Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases

The gene encoding bone morphogenetic protein-7(BMP7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of BMP7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of BMP7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases.

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.

Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Multifaceted role of haptoglobin:Implications for disease development

Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editorial explores the multifaceted roles of haptoglobin,highlighting its involvement in inflammatory responses and immune regulation and its potential implications in chronic diseases such as diabetes,cardiovascular disorders,and cancer.Through a synthesis of recent research findings,this editorial reveals the importance of haptoglobin in disease mechanisms and underscores the need for further investigation to fully elucidate its therapeutic potential.A comprehensive understanding of haptoglobin’s novel functions may catalyze the development of innovative diagnostic and therapeutic modalities in clinical practice.

The generation and properties of human cortical organoids as a disease model for malformations of cortical development

As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.

TGF-β and BMP signaling in osteoblast,skeletal development,and bone formation,homeostasis and disease

INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

Regulation of bone phosphorus retention and bone development possibly by BMP and MAPK signaling pathways in broilers

The bone morphogenetic protein(BMP)and mitogen-activated protein kinase(MAPK)signaling pathways play an important role in regulation of bone formation and development,however,it remains unclear that the effect of dietary different levels of non-phytate phosphorus(NPP)on these signaling pathways and their correlations with bone phosphorus(P)retention and bone development in broilers.Therefore,this experiment was conducted to investigate the effect of dietary P supplementation on BMP and MAPK signaling pathways and their correlations with bone P retention and bone development in broilers.A total of 800 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 5 treatments with 8 replicates in a completely randomized design.The 5 treatments of dietary NPP levels were 0.15,0.25,0.35,0.45 and 0.55%or 0.15,0.22,0.29,0.36 and 0.43%for broilers from 1 to 21 days of age or 22 to 42 days of age,respectively.The results showed that extracellular signal-regulated kinase 1(ERK1)mRNA expression in the tibia of broilers on days 14 and 28,phosphorylated-ERK1(p-ERK1)on day 14,and BMP2 protein expression on days 28 and42 decreased linearly(P<0.04),while c-Jun N-terminal kinase 1(JNK1)mRNA expression on day 42 increased linearly(P<0.02)with the increase of dietary NPP level.At 14 days of age,total P accumulation in tibia ash(TP),bone mineral concentration(BMC),bone mineral density(BMD),bone breaking strength(BBS)and tibia ash were negatively correlated(r=-0.726 to-0.359,P<0.05)with ERK1 and JNK1 mRNA as well as p-ERK1;tibia alkaline phosphatase(ALP)and bone gal protein(BGP)were positively correlated(r=0.405 to 0.665,P<0.01)with ERK1 mRNA and p-ERK1.At 28 days of age,TP,BMC,BMD,BBS and tibia ash were negatively correlated(r=-0.518 to-0.370,P<0.05)with ERK1 mRNA and BMP2 protein,while tibia ALP was positively correlated(r=0.382 to 0.648,P<0.05)with them.The results indicated that TP,BMC,BMD,BBS or tibia ash had negative correlations,while tibia ALP and BGP had positive correlations with ERK1 and JNK1 mRNAs,BMP2 protein and p-ERK1,suggesting that bone P retention and bone development might be regulated by BMP and MAPK signaling pathways in broiler chickens.

Gα_s signaling controls intramembranous ossification during cranial bone development by regulating both Hedgehog and Wnt/β-catenin signaling

How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated intramembranous ossification during cranial bone development in mouse models of skeletal genetic diseases that exhibit craniofacial bone defects. The GNAS gene encodes Gαs that transduces GPCR signaling. GNAS activation or loss-of-function mutations in humans cause fibrous dysplasia(FD) or progressive osseous heteroplasia(POH) that shows craniofacial hyperostosis or craniosynostosis, respectively. We find here that, while Hh ligand-dependent Hh signaling is essential for endochondral ossification, it is dispensable for intramembranous ossification, where Gαsregulates Hh signaling in a ligand-independent manner. We further show that Gαscontrols intramembranous ossification by regulating both Hh and Wnt/β-catenin signaling. In addition, Gαsactivation in the developing cranial bone leads to reduced ossification but increased cartilage presence due to reduced cartilage dissolution, not cell fate switch. Small molecule inhibitors of Hh and Wnt signaling can effectively ameliorate cranial bone phenotypes in mice caused by loss or gain of Gnas function mutations, respectively. Our work shows that studies of genetic diseases provide invaluable insights in both pathological bone defects and normal bone development, understanding both leads to better diagnosis and therapeutic treatment of bone diseases.

Effect of dietary calcium or phosphorus deficiency on bone development and related calcium or phosphorus metabolic utilization parameters of broilers from 22 to 42 days of age

This experiment was conducted to investigate the effect of dietary calcium(Ca)or phosphorus(P)deficiency on bone development and related Ca or P metabolic utilization parameters of broilers from 22 to 42 days of age based on our previous study,which indicated that dietary Ca or P deficiency impaired the bone development by regulating related Ca or P metabolic utilization parameters of broilers from 1 to 21 days of age.A total of 504 one-day-old Arbor Acres male broilers were randomly assigned to 1 of 4 treatments with 7 replicates in a completely randomized design,and fed the normal control and Ca-or P-deficient diets from 1 to 21 days of age.At 22 days of age,the broilers were further fed the normal control diet(0.90%Ca+0.35%non-phytate P(NPP)),the P-deficient diet(0.90%Ca+0.18%NPP),the Ca-deficient diet(0.30%Ca+0.35%NPP)or the Ca and P-deficient diet(0.30%Ca+0.18%NPP),respectively.The results showed that dietary Ca or P deficiency decreased(P<0.05)tibia bone mineral density(BMD),bone breaking strength(BBS),ash content,tibia ash Ca content and serum P content on days 28 and 42,but increased(P<0.05)tibia alkaline phosphatase(ALP)activity of broilers on day 42 compared with the control group.Furthermore,the broilers fed the P-deficient diet had the lowest(P<0.05)tibia BMD,BBS,ash content,serum P content and the highest(P<0.05)serum Ca content on day 28 compared with those fed the Ca-deficient or Ca and P-deficient diets.The results from the present study indicated that the bone development and related Ca or P metabolic utilization parameters of broilers were the most sensitive to dietary P deficiency,followed by dietary Ca deficiency or Ca and P-deficiency;dietary Ca or P deficiency impaired the bone development possibly by regulating serum Ca and P contents as well as tibia Ca content and ALP activity of broilers from 22 to 42 days of age.

Genetic and Environmental Effects on the Bone Development of the Hand and Wrist in Chinese Young Twins

We assessed genetic and environmental effectson bone development of the hand and wrist, andon key anthropometric measures in Chinese youngtwins. In total, 139 monozygotic and 95 dizygotictwin pairs aged from 5 to 18 years were recruited.The twin correlations of total hand and wrist scoresfor monozygotic （MZ） and dizygotic （DZ） twins were0.71 and 0.36, respectively. Bivariate modelanalysis showed moderate genetic correlations onlyfor total skeletal maturity vs. weight and totalskeletal maturity vs. waist circumference （r, 0.51and 0.46, respectively）. Our findings demonstratedthat genetic factors played important roles in bonedevelopment of the hand and wrist in Chineseyoung twins, and that these genetic effects mightbe distinct from those influencing anthropometricmeasures.

Development and Validation of an Indirect Whole-Virus ELISA Using a Predominant Genotype VI Velogenic NewCastle Disease Virus Isolated from Lebanese Poultry

Commercial ELISA kits are commonly used to assess the levels of chicken antibodies against NewCastle Disease Virus (NDV) and trace a field strain infection. Nevertheless, the specificity of these kits vis-à-vis endemic strains in Lebanon remains in question. This study developed an in-house indirect ELISA system to evaluate the level of chicken antibodies against a predominant velogenic NDV strain belonging to Genotype VI. A checkerboard analysis comprised a five-factorial multivariate experiment to optimize the protocol: coating antigen concentration, blocking buffer utilization, serum and conjugate dilution levels, and OD reading wavelength. The developed test was optimized and then validated through parallel testing of the sera of 20 broilers and 5 layers using standard serological assays. There was a strong correlation between the developed ELISA results and those obtained with the Hemagglutination Inhibition test (P < 0.01), and a commercial NDV ELISA kit (P < 0.05). The specificity, sensitivity, and reproducibility of the developed ELISA suggest that it can be used as the test of choice for the assessment of chicken antibody titers against locally circulating velogenic NDV strains, specifically those belonging to Genotype VI. It also offers better help in the serological detection of birds’ exposure to the said strains.

Capacity Development of National Reference Centers (NRC) to Face the Challenges of Emerging Infections in Côte d’Ivoire

Background: Some national and international strategies for the detection and prevention of emerging infectious diseases have been established across sectors. The capacity to carry out these tasks varies from country to country, and that remains largely undervalued. The Pasteur Institute of C?te d’Ivoire has created and implemented the capacity of national reference centers to fight against emerging and other infectious diseases. Objective: Show on the one hand the strategies used to develop the National Reference Centers and the IPCI and on the other hand the results obtained by performing these strategies. Method: Datas collection by documentary analysis (published scientific articles and grey literature) was done on Google Scholar, PUBMED and institutional reference documents. The documentary research was carried out to have a better understanding of strategies used to create and develop the NRCs in microbiology of communicable diseases. Results: Seven integrated strategies were launched: 1-training and workforce development;2-investigation of epidemics or public health events;3-strengthening laboratory epidemiological research;4-strengthening surveillance systems;5-improving communication with partners and stakeholders;6-building national and international collaborations;and 7-strengthening technical and technological platforms. In two decades, the number of researchers has risen from 10 in 2004 to ninety (90) in 2021, with 12 senior researchers and 32 junior researchers. A number of health service staff had attended a qualifying training course, 27 investigations into outbreaks and other public health events had been carried out, 18 short-term research projects had been launched, major surveillance programs and epidemiological research efforts on vector-borne, food-borne and nosocomial infections had begun, and several scientific manuscripts had been published or were edited in the writting press. Conclusion: The Ivorian experience shows that, with concerted effort, considerable progress can be made in the development and implementation of an infectious disease control program.

Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease

BACKGROUND The inflammatory bowel diseases(IBD),Crohn’s disease(CD)and ulcerative colitis(UC)are chronic,immune-mediated disorders of the digestive tract.IBD is considered to be a risk factor for developing osteoporosis;however current literature on this matter is inconsistent.AIM To assess prevalence and development of osteoporosis and low bone mineral density(BMD),and its risk factors,in IBD patients.METHODS Systematic review of population-based studies.Studies were identified by electronic(January 2018)and manual searches(May 2018).Databases searched included EMBASE and PubMed and abstracts from 2014-2018 presented at the United European Gastroenterology Week,the European Crohn’s and Colitis Organisation congress,and Digestive Disease Week were screened.Studies were eligible for inclusion if they investigated either the prevalence of osteoporosis or osteopenia and/or risk factors for osteoporosis or low BMD in IBD patients.Studies on children under the age of 18 were excluded.Only population-based studies were included.All risk factors for osteoporosis and low BMD investigated in any included article were considered.Study quality and the possibility of bias were analysed using the Newcastle-Ottawa scale.RESULTS Twelve studies including 3661 IBD patients and 12789 healthy controls were included.Prevalence of osteoporosis varied between 4%-9%in studies including both CD and UC patients;2%-9% in studies including UC patients, and 7%-15% instudies including CD patients. Among healthy controls, prevalence ofosteoporosis was 3% and 10% in two studies. CD diagnosis, lower body massindex (BMI), and lower body weight were risk factors associated withosteoporosis or low BMD. Findings regarding gender showed inconsistent results.CD patients had an increased risk for osteoporosis or low BMD over time, whileUC patients did not. Increased age was associated with decreased BMD, and therewas a positive association between weight and BMI and BMD over time. Greatheterogeneity was found in the included studies in terms of study methodologies,definitions and the assessment of osteoporosis, and only a small number ofpopulation-based studies was available.CONCLUSIONThis systematic review found a possible increase of prevalence of osteoporosis inCD cohorts when compared to UC and cohorts including both disease types.Lower weight and lower BMI were predictors of osteoporosis or low BMD in IBDpatients. The results varied considerably between studies.

Relationship between osteocyte apoptosis and orbital bone development in rabbits

Objective To investigate whether the osteocyte apoptosis exists in orbital bones and to discuss its effect on the orbital development. Methods Seven young Newzealand white rabbits were selected as experimental animals.At two-month-old ,all rabbits were killed and then zygomas were made into paraffin and electron microscope sections after they were decalcified. Apoptosis of osteocytes was observed by light microscope and transmission electron microscopes and detected by TUNEL staining. Results The classical apoptosis of osteocytes was found under light and transmission electron microscopes. Apoptosis of osteocytes was diffused irregularly in the zygomatic tissue. Conclusion Osteocyte can apoptosis and it may participate in the development of the bony orbit.

The essential roles of m^(6)A modification in osteogenesis and common bone diseases

N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stability,splicing,and translation,and plays an important role in post-transcriptional regulation.Bones play a key role in supporting and pro-tecting muscles and other organs,facilitating the movement of the organism,ensuring blood production,etc.Bone diseases such as osteoarthritis,osteoporosis,and bone tumors are serious public health problems.The processes of bone development and osteogenic differen-tiation require the precise regulation of gene expression through epigenetic mechanisms including histone,DNA,and RNA modifications.As a reversible dynamic epigenetic mark,m^(6)A modifications affect nearly every important biological process,cellular component,and molecular function,including skeletal development and homeostasis.In recent years,studies have shown that m^(6)A modification is involved in osteogenesis and bone-related diseases.In this review,we summarized the proteins involved in RNA m^(6)A modification and the latest progress in elucidating the regulatory role of m^(6)A modification in bone formation and stem cell direc-tional differentiation.We also discussed the pathological roles and potential molecular mech-anisms of m^(6)A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone de-fects and bone diseases.

Intellectual Property Protection and High Quality Development of Radix Glycyrrhizae for Treatment of COVID-19

Radix Glycyrrhizae is the dominant native medicinal material variety in the north and northwestern medicinal materials producing areas.It is a main Chinese medicine of effective TCM drugs and formulas for the treatment of new coronavirus disease(COVID-19).This paper introduces the medicinal value of Radix Glycyrrhizae,involving the labeling,cultural heritage,and creative intellectual property rights of the Chinese medicinal materials,analyzes the poverty-stricken areas that are ecologically suitable for Radix Glycyrrhizae cultivation,and the superior counties and production bases of the Chinese medicinal materials.Besides,mainly from the aspects of perfect intellectual property rights,the establishment of authentic medicinal material production bases,and the construction of quality control systems,etc.,it discusses the rural revitalization strategy and the development strategy of traditional Chinese medicine(TCM),agricultural intellectual property protection and high-quality development strategy of Radix Glycyrrhizae.

Skeletal stem cells in bone development,homeostasis,and disease

Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem cells.Recent studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and disease.These investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time points.Furthermore,recent studies have shed light on the characteristics of ssCs in both physiological and pathological conditions.This review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

The Development of Early Life Microbiota in Human Health and Disease

The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus represents a crucial window in our long-term development.This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-,allergic-,and auto-immune-disorder-related diseases,including obesity,diabetes,allergy,autism,inflammatory bowel disease,and stunting.It discusses the development process and various factors shaping the gut micro-biota,as well as the crosstalk between the gut microbiota and the host’s physiological systems(especially intestinal immune development and homeostasis,and the central nervous system in the course of neu-rodevelopment),during the early life establishment of the gut microbiota,in order to decipher the mech-anisms of diseases associated with the intestinal microbiome of early life.In addition,it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases.The true process of gut microbiome maturation,which depends on genetics,nutrition,and environmental factors,must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.