Roles of Upper-Level Descending Inflow in Moat Development in Simulated Tropical Cyclones with Secondary Eyewall Formation

This study investigated the effects of upper-level descending inflow(ULDI)associated with inner-eyewall convection on the formation of the moat in tropical cyclones(TCs)with secondary eyewall formation(SEF).In our numerical experiments,a clear moat with SEF occurred in TCs with a significant ULDI,while no SEF occurred in TCs without a significant ULDI.The eyewall convection developed more vigorously in the control run.A ULDI occurred outside the inner-eyewall convection,where it was symmetrically unstable.The ULDI was initially triggered by the diabatic warming released by the inner eyewall and later enhanced by the cooling below the anvil cloud.The ULDI penetrated the outer edge of the inner eyewall with relatively dry air and prevented excessive solid-phase hydrometeors from being advected further outward.It produced extensive sublimation cooling of falling hydrometeors between the eyewall and the outer convection.The sublimation cooling resulted in negative buoyancy and further induced strong subsidence between the eyewall and the outer convection.As a result,a clear moat was generated.Development of the moat in the ongoing SEF prevented the outer rainband from moving farther inward,helping the outer rainband to symmetrize into an outer eyewall.In the sensitivity experiment,no significant ULDI formed since the eyewall convection was weaker,and the eyewall anvil developed relatively lower,meaning the formation of a moat and thus an outer eyewall was less likely.This study suggests that a better-represented simulation of inner-eyewall convective structures and distribution of the solid-phase hydrometeors is important to the prediction of SEF.

Upregulation of the glycine-rich protein-encoding gene GhGRPL enhances plant tolerance to abiotic and biotic stressors by promoting secondary cell wall development

Abiotic and biotic stressors adversely affect plant survival,biomass generation,and crop yields.As the global availability of arable land declines and the impacts of global warming intensify,such stressors may have increasingly pronounced effects on agricultural productivity.Currently,researchers face the overarching challenge of comprehensively enhancing plant resilience to abiotic and biotic stressors.The secondary cell wall plays a crucial role in bolstering the stress resistance of plants.To increase plant resistance to stress through genetic manipulation of the secondary cell wall,we cloned a cell wall protein designated glycine-rich protein-like(GhGRPL)from cotton fibers,and found that it is specifically expressed during the period of secondary cell wall biosynthesis.Notably,this protein differs from its Arabidopsis homolog,AtGRP,since its glycine-rich domain is deficient in glycine residues.GhGRPL is involved in secondary cell wall deposition.Upregulation of GhGRPL enhances lignin accumulation and,consequently,the thickness of the secondary cell walls,thereby increasing the plant’s resistance to abiotic stressors,such as drought and salinity,and biotic threats,including Verticillium dahliae infection.Conversely,interference with GhGRPL expression in cotton reduces lignin accumulation and compromises that resistance.Taken together,our findings elucidate the role of GhGRPL in regulating secondary cell wall development through its influence on lignin deposition,which,in turn,reinforces cell wall robustness and impermeability.These findings highlight the promising near-future prospect of adopting GhGRPL as a viable,effective approach for enhancing plant resilience to abiotic and biotic stress factors.

Combining genome-wide association study and transcriptome analysis to identify molecular markers and genetic basis of population-asynchronous ovarian development in Coilia nasus

Coilia nasus,a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China,possesses considerable aquacultural and economic potential.However,the species faces challenges due to significant variation in the gonadal development rate among females,resulting in inconsistent ovarian maturation times at the population level,an extended reproductive period,and limitations on fish growth rate due to ovarian prematurity.In the present study,we combined genome-wide association study(GWAS)and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms(SNPs)and candidate genes associated with population-asynchronous ovarian development in C.nasus.Genotyping of the female population based on whole-genome resequencing yielded 2120695 high-quality SNPs,39 of which were suggestively associated with ovarian development.Of note,a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified,with cpne5a determined as the causal gene of the peak.Therefore,single-marker and haplotype association analyses were performed on cpne5a,revealing four genetic markers(P<0.05)and seven haplotypes(r2>0.9)significantly associated with the phenotype.Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary,respectively,between individuals of different body sizes.Integrating the GWAS and transcriptome analysis results,this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion,extracellular matrix,angiogenesis,and gap junctions involved in population-asynchronous ovarian development.The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C.nasus strains exhibiting population-synchronous ovarian development in the future.

The Role and Place of Artificial Neural Network Architectures Structural Redundancy in the Input Data Prototypes and Generalization Development

Neural Networks (NN) are the functional unit of Deep Learning and are known to mimic the behavior of the human brain to solve complex data-driven problems. Whenever we train our own neural networks, we need to take care of something called the generalization of the neural network. The performance of Artificial Neural Networks (ANN) mostly depends upon its generalization capability. In this paper, we propose an innovative approach to enhance the generalization capability of artificial neural networks (ANN) using structural redundancy. A novel perspective on handling input data prototypes and their impact on the development of generalization, which could improve to ANN architectures accuracy and reliability is described.

Rapid Prototype Development Approach for Genetic Programming

Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of genetic operators, evolutionary controls and implementations of heuristic strategy, evaluations and other mechanisms. When designing genetic operators, it is necessary to consider the possible limitations of encoding methods of individuals. And when selecting evolutionary control strategies, it is also necessary to balance search efficiency and diversity based on representation characteristics as well as the problem itself. More importantly, all of these matters, among others, have to be implemented through tedious coding work. Therefore, GP development is both complex and time-consuming. To overcome some of these difficulties that hinder the enhancement of GP development efficiency, we explore the feasibility of mutual assistance among GP variants, and then propose a rapid GP prototyping development method based on πGrammatical Evolution (πGE). It is demonstrated through regression analysis experiments that not only is this method beneficial for the GP developers to get rid of some tedious implementations, but also enables them to concentrate on the essence of the referred problem, such as individual representation, decoding means and evaluation. Additionally, it provides new insights into the roles of individual delineations in phenotypes and semantic research of individuals.

Melatonin promotes the development of the secondary hair follicles by regulating circMPP5

Background The quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats.The higher the density of secondary hair follicles,the higher the quality and yield of cashmere from the fleece.Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth.Preliminary experimental results from our laboratory showed that melatonin(MT)treatment of goat kids after their birth could increase the density of secondary hair follicles and,thus,improve the subsequent yield and quality of cashmere.These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein,and from a reduction in apoptosis.The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.Results MT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere,and this dominant effect continued to the second year.Melatonin promotes the proliferation of secondary hair follicle cells at an early age.The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year.The genome-wide data results involved KEGG analysis of 1044 DEmRNAs,91 DElncRNAs,1054 DEcircRNAs,and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase(MAPK)signaling pathway is involved in the development of secondary hair follicles,with key genes(FGF2,FGF21,FGFR3,MAPK3(ERK1))being up-regulated and expressed.We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3.Conclusions We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211,regulating the expression of MAPK3,to induce the differentiation and proliferation of secondary hair follicle cells.In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells.Collectively,these events increase the numbers of secondary hair follicles,thus improving the production of cashmere from these goats.

Anethole improves the developmental competence of porcine embryos by reducing oxidative stress via the sonic hedgehog signaling pathway

Background Anethole(AN)is an organic antioxidant compound with a benzene ring and is expected to have a positive impact on early embryogenesis in mammals.However,no study has examined the effect of AN on porcine embryonic development.Therefore,we investigated the effect of AN on the development of porcine embryos and the underlying mechanism.Results We cultured porcine in vitro-fertilized embryos in medium with AN(0,0.3,0.5,and 1 mg/mL)for 6 d.AN at 0.5 mg/mL significantly increased the blastocyst formation rate,trophectoderm cell number,and cellular survival rate compared to the control.AN-supplemented embryos exhibited significantly lower reactive oxygen species levels and higher glutathione levels than the control.Moreover,AN significantly improved the quantity of mitochondria and mitochondrial membrane potential,and increased the lipid droplet,fatty acid,and ATP levels.Interestingly,the levels of proteins and genes related to the sonic hedgehog(SHH)signaling pathway were significantly increased by AN.Conclusions These results revealed that AN improved the developmental competence of porcine preimplantation embryos by activating SHH signaling against oxidative stress and could be used for large-scale production of high-quality porcine embryos.

Strigolactones modulate cotton fiber elongation and secondary cell wall thickening

Cotton is one of the most important economic crops in the world,and it is a major source of fiber in the textile industry.Strigolactones(SLs)are a class of carotenoid-derived plant hormones involved in many processes of plant growth and development,although the functions of SL in fiber development remain largely unknown.Here,we found that the endogenous SLs were significantly higher in fibers at 20 days post-anthesis(DPA).Exogenous SLs significantly increased fiber length and cell wall thickness.Furthermore,we cloned three key SL biosynthetic genes,namely GhD27,GhMAX3,and GhMAX4,which were highly expressed in fibers,and subcellular localization analyses revealed that GhD27,GhMAX3,and GhMAX4 were localized in the chloroplast.The exogenous expression of GhD27,GhMAX3,and GhMAX4 complemented the physiological phenotypes of d27,max3,and max4 mutations in Arabidopsis,respectively.Knockdown of GhD27,GhMAX3,and GhMAX4 in cotton resulted in increased numbers of axillary buds and leaves,reduced fiber length,and significantly reduced fiber thickness.These findings revealed that SLs participate in plant growth,fiber elongation,and secondary cell wall formation in cotton.These results provide new and effective genetic resources for improving cotton fiber yield and plant architecture.

Research on Coordinated Development and Optimization of Distribution Networks at All Levels in Distributed Power Energy Engineering

The uncertainty of distributed generation energy has dramatically challenged the coordinated development of distribution networks at all levels.This paper focuses on the multi-time-scale regulation model of distributed generation energy under normal conditions.The simulation results of the example verify the self-optimization characteristics and the effectiveness of real-time dispatching of the distribution network control technology at all levels under multiple time scales.

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

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

Exploring the moderating role of financial development in environmental Kuznets curve for South Africa:fresh evidence from the novel dynamic ARDL simulations approach

The extant literature has produced mixed evidence on the relationship between finan-cial development and ecological sustainability.This work addresses this conundrum by investigating financial development’s direct and indirect consequences on ecologi-cal quality utilizing the environmental Kuznets curve(EKC)methodological approach.Our empirical analysis is based on the novel dynamic autoregressive distributed lag simulations approach for South Africa between 1960 and 2020.The results,which used five distinct financial development measures,demonstrate that financial develop-ment boosts ecological integrity and environmental sustainability over the long and short terms.In the instance of South Africa,we additionally confirm the validity of the EKC theory.More importantly,the outcomes of the indirect channels demonstrate that financial development increases energy usage’s role in causing pollution while attenuating the detrimental impacts of economic growth,trade openness,and foreign direct investment on ecological quality.Moreover,the presence of an inadequate financial system is a requirement for the basis of the pollution haven hypothesis(PHH),which we examine using trade openness and foreign direct investment variables.PHH for both of these variables disappears when financial development crosses specified thresholds.Finally,industrial value addition destroys ecological quality while tech-nological innovation enhances it.This research provides some crucial policy recom-mendations and fresh perspectives for South Africa as it develops national initiatives to support ecological sustainability and reach its net zero emissions goal.

The secondary injury cascade after spinal cord injury:an analysis of local cytokine/chemokine regulation

After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.

Metabolic and transcriptomic analyses elucidate a novel insight into the network for biosynthesis of carbohydrate and secondary metabolites in the stems of a medicinal orchid Dendrobium nobile

Dendrobium nobile is an important medicinal and nutraceutical herb.Although the ingredients of D.nobile have been identified as polysaccharides,alkaloids,amino acids,flavonoids and bibenzyls,our understanding of the metabolic pathways that regulate the synthesis of these compounds is limited.Here,we used transcriptomic and metabolic analyses to elucidate the genes and metabolites involved in the biosynthesis of carbohydrate and several secondary metabolites in the stems of D.nobile.A total of 1005 metabolites and 31,745 genes were detected in the stems of D.nobile.The majority of these metabolites and genes were involved in the metabolism of carbohydrates(fructose,mannose,glucose,xylulose and starch),while some were involved in the metabolism of secondary metabolites(alkaloids,β-tyrosine,ferulic acid,4-hydroxybenzoate and chrysin).Our predicted regulatory network indicated that five genes(AROG,PYK,DXS,ACEE and HMGCR) might play vital roles in the transition from carbohydrate to alkaloid synthesis.Correlation analysis identified that six genes(ALDO,PMM,BGLX,EGLC,XYLB and GLGA) were involved in carbohydrate metabolism,and two genes(ADT and CYP73A) were involved in secondary metabolite biosynthesis.Our analyses also indicated that phosphoenol-pyruvate(PEP) was a crucial bridge that connected carbohydrate to alkaloid biosynthesis.The regulatory network between carbohydrate and secondary metabolite biosynthesis established will provide important insights into the regulation of metabolites and biological systems in Dendrobium species.

Selenium: A Game Changer in Plant Development, Growth, and Stress Tolerance, via the Modulation in Gene Expression and Secondary Metabolite Biosynthesis

The presence of selenium(Se)is not widely established as crucial for crops,although it is commonly recognized as an important nutrient for animals as well as humans.Even so,it is inevitably accepted that Se usually contributes positively to the life cycle of plants.Previousfindings suggested that small amounts of Se seem to have a productive role in growth and production.As a result,Se is assumed to function in multiple ways,primarily by influencing a variety of biochemical and physiological functions.Also,Se also acts as a plant antioxidant and pro-oxidant and confers tolerance against different abiotic stresses,including salinity,drought,extreme temperature,and toxic metals/metalloids stresses.It reflects a defensive barrier against stress by increasing chlorophyll content synthesis,photosynthesis,oxygen supply,osmoprotectant concentration,and secondary metabolite acquisition.One other crucial role of Se is its ability to strengthen antioxidant performance in plants,thereby decreasing the concentration of reactive-oxygen-species(ROS).Furthermore,Se generates and modifies genes and proteins that respond situationally to stress,and the presence of high Se concentrations in the growth-medium can cause phytotoxic conditions via excessive ROS production,and through pro-oxidative Se occurrence,suppression of chlorophyll contents in the biosynthetic pathway,and the inhibition of plant developmental and normal physiological functions.Like a phytofortifier,the correct amount of Se can indeed enhance the nutrient quality of both crop and fodder production.Furthermore,crops have naturally developed ways to combat Se-deficiency and Se-toxicity.The current review focuses on recent advances in understanding the dynamics of Se,the positive and negative roles of Se in crop management,and its efficiency in countering abiotic stress.

Advances in understanding epigenetic regulation of plant trichome development: a comprehensive review

Plant growth and development are controlled by a complex gene regulatory network,which is currently a focal point of research.It has been established that epigenetic factors play a crucial role in plant growth.Trichomes,specialized appendages that arise from epidermal cells,are of great significance in plant growth and development.As a model system for studying plant development,trichomes possess both commercial and research value.Epigenetic regulation has only recently been implicated in the development of trichomes in a limited number of studies,and microRNA-mediated post-transcriptional regulation appears to dominate in this context.In light of this,we have conducted a review that explores the interplay between epigenetic regulations and the formation of plant trichomes,building upon existing knowledge of hormones and transcription factors in trichome development.Through this review,we aim to deepen our understanding of the regulatory mechanisms underlying trichome formation and shed light on future avenues of research in the field of epigenetics as it pertains to epidermal hair growth.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

Regional Economic Development Trend Prediction Method Based on Digital Twins and Time Series Network

At present,the interpretation of regional economic development(RED)has changed from a simple evaluation of economic growth to a focus on economic growth and the optimization of economic structure,the improvement of economic relations,and the change of institutional innovation.This article uses the RED trend as the research object and constructs the RED index to conduct the theoretical analysis.Then this paper uses the attention mechanism based on digital twins and the time series network model to verify the actual data.Finally,the regional economy is predicted according to the theoretical model.The specific research work mainly includes the following aspects:1)This paper introduced the development status of research on time series networks and economic forecasting at home and abroad.2)This paper introduces the basic principles and structures of long and short-term memory(LSTM)and convolutional neural network(CNN),constructs an improved CNN-LSTM model combined with the attention mechanism,and then constructs a regional economic prediction index system.3)The best parameters of the model are selected through experiments,and the trained model is used for simulation experiment prediction.The results show that the CNN-LSTM model based on the attentionmechanism proposed in this paper has high accuracy in predicting regional economies.

Secondary diabetes due to different etiologies:Four case reports

BACKGROUND As research on diabetes continues to advance,more complex classifications of this disease have emerged,revealing the existence of special types of diabetes,and many of these patients are prone to misdiagnosis and underdiagnosis,leading to treatment delays and increased health care costs.The purpose of this study was to identify four causes of secondary diabetes.CASE SUMMARY Secondary diabetes can be caused by various factors,some of which are often overlooked.These factors include genetic defects,autoimmune disorders,and diabetes induced by tumours.This paper describes four types of secondary diabetes caused by Williams–Beuren syndrome,Prader–Willi syndrome,pituitary adenoma,and IgG4-related diseases.These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity,often leading to their neglect in clinical practice.In comparison to regular diabetes patients,the four individuals described here exhibited distinct characteristics.Standard hypoglycaemic treatments failed to effectively control the disease.Subsequently,a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes.Upon addressing the primary condition,such as excising a pituitary adenoma,providing glucocorticoid supplementation,and implementing symptomatic treatments,all patients experienced a considerable decrease in blood glucose levels,which were subsequently maintained within a stable range.Furthermore,other accompanying symptoms improved.CONCLUSION Rare diseases causing secondary diabetes are often not considered in the diag-nosis of diabetes.Therefore,it is crucial to conduct genetic tests,antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition,ultimately improving patient outcomes.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.