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.

Human Rights and Development:China's Contributions Based on a Larger Concept of Human Rights

The Western liberal view of global governance can no longer effectively address the challenges facing the world today or respond to the demands of developing countries in the fields of human rights and development.Meanwhile,the United Nations human rights and development agenda also has its limitations.Against such a backdrop,China's path of human rights development has avoided the trap of human rights confrontation and the clash of civilizations.It has set an example of complementarity and positive interaction between human rights and development by unifying collective human rights with individual human rights and integrating the universality and particularity of human rights.Xi Jinping,general secretary of the Communist Party of China(CPC)Central Committee,delivered a speech at the 37th group study session of the Political Bureau of the CPC Central Committee on China's Path of Human Rights Development.This elevated China's human rights development to a new historical height.Practice has proved that China's concept and path of human rights in the new era have not only effectively promoted the development of its human rights cause,but also contributed Chinese wisdom to the global cause of human rights and development with a larger concept of human rights.Under the framework of the concept of building a community with a shared future for mankind,the Belt and Road Initiative,and the Global Development Initiative,China has contributed to enhancing the discourse power of developing countries in human rights and building a fairer,more just,more reasonable and more inclusive system for global human rights governance.

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.

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.

Research on the Constitutional,Historical and Practical Logic of the Chinese Path of Human Rights Development——From the Perspective of the Inclusion of Human Rights Clause in the Constitution

The inclusion of the human rights clause in the Chi-nese Constitution is a concern and expression of the spirit of the Con-stitution,which has laid the institutional regulations of the fundamen-tal law for the development of human rights in China,provided the principles and value norms of the highest level of effectiveness for the legal protection of human rights,and built a profound constitutional basis for the formation and improvement of the Chinese path of human rights development.The human rights clause is not only a summariza-tion and affirmation of the historical practice of Chinese human rights development under the leadership of the Communist Party of China,but also a new starting point for the development of human rights in China under the leadership of the Communist Party of China.It marks that the development of human rights in China has entered a new era.The Party and the state have finally embarked on a path of human rights development with Chinese characteristics by formulating and implementing the Human Rights Action Plan of China,eliminating ab-solute poverty through the national poverty alleviation campaign,and promoting human rights protection through the rule of law.

Exploring the Association between Climate Change and Human Development: A Visual Analytics Study

This study explores the complex relationship between climate change and human development. The aim is to understand how climate change affects human development across countries, regions, and the global population. Visual analytics were used to examine the impact of various climate change indicators on different aspects of human development. The study highlights the urgent need for climate change action and encourages policymakers to make decisive moves. Climate change adversely affects numerous aspects of daily life, leading to significant consequences that must be addressed through policy changes and global governance recommendations. Key findings include that regions with higher CO2 emissions experience a significantly higher incidence of life-threatening diseases compared to regions with lower emissions. Additionally, higher CO2 emissions correlate with consistent death rates. Increased pollution exposure is associated with a higher prevalence of life-threatening diseases and higher rates of malnutrition. Moreover, greater mineral depletion is linked to more frequent life-threatening diseases, suggesting that industrialization contributes to adverse health effects. These results provide valuable insights for policy and decision-making aimed at mitigating the impact of climate change on human development.

The Impact of Human Resource Management on University Development

As competition in the education industry intensifies and the knowledge economy evolves,the significance of Human Resource Management(HRM)in university institutions.This study aims to explore how HRM affects the sustainable development and competitiveness improvement of universities.This article begins with a theoretical analysis to define the concept of HRM and its particular relevance within university education.The subsequent analysis examines the multi-dimensional framework of university development,encompassing its connotation,goals,and key influencing factors.The article further elaborates on the positive effects of HRM on university teaching quality,scientific research capabilities,organizational culture,and social services.On this basis,the main challenges currently faced by university HRM are discussed,such as talent mobility,institutional constraints,resource limitations,and internationalization pressure.Finally,optimization strategies are proposed,including building a scientific human resources system,enhancing talent training and development,fostering diversity among teaching staff,and improving decision-making efficiency and transparency.The conclusions of this study aim to provide strategic insights for university education managers to better utilize human resource advantages and promote the comprehensive and sustainable development of universities.

The Impact of Human Resource Management on Regional Economic Development

A company that does a good job in human resource management will promote the process of regional economic development,and related enterprises will develop rapidly as a result.In future work,enterprises should carefully study the relationship between the two,and innovate their human resource management and development methods while fully considering the needs of talent development and regional economic development,in order to fundamentally optimize the regional economic development status.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma

Objective This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma(NHL).Methods We compared the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and the ASMR to ASIR ratio(MIR)at national and regional levels and studied the correlation between the MIR and the human development index(HDI)in 2012 and 2018.Results The highest ASIR was in North America in 2012 and in Australia in 2018,and the lowest ASIR was in Central and South Asia in both 2012 and 2018.The highest ASMR was in North Africa in both 2012 and 2018,and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018.The lowest MIR was in Australia in both 2012 and 2018,and the highest MIR was in Western Africa in both 2012 and 2018.HDI was strongly negatively correlated with MIR(r:−0.8810,P<0.0001,2012;r:−0.8895,P<0.0001,2018).Compared to the 2012 data,the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018.Conclusion The MIR is negatively correlated with HDI.Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

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.

Leveraging Robust Artificial Intelligence for Mechatronic Product Development—A Literature Review

Mechatronic product development is a complex and multidisciplinary field that encompasses various domains, including, among others, mechanical engineering, electrical engineering, control theory and software engineering. The integration of artificial intelligence technologies is revolutionizing this domain, offering opportunities to enhance design processes, optimize performance, and leverage vast amounts of knowledge. However, human expertise remains essential in contextualizing information, considering trade-offs, and ensuring ethical and societal implications are taken into account. This paper therefore explores the existing literature regarding the application of artificial intelligence as a comprehensive database, decision support system, and modeling tool in mechatronic product development. It analyzes the benefits of artificial intelligence in enabling domain linking, replacing human expert knowledge, improving prediction quality, and enhancing intelligent control systems. For this purpose, a consideration of the V-cycle takes place, a standard in mechatronic product development. Along this, an initial assessment of the AI potential is shown and important categories of AI support are formed. This is followed by an examination of the literature with regard to these aspects. As a result, the integration of artificial intelligence in mechatronic product development opens new possibilities and transforms the way innovative mechatronic systems are conceived, designed, and deployed. However, the approaches are only taking place selectively, and a holistic view of the development processes and the potential for robust and context-sensitive artificial intelligence along them is still needed.

Ways to Cultivate and Develop Human Resources in the New Situation

In the trend of globalization,digitization,and economic integration,human resources are the core competitiveness of enterprises,and cultivating and developing them is crucial for enhancing competitive advantages.This article delves into how human resource development drives enterprise innovation,promotes team collaboration,and optimizes performance management.Currently,although many enterprises are beginning to attach importance to human resource development,they still face problems such as insufficient investment,weak targeted training,and insufficient exploration of employee potential.Therefore,it is proposed that in the new situation,enterprises need to strengthen diversified training strategies,use digital tools to improve training efficiency,build a fair performance evaluation system,stimulate employee potential,and promote internal talent mobility.The implementation of these strategies will effectively enhance the efficiency of enterprise human resource management and consolidate market position.

A Study on the Challenges of Human-Centric Cyber-Security and the Guarantee of Information Quality

Information security and quality management are often considered two different fields. However, organizations must be mindful of how software security may affect quality control. This paper examines and promotes methods through which secure software development processes can be integrated into the Systems Software Development Life-cycle (SDLC) to improve system quality. Cyber-security and quality assurance are both involved in reducing risk. Software security teams work to reduce security risks, whereas quality assurance teams work to decrease risks to quality. There is a need for clear standards, frameworks, processes, and procedures to be followed by organizations to ensure high-level quality while reducing security risks. This research uses a survey of industry professionals to help identify best practices for developing software with fewer defects from the early stages of the SDLC to improve both the quality and security of software. Results show that there is a need for better security awareness among all members of software development teams.

Human development index is associated with mortality-to-incidence ratios of gastrointestinal cancers

AIM:To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide.METHODS:The age-standardized incidence and mortality rates for gastrointestinal cancers,including cancers of the esophagus,stomach,pancreas,liver,gallbladder,and colorectum,were obtained from the GLOBOCAN 2008 database and United States Cancer Statistics(USCS)report.The human development index(HDI)data were calculated according to the 2011 Human Development Report.We estimated the mortality-toincidence ratios(MIRs)at the regional and national levels,and explored the association of the MIR with development levels as measured by the HDI using a modified"drug dose to inhibition response"model.Furthermore,countries were divided into four groups according to the HDI distribution,and the MIRs of the four HDI groups were compared by one-way ANOVA followed by the Tukey-Kramer post-hoc test.Statespecific MIRs in the United States were predicted from the estimated HDI using the fitted non-linear model,and were compared with the actual MIRs calculated from data in the USCS report.RESULTS:The worldwide incidence and mortality rates of gastrointestinal cancers were as high as 39.4and 54.9 cases per 100000 individuals,respectively.Linear and non-linear regression analyses revealed an inverse correlation between the MIR of gastrointestinal cancers and the HDI at the regional and national levels(<0;P=0.0028 for regional level and<0.0001 for national level,ANOVA).The MIR differed significantly among the four HDI areas(very high HDI,0.620±0.033;high HDI,0.807±0.018;medium HDI,0.857±0.021;low HDI,0.953±0.011;P<0.001,oneway ANOVA).Prediction of the MIRs for individual United States states using best-fitted non-linear models showed little deviation from the actual MIRs in the United States.Except for 28 data points(9.93%of282),the actual MIRs of all gastrointestinal cancers were mostly located in the prediction intervals via the best-fit non-linear regression models.CONCLUSION:The inverse correlation between HDI and MIR demonstrates that more developed areas have a relatively efficacious healthcare system,resulting in low MIRs,and HDI can be used to estimate the MIR.

Cultivating New-type Farmers Based on the Theory of Human Resources Development

Under the direction of theory of human resources development,this thesis analyzes the impact of rural human resources development oncultivating new-type farmers.Firstly,it increases the input of rural basic education;secondly,it reinforces the vocational education and technologytraining;thirdly,it promotes the rural medical and public health services;fourthly,it quickens the rural labor transfer.The status quo of China's ruralhuman resources has been analyzed as follows:in terms of the quantity of rural human resources,the status quo is large and quick-developed baseof rural human resources,high labor participatory rate,and constitution of low age;in terms of the quality of rural human resources,the status quois the ubiquitous low quality of rural human resources,low technological level of rural human resources,and overall low physical quality of farmers;in terms of the structure of rural human resources,the status quo is the irrational industrial structure distribution and imbalanced regional structuredistribution.The thesis also discusses the edification of theory of human resources development in cultivating new-type farmers.First,in terms ofthe control over quantity of rural human resources,it is to keep the stability of family planning policy,and expedite the transfer of rural surplus la-bor;second,in terms of promoting the quality of rural human resources,it is to bolster the development of reserve rural labor force resources,toconstruct the adult educational training system with Chinese characteristics,and to build rural primary health care system;third,in terms of adjus-ting the structure of rural human resources,it is to perfect rural human resources market,and adjust rural economical structure and talents struc-ture.

A Multi-Level Evaluation of Policy Integration of Human Resource Development in Agriculture Sector

Human resource development assumes as a golden key for a knowledge-based economy and competitiveness. This study evaluates policy integration of human resource development (HRD) in agricultural sector within the context of multi-level governance (i.e., interdependence of administrative levels in decision making) and suggests means to enhance policy integration in Bangladesh. Conducting a critical review of major policy instruments, key informant interview and two case studies, this study concluded that HRD issue has fairly included and observed consistency (between the aim of HRD and policy) in all policies and strategies;majority of policy instruments have significantly addressed the significance of HRD and added plans for its development;reporting, monitoring and evaluation of policies and strategies are rather weak and there is no adequate flow of financial arrangement that is largely determined by the availability of government project. Based on the findings, the following means should be useful for improving HRD policy integration such as providing a handsome amount of development budget at the sub-district agricultural office, formulating coherent strategies to build effective cooperation, coordination and participation among stakeholders, initiating special capacity building programmes for rural women, young farmers and smallholders and mainstreaming HRD issue in governmental planning and programmes, and accordingly crafting policies and implementation.

Development of a sensitive and rapid method for quantitation of (S)-(-)- and (R)-(+)-metoprolol in human plasma by chiral LC–ESI–MS/MS

A selective, sensitive and high throughput liquid chromatography-tandem mass spectro-metry （LC-ESI-MS/MS） method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose-2 （250 mm＆#215;4.6 mm, 5 mm） column. Solid phase extraction of （S）-（-）- and （R）-（t）-metoprolol and rac-metoprolol-d6 as an internal standard （IS） was achieved on Lichrosep DVB HL cartridges employing 200 mL human plasma. Both the analytes were chromatographically separated with a resolution factor of 2.24 using 15 mM ammonium acetate in water, pH 5.0 and 0.1% （v/v） diethyl amine in acetonitrile （50：50, v/v） as the mobile phase within 7.0 min. The precursor-product ion transitions for the enantiomers and IS were monitored in the multiple reaction monitoring and positive ionization mode. The method was validated over the concentration range of 0.500-500 ng/mL for both the enantiomers. Matrix effect was assessed by post-column analyte infusion experiment and the mean extraction recovery was greater than 94.0% for both the enantiomers at all quality control levels. The stability of analytes was evaluated in plasma and whole blood under different storage conditions. The method was successfully applied to a clinical study in 14 healthy volunteers after oral administration of 200 mg metoprolol tablet under fasting conditions. The assay reproducibility is shown by reanalysis of 68 incurred samples. The suitability of the developed method was assessed in comparison with＆amp;nbsp;different chromatographic methods developed for stereoselective analysis of metoprolol in biological matrices.

Location and expression of neurotrophin-3 and its receptor in the brain of human embryos during early development

BACKGROUND： Cell culture in vitro trials have demonstrated that neurotrophin-3 （NT-3） can enhance the survival of sensory neurons and sympathetic neurons, and can also support embryo-derived motor neurons. This effect is dependent on nerve growth factor on the surface of cells. Understanding the role of NT-3 and its receptor in the early development of human embryonic brains will help to investigate the correlation between early survival of nerve cells and the microenvironment of neural regeneration. OBJECTIVE： To observe the proliferation of cerebral neurons in the development of human embryonic brain, and to investigate the location, expression and distribution of NT-3 and its receptor TrkC during human brain development. DESIGN, TIME AND SETTING： An observation study on cells was performed in the Department of ttuman Anatomy, Histology and Embryology, Chengdu Medical College in September 2007. MATERIALS： Fifteen specimens of flesh human embryo, aged 6 weeks, were used in this study. METHODS： The proliferation of cerebral neurons was detected using proliferating cell nuclear antigen, and the immunocytochemistry ABC technique was applied to observe the location, expression and distribution of NT-3 and its receptor TrkC in the brain of the human embryo. MAIN OUTCOME MEASURES： Location, expression and distribution of NT-3 and its receptor in the brain of the human embryo. RESULTS： In the early period （aged 6 weeks） of human embryonic development, proliferating cell nuclear antigen-positive reactive substances were mainly observed in the nucleus of the forebrain ventricular zone and subventricular zone, and the intensity was stronger in the subventricular zone than the forebrain ventricle. NT-3 positive reactive substance was mainly distributed in the cytoblastema of the forebrain neuroepithelial layer and nerve cell process, while TrkC was mainly distributed in the cell membrane of the forebrain ventricular zone and subventricular zone. During embryonic development, NT-3 and TrkC showed a positive immune reaction to a greater or lesser extent in ependymal epithelium. CONCLUSION： During early human embryonic development, cerebral nerve cells proliferate in the ventricular zone and subventricular zone, and NT-3 is expressed in the neural axon. The results show that the highly expressed NT-3 could promote the proliferation of neural axons and maintain the neuron body＇s survival.

Understanding Human Development Potentials and Demands for Greenhouse Gas Emissions:with Empirical Analysis using time series and cross-sectional data

Based on an investigation of the meaning of development, the neo-classical economic approach to development, and the post-welfarist theory of development, this paper proposes a conceptual framework for understanding human development potentials, while undertaking empirical analysis using cross-sectional and time series data on human development. Human development is associated with basic necessities for subsistence, the quality of life, and political and civil rights, in addition to income indicators. Our analysis suggests that the concept of human development potentials has two dimensions: the rights of development and limits to human development. Both are largely ignored in the neoclassical theory of development. However, human development is not unbounded, which approaches to a relatively fixed constant at given economic, technological and institutional conditions. This conceptual understanding is supported by results from the empirical examination of the relationships between demands for carbon