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.

"Three-in-One" Ecological Development and Efficient Utilization Model of Aggregates

Green mining and the formation of an effective and efficient development model have become key issues that aggregates enterprises around the world need to solve urgently.On the basis of analyzing the development status of aggregates industry in Xiluodu area,the paper studied the main problems faced in the construction of green aggregates mines at present,and proposed a"three-in-one"ecological,intelligent and efficient green mine construction model for"ecological development","green logistics"and"solid waste recycling"of aggregates.The study has certain theoretical value and practical significance for the construction of green aggregates mine in Xiluodu area.

The Development Trend of Enterprise Business Administration and the Innovation of Management Mode

In the context of the new period,the continuous growth of social and economic levels and the rapid update of information technology have significantly impacted the business management of Chinese enterprises,presenting substantial challenges.The intensification of market competition exerts development pressure on many enterprises,and coupled with the unstable strength of some businesses,numerous problems in business management arise.These issues hinder the smooth execution of various business activities.Therefore,it is crucial to ensure effective business administration to conduct different business activities in an orderly manner,promptly avoid adverse risks,and strengthen control over multiple factors.The innovation and improvement of business administration are of great significance for enhancing the management level and market competitiveness of modern enterprises,accelerating their healthy development,and creating numerous opportunities.Consequently,this paper analyzes and explores the development trends of enterprise business administration and the innovation of management models for reference.

China’s Industrial Modernization:Development Rationale,Current Status,and Policy Directions

Economies that have effectively escaped the“middle-income trap”demonstrate common traits in their industrial restructuring as they progressed to high-income status.These include a relatively stable share of an economy’s manufacturing sector,a reasonable economic structure,enhanced industrial capabilities,and growth driven by innovation.However,late-moving countries face a number of hurdles as they strive to cross this threshold.China’s development advantages include,among other things,a complete industrial system,a more balanced industrial structure,growing indigenous innovation capabilities,continual expansion and upgrading of domestic demand,and a greater degree of openness.These capabilities have provided continuous momentum for industrial growth,allowing China to capitalize on the next wave of technological and industrial revolutions while also promoting long-term,steady industrial development.During its modernization efforts,China has seen substantial changes in the external environment surrounding its industrial development.We must not only recognize the increasing complexity,intensity,and uncertainty of these changes,but also take proactive steps to solve diverse issues and capitalize on opportunities arising from global digital and green transitions.Equal focus should be placed on strengthening reforms and promoting high-level openness,improving policy coordination and consistency,and pursuing an innovation-driven strategy.This will speed the development of a modern industrial system and encourage the formation of new,high-quality productive forces.

Economy Function in the Mode of Sustainable Development

To implement the previously formulated principles of sustainable economic development, all solutions of the linear system of equations and inequalities, which are satisfied by the vector of real consumption, are completely described. It is established that the vector of real consumption with the minimum level of excess supply is determined by the solution of some quadratic programming problem. The necessary and sufficient conditions are established under which the economic system, described by the “input-output” production model, functions in the mode of sustainable development. A complete description of the equilibrium states for which markets are partially cleared in the economy model of production “input-output” is given, on the basis that all solutions of system of linear equations and inequalities are completely described. The existence of a family of taxation vectors in the “input-output” model of production, under which the economic system is able to function in the mode of sustainable development, is proved. Restrictions were found for the vector of taxation in the economic system, under which the economic system is able to function in the mode of sustainable development.

HV Process Model of Software Development

Software Development Life Cycle (SDLC) is one of the major ingredients for the development of efficient software systems within a time frame and low-cost involvement. From the literature, it is evident that there are various kinds of process models that are used by the software industries for the development of small, medium and long-term software projects, but many of them do not cover risk management. It is quite obvious that the improper selection of the software development process model leads to failure of the software products as it is time bound activity. In the present work, a new software development process model is proposed which covers the risks at any stage of the development of the software product. The model is named a Hemant-Vipin (HV) process model and may be helpful for the software industries for development of the efficient software products and timely delivery at the end of the client. The efficiency of the HV process model is observed by considering various kinds of factors like requirement clarity, user feedback, change agility, predictability, risk identification, practical implementation, customer satisfaction, incremental development, use of ready-made components, quick design, resource organization and many more and found through a case study that the presented approach covers many of parameters in comparison of the existing process models. .

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.

A Hybrid Model for Improving Software Cost Estimation in Global Software Development

Accurate software cost estimation in Global Software Development(GSD)remains challenging due to reliance on historical data and expert judgments.Traditional models,such as the Constructive Cost Model(COCOMO II),rely heavily on historical and accurate data.In addition,expert judgment is required to set many input parameters,which can introduce subjectivity and variability in the estimation process.Consequently,there is a need to improve the current GSD models to mitigate reliance on historical data,subjectivity in expert judgment,inadequate consideration of GSD-based cost drivers and limited integration of modern technologies with cost overruns.This study introduces a novel hybrid model that synergizes the COCOMO II with Artificial Neural Networks(ANN)to address these challenges.The proposed hybrid model integrates additional GSD-based cost drivers identified through a systematic literature review and further vetted by industry experts.This article compares the effectiveness of the proposedmodelwith state-of-the-artmachine learning-basedmodels for software cost estimation.Evaluating the NASA 93 dataset by adopting twenty-six GSD-based cost drivers reveals that our hybrid model achieves superior accuracy,outperforming existing state-of-the-artmodels.The findings indicate the potential of combining COCOMO II,ANN,and additional GSD-based cost drivers to transform cost estimation in GSD.

Analysis on the Development Model of Relic and Museum Tourism Products Based on ERP Analysis:A Case Study on Shandong Province

In recent years, the trend of people choosing relic and museum tourism during their vacationand leisure time is growing day by day, mainly because it touches people's feelings about historical relicsand cultural heritage. The development of relic and museum tourism products is not only the inheritanceof culture and the protection of cultural relics, but also the promotion of tourism consumption under thebackground of cultural tourism integration, which has promoted the development of regional economy.With the relic and museum tourism resources in Shandong Province as the research object, through theanalysis of its resources, market and products, this paper put forward three applicable modes of relic andmuseum tourism product development, including independent development, joint development, and artauthorization, and proposed specific suggestions around the three modes.

Application of Classical Prescriptions of Rhizome Chinese Herbal Medicines for Medicine and Food Homology and Development Status of Its Modern Food

The efficacy,application and compatibility of five kinds of Chinese Herbal Medicines medicine(including yam,licorice,Platyc-odonisi Radix,Polygonati Rhizoma,and Pueraria Lobata)for medicine and food homology in the past five years were systematically searched and summarized,and the current situation of their food development was reviewed to provide theoretical basis for the research and development of this kind of CHMs for health care.

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.

Viewing Chinese modernization and Its Requirements for Human Rights Protection from the Perspective of Human Development

Modernization,as a specific stage in the historical development of human society,possesses a multi-layered composite structure,with each layer playing both a promoting and inhibiting role in human development and dignity simultaneously.Chinese modernization is a strategic choice made based on lessons learned from various experiences of modernization processes in other countries,reflecting judgments on the benefits and choices on the values of human development and dignity in modernization.It values the promotion of the free and well-rounded development of all individuals as its standard,demanding the full realization of the positive effects of modernization on human development and the overcoming of its negative effects.Human rights,aiming to promote the free and well-rounded development of every person as the ultimate value goal,are not only an intrinsic structural element of the modernization stage but also a social normative tool that restrains the direction of modernization development,aligning closely with the values pursued by Chinese modernization.Chinese modernization poses dual requirements for human rights protection:on the one hand,it demands the affirmation and promotion of the positive effects of modernization on human development and dignity through human rights standards,and on the other hand,it requires the prevention and mitigation of the negative effects of modernization on human development and dignity through human rights standards.There exists a certain tension between these two dimensions,necessitating an appropriate balance and thereby presenting corresponding requirements for China’s approach to human rights protection.

Constructing a Triangular Linkage Model of Government Audit,Social Audit,and Internal Audit to Promote High-Quality Development of Audit Services

It is a complex and important topic to study the linkage mechanism of government audit,social audit,and internal audit in the context of China’s high-quality economic development.The implementation of measures,such as establishing a sound and perfect organizational safeguard mechanism,strengthening project collaborative audit mechanism,enhancing the mechanism for utilizing audit results,and establishing an audit and rectification joint mechanism can promote the efficient operation of the audit supervision system and the high-quality development of audit services.

The Impact of Music Education on Children’s Cognitive Development:From Traditional Classrooms to Modern Digital Platforms

Music education has long been debated for its influence on children’s cognitive development,particularly regarding their thinking methods and adaptability.This article synthesizes research data to examine the cognitive benefits of music instruction,including increased IQ,language proficiency,memory,and attention.Traditional face-to-face training,while personalized and socially interactive,faces limitations such as budget constraints and accessibility.Modern digital platforms offer individualized learning paths with AI-driven feedback but may lack necessary interpersonal interaction.This paper proposes a hybrid approach to music education,integrating traditional and digital methods to maximize cognitive gains.Further research is recommended to explore the implementation of these integrated learning strategies in varied educational settings.

Innovation and Development Trends in ASEAN Marketing Models in the Digital Age

The digital wave is reshaping the global economic landscape with unprecedented force,especially in the dynamic and promising ASEAN region.Southeast Asia,a multicultural gathering place composed of ten countries,is experiencing profound changes due to the digital revolution,and its marketing model is also displaying new vitality.With soaring internet penetration,widespread use of smartphones,and the booming rise of social media,ASEAN markets have become at the forefront of global digital marketing innovation.This transformation is not only about the application of technology but also involves a comprehensive shift in thinking,consumer behavior,and business strategy.The purpose of this paper is to explore in depth how ASEAN marketing models are innovating in this era and to identify future trends,with a view to providing insights for companies to help them remain competitive in the rapidly changing market.

Comparison of the Development Model of DTP Pharmacy between China and the United States and Its Enlightenment

Objective To systematically analyze the development status of DTP pharmacy in the United States and China,and to find out the problems in China’s DTP pharmacy and put forward some countermeasures and suggestions.Methods Relevant literature was searched and reviewed to study the history,market scale and development trend of DTP pharmacy in the United States and China.Then,the problems in China’s DTP pharmacy were found out.Results and Conclusion DTP pharmacy model in the U.S.has taken shape and is maturing.The high degree of industry concentration is an important feature of the U.S.pharmacy.In contrast,China’s DTP pharmacy started late,and the industry pattern has not yet been finalized.There are still some problems in the DTP pharmacy certification and quality management.It is recommended to promote the rapid development of DTP pharmacies in China by encouraging the outflow of prescription drugs,establishing a third-party pharmacy accreditation organization and strengthening the team of licensed pharmacists and other personnel.

The Integration of Modern Electronic Technology and E-Commerce:the Driving Force of Innovation Development

In the 21st century,which is known as the age of information,the integration of electronic technology and e-commerce has become an irreversible trend in the field of business.This trend not only promotes the innovative development of e-commerce,but also brings unprecedented opportunities and challenges for enterprises.With the continuous development and popularization of Internet technology,more and more people choose to carry out shopping,payment and other consumption activities through e-commerce platforms,which also provides merchants with a broader market space and more sales channels.At the same time,e-commerce also brings more convenience and choice to consumers,making it easier for consumers to obtain the goods and services they need.However,the development of e-commerce has also brought some new challenges,such as how to ensure the quality of goods,how to protect consumer privacy and so on.Therefore,enterprises and government departments need to strengthen the supervision and management of e-commerce to ensure its healthy and orderly development.In general,the integration of electronic technology and e-commerce has become an important trend in today’s business field,which brings both opportunities and challenges to enterprises.

The Impact of The Three-Dimensional Cultivation Model on the Development of the Suzhou Tea Industry:Estimating Value of Output Per Acre and Diversified Sales Models

This article explores the impact of the three-dimensional cultivation mode on the development of the Suzhou tea industry,focusing on the diversified estimation of the value of output per acre and sales mode.It introduces the history and traditional cultivation practices of tea in Suzhou,as well as the current challenges and problems faced by the industry.An in-depth analysis was conducted on the overview and improvement plans of the three-dimensional cultivation mode,covering relevant technical methods.Based on this analysis,the impact of the three-dimensional cultivation on the value of output per acre was studied and predicted.Its potential and advantages were explored and compared with the effectiveness of traditional cultivation models.Additionally,the impact of the three-dimensional cultivation mode on sales was analyzed,examining its market adaptability and competitiveness,as well as its advantages in expanding sales channels and market coverage.The study also focused on the promoting effect of diversified sales models on the Suzhou tea industry,including direct consumption market development,tea processing product development and promotion,and the integration of tea culture and the tourism industry.To ensure sustainable development,the article evaluates the environmental impact,economic feasibility,social benefits,and farmer benefits of the three-dimensional cultivation model.Finally,the prospects for the development of the Suzhou tea industry were discussed,and the positioning and response strategies of the threedimensional cultivation model were proposed.

Pioneering a New Realm of Human Rights Civilization in the Chinese Path to Modernization——An Overview of the Symposium on“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”

On October 14,2023,a symposium themed“The Chinese Path to Modernization and the Promotion of Free and Comprehensive Human Development”was held in Changchun,Jilin Province,China.More than fifty experts,scholars,and researchers from national institutions and universities engaged in discussions and exchanges on human rights on the Chinese path to modernization,including the path,practice,knowledge systems,and civilization forms of human rights.This symposium played a significant role in advancing the construction of the disciplinary system,academic system,and discourse system of human rights in China.

The generation and properties of human cortical organoids as a disease model for malformations of cortical development

As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.