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.

Reform and Development of English Teaching in Colleges and Universities with the Integration of ChatGPT Technology

As an artificial intelligence-powered language generation model based on natural language processing,ChatGPT,like other artificial intelligence technologies,possesses super real-time dialogue capabilities and is considered an innovative and intelligent auxiliary teaching tool in the field of language learning.This article first analyzes the current state of development of artificial intelligence technologies such as ChatGPT.Secondly,it examines the challenges encountered in the reform and development of English teaching in colleges and universities in China.Lastly,it summarizes the applications and recommendations for using ChatGPT technology in college-level English teaching.

China's Infrastructure Development and Supply-Side Structural Reforms

Despite significant improvements in transport, energy and information communication technology （ICT） infrastructures, inadequacies still exist in China＇s infrastructure development in light of emerging demand and industrial transition and upgrade. China lags far behind advanced economies such as the United States, Germany and Japan in terms of the quality of transport infrastructures except railroad,＂ electricity infrastructure is insufficient and service efficiency needs improvement; ICT infrastructure requires all-round upgrade and gaps in Internet bandwidth are striking. This paper suggests that, based on the needs of supply-side structural reform, China must reform its investment and financing systems to enhance the efficiency of infrastructure investment. Efforts must be made to enhance air transport and port infrastructure to support industrial upgrade; to develop the energy Internet to address emerging demands; and to forge a new generation of ICT infrastructure with industrial Internet as the priority to prepare China for the new round of industrial competition.

Research on the Reform and Development of School Sports Education under the Perspective of Lifetime Sports and Nationwide Fitness

In this paper, we conduct research on the reform and development of school sports education under the perspective of lifetime sports and nationwide fitness. School physical education is the foundation and the strategic focus of the development of sports which is the foundation of the national fitness program which is also an important part of the whole education career. Our proposed approach and reform combines the advances of the state-of-the-art methodologies which will not only enhance the current model but set up for prospect and rnnrlifieatinn as well

Key Technical Problems to be Solved in theCurrent Power Industy Development——Excerpted from the speech on the Seminar on Analysis Forecast of Economic Situation and Enterprise Reform

This paper briefs the development policies and focal construction points of powerindustry in China in 10th Five-year Plan period, and in accordance with the developmentaltrends of international power technology, puts forward the key technological problems tobe studies in China power industry currently.[

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.

Economic reform, open-door policy and changes in spatial development patterns in China

The study profiles and explains the significant changes that have taken place in China's spatial development patterns since the inception of its economic reform and opening two decades ago. Principal component analysis is used to delineate spatial patterns. The analyses show that prior to the reform China's spatial development pattern was characterized by the dominance of the three municipalities and the Northeast, as well as by both the coast-interior and the north-south disparities. Northern provinces were generally more industrialized and economically powerful than the southern ones. After two decades of reform, regional development has become multi-centered with South China, the Yangtze Delta and the Beijing-Tianjin area being the three most important regions of the country. The coastal provinces as a whole rose to prominence on China's economic map while the Northeast has diminished its clout. The coast-interior gap not only remains but may have widened. The north-south disparity also still exists but there has been a role reversal with the south now in the lead position. Virtually all inland provinces now find themselves at or near the low end of the development spectrum. We argue that the major reason for the recent shifts in Chinese space economy is the spatially differentiated economic growth resulted from the reform and open door policy and from the new, uneven development strategy adopted by the Chinese government. The paper discusses four specific factors that have reshaped China's spatial development patterns.

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.

Reform of Theory-practice Alternating Teaching of the Introduction to Architecture Course Oriented to“Employment Priority and Integration of Industry and Education”

In the new era of building a socialist modernization country with the goal of promoting high-quality development,we deeply analyze the knowledge system of the Introduction to Architecture course.This analysis is based on the cross-disciplinary specialties of local applied universities and the orientation of prioritizing employment and integrating industry and education.We propose the teaching reform of“theory-practice alternation”which is adapted to the current times and societal needs.Finally,we comprehensively summarize the effectiveness of curriculum construction,in order to provide theoretical references for the implementation of fostering character and civic virtue and deepening the reform of collaborative education mechanisms.

Deforestation, Agrarian Reform and Oil Development in Ecuador, 1964-1994

Recent biodiversity research in the Western Amazon has emphasized the linkages among road construction, deforestation and loss of indigenous lands. Many observers have concluded that hydrocarbon production inevitably means destruction of forests and expropriation of native territory. Yet evidence from the eastern lowlands of Ecuador (known as the Oriente) shows that oil can be developed without roads or harmful impacts. The Oriente also provides another contrasting case: in areas where no oil was discovered, the government often built roads to support its agricultural colonization efforts. In these areas, a great deal of deforestation and indigenous displacement occurred. Such evidence suggests that a different set of agrarian and environmental policies might permit oil activity without loss of rain forest or indigenous territory.

Research on the Reform of the Process-Tracking Ideological and Political Assessment System in Applied Universities:Taking the Personal Finance Course as an Example

Using the Xi’an Mingde Institute of Technology students as the teaching object and the Personal Finance course as an example,we explore the reform of the ideological and political assessment system of process-tracking courses in applied universities.The article analyzes the feasibility of applying the curriculum ideological and political assessment system in college courses and compares the traditional assessment system.It also proposes that applying curriculum ideological and political assessment to the college curriculum assessment system will help improve students’understanding of the“value guidance”in curriculum ideological and political education and enhance the teaching effect.

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.

Optimizing the sulfur-resistance and activity of perovskite oxygen carrier for chemical looping dry reforming of methane

Perovskite oxides has been attracted much attention as high-performance oxygen carriers for chemical looping reforming of methane,but they are easily inactivated by the presence of trace H_(2)S.Here,we propose to modulate both the activity and resistance to sulfur poisoning by dual substitution of Mo and Ni ions with the Fe-sites of LaFeO_(3)perovskite.It is found that partial substitution of Ni for Fe substantially improves the activity of LaFeO_(3)perovskite,while Ni particles prefer to grow and react with H_(2)S during the long-term successive redox process,resulting in the deactivation of oxygen carriers.With the presence of Mo in LaNi_(0.05)Fe_(0.95)O_(3−σ)perovskite,H_(2)S preferentially reacts with Mo to generate MoS_(2),and then the CO_(2)oxidation can regenerate Mo via removing sulfur.In addition,Mo can inhibit the accumulation and growth of Ni,which helps to improve the redox stability of oxygen carriers.The LaNi_(0.05)Mo_(0.07)Fe_(0.88)O_(3−σ)oxygen carrier exhibits stable and excellent performance,with the CH_(4)conversion higher than 90%during the 50 redox cycles in the presence of 50 ppm H_(2)S at 800℃.This work highlights a synergistic effect in the perovskite oxides induced by dual substitution of different cations for the development of high-performance oxygen carriers with excellent sulfur tolerance.

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.

Revisiting the Relationship Between Urbanization and Economic Development in China Since the Reform and Opening-up

The relationship between urbanization and economic development has become a hot topic in the scientific community due to its great practical significance,and economic and social value.However,this relationship continues to change dynamically.In the new stage of urbanization,it is urgent to reveal the causal relationship quantitatively and diagnose the future direction systematically.Based on this,this paper calculates the contribution rate of China’s urbanization to economic development from 1978 to 2019 and uses the panel data cointegration test method to explore the causal relationship between urbanization and economic development in China.The study has three principal results.First,the contribution rate of urbanization to economic growth has maintained the overall growth trend from1978 to 2019,but the growth rate of urbanization’s contribution to economic growth has been relatively low since 2012.It is an important reason that the real estate sector has moved into a new stage of transformation.Second,the cointegration test shows that economic development is a significant factor in advancing urbanization and the urbanization is the product of economic development.Urbanization has a positive feedback effect on economic development,but this effect does not pass the 5%significance level test.The impulse response function shows that the impact of urbanization on economic development is relatively small and stable,indicating that it is limited that the boost of economic development by land-centered urbanization.Third,China’s urbanization and economic development have both shown rapid growth for some time,but their relationship is still the low level of coordination,which has also led to a downward trend in the contribution of new-type,people-oriented urbanization to economic growth in recent years.In the future,China’s urbanization and economy need to maintain relatively medium-low speed growth in the medium-long term,and we should boost the coordinated development of urbanization and economy from low level to high level.

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.

Influencing factors analysis of hard limestone reformation and strength weakening under acidic effect

Roof disaster has always been an important factor restricting coal mine safety production.Acidic effect can reform the rock mass structure to weaken the macroscopic strength characteristics,which is an effective way to control the hard limestone roof.In this study,the effects of various factors on the reaction characteristics and mechanical properties of limestone were analyzed.The results show that the acid with stronger hydrogen production capacity after ionization(pK_(a)<0)has more prominent damage to the mineral grains of limestone.When pKa increases from−8.00 to 15.70,uniaxial compressive strength and elastic modulus of limestone increase by 117.22%and 75.98%.The influence of acid concentration is manifested in the dissolution behavior of mineral crystals,the crystal defects caused by large-scale acid action will lead to the deterioration of limestone strength,and the strength after 15%concentration reformation can be reduced by 59.42%.The effect of acidification time on limestone has stages and is the most obvious in the initial metathesis reaction stage(within 60 min).The key to the strength damage of acidified limestone is the participation of hydrogen ions in the reaction system.Based on the analytic hierarchy process method,the influence weights of acid type,acid concentration and acidification time on strength are 24.30%,59.54% and 16.16%,respectively.The research results provide theoretical support for the acidification control of hard limestone roofs in coal mines.