New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

基于向量夹角余弦IPD模式参与方关系质量评价研究

IPD模式参与方的关系对IPD模式的发展至关重要。引入关系质量的概念,从参与方供求关系出发,建立IPD模式参与方关系质量评价指标体系;并借鉴供应链稳定性思想,基于向量夹角余弦法构建了IPD模式参与方关系质量评价模型;进而提出判定标准,通过对IPD模式参与方关系质量水平的分析,实现了IPD模式参与方关系的评价。研究表明,该模型不仅能够对两两参与方、三方及IPD参与方关系系统的关系质量进行简单有效的定量化,还能找到影响关系质量的短板进行改进和提高,从而为IPD模式参与方关系管理提供了科学的依据和合理的视角。

基于IPD技术的LC滤波器制备工艺

介质层制备工艺是基于IPD技术的LC滤波器制备的关键工艺。从介质层的制备流程入手,研究了影响PI介质层质量的匀胶、曝光、固化三个关键工艺因素,确定了LC滤波器中介质层的制备工艺参数,实现了厚度8μm、厚度均匀性优于5%、最小互连孔径25μm的介质层制备。按此工艺参数加工,得到LC滤波器样件,经性能测试,所制备LC滤波器的电学性能满足设计指标要求。

基于ANFIS-IPD的飞行模拟器座椅舒适度评价模型

为提升现有飞行模拟器座椅舒适度,减轻驾驶员长时间训练的疲劳感,基于自适应神经模糊推理系统(Adaptive Network-based Fuzzy Inference System,ANFIS)和理想压力分布(Ideal Pressure Distribution,IPD)构建一种飞行模拟器座椅舒适度评价模型。通过座椅压力分布采集系统获取压力分布数据,采用IPD将所得数据归一化作为模型输入数据,同时收集受试人员主观评分作为模型输出数据。采用非均匀有理B样条曲线(Non-Uniform Rational B-Splines,NURBS)对座椅进行改进设计,将处理后的试验数据通过ANFIS工具训练模型进行验证,并用评价模型评估设计方案及优越性。结果表明:该评价模型对飞行模拟器座椅舒适度有较好的预测能力,为提升飞行模拟器座椅舒适度提供指导和参考。

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

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.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

IPD模式下绿色建筑项目的价值维确定

绿色建筑是实现人与自然和谐共处的高质量建筑,对其价值关系的客观反映即价值评价逐渐受到社会各界重视,而原始的成本、质量和安全的价值评价维度逐渐不再适应当今复杂和价值诉求更高的绿色建筑项目。以绿色建筑国家级政策为研究对象,利用Python提取政策文本关键词与CiteSpace可视化软件构建知识图谱网络的研究方法,反推出了绿色建筑项目价值评价的内容,包括建筑物自身性能目标向高性能发展及项目价值理念落实到具体的项目目标和指标。同时,基于IPD要素和原则,合理拓展了IPD模式,明确了IPD模式下绿色建筑项目的价值维。

Construction Method of Civil Aircraft Airborne⁃system Supplier Development Process System

Based on the analysis of the development process system status of domestic and foreign civil aircraft airborne system suppliers,this paper proposes the overall construction idea of"a set of civil aircraft process system"based on IPD(Integrated product development)in the organization.The development stage,process,activity and task are the logical framework elements of the system construction."Based on process decomposition,vertical stratification,horizontal segmentation,combination of special and common,process customized to tools,role and process integration,giving full consideration to the interface between supplier management and process modules"etc.are the concrete ideas.Moreover,formulate top⁃level system construction standards,implemented by process system management tool platform,so that the process system and development work can be effectively integrated to effectively guide the development work of airborne system suppliers,and meet the quality and airworthiness requirements of civil aircraft development.Through the development application of a certain type of flight control system,the process system and tool platform were verified and optimized in practice.

基于IPD模式的大跨型钢混凝土梁起拱

基于IPD模式的某实际工程,研究分析了大跨型钢混凝土梁起拱高度的确定方法,利用有限元软件分析验证了起拱高度的准确性,设计应用了大跨型钢混凝土梁的精准起拱施工工法。结果表明,IPD模式能够有效集成各方资源,实现项目利益的最大化;综合考虑施工和结构设计阶段确定的起拱高度能够有效抵消大跨梁的竖向位移,使结构面最终能达到水平的理想状态;同时精准起拱施工工法在实际工程中施工便捷,起拱误差小,应用前景好。

FE65:a hub for neurodevelopment

FE65,initially identified as a binding partner of amyloid precursor protein(APP),is an adaptor protein enriched in the brain and regulated during development.FE65 belongs to the FE65 protein family.This family is comprised of three members,FE65,FE65 like-1(FE65L1),and FE65 like-2(FE65L2).

Constructing a standard system of city sustainable development assessment technology based on the SDGs

Given the rapid development of China’s new urbanization,cities with different locations and varying functional positioning,resource endowments,and development stages have insufficient scientific and applicable technical tools for implementing the United Nations Sustainable Development Goals(SDGs).City managers and policymakers must urgently establish SDG benchmarks to diagnose city development.Moreover,successful experiences from similar cities regarding sustainable development and self-improvement must be learned from to promote diversified,sustainable development across the country.Furthermore,emerging technologies such as artificial intelligence,the Internet of Things,big data and 5G are widely used in smart cities.Therefore,there is a growing need for“knowledge-based,personalized and intelligent”technologies to support monitoring,evaluation,and decision-making processes facilitating sustainable development in cities.This paper uses standardization as the theoretical support and technical basis.This approach can help clarify the sustainable development processes in China and clarify the evaluation results of and provide data on horizontal city comparisons,which can be used to develop evaluation technology for sustainable development in cities and construct a standardized system.The results provide a standard framework for intelligent assessment and decision-making regarding cities’sustainable development capabilities in China.Evaluating major international standardization institutions reveals that the practices of Chinese national standards should be fully absorbed and integrated to guide the evaluation of smart,resilient,and low-carbon cities.To this end,an indicator library of city sustainable development is proposed to provide standard evaluation technology methods.Finally,analyzing the response relationship of the indicator library to SDGs reveals the need for a standardized knowledge map of sustainable development assessment techniques and methods from the perspective of integrated management for sustainable development in cities.

Spatial Differentiation and Convergence Trend of High-quality Development Level of China’s Tourism Economy

This paper aims to interpret the connotation of high-quality development of tourism economy(HQTE)from the perspective of the new development concepts of innovation,coordination,green,openness and sharing,and then to evaluate the spatial differenti-ation of China’s HQTE based on provincial panel data from 2009 to 2018.Specifically,we employ the spatial convergence model to ex-plore the absolute and conditionalβconvergence trends of HQTE in the whole country and the eastern,central and western regions of China.Our empirical results reveal that:1)within the decade,from 2009 to 2018,regions of China with the highest HQTE index is its eastern region followed by the central region and then the western region,but the fastest growing one is the western region of China fol-lowed by the central region and then the eastern region.2)Whether or not the spatial effect is included,there are absolute and condition-alβconvergence in HQTE in the whole country and aforementioned three regions.3)The degree of government attention as well as the level of economic development and location accessibility are the positive driving factors for the convergence of HQTE in the whole country and the three regions.The degree of marketization and human capital have not passed the significance test either in the whole country or in the three regions.The above conclusions could deepen the understanding of the regional imbalance and spatial conver-gence characteristics of HQTE,clarify the primary development objects,and accomplish the goal of China’s HQTE.

Development and Validation of a UPLC Method for the Determination of Docetaxel and Its Related Substances in Pharmaceutical Dosage Forms, an Antineoplastic Agent

A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.

The HD-Zip transcription factor LcATHB15 is involved in litchi seed development by promoting the expression of the splicing regulator LcSR45

Litchi (Litchi chinensis Sonn.) is a well-known tropical and subtropical woody fruit that originated from southern China (Wei et al.,2017;Hu et al.,2022).Based on the development of the embryo,litchi varieties can be divided into three distinct groups:large-seeded cultivars,small (abortive)-seeded cultivars and partial abortive-seeded cultivars.Seedless or the reduction in seed size due to embryo abortion is a desirable trait in fruit trees as it directly influences the texture and economic value of fleshy fruits,making small (abortive)-seeded litchi cultivars the most preferred.However,in current production practices,there is no efficient method available to induce or promote high seed abortion in litchi fruit.Therefore,understanding the stenospermy mechanisms of litchi seed development is of great significance for improving agricultural practices and managing genetic resources.

Embryonic and Larval Development of Reciprocal Crosses between Clarias gariepinus (Burchell, 1822) and Clarias jaensis (Boulenger, 1909) in West Cameroon

Establishing intraspecific breeding and hybridization programs and determining genetic variability are two important issues for aquaculture. However, interspecific hybridization to improve growth and feeding efficiency is limited. For this purpose, the embryonic and larval development of reciprocal crosses of Clarias gariepinus (Burchell, 1822) and Clarias jaensis (Boulenger, 1909) were studied under laboratory conditions. The fertilization rate varied from 63.33% to 92%, while the hatching rate ranged from 55.68% to 76% with the highest value in hybrids ♀Cg × ♂Cj. Crosses between ♀Cj × ♂Cj, ♀Cg × ♂Cj and ♀Cj × ♂Cg had embryonic stages similar to those of the pure sib ♀Cg x ♂Cg. All crosses, however, had different timing for the various embryological stages. Hatching occurred at 32 h 15 min and 38 h for ♀Cj × ♂Cj and ♀Cj × ♂Cg, and 23 h and 23 h 30 min, respectively, for ♀Cg × ♂Cg and ♀Cg × ♂Cj. However, both crosses produced viable larvae until the first external feeding. The external morphological features of the larvae were completely formed by the 10th day after hatching. The body forms of the crosses at this time were indistinguishable from the pure sib. This study thus laid the groundwork for further comparative studies on hybrid performance and characterization.

Role of self-help groups on socioeconomic development and the achievement of Sustainable Development Goals(SDGs)among rural women in Cooch Behar District,India

This study examines the transformative role of self-help groups(SHGs)in the socioeconomic development of rural women in Cooch Behar District,India,and their contribution toward achieving Sustainable Development Goals(SDGs)of the United Nations.In this study,we explored the effect of SHGs on rural women by specifically addressing SDGs,such as no poverty(SDG 1),zero hunger(SDG 2),good health and well-being(SDG 3),quality education(SDG 4),and gender equality(SDG 5).Given this issue,a cross-sectional survey and comparison analyses are needed to assess the socioeconomic development of rural women and their awareness level before and after the participation of rural women in SHGs.The survey conducted as part of this study was divided into three sections,namely,demographic characteristics,socioeconomic development,and awareness level,with each focusing on different aspects.A group of 400 individuals who were part of SHGs completed the questionnaire survey form.The results showed that the participation of rural women in SHGs significantly improved their socioeconomic development and awareness level,as supported by both mean values and t test results.Memberships in SHGs and microcredit programs were the major elements that boosted the socioeconomic development of rural women,which also achieves SDGs 1,2,3,4,and 5.This study revealed that participation in SHGs and related financial services significantly aided rural women in economically disadvantaged communities in accumulating savings and initiating entrepreneurial ventures.Moreover,participation in SHGs was instrumental in enhancing the self-confidence,self-efficacy,and overall self-esteem of rural women.Finally,doing so enabled them to move more freely for work and other activities and to make family and common decisions.