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
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-li...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.展开更多
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 contin...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.展开更多
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are...The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.展开更多
The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis acro...The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.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
BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lac...BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.展开更多
Salinity stress is a major environmental stress affecting crop productivity,and its negative impact on global food security is only going to increase,due to current climate trends.Salinity tolerance was present in wil...Salinity stress is a major environmental stress affecting crop productivity,and its negative impact on global food security is only going to increase,due to current climate trends.Salinity tolerance was present in wild crop relatives but significantly weakened during domestication.Regaining it back requires a good understanding of molecular mechanisms and traits involved in control of plant ionic and ROS homeostasis.This review summarizes our current knowledge on the role of major plant hormones(auxin,cytokinins,abscisic acid,salicylic acid,and jasmonate)in plants adaptation to soil salinity.We firstly discuss the role of hormones in controlling root tropisms,root growth and architecture(primary root elongation,meristematic activity,lateral root development,and root hairs formation).Hormone-mediated control of uptake and sequestration of key inorganic ions(sodium,potassium,and calcium)is then discussed followed by regulation of cell redox balance and ROS signaling in salt-stressed roots.Finally,the role of epigenetic alterations such as DNA methylation and histone modifications in control of plant ion and ROS homeostasis and signaling is discussed.This data may help develop novel strategies for breeding and cultivating salt-tolerant crops and improving agricultural productivity in saline regions.展开更多
Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been...Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.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
Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of posts...Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.展开更多
Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive propor...Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive proportion of the population to CVD risk factors,and this situation is further worsened due to the accelerated aging population in China.CVD remains one of the greatest threats to the health of Chinese residents.In terms of the proportions of disease mortality among urban and rural residents in China,CVD has persistently ranked first.In 2021,CVD accounted for 48.98%and 47.35%of deaths in rural and urban areas,respectively.Two out of every five deaths can be attributed to CVD.To implement a national policy“focusing on the primary health institute and emphasizing prevention”and truly achieve a shift of CVD prevention and treatment from hospitals to communities,the National Center for Cardiovascular Diseases has organized experts from relevant fields across China to compile the“Report on Cardiovascular Health and Diseases in China”annually since 2005.The 2024 report is established based on representative,published,and high-quality big-data research results from cross-sectional and cohort population epidemiological surveys,randomized controlled clinical trials,large sample registry studies,and typical community prevention and treatment cases,along with data from some projects undertaken by the National Center for Cardiovascular Diseases.These firsthand data not only enrich the content of the current report but also provide a more timely and comprehensive reflection of the status of CVD prevention and treatment in China.展开更多
With rapid economic development,the size of urban land in China is expanding dramatically.The Urban Growth Boundary(UGB)is an expandable spatial boundary for urban construction in a certain period in order to control ...With rapid economic development,the size of urban land in China is expanding dramatically.The Urban Growth Boundary(UGB)is an expandable spatial boundary for urban construction in a certain period in order to control the urban sprawl.Reasonable delineation of UGB can inhibit the disorderly spread of urban space and guide the normal development of the city.It is of practical significance for the construction of green urban space.The study utilizes GIS technology to establish a land construction suitability evaluation system for Nankang city,which is experiencing rapid urban expansion,and outlines the preliminary UGB under the future land use simulation(FLUS)model.At the same time,considering the coupled coordination of"Production-Living-Ecological Space",and based on the suitability evaluation,we revised the preliminary UGB by combining the advantages of the patch-generating land use simulation(PLUS)model and the convex hull model to delineate the final UGB.The results show that:1)the comprehensive score of the evaluation of the suitability of the construction of land from high to low shows the distribution of the center of the city to the surrounding circle type spread,the center of the city has the highest suitability score.The results of convex hull model show that the urban expansion type of Nankang is epitaxial.In the future,the urban expansion will mainly occur in the northern part of the city.The PLUS model predicts an increase of 3359.97 hm^(2)of construction land in Nankang by 2035,of which 2022.97 hm^(2)is urban construction land.2)The FLUS model has a prediction accuracy of 86.3%and delineates a preliminary UGB area of 9215.07 hm^(2).3)We used the results of the construction suitability evaluation,PLUS model simulation results,and convex hull model predictions to revise the originally delineated UGB.The final delineated UGB area is 8895.67 hm^(2)and it is capable of meeting the future development of the study area.The results of the delineation can promote sustainable urban development,and the delineation methodology can provide a reference basis for the preparation of territorial spatial planning.展开更多
This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demogra...This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demographic and Health Surveys(DHS).Results from both fixed effects(FE)and instrumental variable(IV)estimates show that using non-solid cooking fuel significantly improves the nutrition outcomes of under-five children.Compared with their peers from households mainly using solid fuel,children from households mainly using non-solid fuel exhibit a lower probability of experiencing stunting(by 5.9 percentage points)and being underweight(by 1.2 percentage points).Our further investigation provides evidence for several underlying mechanisms,such as improved indoor air quality,induced reduction in children’s respiratory symptoms,benefits on maternal health,and reduction in maternal time spent on fuel collection or cooking.Heterogenous analyses suggest that the nutrition benefits of using non-solid cooking fuel are more prominent among boys,children above three years old,and those from households of lower socioeconomic status,rural areas,and Southeast Asia.展开更多
AIM:To investigate the prevalence of visual impairment(VI)and provide an estimation of uncorrected refractive errors in school-aged children,conducted by optometry students as a community service.METHODS:The study was...AIM:To investigate the prevalence of visual impairment(VI)and provide an estimation of uncorrected refractive errors in school-aged children,conducted by optometry students as a community service.METHODS:The study was cross-sectional.Totally 3343 participants were included in the study.The initial examination involved assessing the uncorrected distance visual acuity(UDVA)and visual acuity(VA)while using a+2.00 D lens.The inclusion criteria for a subsequent comprehensive cycloplegic eye examination,performed by an optometrist,were as follows:a UDVA<0.6 decimal(0.20 logMAR)and/or a VA with+2.00 D≥0.8 decimal(0.96 logMAR).RESULTS:The sample had a mean age of 10.92±2.13y(range 4 to 17y),and 51.3%of the children were female(n=1715).The majority of the children(89.7%)fell within the age range of 8 to 14y.Among the ethnic groups,the highest representation was from the Luhya group(60.6%)followed by Luo(20.4%).Mean logMAR UDVA choosing the best eye for each student was 0.29±0.17(range 1.70 to 0.22).Out of the total,246 participants(7.4%)had a full eye examination.The estimated prevalence of myopia(defined as spherical equivalent≤-0.5 D)was found to be 1.45%of the total sample.While around 0.18%of the total sample had hyperopia value exceeding+1.75 D.Refractive astigmatism(cil<-0.75 D)was found in 0.21%(7/3343)of the children.The VI prevalence was 1.26%of the total sample.Among our cases of VI,76.2%could be attributed to uncorrected refractive error.Amblyopia was detected in 0.66%(22/3343)of the screened children.There was no statistically significant correlation observed between age or gender and refractive values.CONCLUSION:The primary cause of VI is determined to be uncorrected refractive errors,with myopia being the most prevalent refractive error observed.These findings underscore the significance of early identification and correction of refractive errors in school-aged children as a means to alleviate the impact of VI.展开更多
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"a...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.展开更多
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...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.展开更多
Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered ...Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.展开更多
Regional inequality significantly influences sustainable development and human well-being.In China,there exists pronounced regional disparities in economic and digital advancements;however,scant research delves into t...Regional inequality significantly influences sustainable development and human well-being.In China,there exists pronounced regional disparities in economic and digital advancements;however,scant research delves into the interplay between them.By analyzing the economic development and digitalization gaps at regional and city levels in China,extending the original Cobb-Douglas production function,this study aims to evaluate the impact of digitalization on China's regional inequality using seemingly unrelated regression.The results indicate a greater emphasis on digital inequality compared to economic disparity,with variable coefficients of 0.59 for GDP per capita and 0.92 for the digitalization index over the past four years.However,GDP per capita demonstrates higher spatial concentration than digitalization.Notably,both disparities have shown a gradual reduction in recent years.The southeastern region of the Hu Huanyong Line exhibits superior levels and rates of economic and digital advancement in contrast to the northwestern region.While digitalization propels economic growth,it yields a nuanced impact on achieving balanced regional development,encompassing both positive and negative facets.Our study highlights that the marginal utility of advancing digitalization is more pronounced in less developed regions,but only if the government invests in the digital infrastructure and education in these areas.This study's methodology can be utilized for subsequent research,and our findings hold the potential to the government's regional investment and policy-making.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
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 National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘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.
基金supported by NIH grants AG079264(to PHR)and AG071560(to APR)。
文摘The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.
基金Supported by the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2023A1515012762 and No.2021A1515010846+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.
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Graduate Student Project of Xi’an International Studies University,No.2021BS012Nanchong City-Universities Project,No.22SXCXTD0004.
文摘BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.
基金supported by Australian Research Council and National Natural Science Foundation of China grants to Sergey Shabala。
文摘Salinity stress is a major environmental stress affecting crop productivity,and its negative impact on global food security is only going to increase,due to current climate trends.Salinity tolerance was present in wild crop relatives but significantly weakened during domestication.Regaining it back requires a good understanding of molecular mechanisms and traits involved in control of plant ionic and ROS homeostasis.This review summarizes our current knowledge on the role of major plant hormones(auxin,cytokinins,abscisic acid,salicylic acid,and jasmonate)in plants adaptation to soil salinity.We firstly discuss the role of hormones in controlling root tropisms,root growth and architecture(primary root elongation,meristematic activity,lateral root development,and root hairs formation).Hormone-mediated control of uptake and sequestration of key inorganic ions(sodium,potassium,and calcium)is then discussed followed by regulation of cell redox balance and ROS signaling in salt-stressed roots.Finally,the role of epigenetic alterations such as DNA methylation and histone modifications in control of plant ion and ROS homeostasis and signaling is discussed.This data may help develop novel strategies for breeding and cultivating salt-tolerant crops and improving agricultural productivity in saline regions.
基金supported by funding from the Bluesand Foundation,Alzheimer's Association(AARG-21-852072 and Bias Frangione Early Career Achievement Award)to EDan Australian Government Research Training Program scholarship and the University of Sydney's Brain and Mind Centre fellowship to AH。
文摘Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.
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.
基金supported by the National Natural Science Foundation of China(82171506 and 31872778)Discipline Innovative Engineering Plan(111 Program)of China(B13036)+3 种基金Key Laboratory Grant from Hunan Province(2016TP1006)Department of Science and Technology of Hunan Province(2021DK2001,Innovative Team Program 2019RS1010)Innovation-Driven Team Project from Central South University(2020CX016)Hunan Hundred Talents Program for Young Outstanding Scientists。
文摘Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.
文摘Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive proportion of the population to CVD risk factors,and this situation is further worsened due to the accelerated aging population in China.CVD remains one of the greatest threats to the health of Chinese residents.In terms of the proportions of disease mortality among urban and rural residents in China,CVD has persistently ranked first.In 2021,CVD accounted for 48.98%and 47.35%of deaths in rural and urban areas,respectively.Two out of every five deaths can be attributed to CVD.To implement a national policy“focusing on the primary health institute and emphasizing prevention”and truly achieve a shift of CVD prevention and treatment from hospitals to communities,the National Center for Cardiovascular Diseases has organized experts from relevant fields across China to compile the“Report on Cardiovascular Health and Diseases in China”annually since 2005.The 2024 report is established based on representative,published,and high-quality big-data research results from cross-sectional and cohort population epidemiological surveys,randomized controlled clinical trials,large sample registry studies,and typical community prevention and treatment cases,along with data from some projects undertaken by the National Center for Cardiovascular Diseases.These firsthand data not only enrich the content of the current report but also provide a more timely and comprehensive reflection of the status of CVD prevention and treatment in China.
基金supported by the Humanities and Social Sciences Program of Jiangxi Universities(Grant No.GL21129)the Graduate Student Innovation Fund Program of Gannan Normal University(Grant No.YCX23A043)the Open Subject of Geography Discipline Construction of Gannan Normal University(Grant No.200084).
文摘With rapid economic development,the size of urban land in China is expanding dramatically.The Urban Growth Boundary(UGB)is an expandable spatial boundary for urban construction in a certain period in order to control the urban sprawl.Reasonable delineation of UGB can inhibit the disorderly spread of urban space and guide the normal development of the city.It is of practical significance for the construction of green urban space.The study utilizes GIS technology to establish a land construction suitability evaluation system for Nankang city,which is experiencing rapid urban expansion,and outlines the preliminary UGB under the future land use simulation(FLUS)model.At the same time,considering the coupled coordination of"Production-Living-Ecological Space",and based on the suitability evaluation,we revised the preliminary UGB by combining the advantages of the patch-generating land use simulation(PLUS)model and the convex hull model to delineate the final UGB.The results show that:1)the comprehensive score of the evaluation of the suitability of the construction of land from high to low shows the distribution of the center of the city to the surrounding circle type spread,the center of the city has the highest suitability score.The results of convex hull model show that the urban expansion type of Nankang is epitaxial.In the future,the urban expansion will mainly occur in the northern part of the city.The PLUS model predicts an increase of 3359.97 hm^(2)of construction land in Nankang by 2035,of which 2022.97 hm^(2)is urban construction land.2)The FLUS model has a prediction accuracy of 86.3%and delineates a preliminary UGB area of 9215.07 hm^(2).3)We used the results of the construction suitability evaluation,PLUS model simulation results,and convex hull model predictions to revise the originally delineated UGB.The final delineated UGB area is 8895.67 hm^(2)and it is capable of meeting the future development of the study area.The results of the delineation can promote sustainable urban development,and the delineation methodology can provide a reference basis for the preparation of territorial spatial planning.
基金This work was supported by the National Natural Science Foundation of China(71861147003 and 71925009).
文摘This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demographic and Health Surveys(DHS).Results from both fixed effects(FE)and instrumental variable(IV)estimates show that using non-solid cooking fuel significantly improves the nutrition outcomes of under-five children.Compared with their peers from households mainly using solid fuel,children from households mainly using non-solid fuel exhibit a lower probability of experiencing stunting(by 5.9 percentage points)and being underweight(by 1.2 percentage points).Our further investigation provides evidence for several underlying mechanisms,such as improved indoor air quality,induced reduction in children’s respiratory symptoms,benefits on maternal health,and reduction in maternal time spent on fuel collection or cooking.Heterogenous analyses suggest that the nutrition benefits of using non-solid cooking fuel are more prominent among boys,children above three years old,and those from households of lower socioeconomic status,rural areas,and Southeast Asia.
文摘AIM:To investigate the prevalence of visual impairment(VI)and provide an estimation of uncorrected refractive errors in school-aged children,conducted by optometry students as a community service.METHODS:The study was cross-sectional.Totally 3343 participants were included in the study.The initial examination involved assessing the uncorrected distance visual acuity(UDVA)and visual acuity(VA)while using a+2.00 D lens.The inclusion criteria for a subsequent comprehensive cycloplegic eye examination,performed by an optometrist,were as follows:a UDVA<0.6 decimal(0.20 logMAR)and/or a VA with+2.00 D≥0.8 decimal(0.96 logMAR).RESULTS:The sample had a mean age of 10.92±2.13y(range 4 to 17y),and 51.3%of the children were female(n=1715).The majority of the children(89.7%)fell within the age range of 8 to 14y.Among the ethnic groups,the highest representation was from the Luhya group(60.6%)followed by Luo(20.4%).Mean logMAR UDVA choosing the best eye for each student was 0.29±0.17(range 1.70 to 0.22).Out of the total,246 participants(7.4%)had a full eye examination.The estimated prevalence of myopia(defined as spherical equivalent≤-0.5 D)was found to be 1.45%of the total sample.While around 0.18%of the total sample had hyperopia value exceeding+1.75 D.Refractive astigmatism(cil<-0.75 D)was found in 0.21%(7/3343)of the children.The VI prevalence was 1.26%of the total sample.Among our cases of VI,76.2%could be attributed to uncorrected refractive error.Amblyopia was detected in 0.66%(22/3343)of the screened children.There was no statistically significant correlation observed between age or gender and refractive values.CONCLUSION:The primary cause of VI is determined to be uncorrected refractive errors,with myopia being the most prevalent refractive error observed.These findings underscore the significance of early identification and correction of refractive errors in school-aged children as a means to alleviate the impact of VI.
基金the financial support from the Scientific Research and Technology Development Project of China Energy Engineering Corporation Limited(CEEC-KJZX-04).
文摘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.
基金supported by grants from the National Health and Medical Research Council(NHMRC)of Australia(Nos.571100 and 1048082)the Baxter Charitable Foundation(to TCL)+1 种基金Medical Research grants from the Rebecca L.Cooper Medical Research Foundation(to MWW,TCL,and MDL)supported by a Charles D.Kelman,M.D.Postdoctoral Award(2010)from the International Retinal Research Foundation(USA)。
文摘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.
基金partially supported by the Natural Science Foundation of Zhejiang Province(Award number:D21C170001)the National Natural Science Foundation of China(Award number:31973000)。
文摘Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.
基金funded by National Natural Science Foundation of China(Grants No.42171210,42371194)Major Project of Key Research Bases for Humanities and Social Sciences Funded by the Ministry of Education of China(Grant No.22JJD790015).
文摘Regional inequality significantly influences sustainable development and human well-being.In China,there exists pronounced regional disparities in economic and digital advancements;however,scant research delves into the interplay between them.By analyzing the economic development and digitalization gaps at regional and city levels in China,extending the original Cobb-Douglas production function,this study aims to evaluate the impact of digitalization on China's regional inequality using seemingly unrelated regression.The results indicate a greater emphasis on digital inequality compared to economic disparity,with variable coefficients of 0.59 for GDP per capita and 0.92 for the digitalization index over the past four years.However,GDP per capita demonstrates higher spatial concentration than digitalization.Notably,both disparities have shown a gradual reduction in recent years.The southeastern region of the Hu Huanyong Line exhibits superior levels and rates of economic and digital advancement in contrast to the northwestern region.While digitalization propels economic growth,it yields a nuanced impact on achieving balanced regional development,encompassing both positive and negative facets.Our study highlights that the marginal utility of advancing digitalization is more pronounced in less developed regions,but only if the government invests in the digital infrastructure and education in these areas.This study's methodology can be utilized for subsequent research,and our findings hold the potential to the government's regional investment and policy-making.
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.