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.

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.

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.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

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.

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.

Development of RPA-Cas12a-fluorescence assay for rapid and reliable detection of human bocavirus 1

Human bocavirus(HBoV)1 is considered an important pathogen that mainly affects infants aged 6–24 months,but preventing viral transmission in resource-limited regions through rapid and affordable on-site diagnosis of individuals with early infection of HBoV1 remains somewhat challenging.Herein,we present a novel faster,lower cost,reliable method for the detection of HBoV1,which integrates a recombinase polymerase amplification(RPA)assay with the CRISPR/Cas12a system,designated the RPA-Cas12a-fluorescence assay.The RPA-Cas12a-fluorescence system can specifically detect target gene levels as low as 0.5 copies of HBoV1 plasmid DNA per microliter within 40 min at 37℃without the need for sophisticated instruments.The method also demonstrates excellent specificity without cross-reactivity to non-target pathogens.Furthermore,the method was appraised using 28 clinical samples,and displayed high accuracy with positive and negative predictive agreement of 90.9%and 100%,respectively.Therefore,our proposed rapid and sensitive HBoV1 detection method,the RPA-Cas12a-fluorescence assay,shows promising potential for early on-site diagnosis of HBoV1 infection in the fields of public health and health care.The established RPA-Cas12a-fluorescence assay is rapid and reliable method for human bocavirus 1 detection.The RPA-Cas12a-fluorescence assay can be completed within 40 min with robust specificity and sensitivity of 0.5 copies/μl.

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 Three Global Initiatives Contribute to the Sound Development of Global Human Rights Governance

At the 10^(th)collective study session of the Political Bureau of the CPC Central Committee held on the afternoon of November 27,2023,Xi Jinping,general secretary of the CPC Central Committee,emphasized that“China will actively participate in the reform and development of the global governance system,promote its development towards a more just and reasonable direction,use good international laws to promote global governance,and contribute to the building of a human community with a shared future.”Obviously,“global human rights governance”is an inherent part of“global governance.”

Against all odds:The road to success in the development of human immune reconstitution mice

The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.

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.

Integration and development of veterinary Chinese medicine insight into the development of human Chinese medicine

Chinese veterinarians shine brightly in the long river of history.To examine the beginnings and growth of Chinese Medicine(CM)and Chinese Veterinary Medicine(CVM),the evolution of veterinary Chinese medicine and the common use of herbs by humans and animals were presented.This study summarizes the history of development and the current situation of Chinese veterinary medicine.Explain that veterinary Chinese medicine refers to drugs and their preparations applied under the guidance of CVM theory.Focus on distinguishing the similarities and differences between veterinary Chinese medicine and plant medicine,veterinary Chinese medicine with the complexity and efficacy of integrity,low harmful residue,not easy to produce resistance,and other characteristics.Veterinary Chinese medicine places great emphasis on clinical practice.veterinary Chinese medicine has a long history of veterinary clinical experience and data,which reflects the practical characteristics of veterinary Chinese medicine.The application experience of CM in the prevention and control of animal diseases and promoting animal growth was introduced.

Revisiting the Spirit of the UDHR and Discussing Human Rights Development——Summary of Views from the Seminar Commemorating the 75th Anniversary of the Universal Declaration of Human Rights

On December 4,2023,the China Society for Human Rights Studies hosted a seminar in Beijing commemorating the 75^(th) Anniversary of the Universal Declaration of Human Rights.Participants discussed topics such as the significance of the Universal Declaration of Human Rights,China’s theories and practices in respecting and safeguarding human rights,the three global initiatives and global human rights governance,human rights protection in the digital age,and telling Chinese stories of human rights in the new era.The discussions led to a broad consensus and achieved positive results.

Development of Framework for ACI-Powered Human Resource Recruitment Assistant

The landscape of human resource management within large enterprises necessitates efficient and unbiased recruitment practices to ensure organisational effectiveness and foster diversity(Ayoko&Fujimoto,2023).Traditional hiring processes often create biases,which cause additional challenges in achieving proper objectives(Bogen,2021).According to Workable(workable.com),the average time to fill a job requisition is 41 days(Howden,2023).This paper proposes a framework for the development and implementation of an Artificially Capable Intelligent(ACI)-powered Human Resource(HR)Assistant for large enterprises(possibly more than 300 employees)to eliminate these unnecessary challenges caused by biases in hiring practices,therefore directly addressing fair and just participation in society and the world of work.The framework integrates ACI technologies,particularly candidate identification,to revolutionise HR practices.By leveraging ACI algorithms,the proposed hyper-realistic assistant aims to revolutionise the recruitment process.It will significantly reduce the average time to fill job requisitions.Moreover,the ACI-powered system is designed to mitigate biases inherent in traditional hiring practices,thus fostering a fair and inclusive environment for all candidates in the shortest possible time frame.This paper includes the key components and working processes of the ACI-powered HR Assistant framework.Through a comprehensive theoretical analysis,the paper investigates the system’s working process and how the framework aligns with the goal of promoting a fair and participatory environment in the world of work.Ultimately,the proposed framework represents a main step towards enhancing organisational effectiveness,fostering diversity,and advancing equitable recruitment practices in the futuristic workplace.

Promoting Human Rights Through Development

China’s human rights practice focuses on the rights of subsistence and development,China always regards rights to subsistence and development as primary and basic human rights.As a goal humanity has pursued for a long time,the Chinese people have worked tirelessly to protect human rights for all.Consistent with its rising global stature,the nation has moved from its traditionally more defensive posture to a more activist role in the field of global human rights protection,especially in the United Nations Human Rights Council.

Development of Human Rights-Based Practices in Psychiatry from People Living with Mental Health Problems During Involuntary Hospitalization or Treatment - A Secondary Publication

This article presents the research protocol of an interpretative phenomenological study that aims to understand the lived experiences of coercion and human rights-based practices in psychiatry from the perspectives of people living with mental health problems during involuntary hospitalization or treatment.This qualitative study used an interpretative phenomenological analysis design.In-depth,one-on-one interviews along with a socio-demographic questionnaire were conducted with approximately 10 participants.Data analysis was followed by an iterative and hermeneutic emergence coding process.By centering human rights-based practices on the lived experiences of people living with mental health problems who encountered coercion,this study highlighted the contributing and limiting factors to the recognition of human rights in nursing practices.This study also promoted the development of nursing knowledge and practices that can significantly contribute to an individual’s recovery process.

基于主题的英语跨学科学习任务群教学——以高中必修三The Human Development Report为例

《普通高中英语课程标准(2022年版)》将英语学科核心素养确定为英语课程的育人目标,这表明,教师应通过基于真实情境的具体学习任务,让学生综合运用各维度的知识和能力,主动探究,将知识、能力转化为素养。本文以外研版高中英语必修三The Human Development Report一课的群文教学为例,探究基于跨学科学习任务群的教学实践。