perovskite solar cells

The defects from electron transport layer,perovskite layer and their interface would result in carrier nonradiative recombination losses.Poor buried interfacial contact is detrimental to charge extraction and device stability.Here,we report a bottom-up holistic carrier management strategy induced synergistically by multiple chemical bonds to minimize bulk and interfacial energy losses for high-performance perovskite photovoltaics.4-trifluoromethyl-benzamidine hydrochloride(TBHCl)containing–CF_(3),amidine cation and Cl^(-)is in advance incorporated into SnO_(2)colloid solution to realize bottom-up modification.The synergistic effect of multiple functional groups and multiple-bond-induced chemical interaction are revealed theoretically and experimentally.F and Cl^(-)can passivate oxygen vacancy and/or undercoordinated Sn^(4+)defects by coordinating with Sn^(4+).The F can suppress cation migration and modulate crystallization via hydrogen bond with FA^(+),and can passivate lead defects by coordinating with Pb^(2+).The–NH_(2)–C=NH^(+)_(2)and Cl^(-)can passivate cation and anion vacancy defects through ionic bonds with perovskites,respectively.Through TBHCl modification,the suppression of agglomeration of SnO_(2)nanoparticles,bulk and interfacial defect passivation,and release of tensile strains of perovskite films are demonstrated,which resulted in a PCE enhancement from 21.28%to 23.40%and improved stability.With post-treatment,the efficiency is further improved to 23.63%.

Integrated top-down and bottom-up proteomics mass spectrometry for the characterization of endogenous ribosomal protein heterogeneity

Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of RNA transcripts,post-translational modifications and alterations of protein expression level,have been linked to a diverse range of diseases,including cancer and aging.Comprehensive characterization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets.In the present work,using E.coli 70S RPs as an example,we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry(MS)system,and then applied it to the HeLa 80S ribosome.The results were complemented by a bottom-up approach.In total,50 out of 55 RPs were identified using the top-down approach.Among these,more than 30 RPs were found to have their N-terminal methionine removed.Additional modifications such as methylation,acetylation,and hydroxylation were also observed,and the modification sites were identified by bottomup MS.In a HeLa 80S ribosomal sample,we identified 98 ribosomal proteoforms,among which multiple truncated 80S ribosomal proteoforms were observed,the type of information which is often overlooked by bottom-up experiments.Although their relevance to diseases is not yet known,the integration of topdown and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.

多维液相色谱 bottom-up top-down 阵列式 完整蛋白质 蛋白质分离

蛋白质组学出现之后,多维高效液相色谱（multidimensional HPLC,MD-HPLC）系统以其快速、高效、自动化程度高以及容易与质谱等其他技术联用等优势而成为蛋白质组学相关分析技术中研究应用的热点。本文主要以本实验室在蛋白质组学研究中的技术进展为主线,介绍了多维高效液相色谱技术的发展,包括经典的“bottom-up”技术和“top-down”式的多维高效液相色谱技术路线,以及为了提高系统的分离通量而自行设计搭建的阵列式多维高效液相色谱平台,这些技术路线在蛋白质组学研究中有着极大的潜在应用价值。

Exploring the Path of Shantytown Renewal Based on the Theory of Environment-behavior Studies: A Case Study of the Northwest Area of Saihantala in Baotou City

The application of environment-behavior studies plays an important role in studying the renewal of shantytowns.One of the most humane ways of renewal is designing and constructing the necessary urban spatial environment from the perspective of human daily behavior.Most of the shantytown renovation projects currently carried out in China are mainly focused on demolition and reconstruction,which not only incurs high costs but also damages the original social structure and economic model.During the process of shantytown renewal,it should improve the urban landscape,living environment,and life quality of residents,and ensure the daily life of shantytown residents without increasing their economic burden,and preserve the traces of urban development.In order to achieve this goal,it should explore the renewal strategies of shantytowns from the perspective of environment-behavior studies through behavior maps,on-site research,and literature review.Updating and design from a human perspective often achieve faster and better development;the renewal of shantytowns should be a bottom-up approach and start from a grassroots perspective,completing the renovation design through the composition of the population and behavioral patterns.

Bottom-Up和Top-Down结合的网络资源规划系统结构研究

为了降低CAPEX和OPEX,运营商需要运营恰到好处的网络规模和Service Ready的服务开通。本文提出了Bottom-Up和Top-Down结合的网络资源规划系统结构,其能够预测未来资源利用率过高或过低及容量不足的网络资源,有利于运营商进行准确的网络资源扩容,从而提升网络建设ROI;能够自动化地实现从业务和市场规划到最终的网络资源规划的转换,从而提高网络资源规划的准确性和效率。

“Bottom-up”培训模式及其对我国中职教师在职培训的启示

"Bottom-up"培训模式来源于中国—欧盟工业职业教育培训项目,其要点是在需求调研前,不带任何培训意向,培训班次、培训课程、培训方式等都是根据学员要求来决定。近年来,中职教师在职培训虽然取得了很好的成效,但在培训目标、培训内容、培训方式、培训师资等方面还存在问题。通过借鉴"Bottom-up"培训模式,我们要明确培训目标,进行需求调研;编排培训内容,突出量身定制;筛选培训方式,重视边做边学;遴选培训师资,了解教学实况。

Freestanding and Flexible Interfacial Layer Enables Bottom-Up Zn Deposition Toward Dendrite-Free Aqueous Zn-Ion Batteries

Aqueous rechargeable zinc ion batteries are regarded as a competitive alternative to lithium-ion batteries because of their distinct advantages of high security,high energy density,low cost,and environmental friendliness.However,deep-seated problems including Zn dendrite and adverse side reactions severely impede the practical application.In this work,we proposed a freestanding Zn-electrolyte interfacial layer composed of multicapsular carbon fibers(MCFs)to regulate the plating/stripping behavior of Zn anodes.The versatile MCFs protective layer can uniformize the electric field and Zn^(2+)flux,meanwhile,reduce the deposition overpotentials,leading to high-quality and rapid Zn deposition kinetics.Furthermore,the bottom-up and uniform deposition of Zn on the Zn-MCFs interface endows long-term and high-capacity plating.Accordingly,the Zn@MCFs symmetric batteries can keep working up to 1500 h with 5 mAh cm^(−2).The feasibility of the MCFs interfacial layer is also convinced in Zn@MCFs||MnO_(2) batteries.Remarkably,the Zn@MCFs||α-MnO_(2)batteries deliver a high specific capacity of 236.1 mAh g^(−1)at 1 A g^(−1)with excellent stability,and maintain an exhilarating energy density of 154.3 Wh kg^(−1) at 33%depth of discharge in pouch batteries.

Bottom-up lithium growth guided by Ag concentration gradient in 3D PVDF framework towards stable lithium metal anode

Three-dimensional(3 D)frameworks have received much attention as an effective modification strategy for next-generation high-energy-density lithium metal batteries.However,the top-growth mode of lithium(Li)on the 3 D framework remains a tough challenge.To achieve a uniform bottom-up Li growth,a scheme involving Ag concentration gradient in 3 D PVDF framework(C-Ag/PVDF)is proposed.Ag nanoparticles with a concentration gradient induce an interface activity gradient in the 3 D framework,and this gradient feature is still maintained during the cycle.As a result,the C-Ag/PVDF framework delivers a long lifespan over 1800 h at a current density of 1 mA cm^(-2) with a capacity of 1 mAh cm^(-2),and shows an ultra-long life(>1300 h)even at a high current density of 4 mA cm^(-2) with a capacity of 4 mAh cm^(-2).The advantage of concentration gradient provides further insights into the optimal design of the 3 D framework for stable Li metal anode.

Bottom-Up Engineering Strategies for High-Performance Thermoelectric Materials

The recent advancements in thermoelectric materials are largely credited to two factors,namely established physical theories and advanced materials engineering methods.The developments in the physical theories have come a long way from the“phonon glass electron crystal”paradigm to the more recent band convergence and nanostructuring,which consequently results in drastic improvement in the thermoelectric figure of merit value.On the other hand,the progresses in materials fabrication methods and processing technologies have enabled the discovery of new physical mechanisms,hence further facilitating the emergence of high-performance thermoelectric materials.In recent years,many comprehensive review articles are focused on various aspects of thermoelectrics ranging from thermoelectric materials,physical mechanisms and materials process techniques in particular with emphasis on solid state reactions.While bottom-up approaches to obtain thermoelectric materials have widely been employed in thermoelectrics,comprehensive reviews on summarizing such methods are still rare.In this review,we will outline a variety of bottom-up strategies for preparing high-performance thermoelectric materials.In addition,state-of-art,challenges and future opportunities in this domain will be commented.

A new model for China’s CO_(2) emission pathway using the top-down and bottom-up approaches

Detailed research on China's CO_(2) emission pathway of the 2030 peak and 2060 carbon neutrality goals is fundamental to promote China's climate change action.Previous studies on emission pathways have been based on long-term emission data or model analyses.However,few studies have achieved synergy and pathway optimization at both the micro and macro levels or focused on China's 2060 carbon neutrality goal,making it difficult to support the systematic management of national and regional emission pathways.In this study,we developed an integrated CO_(2) emission pathway model,the Chinese Academy of Environmental Planning Carbon Pathways 1.2 model,under China's climate change goals.Our pathway coupled the top-down and bottom-up approaches and conducted optimization analysis under social fairness and optimal cost conditions.The results provide a clear CO_(2) emission pathway and offer insights for implementing fine management of CO_(2) emissions at the national,regional,sectoral,and spatial gridded levels.

人工智能研究中的Bottom-up方法和Top-down方法

将人工智能研究在方法上区分为Bottom-up派和Top-down派,并且分别叙述了这两种方法的哲学、历史和成果。主张两种方法走向极端是不可取的,人工智能研究要寻找两种方法的结合点,才可能避免任何一种极端方法所导致的研究复杂性。

top-down法与bottom-up法评定黑臭水体氧化还原电位测量不确定度的比较研究

分别对top-down法与bottom-up法(GUM法)中控制图法评定黑臭水体中氧化还原电位测量不确定度的评定过程及结果进行比较,两种方法评定出来的氧化还原电位不确定度基本一致,提出在质控数据符合正态分布的前提下,从控制图法引入移动极差作为中间量进行叠加检验,可更直观的体现出时间参数对质控数据的测量不确定度的影响。

语法教学中“Top-down”和“Bottom-up”方法的整合——名词性从句教学实例

针对高中英语语法教学中常出现的"只见树木不见森林"的现象,本文结合名词性从句教学课堂实例,探索了在语法教学中整合"Top-down(自上而下)"与"Bottom-up(自下而上)"的方法。四节课的设计遵循高频复现原理,侧重复合句结构,一节课强调一个连接词,配合形式多样的教学手段辅助学生形成复合句的整体概念。无论是操练的正确率还是以诗歌为主体的产出成果均验证了整合两种教学方法的有效性,但同时也反映出部分学生在基本概念上的缺失,为接下来的教学活动的调整提供了参考。

“Top-down” and “Bottom-up” approaches to teaching listening,when and which approach may be more useful?

This paper mainly deals with two mainstreams in teaching listening comprehension:bottom-up processing approach and top-down processing approach.In the first part of the essay the importance of listening comprehension in language learning will be demonstrated briefly.Then the author will go on to explore the nature of top-down and bottom-up approaches in teaching listening.Lastly,at the third part of the essay,the author shall try to discuss the possibility of applying these approaches into practice,that is,when and why one of them is more useful.Furthermore in this section,a more integrated view will be introduced.

The Effectiveness of Top-Down and Bottom-Up Process in Listening Comprehension

Top-down and bottom-up processes are two popularly-used method in teaching listening,but each of them has deficiencies.This essay will attempt to demonstrate that both top-down process and bottom-up process are necessarily useful,and adopting them appropriately conduce to effective and efficient listening comprehension.The first section of this paper will critically examine the advantages and disadvantages of the two processes.It will then illustrate the benefit of employing them in an interactive way.

Bottom-up design and assembly with superatomic building blocks

Constructing specific structures from the bottom up with artificial units is an important interdisciplinary topic involving physics,chemistry,materials,and so on.In this work,we theoretically demonstrated the feasibility of using superatoms as building blocks to assemble a complex at atomic-level precision.By using a series of actinide-based endohedral metallofullerene(EMF)superatoms that can form one,two,three and four chemical bonds,a planar complex with intra-and inter-molecular interactions was assembled on the Au(111)surface.This complex is composed of two parts,containing ten and eight superatoms,respectively.The electronic structure analysis shows that the electron density inside each part is connected and the closed-shell electronic arrangement system is designed.There is also an obvious van der Waals boundary by physical adsorption between the two parts,and a stable complex is formed.Since this complex is realized by the first-principles calculations of quantum mechanics,our results help not only achieve atomic-level precision construction with artificial superatomic units but also maintain atomic-level functional properties.

Bottom-Up Saliency Estimation Based on Redundancy Reduction and Global Contrast

A new algorithm for bottom-up saliency estimation is proposed.Based on the sparse coding model,a power spectral filter is proposed to eliminate the second-order residual correlation,which suppresses the global repeated items effectively.In addition,aiming at modeling the mechanism of the human retina prior response to high-contrast stimuli,the effect of color context is considered.Experiments on the three publicly available databases and some psychophysical images show that the proposed model is comparable with the state-of-the-art saliency models,which not only highlights the salient objects in a complex environment but also pops up them uniformly.

Application of the Bottom-up Method on Risk Evaluation of Climate Change in Water Resources System

Traditional approach to evaluate the impacts of climate change on the water resources systems always begins with downscaling general circulation models( GCMs) and proceeding back to the hydrological model. This approach has some distinct disadvantages: 1) GCM must be downscaled; 2) different GCMs are difficult to be reconciled for a given climate change scenario;3) the uncertainty of GCMs is far from the requirement of the evaluation of climate change impacts. To overcome these limits of the traditional method,a new method termed as "bottom-up"was used for climate risk assessment that linked vulnerability assessment with climate information to assess the risk of climate change impacts on the Quabbin Reservoir,and United States under A2 scenario.The result shows that the risks are around 20% in 2006-2035 and 2036-2055,50% in 2066-2095.