The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitte...The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.展开更多
BACKGROUND Hip dysplasia is a widespread and debilitating musculoskeletal disorder that affects children.Its prevalence varies across different nations.AIM To evaluate the prevalence of developmental hip dysplasia(DDH...BACKGROUND Hip dysplasia is a widespread and debilitating musculoskeletal disorder that affects children.Its prevalence varies across different nations.AIM To evaluate the prevalence of developmental hip dysplasia(DDH)within the pediatric population of Al Jouf province.METHODS From January 2018 to December 2023,children with DDH from all cities of Al Jouf were included in this retrospective cross-sectional study.The disease prevalence was calculated for the entire province as well as for individual cities within the territory.RESULTS The study included 427 patients with DDH with an overall prevalence of 0.50%,or 5.0 per 1000 live births.At the city level,Sakaka had the highest prevalence at 14.2 per 1000 Live births followed by Qurayyat at 2.2 per 1000 live births.In contrast,cities like Suwayr,Abu Ajram,and Meegowa did not show any incidence of DDH.Significant differences were observed in the sociodemographic characteristics,such as age,sex,and nationality,across the different cities(P<0.05).CONCLUSION The prevalence of DDH in the Al Jouf province is high.The data delivers invaluable insights into the epidemiology of DDH in the Al Jouf locality.The findings highlight the need for targeted screening of DDH across the province.展开更多
Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to asse...Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to assess this complex toxicity endpoint and will be valuable for screening emerging pollutants as well as for m anaging new chemicals in China.Currently,there are few published DART prediction models in China,but many related research and development projects are in progress.In 2013,WU et al.published an expert rule-based DART decision tree(DT).This DT relies on known chemical structures linked to DART to forecast DART potential of a given chemical.Within this procedure,an accurate DART data interpretation is the foundation of building and expanding the DT.This paper excerpted case studies demonstrating DART data curation and interpretation of four chemicals(including 8-hydroxyquinoline,3,5,6-trichloro-2-pyridinol,thiacloprid,and imidacloprid)to expand the existing DART DT.Chemicals were first selected from the database of Solid Waste and Chemicals Management Center,Ministry of Ecology and Environment(MEESCC)in China.The structures of these 4 chemicals were analyzed and preliminarily grouped by chemists based on core structural features,functional groups,receptor binding property,metabolism,and possible mode of actions.Then,the DART conclusion was derived by collecting chemical information,searching,integrating,and interpreting DART data by the toxicologists.Finally,these chemicals were classified into either an existing category or a new category via integrating their chemical features,DART conclusions,and biological properties.The results showed that 8-hydroxyquinoline impacted estrous cyclicity,s exual organ weights,and embryonal development,and 3,5,6-trichloro-2-pyridinol caused central nervous system(CNS)malformations,which were added to an existing subcategory 8e(aromatic compounds with multi-halogen and nitro groups)of the DT.Thiacloprid caused dystocia and fetal skeletal malformation,and imidacloprid disrupted the endocrine system and male fertility.They both contain 2-chloro-5-methylpyridine substituted imidazolidine c yclic ring,which were expected to create a new category of neonicotinoids.The current work delineates a t ransparent process of curating toxicological data for the purpose of DART data interpretation.In the presence of sufficient related structures and DART data,the DT can be expanded by iteratively adding chemicals within the a pplicable domain of each category or subcategory.This DT can potentially serve as a tool for screening emerging pollutants and assessing new chemicals in China.展开更多
BACKGROUND Postpartum depression(PPD)represents a significant public health concern,adversely affecting both new mothers and their infants.Despite routine early screening,PPD can persist beyond the initial postpartum ...BACKGROUND Postpartum depression(PPD)represents a significant public health concern,adversely affecting both new mothers and their infants.Despite routine early screening,PPD can persist beyond the initial postpartum months,with notably high incidence rates even one year after childbirth.Persistent PPD has been associated with poor developmental outcomes in infants,highlighting the need for continued monitoring and support during this critical period.Understanding the broader impacts of persistent PPD is essential for developing effective interventions to improve maternal and infant well-being.AIM To explore the impact of persistent PPD on infant developmental behavior and maternal self-efficacy.METHODS We recruited 60 postpartum women who experienced persistent depression after childbirth in our hospital from January 2020 to December 2024 as the research subjects.The study collected basic characteristics of both infants and mothers,analyzed the self-efficacy of the mothers and the developmental behaviors of the infants,and conducted a correlation analysis to examine the relationship between postpartum persistent depression in mothers and the developmental behaviors and self-efficacy of infants.The Bootstrap method was used to verify the significance of the mediating effect.RESULTS The basic characteristics of infants and mothers show that 53.33%are male,58.33%are born via vaginal delivery,88.33%have a normal body mass index,51.67%are aged between 25 and 29 years,70%are non-agricultural workers,51.67%have a per capita household income over 4000 yuan,96.67%are full-term births,and 58.33%of the fathers are aged between 26 and 32 years.In terms of infant development behavior,the gross motor skills score is relatively low(38.44±12.15).Regarding maternal self-efficacy,the skill score(45.68±5.49)and mental activity score(46.37±3.72)are both at a low level.Correlation analysis reveals that postpartum persistent depression is significantly negatively correlated with maternal self-efficacy and infant development behavior(β=-0.439,-0.657,P<0.001),while self-efficacy is positively correlated with infant development behavior(β=0.728,P<0.001).The path coefficient and Bootstrap method test indicate that self-efficacy acts as a mediator between postpartum persistent depression and infant development behavior,accounting for 54.80%of the effect(P<0.05),while the direct effect of postpartum persistent depression on infant development behavior is 45.20%(P<0.05).CONCLUSION Persistent PPD significantly negatively impacts infant developmental outcomes,with maternal self-efficacy serving as a partial mediator.These findings suggest that interventions targeting both depressive symptoms and selfenhancement may effectively promote infant health development.展开更多
The rhizosphere bacteria play crucial roles in plant health and growth as they are involved in assimilating nutrients and resisting adverse conditions such as nutrient stress,drought,and wind erosion.Agriophyllum squa...The rhizosphere bacteria play crucial roles in plant health and growth as they are involved in assimilating nutrients and resisting adverse conditions such as nutrient stress,drought,and wind erosion.Agriophyllum squarrosum(L.)Moq.is a pioneer plant used in sand fixation due to its strong resistance to drought and wind erosion.However,the bacterial community characteristics and ecological function in the rhizosphere of A.squarrosum are poorly understood.In this study,soil samples were collected from different developmental stages(seedling stage,vegetative stage,reproductive stage,and withering stage)of A.squarrosum.Illumina Miseq sequencing was used to detect differences in soil bacterial abundance.The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt)program was used to predict bacterial functions,and the relationships among bacteria,functional populations,and soil nutrients were examined using a heatmap analysis.The results showed that the Shannon and Sobs indices of rhizosphere bacteria were significantly higher during the reproductive stage than during the other stages.Pantoea sp.(7.03%)was the dominant genus during the seedling stage;Arthrobacter sp.was the dominant genus during the vegetative(13.94%),reproductive(7.57%),and withering(12.30%)stages.The relative abundances of Chloroflexi,Acidobacteria,and Gemmatimonadetes were significantly high during the reproductive stage.According to the PICRUSt analysis,membrane transport,signal transduction,and environmental adaptation of the bacterial functional population occurred during the seedling stage.Carbohydrate metabolism increased during the vegetative stage,while energy metabolism,lipid metabolism,and biosynthesis of other secondary metabolites of the bacterial functional population significantly increased during the reproductive stage.The abundances of bacterial communities,functional genes,and soil nutrients were synergistically altered during various developmental stages.Our findings suggest that the developmental stages of A.squarrosum play a significant role in defining the composition and structure of bacterial communities in the rhizosphere.The results will provide a basis for better prediction and understanding of soil bacterial metabolic potential and functions of A.squarrosum rhizosphere in sandy areas.展开更多
BACKGROUND Visual impairment during early childhood can hinder motor,language,and social development,yet data on its developmental impact across common pediatric ocular diseases remain limited.AIM To investigate the d...BACKGROUND Visual impairment during early childhood can hinder motor,language,and social development,yet data on its developmental impact across common pediatric ocular diseases remain limited.AIM To investigate the developmental impact of low vision and blindness on children under six with common ocular diseases.METHODS This retrospective study reviewed records of new patients under six with visual impairment at Siriraj Hospital’s low vision rehabilitation center(January 2017-October 2022).We collected ocular,systemic,and developmental data;recorded visual acuity in the better-seeing eye after refractive correction;and assessed developmental domains with the DenverⅡ.Univariable and multi-variable logistic regression identified factors associated with developmental delay.RESULTS A total of 161 pediatric patients(mean age 24.9±18.9 months)were enrolled and evaluated based on their ability to fix on and follow an object or light source.Some were further assessed using the Allen picture chart and all had visual acuity worse than 1.07±0.58 LogMAR,and 83.2%were identified as having global developmental delay(GDD).The three most common ocular causes were cortical visual impairment(CVI),optic neuropathy/atrophy,and optic nerve hypoplasia.Extremely poor visual acuity(inability to fixate and follow)was significantly associated with GDD[adjusted odds ratio(AOR)41.0]and delays in all developmental domains:Gross motor(AOR 10.0),fine motor(AOR 12.8),language(AOR 5.3),and personal-social skills(AOR 13.4)(P≤0.002).Multiple disabilities,most often visual impairment with cerebral palsy,were also significantly associated with gross motor delays(AOR 7.7)and fine motor delays(AOR 4.0)(P<0.05).CVI was also related to delays in language and personal-social skills(AOR 9.1 each)(P<0.05).CONCLUSION This study underscores the developmental issues in children with visual impairment,especially those with poorer acuity,CVI,and multiple disabilities.Significant delays were observed in all domains,including GDD.A timely referral to specialists is strongly recommended.展开更多
Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This stu...Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This study was performed to evaluate the lipidomics signatures associated with DDH by analyzing plasma samples.Methods:Fifty infants were recruited,including 25 diagnosed with DDH and 25 age-matched healthy controls.In addition to plasma samples,comprehensive laboratory test results and medical records were collected for each participant.An untargeted lipidomics profiling approach was employed to identify distinguishing metabolic signatures.Results:Lipidomics profiles differed significantly between patients with DDH and healthy controls.Several differential metabolites were identified,including triacylglycerol(TAG)(17:0/18:1/20:1),TAG(17:0/17:0/17:0),phosphatidylethanolamine(PE)(10:0/26:4),TAG(17:0/18:0/18:0),TAG(16:0/17:0/22:1),TAG(16:0/18:0/22:0),TAG(17:0/19:0/19:0),TAG(13:0/20:0/20:0),TAG(18:0/18:0/22:0),and TAG(16:0/20:0/20:0).The primary lipid species showing differences were TAGs and PE.Conclusions:Distinct shifts in lipidomics profiles were observed in infants with DDH.To the best of our knowledge,this study is the first to explore lipidomics signatures in patients with DDH.The combined assessment of TAG(17:0/18:1/20:1)and TAG(17:0/17:0/17:0)may serve as a potential diagnostic tool for DDH.展开更多
Objectives:Positive family functioning(FF)is critical for adolescent development,yet only a few studies have examined this developmental trajectory pathway.This study aimed to identify different types of FF developmen...Objectives:Positive family functioning(FF)is critical for adolescent development,yet only a few studies have examined this developmental trajectory pathway.This study aimed to identify different types of FF development trajectories during junior high school students,investigate their influence on social avoidance(SA),and further examine the mediating role of preference for solitude(PS)between them.Methods:A three-wave longitudinal study was used with six-month intervals.Questionnaire data were collected from 436 junior high school students in Jiangxi Province,China.Participants ranged in age from 11 to 14 years old(Mean=12.89 years,SD=1.08;50.2%male).Results:Four heterogeneous types of FF trajectories were identified:(1)a high and increasing group(14.7%);(2)a consistently high group(36.24%);(3)a consistently moderate group(45.86%);and(4)a rapid growth group(3.2%).The developmental trajectories of FF among junior high students significantly varied in their levels of SA(F(3,432)=32.03,p<0.001).Compared to the high and increasing groups,the consistently high,consistently medium,and rapid growth groups exhibited higher levels of SA.PS mediated the association between the developmental trajectory of FF and SA.Conclusion:There was a close relationship between the developmental trajectory of FF and SA.Interventions focusing on family system optimization and solitary preference management could effectively mitigate SA behaviors.These findings are important for promoting healthy socialization in adolescents.展开更多
As universities in Kazakhstan continue to address the challenges that come with developing English-medium instruction(EMI)programs,university Science,Technology,Engineering,and Mathematics(STEM)teachers need to develo...As universities in Kazakhstan continue to address the challenges that come with developing English-medium instruction(EMI)programs,university Science,Technology,Engineering,and Mathematics(STEM)teachers need to develop capacities to teach in English,while their English teacher counterparts need to develop content-specific pedagogical knowledge.Content and Language Integrated Learning(CLIL)pedagogies,defined as the integration of both language and content curricular goals,have emerged as a vehicle to facilitate this development for both types of teachers.However,what it means to be a CLIL teacher may vary considerably as teachers leverage their professional knowledge and personal experiences.We,therefore,explore teachers’conceptions of CLIL and how their disciplinary,linguistic,and pedagogical backgrounds enable or burden them to forge a“CLIL teacher”identity.This qualitative study illustrates the salient points of the journeys taken by two university teachers,one a specialist in oil and gas,the other an English teacher and teacher educator.Drawing on extended one-on-one interviews,we present two teachers’experiences through a series of CLIL-informed workshops.Using a multidisciplinary analytical framework,we map the ways in which the two teacher participants negotiate their identities in relation to CLIL.The findings highlight the importance of understanding teacher experiences,particularly their language learning backgrounds,attitudes toward supporting student learning,and relationships with their colleagues as they work to adapt to teaching English and STEM subjects in university EMI contexts.展开更多
Objective:To explore the positive role of developmental care measures in promoting the growth and development of premature infants,and analyze their specific effects on improving the sleep duration and quality of prem...Objective:To explore the positive role of developmental care measures in promoting the growth and development of premature infants,and analyze their specific effects on improving the sleep duration and quality of premature infants.Methods:A total of 80 premature infants who met the inclusion criteria were selected by convenient sampling method and divided into an experimental group and a control group,with 40 cases in each group.The experimental group received comprehensive nursing intervention of developmental care during the nursing process;the control group adopted the traditional conventional nursing model.Results:There was no statistically significant difference in various physical indicators between the two groups of premature infants before nursing intervention.After nursing intervention,the scores of intellectual development level,psychomotor development index and various physical indicators of premature infants in the experimental group were significantly higher than those in the control group,and the difference was statistically significant.Conclusion:The implementation of developmental care for premature infants can significantly improve their various developmental indicators,which can not only effectively promote the rapid development of premature infants’mental and physical growth,but also improve their sleep quality.展开更多
Dear Editors,The term“developmental disconnection syndromes”(DDSs)was first coined by Geshwind and Levitt in 2007[1]to describe the weakening of already formed connections or an absence of certain connections to est...Dear Editors,The term“developmental disconnection syndromes”(DDSs)was first coined by Geshwind and Levitt in 2007[1]to describe the weakening of already formed connections or an absence of certain connections to establish correct organization de novo in early developmental stages.DDSs include a number of neuropsychiatric diseases,such as autistic spectrum disorder(ASD)[1,2],which is characterized by impaired social communication and repetitive and stereotyped behaviors.Nevertheless,the exact etiology underlying these“disconnections”and their abnormal developmental trajectory remains largely unclear.Even less known is whether developmental disconnections relevant to autism can be rescued by early intervention thereby preventing neuropsychiatric and repetitive symptoms in later stages.This study addresses these important questions.展开更多
Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to asse...Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.展开更多
Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate...Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.展开更多
Research on the distribution and development of black shales in the Lianggaoshan Formation has been deficient,which has hindered exploration for lacustrine shale oil in the Sichuan Basin.Our study characterized the we...Research on the distribution and development of black shales in the Lianggaoshan Formation has been deficient,which has hindered exploration for lacustrine shale oil in the Sichuan Basin.Our study characterized the well logging data,core samples,outcrops,and geochemistry of black shales in the Lianggaoshan Formation in the Sichuan Basin.Our analysis focused on the lake basin evolution and the migration characteristics,paleoenvironmental features,formation mechanisms,and developmental model of the black shales.The results indicated that black shales in the Lianggaoshan Formation exhibited significant lateral migration,with an overall thickening trend from east to west.Within the 1st Member of the formation,black shale occurred as a single thick layer in the eastern region that gradually thinned toward the central region.Multiple sets of shale developed within the 2nd and 3rd members,and these had lower thicknesses than the 1st Member and migrated toward central Sichuan.Paleoproductivity and terrigenous input were the main factors controlling the deposition of black shales.A semi-humid climate influenced the deposition of black shales,bringing abundant freshwater,terrigenous debris,and nutrients into the basin.Decomposition of organic matter consumed oxygen in sediment and bottom water,causing localized oxygen deficiency in the strata.展开更多
Pigs have emerged as valuable large-animal models for cardiac xenotransplantation;however,the temporal dynamics of myocardial development in this species remains insufficiently defined.This study analyzed gene express...Pigs have emerged as valuable large-animal models for cardiac xenotransplantation;however,the temporal dynamics of myocardial development in this species remains insufficiently defined.This study analyzed gene expression patterns across four key developmental stages(neonatal,juvenile,sexual maturity,and adulthood)to delineate the molecular mechanisms driving porcine myocardial development.Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size,reflecting coordinated structural development.Transcriptomic profiling of myocardial tissue by RNA sequencing(RNA-seq)identified 2189 differentially expressed genes(DEGs)across stage comparisons.Short time-series expression miner(STEM)analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development,immune responses,cell proliferation,and metabolic processes.Among 359 DEGs conserved across all developmental stages,six candidate genes were strongly associated with myocardial development.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue.These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.展开更多
In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those co...In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to animals.Thus,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during development.We employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals.We show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers up-regulated.Human liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and OPEs.Our findings suggest that NEOs and OPEs interfere with human early embryonic development.展开更多
The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding...The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.展开更多
Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Cur...Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.展开更多
Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement d...Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement during the early stages of brain development.We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice.Mice were anaesthetized with sevoflurane on postnatal days 6,8,and 10.Behavioral performance was assessed using the open field test and Morris water maze test.Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments.Western blotting,immunofluorescence,electron microscopy,three-dimensional reconstruction,Golgi staining,and whole-cell patch-clamp recordings were performed.Sevoflurane exposures upregulated the protein expression of TREM2,increased microglia-mediated pruning of dendritic spines,and reduced synaptic multiplicity and excitability of CA1 neurons.TREM2 genetic knockdown significantly decreased dendritic spine pruning,and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice.In contrast,TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction.TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons.This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.展开更多
Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabol...Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabolic activity of small birds are important phenotypes closely related to their winter survival.In the context of climate change,it is necessary to determine whether temperature variation during incubation in birds leads to developmental plasticity of these cold responsive phenotypes.We incubated Japanese Quail(Coturnix japonica)eggs at 36.8℃,37.8℃,and 38.8℃,and raised the chicks to 35-day old at 22℃with same raising conditions,then all the quails were exposed to gradually temperature dropping environment(from 15℃to 0℃).After cold treatment,serum T3 level,resting metabolic rate,skeletal muscle and liver metabolomes of the birds were measured.The serum T3 levels were significantly lower in the 38.8℃group and significantly higher in the 36.8℃group compared to the 37.8℃group.The metabolic rate in the 38.8℃group was significantly lower compared to the 37.8℃group.Compared with the 37.8℃group,metabolites involved in the tricarboxylic acid cycle in the liver were significantly lower in the 38.8℃group,and metabolites related to lipid oxidation metabolism and fatty acid biosynthesis were significantly lower in the skeletal muscles in the 38.8℃group but significantly higher in the 36.8℃group.These results indicate that incubation temperature variation can lead to developmental plasticity in cold responsive physiological phenotypes.Higher incubation temperature may impair the capacity of birds coping with cold challenge.展开更多
基金supported by the Center for Cognition and Sociality,Institute for Basic Science(IBS)(IBS-R001-D2)(to WK).
文摘The early developmental period is a critical window during which brain cells mature and contribute to both brain development and later life functions.Gamma-aminobutyric acid(GABA),recognized as a major neurotransmitter,plays a crucial role in coordinating synapse formation,neuronal proliferation,and migration during this time.
文摘BACKGROUND Hip dysplasia is a widespread and debilitating musculoskeletal disorder that affects children.Its prevalence varies across different nations.AIM To evaluate the prevalence of developmental hip dysplasia(DDH)within the pediatric population of Al Jouf province.METHODS From January 2018 to December 2023,children with DDH from all cities of Al Jouf were included in this retrospective cross-sectional study.The disease prevalence was calculated for the entire province as well as for individual cities within the territory.RESULTS The study included 427 patients with DDH with an overall prevalence of 0.50%,or 5.0 per 1000 live births.At the city level,Sakaka had the highest prevalence at 14.2 per 1000 Live births followed by Qurayyat at 2.2 per 1000 live births.In contrast,cities like Suwayr,Abu Ajram,and Meegowa did not show any incidence of DDH.Significant differences were observed in the sociodemographic characteristics,such as age,sex,and nationality,across the different cities(P<0.05).CONCLUSION The prevalence of DDH in the Al Jouf province is high.The data delivers invaluable insights into the epidemiology of DDH in the Al Jouf locality.The findings highlight the need for targeted screening of DDH across the province.
文摘Developmental and reproductive toxicity(DART)endpoint entails a toxicological assessment of all developmental stages and reproductive cycles of an organism.In silico tools to predict DART will provide a method to assess this complex toxicity endpoint and will be valuable for screening emerging pollutants as well as for m anaging new chemicals in China.Currently,there are few published DART prediction models in China,but many related research and development projects are in progress.In 2013,WU et al.published an expert rule-based DART decision tree(DT).This DT relies on known chemical structures linked to DART to forecast DART potential of a given chemical.Within this procedure,an accurate DART data interpretation is the foundation of building and expanding the DT.This paper excerpted case studies demonstrating DART data curation and interpretation of four chemicals(including 8-hydroxyquinoline,3,5,6-trichloro-2-pyridinol,thiacloprid,and imidacloprid)to expand the existing DART DT.Chemicals were first selected from the database of Solid Waste and Chemicals Management Center,Ministry of Ecology and Environment(MEESCC)in China.The structures of these 4 chemicals were analyzed and preliminarily grouped by chemists based on core structural features,functional groups,receptor binding property,metabolism,and possible mode of actions.Then,the DART conclusion was derived by collecting chemical information,searching,integrating,and interpreting DART data by the toxicologists.Finally,these chemicals were classified into either an existing category or a new category via integrating their chemical features,DART conclusions,and biological properties.The results showed that 8-hydroxyquinoline impacted estrous cyclicity,s exual organ weights,and embryonal development,and 3,5,6-trichloro-2-pyridinol caused central nervous system(CNS)malformations,which were added to an existing subcategory 8e(aromatic compounds with multi-halogen and nitro groups)of the DT.Thiacloprid caused dystocia and fetal skeletal malformation,and imidacloprid disrupted the endocrine system and male fertility.They both contain 2-chloro-5-methylpyridine substituted imidazolidine c yclic ring,which were expected to create a new category of neonicotinoids.The current work delineates a t ransparent process of curating toxicological data for the purpose of DART data interpretation.In the presence of sufficient related structures and DART data,the DT can be expanded by iteratively adding chemicals within the a pplicable domain of each category or subcategory.This DT can potentially serve as a tool for screening emerging pollutants and assessing new chemicals in China.
基金Supported by the Key Medical Research Project of Hebei Province in 2020,No.20201360.
文摘BACKGROUND Postpartum depression(PPD)represents a significant public health concern,adversely affecting both new mothers and their infants.Despite routine early screening,PPD can persist beyond the initial postpartum months,with notably high incidence rates even one year after childbirth.Persistent PPD has been associated with poor developmental outcomes in infants,highlighting the need for continued monitoring and support during this critical period.Understanding the broader impacts of persistent PPD is essential for developing effective interventions to improve maternal and infant well-being.AIM To explore the impact of persistent PPD on infant developmental behavior and maternal self-efficacy.METHODS We recruited 60 postpartum women who experienced persistent depression after childbirth in our hospital from January 2020 to December 2024 as the research subjects.The study collected basic characteristics of both infants and mothers,analyzed the self-efficacy of the mothers and the developmental behaviors of the infants,and conducted a correlation analysis to examine the relationship between postpartum persistent depression in mothers and the developmental behaviors and self-efficacy of infants.The Bootstrap method was used to verify the significance of the mediating effect.RESULTS The basic characteristics of infants and mothers show that 53.33%are male,58.33%are born via vaginal delivery,88.33%have a normal body mass index,51.67%are aged between 25 and 29 years,70%are non-agricultural workers,51.67%have a per capita household income over 4000 yuan,96.67%are full-term births,and 58.33%of the fathers are aged between 26 and 32 years.In terms of infant development behavior,the gross motor skills score is relatively low(38.44±12.15).Regarding maternal self-efficacy,the skill score(45.68±5.49)and mental activity score(46.37±3.72)are both at a low level.Correlation analysis reveals that postpartum persistent depression is significantly negatively correlated with maternal self-efficacy and infant development behavior(β=-0.439,-0.657,P<0.001),while self-efficacy is positively correlated with infant development behavior(β=0.728,P<0.001).The path coefficient and Bootstrap method test indicate that self-efficacy acts as a mediator between postpartum persistent depression and infant development behavior,accounting for 54.80%of the effect(P<0.05),while the direct effect of postpartum persistent depression on infant development behavior is 45.20%(P<0.05).CONCLUSION Persistent PPD significantly negatively impacts infant developmental outcomes,with maternal self-efficacy serving as a partial mediator.These findings suggest that interventions targeting both depressive symptoms and selfenhancement may effectively promote infant health development.
基金supported by the Natural Science Foundation Project of Inner Mongolia Autonomous Region(2024LHMS03017)Research Capacity Enhancement“Unveiling and Leading”Project of Inner Mongolia Forestry Science Research Institute(2024NLTS03).
文摘The rhizosphere bacteria play crucial roles in plant health and growth as they are involved in assimilating nutrients and resisting adverse conditions such as nutrient stress,drought,and wind erosion.Agriophyllum squarrosum(L.)Moq.is a pioneer plant used in sand fixation due to its strong resistance to drought and wind erosion.However,the bacterial community characteristics and ecological function in the rhizosphere of A.squarrosum are poorly understood.In this study,soil samples were collected from different developmental stages(seedling stage,vegetative stage,reproductive stage,and withering stage)of A.squarrosum.Illumina Miseq sequencing was used to detect differences in soil bacterial abundance.The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt)program was used to predict bacterial functions,and the relationships among bacteria,functional populations,and soil nutrients were examined using a heatmap analysis.The results showed that the Shannon and Sobs indices of rhizosphere bacteria were significantly higher during the reproductive stage than during the other stages.Pantoea sp.(7.03%)was the dominant genus during the seedling stage;Arthrobacter sp.was the dominant genus during the vegetative(13.94%),reproductive(7.57%),and withering(12.30%)stages.The relative abundances of Chloroflexi,Acidobacteria,and Gemmatimonadetes were significantly high during the reproductive stage.According to the PICRUSt analysis,membrane transport,signal transduction,and environmental adaptation of the bacterial functional population occurred during the seedling stage.Carbohydrate metabolism increased during the vegetative stage,while energy metabolism,lipid metabolism,and biosynthesis of other secondary metabolites of the bacterial functional population significantly increased during the reproductive stage.The abundances of bacterial communities,functional genes,and soil nutrients were synergistically altered during various developmental stages.Our findings suggest that the developmental stages of A.squarrosum play a significant role in defining the composition and structure of bacterial communities in the rhizosphere.The results will provide a basis for better prediction and understanding of soil bacterial metabolic potential and functions of A.squarrosum rhizosphere in sandy areas.
文摘BACKGROUND Visual impairment during early childhood can hinder motor,language,and social development,yet data on its developmental impact across common pediatric ocular diseases remain limited.AIM To investigate the developmental impact of low vision and blindness on children under six with common ocular diseases.METHODS This retrospective study reviewed records of new patients under six with visual impairment at Siriraj Hospital’s low vision rehabilitation center(January 2017-October 2022).We collected ocular,systemic,and developmental data;recorded visual acuity in the better-seeing eye after refractive correction;and assessed developmental domains with the DenverⅡ.Univariable and multi-variable logistic regression identified factors associated with developmental delay.RESULTS A total of 161 pediatric patients(mean age 24.9±18.9 months)were enrolled and evaluated based on their ability to fix on and follow an object or light source.Some were further assessed using the Allen picture chart and all had visual acuity worse than 1.07±0.58 LogMAR,and 83.2%were identified as having global developmental delay(GDD).The three most common ocular causes were cortical visual impairment(CVI),optic neuropathy/atrophy,and optic nerve hypoplasia.Extremely poor visual acuity(inability to fixate and follow)was significantly associated with GDD[adjusted odds ratio(AOR)41.0]and delays in all developmental domains:Gross motor(AOR 10.0),fine motor(AOR 12.8),language(AOR 5.3),and personal-social skills(AOR 13.4)(P≤0.002).Multiple disabilities,most often visual impairment with cerebral palsy,were also significantly associated with gross motor delays(AOR 7.7)and fine motor delays(AOR 4.0)(P<0.05).CVI was also related to delays in language and personal-social skills(AOR 9.1 each)(P<0.05).CONCLUSION This study underscores the developmental issues in children with visual impairment,especially those with poorer acuity,CVI,and multiple disabilities.Significant delays were observed in all domains,including GDD.A timely referral to specialists is strongly recommended.
基金graciously funded by the Central Government Guidance Fund for Supporting the Local Science and Technology Development(No.XZ202101YD0002C).
文摘Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This study was performed to evaluate the lipidomics signatures associated with DDH by analyzing plasma samples.Methods:Fifty infants were recruited,including 25 diagnosed with DDH and 25 age-matched healthy controls.In addition to plasma samples,comprehensive laboratory test results and medical records were collected for each participant.An untargeted lipidomics profiling approach was employed to identify distinguishing metabolic signatures.Results:Lipidomics profiles differed significantly between patients with DDH and healthy controls.Several differential metabolites were identified,including triacylglycerol(TAG)(17:0/18:1/20:1),TAG(17:0/17:0/17:0),phosphatidylethanolamine(PE)(10:0/26:4),TAG(17:0/18:0/18:0),TAG(16:0/17:0/22:1),TAG(16:0/18:0/22:0),TAG(17:0/19:0/19:0),TAG(13:0/20:0/20:0),TAG(18:0/18:0/22:0),and TAG(16:0/20:0/20:0).The primary lipid species showing differences were TAGs and PE.Conclusions:Distinct shifts in lipidomics profiles were observed in infants with DDH.To the best of our knowledge,this study is the first to explore lipidomics signatures in patients with DDH.The combined assessment of TAG(17:0/18:1/20:1)and TAG(17:0/17:0/17:0)may serve as a potential diagnostic tool for DDH.
基金supported by the National Natural Science Foundation of China(72164018)National Social Science Fund Project(BFA200065)Jiangxi Social Science Foundation Project(21JY13).
文摘Objectives:Positive family functioning(FF)is critical for adolescent development,yet only a few studies have examined this developmental trajectory pathway.This study aimed to identify different types of FF development trajectories during junior high school students,investigate their influence on social avoidance(SA),and further examine the mediating role of preference for solitude(PS)between them.Methods:A three-wave longitudinal study was used with six-month intervals.Questionnaire data were collected from 436 junior high school students in Jiangxi Province,China.Participants ranged in age from 11 to 14 years old(Mean=12.89 years,SD=1.08;50.2%male).Results:Four heterogeneous types of FF trajectories were identified:(1)a high and increasing group(14.7%);(2)a consistently high group(36.24%);(3)a consistently moderate group(45.86%);and(4)a rapid growth group(3.2%).The developmental trajectories of FF among junior high students significantly varied in their levels of SA(F(3,432)=32.03,p<0.001).Compared to the high and increasing groups,the consistently high,consistently medium,and rapid growth groups exhibited higher levels of SA.PS mediated the association between the developmental trajectory of FF and SA.Conclusion:There was a close relationship between the developmental trajectory of FF and SA.Interventions focusing on family system optimization and solitary preference management could effectively mitigate SA behaviors.These findings are important for promoting healthy socialization in adolescents.
基金funding from the U.S.-Kazakhstan University Partnerships program funded by the U.S.Mission to Kazakhstan and administered by American Councils[Award number SKZ100-19-CA-0149].
文摘As universities in Kazakhstan continue to address the challenges that come with developing English-medium instruction(EMI)programs,university Science,Technology,Engineering,and Mathematics(STEM)teachers need to develop capacities to teach in English,while their English teacher counterparts need to develop content-specific pedagogical knowledge.Content and Language Integrated Learning(CLIL)pedagogies,defined as the integration of both language and content curricular goals,have emerged as a vehicle to facilitate this development for both types of teachers.However,what it means to be a CLIL teacher may vary considerably as teachers leverage their professional knowledge and personal experiences.We,therefore,explore teachers’conceptions of CLIL and how their disciplinary,linguistic,and pedagogical backgrounds enable or burden them to forge a“CLIL teacher”identity.This qualitative study illustrates the salient points of the journeys taken by two university teachers,one a specialist in oil and gas,the other an English teacher and teacher educator.Drawing on extended one-on-one interviews,we present two teachers’experiences through a series of CLIL-informed workshops.Using a multidisciplinary analytical framework,we map the ways in which the two teacher participants negotiate their identities in relation to CLIL.The findings highlight the importance of understanding teacher experiences,particularly their language learning backgrounds,attitudes toward supporting student learning,and relationships with their colleagues as they work to adapt to teaching English and STEM subjects in university EMI contexts.
文摘Objective:To explore the positive role of developmental care measures in promoting the growth and development of premature infants,and analyze their specific effects on improving the sleep duration and quality of premature infants.Methods:A total of 80 premature infants who met the inclusion criteria were selected by convenient sampling method and divided into an experimental group and a control group,with 40 cases in each group.The experimental group received comprehensive nursing intervention of developmental care during the nursing process;the control group adopted the traditional conventional nursing model.Results:There was no statistically significant difference in various physical indicators between the two groups of premature infants before nursing intervention.After nursing intervention,the scores of intellectual development level,psychomotor development index and various physical indicators of premature infants in the experimental group were significantly higher than those in the control group,and the difference was statistically significant.Conclusion:The implementation of developmental care for premature infants can significantly improve their various developmental indicators,which can not only effectively promote the rapid development of premature infants’mental and physical growth,but also improve their sleep quality.
基金support JCS,QX,and BQ,as well as covering all experimental and material costs for this project,NIH/NIMH R01 MH094360-06(HWD)grant to support HX,MZ,Lei Gao,Lin Gou,HH and HWD.
文摘Dear Editors,The term“developmental disconnection syndromes”(DDSs)was first coined by Geshwind and Levitt in 2007[1]to describe the weakening of already formed connections or an absence of certain connections to establish correct organization de novo in early developmental stages.DDSs include a number of neuropsychiatric diseases,such as autistic spectrum disorder(ASD)[1,2],which is characterized by impaired social communication and repetitive and stereotyped behaviors.Nevertheless,the exact etiology underlying these“disconnections”and their abnormal developmental trajectory remains largely unclear.Even less known is whether developmental disconnections relevant to autism can be rescued by early intervention thereby preventing neuropsychiatric and repetitive symptoms in later stages.This study addresses these important questions.
基金supported by the National Natural Science Foundation of China[81701350 and 31671252]the Health Technology Plan of Zhejiang Province[2023RC205].
文摘Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
基金supported by the Natural Science Foundation of China(32394032,82201699,and 82221001)the Natural Science Foundation of Zhejiang Province(LTGD24H250001)+1 种基金the Kay R&D Program of Shaanxi Province(2023-YBSF-093),the Young Talent Fund of University Association for Science and Technology in Shaanxi(20220306)the Joint Founding Project of Innovation Research Institute,Xijing Hospital(LHJJ24JH02).
文摘Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
基金funded by Science and Technology Cooperation Project of the CNPC-SWPU Innovation Alliance(2020CX050103).
文摘Research on the distribution and development of black shales in the Lianggaoshan Formation has been deficient,which has hindered exploration for lacustrine shale oil in the Sichuan Basin.Our study characterized the well logging data,core samples,outcrops,and geochemistry of black shales in the Lianggaoshan Formation in the Sichuan Basin.Our analysis focused on the lake basin evolution and the migration characteristics,paleoenvironmental features,formation mechanisms,and developmental model of the black shales.The results indicated that black shales in the Lianggaoshan Formation exhibited significant lateral migration,with an overall thickening trend from east to west.Within the 1st Member of the formation,black shale occurred as a single thick layer in the eastern region that gradually thinned toward the central region.Multiple sets of shale developed within the 2nd and 3rd members,and these had lower thicknesses than the 1st Member and migrated toward central Sichuan.Paleoproductivity and terrigenous input were the main factors controlling the deposition of black shales.A semi-humid climate influenced the deposition of black shales,bringing abundant freshwater,terrigenous debris,and nutrients into the basin.Decomposition of organic matter consumed oxygen in sediment and bottom water,causing localized oxygen deficiency in the strata.
基金supported by the National Natural Science Foundation of China(32222079 to L.J.and 32202621 to D.D.W.)。
文摘Pigs have emerged as valuable large-animal models for cardiac xenotransplantation;however,the temporal dynamics of myocardial development in this species remains insufficiently defined.This study analyzed gene expression patterns across four key developmental stages(neonatal,juvenile,sexual maturity,and adulthood)to delineate the molecular mechanisms driving porcine myocardial development.Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size,reflecting coordinated structural development.Transcriptomic profiling of myocardial tissue by RNA sequencing(RNA-seq)identified 2189 differentially expressed genes(DEGs)across stage comparisons.Short time-series expression miner(STEM)analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development,immune responses,cell proliferation,and metabolic processes.Among 359 DEGs conserved across all developmental stages,six candidate genes were strongly associated with myocardial development.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue.These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.
基金supported by the Ministry of Science and Technology of the People’s Republic of China (No.2020YFA0907500)the National Natural Science Foundation of China (Nos.22150710514,22021003,and 22106174)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDPB200202)the Postdoc Science Foundation of China (No.2021M693322)。
文摘In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to animals.Thus,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during development.We employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals.We show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers up-regulated.Human liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and OPEs.Our findings suggest that NEOs and OPEs interfere with human early embryonic development.
基金supported by the National Natural Science Foundation of China(31790410,32160781)。
文摘The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.
基金supported by the National Key Research and Development Program of China (No.2020YFA0803900)。
文摘Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.
基金National Natural Science Foundation of China(82072130 and 82001126)Key Medical Research Projects in Jiangsu Province(ZD2022021)+6 种基金Six Talent Peaks Project in Jiangsu Province(WSN-022)Suzhou Clinical Medical Center for Anaesthesiology(Szlcyxzxj202102)Jiangsu Medical Association Anaesthesia Research Project(SYH-32021-0036(2021031))Suzhou Medical Health Science and Technology Innovation Project(SKY2022136)Jiangsu Provincial Colleges of Natural Science General Program(22KJD320002)Health Talent Plan Project in Suzhou(GSWS2022007)Gusu Health Talent Project of Soochow(GSWS2021062).
文摘Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement during the early stages of brain development.We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice.Mice were anaesthetized with sevoflurane on postnatal days 6,8,and 10.Behavioral performance was assessed using the open field test and Morris water maze test.Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments.Western blotting,immunofluorescence,electron microscopy,three-dimensional reconstruction,Golgi staining,and whole-cell patch-clamp recordings were performed.Sevoflurane exposures upregulated the protein expression of TREM2,increased microglia-mediated pruning of dendritic spines,and reduced synaptic multiplicity and excitability of CA1 neurons.TREM2 genetic knockdown significantly decreased dendritic spine pruning,and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice.In contrast,TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction.TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons.This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.
基金funded by the National Natural Science Foundation of China(32071515 to S.Z.)Graduate Research and Practice Projects of Minzu University of China(SZKY2024035 to R.Z.)。
文摘Embryonic development is a critical period for phenotype formation.Environmental variation during embryonic development can induce changes in postnatal phenotypes of animals.The thyroxine secretion and aerobic metabolic activity of small birds are important phenotypes closely related to their winter survival.In the context of climate change,it is necessary to determine whether temperature variation during incubation in birds leads to developmental plasticity of these cold responsive phenotypes.We incubated Japanese Quail(Coturnix japonica)eggs at 36.8℃,37.8℃,and 38.8℃,and raised the chicks to 35-day old at 22℃with same raising conditions,then all the quails were exposed to gradually temperature dropping environment(from 15℃to 0℃).After cold treatment,serum T3 level,resting metabolic rate,skeletal muscle and liver metabolomes of the birds were measured.The serum T3 levels were significantly lower in the 38.8℃group and significantly higher in the 36.8℃group compared to the 37.8℃group.The metabolic rate in the 38.8℃group was significantly lower compared to the 37.8℃group.Compared with the 37.8℃group,metabolites involved in the tricarboxylic acid cycle in the liver were significantly lower in the 38.8℃group,and metabolites related to lipid oxidation metabolism and fatty acid biosynthesis were significantly lower in the skeletal muscles in the 38.8℃group but significantly higher in the 36.8℃group.These results indicate that incubation temperature variation can lead to developmental plasticity in cold responsive physiological phenotypes.Higher incubation temperature may impair the capacity of birds coping with cold challenge.
