The Sustainable Development Pathway of the Biomedical Industry Based on Environmental,Social,and Governance(ESG)Concepts

There is a growing global awareness of environmental,social,and governance(ESG)concerns.The biopharmaceutical industry is an important field that affects human health and well-being,and its sustainable development is now the industry’s focus.Based on the current state of the green development of China’s biopharmaceutical industry,the article proposes suggestions and paths for promoting the industry to better fulfill its social responsibilities and protect the environment while pursuing economic benefits.By doing so,the industry can make a greater contribution to global public health and become an important factor in promoting human health and social prosperity.

An Effective 3D-CFD Methodology for the Complementary Virtual Development of Alternative Fuels and Engine Concepts

With the aim of reducing the cost of developing internal combustion engines,while at the same time investigating different geometries,layouts and fuels,3D-CFD-CHT simulations represent an indispensable part for the development of new technologies.These tools are increasingly used by manufacturers,as a screening process before building the first prototype.This paper presents an innovative methodology for virtual engine development.The 3D-CFD tool QuickSim,developed at FKFS,allows both a significant reduction in computation time and an extension of the simulated domain for complete engine systems.This is possible thanks to a combination of coarse meshes and self-developed internal combustion engine models,which simultaneously ensure high predictability.The present work demonstrates the capabilities of this innovative methodology for the design and optimization of different engines and fuels with the goal of achieving the highest possible combustion efficiencies and pollutant reductions.The analysis focuses on the influence of different fuels such as hydrogen,methanol,synthetic gasolines and methane on different engine geometries,in combination with suitable injection and ignition systems,including passive and active pre-chambers.Lean operations as well as knock reduction are discussed,particularly for methane and hydrogen injection.Finally,it is shown how depending on the chosen fuel,an appropriate ad-hoc engine layout can be designed to increase the indicated efficiency of the respective engines.

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.

Shale oil development techniques and application based on ternary-element storage and flow concept in Jiyang Depression,Bohai Bay Basin,East China

The ternary-element storage and flow concept for shale oil reservoirs in Jiyang Depression of Bohai Bay Basin,East China,was proposed based on the data of more than 10000 m cores and the production of more than 60 horizontal wells.The synergy of three elements(storage,fracture and pressure)contributes to the enrichment and high production of shale oil in Jiyang Depression.The storage element controls the enrichment of shale oil;specifically,the presence of inorganic pores and fractures,as well as laminae of lime-mud rocks,in the saline lake basin,is conducive to the storage of shale oil,and the high hydrocarbon generating capacity and free hydrocarbon content are the material basis for high production.The fracture element controls the shale oil flow;specifically,natural fractures act as flow channels for shale oil to migrate and accumulate,and induced fractures communicate natural fractures to form complex fracture network,which is fundamental to high production.The pressure element controls the high and stable production of shale oil;specifically,the high formation pressure provides the drive force for the migration and accumulation of hydrocarbons,and fracturing stimulation significantly increases the elastic energy of rock and fluid,improves the imbibition replacement of oil in the pores/fractures,and reduces the stress sensitivity,guaranteeing the stable production of shale oil for a long time.Based on the ternary-element storage and flow concept,a 3D development technology was formed,with the core techniques of 3D well pattern optimization,3D balanced fracturing,and full-cycle optimization of adjustment and control.This technology effectively guides the production and provides a support to the large-scale beneficial development of shale oil in Jiyang Depression.

Changing Concepts of City and Urban Planning Practices in Guangzhou(1949–2010): An Approach to Sustainable Urban Development

By focusing on Guangzhou, this paper examines how different concepts of city in terms of urban-rural relationships are shaped in transforming China since 1949, and explores how they influence the way in which urban planning are practiced. In the pre-reform era, the city was defined as a productive space under the system of urban-rural segregation established for securing rapid industrialization. Urban planning was thus only concerned with the development of urban areas. In the 1980 s and 1990 s after the reform, institutional change and economic transformation mobilized the urban-rural linkages. The development of suburban areas was then considered by urban planning, but this consideration was a passive response to urban problems such as population explosion and water resources protection. Since the new millennium, the agenda for sustainable development and problems of uneven urban-rural development have called for the development of urban-rural integration. In this context, the city is conceptualized as a complex of mountain, city, river, farmland and sea, reconstructing the ideology of urban-rural division in defining urban development. Urban planning has therefore sought in an active way to develop a sustainable city embracing rural and natural elements, and to balance economic growth and environmental protection. It is argued that developing the concept of city as a complex of urban and rural elements contributes to the urban planning for sustainable urban development, while this conceptualization relies on the recognition of the integrated urban-rural relationship.

Concerted Practice of the Four–Pronged Comprehensive Strategy Together with the “Five Development Concepts”

The practice of adhering to and developing socialism with Chinese characteristics requires the concerted practice of the Four-Pronged Comprehensive Strategy together with the five major development concepts.First,the implementation of the five major development concepts can be deemed as the precursor to the country's goal of building a moderately prosperous society.To this end,we shall innovatively tackle the developmental problems,coordinate social and economical development,leverage sound economic growth and resource exploitation,and practice open development strategies for the goal of creating prosperity for the entire population of China.Also,with the five major development concepts as a prerequisite for deepening reform,new measures shall be taken to creatively solve specific reform issues.Coordination shall be considered to keep all measures in one system and entity.We shall take green development concept to remove all the obstacles on our path to reform,and take opening-up concept to keep transparent and impartial reform atmosphere and sharing concept to ensure the beneficial policies and projects for the well being of all people.Moreover,implementing the five major development concepts as the foundation for law-based governance of China,innovation shall be made to develop a complete,standardized legal system,and coordination shall be developed for the legal guarantee of concerted and upgraded national hard and soft power.We shall take the green development concept for an equal legal environment,the opening-up concept to build law-based awareness for the whole society,and the sharing concept to benefit all people with fairness and righteousness in every judicial case.The five major development concepts shall be the cornerstone for strengthening Party self-discipline,by which we shall innovatively enhance Party leadership,coordinately build the Party and the Party's leading role,build a sound,orderly and vigorous political structure within the Party with green development concept.

China’s Development Concepts,Thoughts,and Strategies for the New Era

In the past five years the CPC set two centenary goals and the goal to realize the Chinese Dream of national rejuvenation, which reflects the Party＇s self-confidence. Meanwhile it has demonstrated greater resolve in self- improvement, picking up efforts to exercise full and rigorous self-governance.

An Overview on Biological Markers in Reproductive and Developmental Toxicology: Concepts, Definitions and Use in Risk Assessment

Reproduction and development are complex couple-dependent processes. Risk assessment for these health outcomes requires the use of biomarkers to link exposures to disease. Biological markers of susceptability, external dose, internal dose, biologically effective dose, early or late biological responses, altered reproductive or developmental function, and reproductive or developmental disease are introduced. Using these biomarkers it is possible to define a biologically based risk assessment methodology for reproductive and developmental toxicity. Risk assessment for reproductive toxicity requires definition of male and female fecundity, couple-specific factors, spontaneous abortion, rate, and other factors. Using using sperm count as a biomarker for male fecundity, an example of a reproductive risk assessment using biomarkers is performed.

Historical Tracing of the Development of the Concepts of ＂Competence＂ and ＂Performance＂

Competence and performance is an important pair of concepts in linguistics. Ever since their originality, they have aroused sufficient attention of the linguists. Many linguists have contributed a lot in their attempt to illustrate the concepts and clarification of them. A proper understanding of them can help the readers to gain more insight into the linguistics. What the linguist, Chomsky, originally meant by using competence and performance is somewhat different from what the current linguists mean by using them. The distance and distinction between competence and performance meant by Chomsky is also different from that meant by current linguists. That＇s to say there is some development of competence and performance since they were put forward. The shift is a gradual one, yet a very significant one. It reflects the linguists＇ effort to try to describe and categorize language learners＇ ability and their attempt to make use of them and measure them. This process actually narrows the distance and gap not only between theory and practice, but also between competence and performance. And at the same time, it reflects the linguists＇ frustration and confusion caused by the abstraction and complexity of them. By consulting the literature, the paper tries to follow their development step by step. The paper also points out some assumptions used by linguists when applying competence and performance. At the end of paper, it points out some implications to language teaching, which is important to language teachers and learners.

A Spatio-Temporal Odyssey Around the Concepts of Sustainable Development and Corporate Social Responsibility： Boundaries to Be Determined？

The aim of this research is to analyze the emergence of the concepts of sustainable development （SD） and corporate social responsibility （CSR） in companies in time and space. A spatio-temporal reading will indicate the most important socio-political and environmental events that have emerged with these two concepts. In order to complete the odyssey, a spatio-temporal analysis has retraced the epistemological evolution of these latter, whilst at the same time remarking the appropriation that has been made by the different institutional and organizational actors. The historical and epistemological reviews tell us that these two concepts, which came into existence almost 80 years, have indefinite outlines; one can be substituted for the other. However, thanks to this odyssey, we have reduced the boundaries even further between sustainable development and social responsibility and shown their theoretic and historical association. The perspective adopted shows that the concept of corporate social responsibility is closely connected to that of sustainable development. This connection means that researchers in management science are faced with more new problem issues reaching further than the simple lack of conceptual consensuses.

The Understanding and Development of“Curriculum Gamification”and“Curriculum-Based Game”Concepts in Chinese Kindergartens

Games are one of the basic activities in kindergartens,so what do“Curriculum gamification”and“Curriculum based Game”mean?Could kindergarten games become the curriculum?Combined with the history of curriculum development in China,Piaget’s play-stage theory and Vygotsky’s scaffold teaching theory,this paper discusses the differences in the understanding of the concept of“the transformation of curriculum and games”.Using representative cases in Jiangsu and Zhejiang provinces as examples,and through the analysis of the reform process of“Curriculum Gamification”and“Curriculum-based Game”in the Early Childhood Education(ECE)field,it was found that further exploration both in concept and practice is required to achieve high quality kindergarten education.

Comparison Between Development Concepts of American Democratic Culture and Chinese Social Culture

The cornerstone of the US social development lies in the general consensus about the mainstream social values of the democratic culture. The differences of the development concepts between its value of individual supremacy and the China's collectivism result in the different social development patterns in China and the US. The individual value and liberalism lead to the convergence in the group formed under the Chinese moral education and supported by the values,which will generate the divergence of the core concepts about the directions of the two kinds of social cultures. The difference of the social development under the US democratic theory and China's traditional spirit of rites makes them a pluralistic existence which can be enriched and improved in the exchanging and mutual learning process rather than an existence of antagonism.

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

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

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.

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.

Development of Productive Forces and the Changes of Rural President's Consumption Concept

The developmental status of productivity in Chinese rural area is introduced. Since the implementation of the agriculture supporting policies in 2004, the productive forces in rural areas have been improved greatly. It is reflected on the following aspects: great enhancement of rural labors' cultural quality; the quantity of agricultural machines has been increased; the level of production management and decision has been increased greatly. The paper analyzes the promotion role played by the development of productive forces to rural residents' consumption conception. The development of productive forces has laid a solid foundation for changing rural residents' consumption concept; changed rural residents' consumption structure and improved the socialized degree of rural residents' consumption. Countermeasures on cultivating new consumption fields in rural areas are put forward including leading rural residents to foster the modern consumption conception; intensifying the governmental support and leading rural residents to set up healthy consumption concept.

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.