Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Graph-based structural joint pose estimation in non-line-of-sight conditions

In post-earthquake surveys,it is difficult(and often infeasible)to observe and quantify displacements beyond line-of-sight(LOS),given seismic force-resisting and gravity systems exist completely or partially within a building′s enclosure.To overcome this limitation,we develop a novel framework that generalizes graph-based state estimation towards structural joint localization via engineered landmarks.These landmarks provide an indirect means to estimate residual displacements where direct LOS is unavailable.Within our framework,engineered landmarks define topologies of uniquely identifiable landmarks that are either visible or non-visible to a robot performing simultaneous localization and mapping(SLAM).Within the SLAM approach,factors encoding robot odometry and robot-to-visible landmark measurements are formulated for the cases of wireless sensing and fiducial object detection and tracking.Visible landmarks are rigidly attached to non-visible landmark subsets for each engineered landmark,where the complete set of non-visible landmarks form globally rigid and localizable connectivity graphs via range-based factors.Complimentary subsets of non-visible landmarks are embedded within the base structure and uniquely define joint pose via geometric factors.All factors are unified within a common graph to solve for the maximum a posteriori estimate of robot,landmark,and joint states via nonlinear least squares optimization.To demonstrate the applicability of our approach,we apply the Monte Carlo method over a parameterization of system noise to calculate residual joint pose error distributions,maximum average inter-story drift ratios,and related summary statistics for a 19-story nonlinear structural model.By performing nonlinear time history analyses over sets of service-level and maximum considered earthquakes,our parametric study gives insight into our method′s application towards post-earthquake building evaluation in non-LOS conditions.

聚缩醛树脂义齿修复KennedyⅡ类牙列缺损的生物力学研究

目的利用光弹模型研究聚缩醛树脂义齿(隐形义齿)修复KennedyⅡ类牙列缺损的生物力学。方法建立下颌KennedyⅡ类牙列缺损((?)缺失)光弹模型,分别设计和制作聚缩醛树脂全隐形义齿、混合型隐形义齿和传统的金属支架可摘局部义齿。模拟双侧及单侧后牙加载,观察加载时三种义齿设计基牙和缺牙区牙槽嵴的载荷光弹图像,分别记录应力分布情况并加以分析和比较。结果三种义齿设计光弹模型应力分布分析显示,在单侧和双侧加载时,全隐形义齿基牙和缺牙区牙槽嵴承受压力最大,传统的金属支架可摘局部义齿(金属支架设计)承受压力沿基牙牙体长轴传导,基牙和剩余牙槽嵴承受压力最小且分布最均匀。结论对于KennedyⅡ类牙列缺损,全隐形义齿修复对基牙和剩余牙槽嵴损伤较大;而传统的金属支架可摘局部义齿使支持组织受力均匀、合理,应作为设计的首选。

血管组织工程的发展现状和趋势

心脑血管疾病是全球发病率和死亡率最高的疾病,其主要病因是动脉粥样硬化。临床上主要采用血管移植物重建病损血管,人造合成血管在大口径血管修复中取得了满意的效果,但在小口径血管修复中效果并不理想。近30年来,血管组织工程发展极其迅速,从再生的角度为血管修复提供了新的途径。本文综述血管组织工程的最新进展(体外、体内、原位血管组织工程),并对未来发展趋势进行了前瞻性展望。

Impact of social isolation on behavioral health in elderly: Systematic review

AIM: To examine and compare the effects of subjective and objective social isolation on behavioral health in elderly adults.METHODS: A systematic search of Pub Med was performed for original research articles from peerreviewed journals examining one of the following topics: "Social isolation and sleep disturbance", "social isolation and depression", or "social isolation and fatigue in older adults". Studies were selected following the criteria established based on the aim of this review. Data were extracted from the articles by two independent reviewers. Due to the heterogeneity in study designs and outcome measures of the included studies, qualitative and narrative analyses were conducted.RESULTS: The set criteria were used to select a total of 16 studies for the review. Of the 16, 13 were crosssectional studies. The characteristics of study populations were identified as follows. A total of 12 studies randomly selected subjects irrespective of pre-existing health conditions. Consequently, an unspecified number of the study subjects had chronic diseases in the studies compared. In addition, cultural and ethnic backgrounds of studies in this review were diverse, and included subjects living in North America, South America, Asia, Europe, and Oceania. Both subjective and objective types of social isolation increased behavioral symptoms, such as sleep disturbance, depressive symptoms, and fatigue in older adults. Furthermore, a few recent studies reported stronger effects of subjective social isolation than objective social isolation on sleep disturbance and depressive symptoms.CONCLUSION: Social isolation affects behavioral health in older adults. Compared to the objective social isolation, subjective social isolation contributes more significantly to sleep disturbance and depression.

DNA微阵列技术探讨多形性胶质母细胞瘤基因表达与肿瘤强化间的相关性

目的研究完全与不完全强化的多形性胶质母细胞瘤(GBM)基因表达的差异。

Engineered hydrogels for brain tumor culture and therapy

Brain tumors’severity ranges from benign to highly aggressive and invasive.Bioengineering tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral treatments.Here,we first describe the physiology and cellular composition of brain tumors.Then,we discuss the development of threedimensional tissue models utilizing brain tumor cells.In particular,we highlight the role of hydrogels in providing a biomimetic support for the cells to grow into defined structures.Microscale technologies,such as electrospinning and bioprinting,and advanced cellular models aim to mimic the extracellular matrix and natural cellular localization in engineered tumor tissues.Lastly,we review current applications and prospects of hydrogels for therapeutic purposes,such as drug delivery and co-administration with other therapies.Through further development,hydrogels can serve as a reliable option for in vitro modeling and treatment of brain tumors for translational medicine.

Coronary Calcium Scoring in 2017

Coronary artery calcifi cation(CAC)is as an independent risk predictor of cardiovascular disease and can classify an individual’s risk of atherosclerotic cardiovascular disease,particularly in intermediate-risk individuals.Also,CAC progression is associated with greater rates of cardiovascular events.This article provides available data and expert recommendations for CAC based on current publications.We focus on the utility of CAC for stratifi cation of individuals and describe its diagnostic value in identifying patients at risk.We also describe the important ability of CAC to derisk a patient with a score of zero.

Preliminary performance analysis and optimization based on 1D neutronics model for Indian DEMO HCCB blanket

India,under its breeding blanket R&D program for DEMO,is focusing on the development of two tritium breeding blanket concepts;namely the lead-lithium-cooled ceramic breeder and the helium-cooled ceramic breeder(HCCB).The study presented in this paper focuses on the neutronic design analysis and optimization from the tritium breeding perspective of the HCCB blanket.The Indian concept has an edge-on configuration and is one of the variants of the helium-cooled solid breeder blanket concepts proposed by several partner countries in ITER.The Indian HCCB blanket having lithium titanate(Li2TiO3)as the tritium breeder and beryllium(Be)as the neutron multiplier with reduced-activation ferritic/martensitic steel structure aims at utilizing the low-energy neutrons at the rear part of the blanket.The aim of the optimization study is to minimize the radial blanket thickness while ensuring tritium self-sufficiency and provide data for further neutronic design and thermal-hydraulic layout of the HCCB blanket.It is found that inboard and outboard blanket thicknesses of 40 cm and 60 cm,respectively,can give a tritium breeding ratio(TBR)>1.3,with 60%6Li enrichment,which is assumed to be sufficient to cover potential tritium losses and associated uncertainties.The results also demonstrated that the Be packing fraction(PF)has a more profound impact on the TBR as compared to 6Li enrichment and the PF of Li2TiO3.

Ultrasonographic visualization of lower eyelid structures and dynamic motion analysis

AIM:To define the ultrasonographic structure of normal lower eyelid anatomic compartments and their spacial relationship in dynamic motion.METHODS:High resolution ultrasound(15MHz) was performed on the lower eyelids of 7 normal subjects.Movements of the lower eyelid and its compartments were visualized with ultrasound.In addition,the maximal excursion area of the lower eyelid fat compartments and retractor motions was measured before and after motion.RESULTS:The orbicularis muscle could be seen as an echolucent structure between the dermis and the echodence fat pads.Lower eyelid fat pad seems to be divided into 2 compartments as range of motion and direction of movement of each of them varies.It seems that these compartments have also different behavior.The measured profile area of the visible normal lower eyelid fat pads during movement of globe from up-gaze to down-gaze decreased by 50%.Order of movement of lower eyelid structures seems to be as follows:after globe movement fist we see retractor movement,anterior orbital fat pad,then skin and septum,and finally movement of inferior fat pad.CONCLUSION:Ultrasound represents a noninvasive tool for the visualization of lower eyelid morphology.Expanding its application could help us understand the compartmental changes in physiological eyelid movement,in aging and diseased study populations,as well as assess operative outcomes.

Stem cell treatments for oropharyngeal dysphagia:Rationale,benefits,and challenges

Dysphagia,defined as difficulty swallowing,is a common symptom negatively impacting millions of adults annually.Estimated prevalence ranges from 14 to 33 percent in those over age 65 to over 70 percent in a nursing home setting.The elderly,those with neurodegenerative diseases,head and neck cancer patients,and those with autoimmune conditions such as Sjögren's syndrome are disproportionately affected.Oropharyngeal dysphagia refers specifically to difficulty in initiating a swallow due to dysfunction at or above the upper esophageal sphincter,and represents a large proportion of dysphagia cases.Current treatments are limited and are often ineffective.Stem cell therapy is a new and novel advancement that may fill a much-needed role in our treatment regimen.Here,we review the current literature regarding stem cell treatments for oropharyngeal dysphagia.Topics discussed include tissue regeneration advancements as a whole and translation of these principles into research surrounding tongue dysfunction,xerostomia,cricopharyngeal dysfunction,and finally an overview of the challenges and future directions for investigation.Although this field of study remains in its early stages,initial promising results show potential for the use of stem cell-based therapies to treat oropharyngeal dysphagia and warrant further research.

Phase behavior of rotationally asymmetric Brownian kites containing 90°internal angles

Previous Monte Carlo simulations have shown that ordered tetratic phases can emerge in a dense two-dimensional Brownian system of rotationally asymmetric hard kites having 90°internal angles.However,there have been no experimental investigations yet to compare with these simulation results.Here,we have fabricated two types of micron-sized kites having internal angles of 72°-90°-108°-90°and 72°-99°-90°-99°,respectively,and we have experimentally studied their phase behavior in two-dimensional systems.Interestingly and in contrast to the Monte Carlo simulations,the experimental results show a phase sequence of isotropic fluid-hexagonal rotator crystal-square crystal as the area fractionφA increases for both types of kites.The observed square crystal displays not only a quasi-long-range translational order but also(quasi-)long-range 4-fold bond-and molecular-orientational order;these characteristics confirm that tetratic order can emerge even in dense Brownian systems of rotationally asymmetric particles.A model based on local polymorphic configurations(LPCs)is proposed to understand the origin of the square lattice order in these dense kite systems.The results in this study provide a new route to realize custom-designed self-assembly of colloids by controlling LPCs.

Application of lung microphysiological systems to COVID-19 modeling and drug discovery:a review

There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

Chronic airspace disease:Review of the causes and key computed tomography findings

Chronic airspace diseases are commonly encountered by chest,body or general radiologists in everyday practice.Even though there is significant overlap in the imaging findings of different causes of chronic airspace disease,some key clinical,laboratory and imaging findings can be used to guide the radiologist to the correct diagnosis.The goal of this article is to review and compare these features.

Preface to the Special Issue on Antarctic Meteorology and Climate:Past,Present and Future

The Antarctic,including the continent of Antarctica and the Southern Ocean,is a critically important part of the Earth system.Research in Antarctic meteorology and climate has always been a challenging endeavor.Studying and predicting weather patterns in the Antarctic are important for understanding their role in local-to-global processes and facilitating field studies and logistical operations in the Antarctic(e.g.,Walsh et al.,2018).Studies of climate change in the Antarctic are comparatively neglected compared to those of the Arctic.However,significant climate changes have occurred in the Antarctic in the past several decades,i.e.,a strong warming over the Antarctic Peninsula even with a recent minor cooling,a deepening of the Amundsen Sea low,a rapid warming of the upper ocean north of the circumpolar current,an increase of Antarctic sea ice since the late 1970s followed by a recent rapid decrease,and an accelerated ice loss from the Antarctic ice shelf/sheet since the late 1970s(e.g.,Turner et al.,2005;Raphael et al.,2016;Sallée,2018;Parkinson,2019;Rignot et al.,2019).Investigating recent climate change in the Antarctic and the underlying mechanisms are important for predicting future climate change and providing information to policymakers.

Choriocapillaris in non-neovascular age-related macular degeneration as evaluated by optical coherence tomography angiography

Dramatic advances in retinal imaging technology over the last two decades have significantly improved our understanding of the natural history and pathophysiology of non-neovascular age-related macular degeneration(AMD).Currently,aside from micronutrient supplements,there are no proven treatments for non-neovascular or dry AMD.Recently,a number of pharmacological agents have been evaluated or are under evaluation for treatment of patients with end-stage dry AMD manifesting as geographic atrophy(GA).It may preferable,however,to intervene earlier in the disease before the development of irreversible loss of visual function.Earlier intervention would require a more precise understanding of biomarkers which may increase the risk of progression from early and intermediate stages to the late stage of the disease.The development of optical coherence tomography angiography(OCTA)has allowed the layers of the retinal microcirculation and choriocapillaris(CC)to be visualized and quantified.Flow deficits in the CC have been observed to increase with age,particularly centrally,and these flow deficits appear to worsen with development and progression of AMD.As such,OCTA-based CC assessment appears to be a valuable new biomarker in our assessment and risk-stratification of AMD.Alterations in the CC may also provide new insights into the pathophysiology of the disease.Enhancement of choriocapillaris function may also prove to be a target of future therapeutic strategies or as a biomarker to monitor the effectiveness of therapy.As such,CC imaging may be anticipated to be an integral tool in the management of dry AMD.

In-Depth Metaproteomics Analysis of Oral Microbiome for Lung Cancer

The human oral microbiome correlates with numerous diseases,including lung cancer.Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis,yet characterizing low-abundant bacteria is challenging.Here,we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry-(FFIEF-MS-)based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome.With our method,the number of interfering peptides decreased by 52.87%,whereas the bacterial peptides and species increased by 94.97%and 44.90%,respectively,compared to the conventional metaproteomics approach.We identified 3647 bacterial proteins,which is the most comprehensive oral metaproteomics study to date.Lung cancer-associated bacteria were validated among an independent cohort.The imbalanced Fusobacterium nucleatum and Prevotella histicola and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed.The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.

Additive manufacturing of tungsten,tungsten-based alloys,and tungsten matrix composites

Tungsten(W) materials are gaining more and more attention due to the extended applications of metallic systems in the extreme environments.Given W’s unique characteristics like room-temperature brittleness,additive manufacturing(AM)techniques could give them a higher design flexibility and manufacturability.With the growing focus and thriving development of W-faced AM techniques,since the mechanical performance of additively manufactured W parts is still unsatisfactory,a critical review to further explore the possibilities of combining W and AM processes is urgently needed.In this review,we systematically explain the fundamentals of AM processes for W materials.Following the traditional classification,we further discuss the widely used AM processes including wire arc additive manufacturing(WAAM),electron beam melting(EBM),laser powder bed fusion(LPBF),laser direct energy deposition(laser DED),and other modified yet emergent AM techniques.Accordingly,since additively manufacturing W materials is processing parameter-sensitive,we illustrated the effects of various important processing parameters on the AM process control and final parts’ quality.With this detailed understanding,various categories of AM-compatible W materials(i.e.,pure W,W alloys,and W composites) were presented,and their general mechanical performance,distinct role(particularly the role of different alloying elements and added secondary-phase particles in W),and application-oriented benefits have been summarized.After clarifying the current status,main challenges,and triumphant successes for additively manufacturing W materials,we further provide a concise prospect into the development of additively manufactured(AMed) W materials by integrating potential fabrication,measurement,alloy design,and application’s considerations.In summary,this critical review investigates the fundamental and practical problems crucially limiting the applications of AMed W materials,and the comprehensive discussion concentrates the history of the development and combination between AM techniques and W design.All the understanding is of great importance to achieving foreseeable successful future applications of AMed W materials.

Regulation of the Arabidopsis GSK3-like Kinase BRASSINOSTEROID-INSENSITIVE 2 through Proteasome-Mediated Protein Degradation

肝糖 synthase kinase (GSK3 ) 3 是在许多细胞的过程被含有并且被 phosphorylation 或 proteinprotein 相互作用在动物房间调整的唯一的 serine/threonine kinase。BIN2 是否定地调整发信号的 brassinosteroid (BR ) 的 Arabidopsis 象 GSK3 一样 kinase。基因研究建议 BIN2 在房间表面响应 BR 感觉被禁止在下游的目标上减轻它的禁止的效果；然而，很少对它的抑制的生物化学的机制被知道。这里，我们证明 BIN2 被调停 proteasome 的蛋白质降级调整。一个 BR 生合成禁止者和活跃 BR 的外长的申请增加了并且减少 BIN2 蛋白质的数量分别地。有趣地， gain-of-function bin2-1 变化显著地稳定 BIN2，使它无答复到导致 BR 的 BIN2 弄空。不同植物生长荷尔蒙的外长的申请表明，那 BIN2 弄空被 BR 明确地通过功能的 BR 受体导致一个 proteasome 禁止者的处理， MG132，不是仅仅阻止了导致 BR 的 BIN2 弄空而且废弃在 BIN2 kinase 活动的 BR 的禁止的效果。一起拿，我们的结果强烈建议那调停 proteasome 的蛋白质降级为限制 BIN2 活动组成重要规章的机制。

What impact entrepreneurial intention?Cultural,environmental,and educational factors

Entrepreneurial intention is a key part of entrepreneurship.This paper aims to explore internal and external impact factors on entrepreneurial intention from the perspective of information transfer.It examines how cultural differences,environmental factors,and environmental education affect entrepreneurial intention.A questionnaire-based survey on Chinese and American college students is conducted to verify three hypotheses.The results show that there is no significant difference in entrepreneurial intention level between college students in China and America(American-born Chinese)college students,that individuals’perceived environmental support is positively related to their entrepreneurial intention,and that individuals’entrepreneurial education level is not positively related to their entrepreneurial intention.