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 syste...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.展开更多
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 t...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.展开更多
Drought is a main abiotic stress factor hindering plant growth,development,and crop productivity.Therefore,it is crucial to understand the mechanisms by which plants cope with drought stress.Here,the function of the m...Drought is a main abiotic stress factor hindering plant growth,development,and crop productivity.Therefore,it is crucial to understand the mechanisms by which plants cope with drought stress.Here,the function of the maize peroxidase gene ZmPRX1 in drought stress tolerance was investigated by measurement of its expression in response to drought treatment both in a ZmPRX1 overexpression line and a mutant line.The higher root lignin accumulation and seedling survival rate of the overexpression line than that of the wild type or mutant support a role for ZmPRX1 in maize drought tolerance by regulating root development and lignification.Additionally,yeast one-hybrid,Dule luciferase and ChIP-qPCR assays showed that ZmPRX1 is negatively regulated by a nuclear-localized ZmWRKY86 transcription factor.The gene could potentially be used for breeding of drought-tolerant cultivars.展开更多
Ear differentiation,grain development and their interaction with factors in the growing environment,such as temperature,solar radiation and precipitation,greatly influence grain number and grain weight,and ultimately ...Ear differentiation,grain development and their interaction with factors in the growing environment,such as temperature,solar radiation and precipitation,greatly influence grain number and grain weight,and ultimately affect summer maize production.In this study,field experiments involving different sowing dates were conducted over three years to evaluate the effects of temperature factors,average solar radiation and total precipitation on the growth process,ear differentiation,fertilization characteristics,grain filling and yield of summer maize varieties with different growth durations.Four hybrids were evaluated in Huang-Huai-Hai Plain(HHHP),China from 2018 to 2020 with five different sowing dates.The results showed that the grain yield formation of summer maize was strongly impacted by the environment from the silking(R1)to milking(R3)stage.Average minimum temperature(AT_(min))was the key environmental factor that determined yield.Reductions in the length of the growing season(r=–0.556,P<0.01)and the total floret number on ear(R^(2)=0.200,P<0.001)were found when AT_(min) was elevated from the emerging(VE)to R1 stage.Both grain-filling rate(R^(2)=0.520,P<0.001)and the floret abortion rate on ear(R^(2)=0.437,P<0.001)showed quadratic relationships with AT_(min) from the R1 to physiological maturity(R6)stage,while the number of days after the R1 stage(r=–0.756,P<0.01)was negatively correlated with AT_(min).An increase in AT_(min) was beneficial for the promotion of yield when it did not exceeded a certain level(above 23°C during the R1–R3 stage and 20–21°C during the R1-R6 stage).Enhanced solar radiation and precipitation during R1–R6 increased the grain-filling rate(R^(2)=0.562,P<0.001 and R^(2)=0.229,P<0.05,respectively).Compared with short-season hybrids,full-season hybrids showed much greater suitability for a critical environment.The coordinated regulation of AT_(min),ear differentiation and grain development at the pre-and post-silking stages improved maize yield by increasing total floret number and grain-filling rate,and by reducing the floret abortion rate on ear.展开更多
Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our...Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our previous studies have shown that the PIP5K gene family(PIP5Ks)is associated with inflorescence development.In this study,to determine the function of each PIP5K gene in castor,a female Lm-type castor line,aLmAB2,was used to determine the relative expression levels of the PIP5Ks in castor inflorescences.Six PIP5K genes were heterologously overexpressed in Arabidopsis thaliana,the relative expression of each gene and the effect on plants was determined in A.thaliana,and the relationships among the PIP5Ks in castor were inferred.The expression levels of the PIP5Ks in the female Lm-type castor line aLmAB2 were analyzed.The relative expression levels of the PIP5K9 and PIP5K11 genes were high(p<0.05)in isofemale inflorescences,and those of PIP5K1,PIP5K2,PIP5K6,and PIP5K8 were high(p<0.05)in female inflorescences but low(p<0.05)in bisexual inflorescences.The PIP5Ks were heterologously overexpressed in A.thaliana,and T3-generation plants with stable genetic resistance,i.e.,AT-PIP5K^(+)plants(AT-PIP5K1^(+),AT-PIP5K2^(+),AT-PIP5K6^(+),AT-PIP5K8^(+),AT-PIP5K9^(+),and ATPIP5K11^(+) plants),were obtained.Biological tests of the AT-PIP5K+plants showed that the growth of the main stem was significantly delayed in AT-PIP5K+plants compared with Columbia wild-type(WT)A.thaliana plants;the PIP5K1 and PIP5K2 genes promoted lateral stem growth and flower and silique development;and the PIP5K6,PIP5K8,PIP5K9 and PIP5K11 genes inhibited lateral stem growth and flower and silique development.The correlations among PIP5Ks in castor suggest that there may be a synergistic relationship among PIP5K1,PIP5K2,and PIP5K6 in castor inflorescences,and PIP5K8,PIP5K9,and PIP5K11 are complementary to the other three genes.展开更多
This study evaluated the effectiveness of donor supported agricultural value chain development projects in sustainably narrowing yield gaps for banana smallholder farmer producers in Manicaland, Zimbabwe. The study us...This study evaluated the effectiveness of donor supported agricultural value chain development projects in sustainably narrowing yield gaps for banana smallholder farmer producers in Manicaland, Zimbabwe. The study used a mixed methods research design that relied on farmers records for the quantitative analysis and focus group discussion and in-depth interviews for key experts for the qualitative aspects. A mix of regression analysis, t-tests, Pearsons’s correlation and analysis of variance statistical methods were used for the quantitative analysis while thematic response analysis was used for the qualitative engagements. The findings showed that by the end of the activity, the project had successfully narrowed the banana yield gaps to 18.66 tons per hectare working with a potential yield base of 40 tons. However, 5 years after the project closure the yield gap had fallen to 24.7 tons indicating a lack of sustainability of yield gap reduction. However, the yield gap slump does not override the fact that farmers on average were still able to sell approximately 5 tons per every 6 months after 5 years from the project closure which is beyond any poverty threshold. This suggests genuine upward economic mobility. Additionally, in analyzing what factors had the greatest influence on yield gap reduction, the access to fertilizer ranked highest where genetics, irrigation and improved agronomy followed in that respective order. The study further showed that farmers who receive value chain development support whilst at an already commercialized state tend to maintain productivity thresholds higher in comparison to those who are at a pre commercial state. This is evidenced by the fact that the pre commercial farmers had a yield reduction of 30.83 percent after 5 years of the project closure whereas the former realized a productivity growth of 7.84%. In conclusion, whilst the intervention was successful in transitioning farmers out of poverty, more investment should be made towards transitioning smallholder farmers to integrated soil fertility management practices and improvement of agronomic efficiency through stronger on field collaboration between research institutions, the government and development institutions.展开更多
BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and furthe...BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.展开更多
This paper reviews the basic research means for oilfield development and also the researches and tests of enhanced oil recovery(EOR)methods for mature oilfields and continental shale oil development,analyzes the probl...This paper reviews the basic research means for oilfield development and also the researches and tests of enhanced oil recovery(EOR)methods for mature oilfields and continental shale oil development,analyzes the problems of EOR methods,and proposes the relevant research prospects.The basic research means for oilfield development include in-situ acquisition of formation rock/fluid samples and non-destructive testing.The EOR methods for conventional and shale oil development are classified as improved water flooding(e.g.nano-water flooding),chemical flooding(e.g.low-concentration middle-phase micro-emulsion flooding),gas flooding(e.g.micro/nano bubble flooding),thermal recovery(e.g.air injection thermal-aided miscible flooding),and multi-cluster uniform fracturing/water-free fracturing,which are discussed in this paper for their mechanisms,approaches,and key technique researches and field tests.These methods have been studied with remarkable progress,and some achieved ideal results in field tests.Nonetheless,some problems still exist,such as inadequate research on mechanisms,imperfect matching technologies,and incomplete industrial chains.It is proposed to further strengthen the basic researches and expand the field tests,thereby driving the formation,promotion and application of new technologies.展开更多
Career development for higher education teachers plays a crucial role in enhancing both the quality of education and the professional satisfaction of academic staff.This essay explores the various stages of career dev...Career development for higher education teachers plays a crucial role in enhancing both the quality of education and the professional satisfaction of academic staff.This essay explores the various stages of career development for educators,including entry into academia,professional growth,and leadership advancement.It examines the challenges these educators face-such as the balance between teaching,research,and service-and presents strategies that institutions and individuals can adopt to foster career growth.Key factors like mentorship,continuing education,and institutional support are discussed as critical to enabling sustainable career progression.The essay concludes by underscoring the importance of ongoing development to ensure teachers can meet evolving educational demands.展开更多
In recent years,the integrated development of the tea and tourism has become an important way to promote the rural revitalization of Tai'an tea-producing areas,but the state of industrial upgrading still needs to ...In recent years,the integrated development of the tea and tourism has become an important way to promote the rural revitalization of Tai'an tea-producing areas,but the state of industrial upgrading still needs to be improved.In order to better integrate tea and tourism in Tea Valley,this paper uses questionnaire and SWOT analysis to study.It found the following problems:(i)45.7%of tourists were interested in tea culture,but they know litle about it,and the integration of tea culture and tea tourism products is low.(i)50.54%of the tourists were interested in the tea picking experience project and wanted to add the tea food experience item.(ii)The acceptance of 45.7%of tourists to scenic spots was 1-2 h,which shows that the quality of transportation service facilities and personnel needs to be improved.Combined with the SWOT analysis,it is found that the scenic spot is rich in resources,convenient transportation,profound cultural heritage,and good govern-ment policy support conditions,which is suitable for the SO strategy(growth development strategy),so the scenic spot relies on internal ad-vantages and seizes external opportunities to develop the integration of tea and tourism.Based on the analysis results,it came up with the perti-nent recommendations for the key problems:(i)The infrastructure service is not well established.It is suggested that scenic spots should in-crease investment,regularly train service personnel to improve their quality,and improve transportation services,accommodation,catering and public service hardware facilities.(i)Tea tourism products are insufficient.It is suggested that tea tourism products should be innovatively designed and tea tourism experiential products and tourism commodities should be planned.(i)Tea culture and tourism lack organic combi-nation.It is recommended to deeply excavate tea culture,and take consideration of both spiritual and material aspects.The specific methods include building teahouses,Taishan Mountain(Mount Tai)tea culture throughout the whole process of tea production,development and pro-cessing,and AR tea culture experience hall can be built to make tourists feel tea culture from dfferent perspectives.(iv)The publicity is in-sufficient.Strategies should be made in three aspects:improving the Internet media,taking into account the traditional media,and expanding the market based on the surrounding areas.(v)The tea industry chain is short.It is recommended to add four new industrial chain designs of"tea+accommodation,tea+catering,tea+Intemet,tea+training",hoping to bring some inspiration and ideas to the managers of scenic spots.展开更多
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 a...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.展开更多
The rapidly advancing field of artificial intelligence(AI)has garnered substantial attention for its potential application in drug discovery and development.This opinion review critically examined the feasibility and ...The rapidly advancing field of artificial intelligence(AI)has garnered substantial attention for its potential application in drug discovery and development.This opinion review critically examined the feasibility and prospects of integrating AI as a transformative tool in the pharmaceutical industry.AI,encompassing machine learning algorithms,deep learning,and data analytics,offers unprecedented opportunities to streamline and enhance various stages of drug development.This opinion review delved into the current landscape of AI-driven approaches,discussing their utilization in target identification,lead optimization,and predictive modeling of pharmacokinetics and toxicity.We aimed to scrutinize the integration of large-scale omics data,electronic health records,and chemical informatics,highlighting the power of AI in uncovering novel therapeutic targets and accelerating drug repurposing strategies.Despite the considerable potential of AI,the review also addressed inherent challenges,including data privacy concerns,interpretability of AI models,and the need for robust validation in realworld clinical settings.Additionally,we explored ethical considerations surrounding AI-driven decision-making in drug development.This opinion review provided a nuanced perspective on the transformative role of AI in drug discovery by discussing the existing literature and emerging trends,presenting critical insights and addressing potential hurdles.In conclusion,this study aimed to stimulate discourse within the scientific community and guide future endeavors to harness the full potential of AI in drug development.展开更多
As the world undergoes a digital transformation,China-Arab cooperation in the digital economy has become a pivotal area of international engagement.This article explores the opportunities,challenges,and prospects of t...As the world undergoes a digital transformation,China-Arab cooperation in the digital economy has become a pivotal area of international engagement.This article explores the opportunities,challenges,and prospects of this cooperation,with a particular focus on the Digital Silk Road initiative under the Belt and Road framework.The study highlights the synergies between China’s technological advancements and the digital strategies of Arab countries,examining progress in key areas such as cooperation mechanisms,digital infrastructure,and cross-border e-commerce.Moreover,it identifies significant challenges,including the digital divide and talent shortages,and proposes strategies to enhance China-Arab digital economy cooperation.These strategies include improving digital infrastructure,growing digital talent cultivation,and developing smart city initiatives alongside expanding cross-border e-commerce,all aimed at fostering sustainable and mutually beneficial outcomes.展开更多
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 ...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.展开更多
With the rapid development of our country’s economy,education has gradually become the focus of social attention.The problem of unbalanced distribution of urban and rural educational resources has become increasingly...With the rapid development of our country’s economy,education has gradually become the focus of social attention.The problem of unbalanced distribution of urban and rural educational resources has become increasingly prominent,urban educational resources are relatively rich,while rural educational resources are relatively scarce,and the balanced development of urban and rural compulsory education has become an urgent task.This paper mainly investigates and studies the distribution of urban and rural educational resources,discusses the unbalanced distribution of urban and rural educational resources and analyzes the reasons,and puts forward a series of corresponding solutions to promote the balanced development of urban and rural compulsory education.展开更多
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 r...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.展开更多
The development objectives of the Chinese government have a guiding effect on the school-running characteristics of private colleges and universities.This paper explores the relationship between the characteristics of...The development objectives of the Chinese government have a guiding effect on the school-running characteristics of private colleges and universities.This paper explores the relationship between the characteristics of private colleges and universities and the development objectives of the provincial government,using Jiangsu Province as a case study.All the schools have the consciousness of fully considering the development objectives of Jiangsu Province when formulating the school-running characteristics.Their characteristics all contain some training methods,training courses,or institutional construction aiming at the development objectives.Most universities can support the government’s objectives on employment and innovation.Only a third of the schools provide government support for science research.Private colleges and universities should make full use of the free and flexible advantages of private education,combine them with the continuous changes of policies and markets,and create clear,scientific,and dynamic school-running characteristics,in order to achieve long-term development.展开更多
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 lili...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.展开更多
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 nephrogene...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.展开更多
Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have...Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.展开更多
文摘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.
基金supported by the Japan Society for the Promotion of Science KAKENHI(grant Nos.23K05678 to IM,19H05711 and 20H00466 to KS)the Joint Research Program of Institute for Molecular and Cellular Regulation,Gunma University(to KS)。
文摘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.
基金supported by the State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2022ZZ-4)the Key Research and Development Projects of Hebei Province(21326319D)。
文摘Drought is a main abiotic stress factor hindering plant growth,development,and crop productivity.Therefore,it is crucial to understand the mechanisms by which plants cope with drought stress.Here,the function of the maize peroxidase gene ZmPRX1 in drought stress tolerance was investigated by measurement of its expression in response to drought treatment both in a ZmPRX1 overexpression line and a mutant line.The higher root lignin accumulation and seedling survival rate of the overexpression line than that of the wild type or mutant support a role for ZmPRX1 in maize drought tolerance by regulating root development and lignification.Additionally,yeast one-hybrid,Dule luciferase and ChIP-qPCR assays showed that ZmPRX1 is negatively regulated by a nuclear-localized ZmWRKY86 transcription factor.The gene could potentially be used for breeding of drought-tolerant cultivars.
基金supported by Key Technology Research and Development Program of Shandong Province,China(2021LZGC014-2)the National Natural Science Foundation of China(32172115)the National Modern Agriculture Industry Technology System,China(CARS02-21)。
文摘Ear differentiation,grain development and their interaction with factors in the growing environment,such as temperature,solar radiation and precipitation,greatly influence grain number and grain weight,and ultimately affect summer maize production.In this study,field experiments involving different sowing dates were conducted over three years to evaluate the effects of temperature factors,average solar radiation and total precipitation on the growth process,ear differentiation,fertilization characteristics,grain filling and yield of summer maize varieties with different growth durations.Four hybrids were evaluated in Huang-Huai-Hai Plain(HHHP),China from 2018 to 2020 with five different sowing dates.The results showed that the grain yield formation of summer maize was strongly impacted by the environment from the silking(R1)to milking(R3)stage.Average minimum temperature(AT_(min))was the key environmental factor that determined yield.Reductions in the length of the growing season(r=–0.556,P<0.01)and the total floret number on ear(R^(2)=0.200,P<0.001)were found when AT_(min) was elevated from the emerging(VE)to R1 stage.Both grain-filling rate(R^(2)=0.520,P<0.001)and the floret abortion rate on ear(R^(2)=0.437,P<0.001)showed quadratic relationships with AT_(min) from the R1 to physiological maturity(R6)stage,while the number of days after the R1 stage(r=–0.756,P<0.01)was negatively correlated with AT_(min).An increase in AT_(min) was beneficial for the promotion of yield when it did not exceeded a certain level(above 23°C during the R1–R3 stage and 20–21°C during the R1-R6 stage).Enhanced solar radiation and precipitation during R1–R6 increased the grain-filling rate(R^(2)=0.562,P<0.001 and R^(2)=0.229,P<0.05,respectively).Compared with short-season hybrids,full-season hybrids showed much greater suitability for a critical environment.The coordinated regulation of AT_(min),ear differentiation and grain development at the pre-and post-silking stages improved maize yield by increasing total floret number and grain-filling rate,and by reducing the floret abortion rate on ear.
基金National Natural Science Foundation of China(31860071)Ministry of Education New Agricultural Research and Reform Practice Program(2020114)+4 种基金Surface Program of Inner Mongolia Natural Science Foundation(2021MS03008)Inner Mongolia Autonomous Region Grassland Talent Innovation Team-Rolling Support Program for Castor Molecular Breeding Research Innovation Talent Teams(2022)2023 Inner Mongolia Autonomous Region Science and Technology Department Establishes the Project of Key Laboratory Construction of Castor Breeding and Comprehensive Utilization in Inner Mongolia Autonomous RegionInner Mongolia University for Nationalities 2022 Basic Research Operating Expenses of Colleges and Universities directly under the Autonomous Region Project(237)Open Fund Project of Castor Industry Collaborative Innovation Center of Inner Mongolia Autonomous Region(MDK2021011,MDK2022014).
文摘Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our previous studies have shown that the PIP5K gene family(PIP5Ks)is associated with inflorescence development.In this study,to determine the function of each PIP5K gene in castor,a female Lm-type castor line,aLmAB2,was used to determine the relative expression levels of the PIP5Ks in castor inflorescences.Six PIP5K genes were heterologously overexpressed in Arabidopsis thaliana,the relative expression of each gene and the effect on plants was determined in A.thaliana,and the relationships among the PIP5Ks in castor were inferred.The expression levels of the PIP5Ks in the female Lm-type castor line aLmAB2 were analyzed.The relative expression levels of the PIP5K9 and PIP5K11 genes were high(p<0.05)in isofemale inflorescences,and those of PIP5K1,PIP5K2,PIP5K6,and PIP5K8 were high(p<0.05)in female inflorescences but low(p<0.05)in bisexual inflorescences.The PIP5Ks were heterologously overexpressed in A.thaliana,and T3-generation plants with stable genetic resistance,i.e.,AT-PIP5K^(+)plants(AT-PIP5K1^(+),AT-PIP5K2^(+),AT-PIP5K6^(+),AT-PIP5K8^(+),AT-PIP5K9^(+),and ATPIP5K11^(+) plants),were obtained.Biological tests of the AT-PIP5K+plants showed that the growth of the main stem was significantly delayed in AT-PIP5K+plants compared with Columbia wild-type(WT)A.thaliana plants;the PIP5K1 and PIP5K2 genes promoted lateral stem growth and flower and silique development;and the PIP5K6,PIP5K8,PIP5K9 and PIP5K11 genes inhibited lateral stem growth and flower and silique development.The correlations among PIP5Ks in castor suggest that there may be a synergistic relationship among PIP5K1,PIP5K2,and PIP5K6 in castor inflorescences,and PIP5K8,PIP5K9,and PIP5K11 are complementary to the other three genes.
文摘This study evaluated the effectiveness of donor supported agricultural value chain development projects in sustainably narrowing yield gaps for banana smallholder farmer producers in Manicaland, Zimbabwe. The study used a mixed methods research design that relied on farmers records for the quantitative analysis and focus group discussion and in-depth interviews for key experts for the qualitative aspects. A mix of regression analysis, t-tests, Pearsons’s correlation and analysis of variance statistical methods were used for the quantitative analysis while thematic response analysis was used for the qualitative engagements. The findings showed that by the end of the activity, the project had successfully narrowed the banana yield gaps to 18.66 tons per hectare working with a potential yield base of 40 tons. However, 5 years after the project closure the yield gap had fallen to 24.7 tons indicating a lack of sustainability of yield gap reduction. However, the yield gap slump does not override the fact that farmers on average were still able to sell approximately 5 tons per every 6 months after 5 years from the project closure which is beyond any poverty threshold. This suggests genuine upward economic mobility. Additionally, in analyzing what factors had the greatest influence on yield gap reduction, the access to fertilizer ranked highest where genetics, irrigation and improved agronomy followed in that respective order. The study further showed that farmers who receive value chain development support whilst at an already commercialized state tend to maintain productivity thresholds higher in comparison to those who are at a pre commercial state. This is evidenced by the fact that the pre commercial farmers had a yield reduction of 30.83 percent after 5 years of the project closure whereas the former realized a productivity growth of 7.84%. In conclusion, whilst the intervention was successful in transitioning farmers out of poverty, more investment should be made towards transitioning smallholder farmers to integrated soil fertility management practices and improvement of agronomic efficiency through stronger on field collaboration between research institutions, the government and development institutions.
文摘BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.
基金Supported by the PetroChina Science and Technology Major Project(2023ZZ04,2023ZZ08)。
文摘This paper reviews the basic research means for oilfield development and also the researches and tests of enhanced oil recovery(EOR)methods for mature oilfields and continental shale oil development,analyzes the problems of EOR methods,and proposes the relevant research prospects.The basic research means for oilfield development include in-situ acquisition of formation rock/fluid samples and non-destructive testing.The EOR methods for conventional and shale oil development are classified as improved water flooding(e.g.nano-water flooding),chemical flooding(e.g.low-concentration middle-phase micro-emulsion flooding),gas flooding(e.g.micro/nano bubble flooding),thermal recovery(e.g.air injection thermal-aided miscible flooding),and multi-cluster uniform fracturing/water-free fracturing,which are discussed in this paper for their mechanisms,approaches,and key technique researches and field tests.These methods have been studied with remarkable progress,and some achieved ideal results in field tests.Nonetheless,some problems still exist,such as inadequate research on mechanisms,imperfect matching technologies,and incomplete industrial chains.It is proposed to further strengthen the basic researches and expand the field tests,thereby driving the formation,promotion and application of new technologies.
文摘Career development for higher education teachers plays a crucial role in enhancing both the quality of education and the professional satisfaction of academic staff.This essay explores the various stages of career development for educators,including entry into academia,professional growth,and leadership advancement.It examines the challenges these educators face-such as the balance between teaching,research,and service-and presents strategies that institutions and individuals can adopt to foster career growth.Key factors like mentorship,continuing education,and institutional support are discussed as critical to enabling sustainable career progression.The essay concludes by underscoring the importance of ongoing development to ensure teachers can meet evolving educational demands.
文摘In recent years,the integrated development of the tea and tourism has become an important way to promote the rural revitalization of Tai'an tea-producing areas,but the state of industrial upgrading still needs to be improved.In order to better integrate tea and tourism in Tea Valley,this paper uses questionnaire and SWOT analysis to study.It found the following problems:(i)45.7%of tourists were interested in tea culture,but they know litle about it,and the integration of tea culture and tea tourism products is low.(i)50.54%of the tourists were interested in the tea picking experience project and wanted to add the tea food experience item.(ii)The acceptance of 45.7%of tourists to scenic spots was 1-2 h,which shows that the quality of transportation service facilities and personnel needs to be improved.Combined with the SWOT analysis,it is found that the scenic spot is rich in resources,convenient transportation,profound cultural heritage,and good govern-ment policy support conditions,which is suitable for the SO strategy(growth development strategy),so the scenic spot relies on internal ad-vantages and seizes external opportunities to develop the integration of tea and tourism.Based on the analysis results,it came up with the perti-nent recommendations for the key problems:(i)The infrastructure service is not well established.It is suggested that scenic spots should in-crease investment,regularly train service personnel to improve their quality,and improve transportation services,accommodation,catering and public service hardware facilities.(i)Tea tourism products are insufficient.It is suggested that tea tourism products should be innovatively designed and tea tourism experiential products and tourism commodities should be planned.(i)Tea culture and tourism lack organic combi-nation.It is recommended to deeply excavate tea culture,and take consideration of both spiritual and material aspects.The specific methods include building teahouses,Taishan Mountain(Mount Tai)tea culture throughout the whole process of tea production,development and pro-cessing,and AR tea culture experience hall can be built to make tourists feel tea culture from dfferent perspectives.(iv)The publicity is in-sufficient.Strategies should be made in three aspects:improving the Internet media,taking into account the traditional media,and expanding the market based on the surrounding areas.(v)The tea industry chain is short.It is recommended to add four new industrial chain designs of"tea+accommodation,tea+catering,tea+Intemet,tea+training",hoping to bring some inspiration and ideas to the managers of scenic spots.
文摘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.
基金Supported by the European Union-NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘The rapidly advancing field of artificial intelligence(AI)has garnered substantial attention for its potential application in drug discovery and development.This opinion review critically examined the feasibility and prospects of integrating AI as a transformative tool in the pharmaceutical industry.AI,encompassing machine learning algorithms,deep learning,and data analytics,offers unprecedented opportunities to streamline and enhance various stages of drug development.This opinion review delved into the current landscape of AI-driven approaches,discussing their utilization in target identification,lead optimization,and predictive modeling of pharmacokinetics and toxicity.We aimed to scrutinize the integration of large-scale omics data,electronic health records,and chemical informatics,highlighting the power of AI in uncovering novel therapeutic targets and accelerating drug repurposing strategies.Despite the considerable potential of AI,the review also addressed inherent challenges,including data privacy concerns,interpretability of AI models,and the need for robust validation in realworld clinical settings.Additionally,we explored ethical considerations surrounding AI-driven decision-making in drug development.This opinion review provided a nuanced perspective on the transformative role of AI in drug discovery by discussing the existing literature and emerging trends,presenting critical insights and addressing potential hurdles.In conclusion,this study aimed to stimulate discourse within the scientific community and guide future endeavors to harness the full potential of AI in drug development.
基金funded by the National Social Science Foundation (22CGJ025).
文摘As the world undergoes a digital transformation,China-Arab cooperation in the digital economy has become a pivotal area of international engagement.This article explores the opportunities,challenges,and prospects of this cooperation,with a particular focus on the Digital Silk Road initiative under the Belt and Road framework.The study highlights the synergies between China’s technological advancements and the digital strategies of Arab countries,examining progress in key areas such as cooperation mechanisms,digital infrastructure,and cross-border e-commerce.Moreover,it identifies significant challenges,including the digital divide and talent shortages,and proposes strategies to enhance China-Arab digital economy cooperation.These strategies include improving digital infrastructure,growing digital talent cultivation,and developing smart city initiatives alongside expanding cross-border e-commerce,all aimed at fostering sustainable and mutually beneficial outcomes.
文摘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.
文摘With the rapid development of our country’s economy,education has gradually become the focus of social attention.The problem of unbalanced distribution of urban and rural educational resources has become increasingly prominent,urban educational resources are relatively rich,while rural educational resources are relatively scarce,and the balanced development of urban and rural compulsory education has become an urgent task.This paper mainly investigates and studies the distribution of urban and rural educational resources,discusses the unbalanced distribution of urban and rural educational resources and analyzes the reasons,and puts forward a series of corresponding solutions to promote the balanced development of urban and rural compulsory education.
文摘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.
基金Nanjing Tech University Pujiang Institute School-Level Project“Empirical Research on the Impact of Regional Development Policies on the School-Running Characteristics of Private Universities”(njpj2023-2-15)。
文摘The development objectives of the Chinese government have a guiding effect on the school-running characteristics of private colleges and universities.This paper explores the relationship between the characteristics of private colleges and universities and the development objectives of the provincial government,using Jiangsu Province as a case study.All the schools have the consciousness of fully considering the development objectives of Jiangsu Province when formulating the school-running characteristics.Their characteristics all contain some training methods,training courses,or institutional construction aiming at the development objectives.Most universities can support the government’s objectives on employment and innovation.Only a third of the schools provide government support for science research.Private colleges and universities should make full use of the free and flexible advantages of private education,combine them with the continuous changes of policies and markets,and create clear,scientific,and dynamic school-running characteristics,in order to achieve long-term development.
基金supported by the National Key Research and Development Program of China(2022YFD1200500)the Fundamental Research Funds for the Central Universities(KYZZ2022004)+1 种基金the Project for Crop Germplasm Resources Conservation of Jiangsu(2021-SJ-011)the High Level Talent Project of the Top Six Talents in Jiangsu(NY-077)。
文摘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.
基金the National Natural Science Foundation of China,No.82360148Guizhou Science&Technology Department,No.QKHPTRC2018-5636-2 and No.QKHPTRC2020-2201.
文摘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.
基金supported by the sup-project of National Key R&D Program of China,No.2018YFA0108602CAMS Innovation Fund for Medical Sciences,No.CIFMS,2021-I2M-C&T-B-016National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-112(all to JG).
文摘Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.