Tooth number abnormality: from bench to bedside / 国际口腔科学杂志·英文版

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.

Effects of Toluene on the Development of the Inner Ear and Lateral Line Sensory System of Zebrafish / 生物医学与环境科学（英文）

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.

Insights into epigenetic patterns in mammalian early embryos

Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to the formation of a totipotent embryo. During the development of the pre-implantation embryo, precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality, but the underlying molecular mechanisms remain elusive. For the past few years, unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development, taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies. The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals, including DNA methylation, histone modifications, chromatin accessibility and 3D chromatin organization.

Transcriptome profiling reveals differential expression of genes potentially involved in muscle and adipose tissue development of cattle

BACKGROUND: To identify differentially expressed genes (DEGs) between muscle and adipose in cattle, we analyzed the data from the RNA sequencing of three Angus×Qinchuan crossbred cattle. RESULTS: Searched the Gene Expression Omnibus (GEO) for a microarray dataset of Yan yellow cattle, GSE49992. After the DEGs were identified, we used STRING and Cytoscape to construct a protein­protein interaction (PPI) network, subsequently analyzing the major modules of key genes. In total, 340 DEGs were discovered, including 21 hub genes, which were mainly enriched in muscle contraction, skeletal muscle contraction, troponin complex, lipid particle, Z disc, tropomyosin binding, and actin filament binding. CONCLUSIONS: In summary, these genes can be regarded as candidate biomarkers for the regulation of muscle and adipose development.

Melatonin has a stimulatory effect on osteoblasts by upregulating COL-I and OPN expression/secretion / Melatonina tem efeito estimulador em osteoblastos, pela regulação positiva da expressão/secreção de COL-I e OPN

ABSTRACT Melatonin (MLT) is a potential signaling molecule in the homeostasis of bone metabolism and may be an important mediator of bone formation and stimulation. The aim of this in vitro study was to evaluate the effect of MLT on the viability, mRNA/protein expression and mineralization of pre-osteoblastic cells. The concentrations 5, 2.5, 1, 0.1 and 0.01 mM MLT were tested on pre-osteoblastic cells (MC3T3) compared to control (no MLT), evaluating proliferation and cell viability (C50), gene expression (RT-PCR) and secretion (ELISA) of COL-I and OPN at 24h, 48h and 72h, and the formation of mineral nodules (alizarin red and fast red) after 10 days of treatment. MLT at 5 and 2.5 mM proved to be cytotoxic (C50), so only 0.01, 0.1 and 1 mM were used for the subsequent analyses. OPN mRNA expression increased with MLT at 0.1 mM - 1 mM, which was followed by increased secretion of OPN both at 24h and 72h compared to the remaining groups (p <0.05). COL-I mRNA and COL-1 secretion followed the same pattern as OPN at 0.1 mM MLT at 72h of treatment (p <0.05). Regarding mineralization, all MLT doses (except 1mM) caused an increase (p <0.05) in the formation of mineral nodules compared to the control. Melatonin at 0.01mM - 1mM had a stimulatory effect on osteoblasts by upregulating COL-I and OPN expression/ secretion and mineralization, thereby fostering osteogenesis.

RESUMO A melatonina (MLT) é uma molécula potencial de sinalização na homeostase do metabolismo ósseo e pode ser um importante mediador da formação e estimulação óssea. O objetivo deste estudo in vitro foi avaliar o efeito da MLT na viabilidade, na expressão do mRNA da proteína e mineralização de células préosteoblásticas. As concentrações de MLT 5, 2,5, 1, 0,1 e 0,01 mM foram testadas em células pré-osteoblásticas da linhagem MC3T3 em comparação ao controle (sem MLT), avaliando a proliferação e a viabilidade celular (C50), expressão gênica (rtPCR) e secreção (Elisa) de Colágeno tipo 1 (COL-I) e osteopontina (OPN) às 24, 48 e 72 horas, além da formação de nódulos minerais por meio do teste vermelho de Alizarina fast red após 10 dias de tratamento. MLT a 5 e 2,5 mM provou ser tóxico (C50). Portanto, as concentrações de 0,01, 0,1 e 1 mM foram utilizadas para as análises subsequentes. A expressão do mRNA da OPN aumentou com MLT a 0,1 mM-1mM, seguida pela secreção aumentada de OPN às 24 e 72 horas em comparação aos demais grupos (p<0,05). O mRNA de COL-I e a secreção de COL-I seguiram o mesmo padrão do OPN a 0,1 mM de MLT em 72 horas de tratamento (p<0,05). Em relação à mineralização, todas as doses de MLT (exceto 1mM) causaram aumento (p<0,05) na formação de nódulos minerais em comparação ao controle. A MLT na concentração entre 0,01mM a 1 mM teve um efeito estimulador sobre os osteoblastos, ao regular positivamente a expressão e secreção de COL-I e OPN, além da mineralização, favorecendo a osteogênese.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

Research progress on methylation of histones H3K9 and H3K27 in early-stage embryos / 中华医学遗传学杂志

With the in-depth exploration of all stages in early-stage embryos, in particular zygotic genome activation and first cell lineage differentiation, researchers have found that early embryonic epigenetics follows a strict pattern of temporal and spatial modification. Previous studies have determined the inhibitory effect of H3K9me3 and H3K27me3 on genomic expression, and found that they are involved in many core biological events in the genome such as chromatin reprogramming, genomic imprinting, maintenance of embryonic stem cell pluripotency and somatic cell nuclear transfer, though the detailed molecular mechanism has remained elusive. From the point of developmental biology and epigenetics, this article has expounded the research progress on the methylation of H3K9 and H3K27 histones in early-stage embryos, which may provide a clue for the complex mechanism of embryonic development and improvement of culture method for embryos in vitro.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

Effect of dhfr gene overexpression on ethanol-induced abnormal cardiovascular development in zebrafish embryos / 中国当代儿科杂志

OBJECTIVE@#To study the effect of dhfr gene overexpression on ethanol-induced abnormal cardiac and vascular development in zebrafish embryos and underlying mechanisms.@*METHODS@#dhfr mRNA was transcribed in vitro and microinjected into zebrafish fertilized eggs to induce the overexpression of dhfr gene, and the efficiency of overexpression was verified. Wild-type zebrafish were divided into a control group, an ethanol group, and an ethanol+dhfr overexpression group (microinjection of 6 nL dhfr mRNA). The embryonic development was observed for each group. The transgenic zebrafish Tg (cmlc2:mcherry) with heart-specific red fluorescence was used to observe atrial and ventricular development. Fluorescence microscopy was performed to observe the development of cardiac outflow tract and blood vessels. Heart rate and ventricular shortening fraction were used to assess cardiac function. Gene probes were constructed, and embryo in situ hybridization and real-time PCR were used to measure the expression of nkx2.5, tbx1, and flk-1 in the embryo.@*RESULTS@#Compared with the ethanol group, the ethanol+dhfr overexpression group had a significant reduction in the percentage of abnormal embryonic development and a significant increase in the percentage of embryonic survival (P<0.05), with significant improvements in the abnormalities of the atrium, ventricle, outflow tract, and blood vessels and cardiac function. Compared with the control group, the ethanol group had significant reductions in the expression of nkx2.5, tbx1, and flk-1 (P<0.05), and compared with the ethanol group, the ethanol+dhfr overexpression group had significant increases in the expression of nkx2.5, tbx1, and flk-1 (P<0.05), which were still lower than their expression in the control group.@*CONCLUSIONS@#The overexpression of the dhfr gene can partially improve the abnormal development of embryonic heart and blood vessels induced by ethanol, possibly by upregulating the decreased expression of nkx2.5, tbx1, and flk-1 caused by ethanol.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

Differential expression of microRNA-411 and 376c is associated with hypertension in pregnancy

Preeclampsia is a major reason of morbidity and mortality in pregnant women and perinatal fetus. Hence, it is of prime importance that diagnostic markers are defined to predict chances of preeclampsia in pregnant women. It has been previously shown that microRNA (miRNA)-376c expression is decreased in the placenta of preeclampsia patients at term. Even though this decrease was not mimicked in the placenta at the pre-term stage, miR-376c expression was decreased in the plasma of these patients as early as the second trimester. Plasma and placenta specimens were obtained from pregnant women having unifetal gestation undergoing perinatal care between January 2014 and December 2016 (n=49). Early trimester placentas were collected from patients undergoing terminated pregnancies through dilation and curettage procedure. Our results showed that in addition to miR-376c, miR-441 levels were decreased in the placenta of preeclampsia patients, and this decrease occurred both at pre-term and at term. This decrease is also mimicked in the plasma levels at both early and late weeks of pregnancy, highlighting that miR-441 levels can serve as a diagnostic marker of risk of preeclampsia in pregnant women. Overexpression of the miR-441, as well as miR-376c, promoted cell viability, migration, and invasion in the human immortalized cytotrophoblast cell line HTR8/SVneo, indicating that their decrease in pregnant women would result in anomalous apoptosis and functional imbalance resulting in premature abortion and other complications. MiR-441 level can thus potentially serve as diagnostic marker of preeclampsia in pregnant women.

Expressions of HSP110 family members in the testes and epididymis of mice at different stages of development and their regulation by hormones / 南方医科大学学报

OBJECTIVE@#To study the expressions of the members of HSP110 family in the testis and epididymis of mice at different stages of development and whether they are regulated by hormones.@*METHODS@#The testicular and epididymis tissues of mice at different ages (14, 21, 28, 35, 42, 49, 70, and 90 days after birth, 3 mice at each age) were collected for RT-PCR detection of the expression levels of HSP110 family members. Forty-eight mice were randomized into 3 groups for sham operation, castration, or castration with testosterone injections every other day (starting at 7 days after castration), and at 1, 3, 5, and 7 days after first testosterone injection, the expressions of HSP110 family in the epididymis were detected using RT-PCR.@*RESULTS@#The mRNA expression levels of HSP110 family members underwent obvious variations with the development of the mice: , and expressions in the testicles of the mice first increased and then decreased, and gradually became stable; they also exhibited similar temporal patterns of changes in the epididymis. In the castrated mice, the mRNA expressions of and in the epididymis decreased significantly with the reduction of serum hormone levels ( < 0.05), and became normal after the supplementation of exogenous hormone.@*CONCLUSIONS@#The expression levels of HSP110 family are affected by developmental regulation, and the expressions of and are under the regulation by hormones.

Trichloroethylene interferes with heart development of zebrafish via inhibiting Wnt signal pathway / 中国应用生理学杂志

OBJECTIVE@#To investigate the molecular mechanism of trichloroethylene (TCE) cardiac developmental toxicity on zebrafish embryos and to try to provide experimental data for related intervention.@*METHODS@#Zebrafish embryos were purchased from the National Zebrafish Resource Center. The embryos were divided into DMSO(control group), DMSO+CHIR, DMSO+XAV, TCE, TCE+CHIR and TCE+XAV groups(TCE at the concentration of 1, 10 and 100 ppb, with the DMSO as control; DMSO: Dimethyl suldoxide; CHIR: CHIR-99021, Wnt agonist; XAV: XAV-939, Wnt antagonist), 60 embryos per group. Zebrafish embryos were fed in systematic aquaculture water, 28℃. The water was replaced every 24 h and drugs were added according to the grouping scheme. The cardiac tissues were dissected and analyzed by transcriptome microarray after RNA extraction. The expressions of Wnt signaling pathway related genes were verified by q-PCR. Wnt atagonist XAV and activator CHIR were used alone or in combination to further evaluate the possibility of the Wnt signaling participating in the cardiac developmental toxicity induced by TCE.@*RESULTS@#Compared with control, Zebra fish embryos exposed to TCE showed a significant increase in heart defects, and the main phenotypes were abnormal atrioventricular ratio, looping defects and pericardial edema. The results of microarray profiling showed that the expressions of genes related to Wnt signaling pathway were affected significantly. The results of qPCR further confirmed that TCE inhibited the expressions of Wnt pathway target genes Axin2, Sox9b and Nkx2.5(P＜0.05). Wnt agonist CHIR reduced the TCE-induced cardiac malformation rate significantly, while the addition of Wnt antagonist XAV markedly enhanced the cardiac developmental toxicity of TCE.@*CONCLUSION@#Exposure to TCE leads to heart malformation in zebrafish embryos. Wnt signaling pathway may be involved in the cardiac developmental toxicity induced by TCE.

Ecdysis-related pleiotropic neuropeptides expression during Anopheles albimanus development / Expresión de neuropéptidos pleiotrópicos asociados con ecdisis durante el desarrollo del mosquito Anopheles albimanus

Abstract: Objective: To analyze the transcription pattern of neuropeptides in the ontogeny of a malaria vector, the mosquito Anopheles albimanus. Materials and methods: The transcription pattern of Crustacean CardioActive peptide (CCAP), corazonin, Ecdysis Triggering Hormone (ETH), allatostatin-A, orcokinin, Insulin Like Peptide 2 (ILP2), Insulin Like Peptide 5 (ILP5) and bursicon was evaluated using qPCR on larvae (1st - 4th instar), pupae and adult mosquitoes. Results: Unlike in other insects, transcripts of CCAP (70.8%), ETH (60.2%) and corazonin (76.5%) were expressed in 4th instar larvae, probably because these three neuropeptides are associated with the beginning of ecdysis. The neuropeptide ILP2 showed higher transcription levels in other stages and orcokinin decreased during the development of the mosquito. Conclusion: The CCAP, corazonin and ETH neuropeptides are potential targets for the design of control strategies aimed at disrupting An. albiamnus larval development.

Resumen: Objetivo: Describir la expresión de neuropéptidos durante la ontogenia del mosquito vector de la malaria Anopheles albimanus. Material y métodos: Se midió la expresión de CCAP, corazonina, ETH, allatostatina, orcokinina, ILP2, ILP5 y bursicon en larvas de primer (2mm), segundo (4mm), tercer (5mm) y cuarto (6mm) estadio, pupas y mosquitos adultos, mediante qPCR. Resultados. A diferencia de otros insectos en donde, CCAP, corazonina y ETH se expresan principalmente en estadios pupales, en An. albimanus se expresaron mayoritariamente en larvas de cuarto estadio, CCAP tuvo 70.8% de expresión relativa, corazonina 76.5% y ETH 60.2%. ILP2 fue el neuropéptido que más se expresó en el primer, segundo y tercer estadio y orcokinina disminuyó durante el desarrollo del mosquito. Conclusión. Los péptidos estudiados se expresaron en todos los estadios de desarrollo del mosquito. Sin embargo, su expresión varió en cada uno de ellos. Los neuropéptidos CCAP, corazonina y ETH, que son esenciales para la transformación de lavas a pupas, pueden ser blancos potenciales para el diseño de estrategias de control dirigidas a interrumpir el desarrollo larvario de An. albimanus.

Mãe, obrigada pelos microRNAs / Mom, thanks for the microRNAs

Os microRNAs (miRNAs) são pequenas moléculas de RNA não codificante que têm grande importância nos mais diversos processos celulares, pois atuam na regulação da expressão gênica pós-transcricional. Estima-se que estes RNAs tenham controle de, em média, 30% da regulação de genes codificantes de proteínas em mamíferos. Da mesma forma, na fase zigótica do desenvolvimento embrionário, os miRNAs maternos desempenham funções notáveis e são fundamentais para a degradação dos próprios transcritos maternos. Este evento é determinante para a transição materno­zigótica, momento onde o zigoto passa a expressar completamente e de maneira independente seus próprios mRNAs, e; portanto, são vitais para o desenvolvimento inicial do embrião. O presente estudo, através de uma revisão narrativa de literatura, busca descrever os mecanismos de ação de miRNAs maternos presentes em zigotos de diversas espécies durante o desenvolvimento embrionário. Foram selecionados estudos disponíveis na base de dados PubMed através da busca utilizando palavras­chave descritas pelos Descritores em Ciências da Saúde (DeCS). (AU)

MicroRNAs (miRNAs) are small molecules of non-coding RNA that have great importance in the most diverse cellular processes, since they act in the post-transcriptional regulation of gene expression. It is estimated that these RNAs have a control of, on average, 30% of the regulation of protein-encoding genes in mammals. Likewise, in the zygotic phase of embryonic development, maternal miRNAs perform remarkable functions and are fundamental for the degradation of the maternal transcripts themselves. This event is determinant for the maternal-to-zygotic transition, at which moment the zygote begins to express completely and independently its own miRNAs, and is therefore vital for the initial development of the embryo. The present study, through a review of the literature, aims to describe the mechanisms of action of maternal miRNAs present in zygotes of different species during embryonic development. We selected only the studies listed in the PubMed database through the search using keywords described by the Health Sciences Descriptors (DeCS). (AU)

Expression of Pref-1 and Related Chemokines during theDevelopment of Rat Mesenteric Lymph Nodes / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to investigate the ability of Pref-1+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes (MLNs) and the dynamic expression of related chemokines during the development of rat MLNs.</p><p><b>METHODS</b>Immunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy (TEM) was used to observe the changes in ultrastructure of MLNs.</p><p><b>RESULTS</b>Cells containing lipid droplets were found in all rat MLNs at embryonic day (E) 18.5, 2 and 6 weeks (w) after birth, and they were similar to fibroblastic reticular cells (FRCs) or follicular dendritic cells (FDCs) under TEM. Pref-1+ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1 (P < 0.01; r = 0.897). At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth (P < 0.05), while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth (P < 0.05).</p><p><b>CONCLUSION</b>Adipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.</p>

Expression of gene in wild type zebrafish embryos of early development / 浙江大学学报·医学版

OBJECTIVE@#: To observe the expression of gene in the early development stage of wild zebrafish embryos.@*METHODS@#: The collinearity of gene and the sequence similarity of G6pd protein were analyzed with gene database and BLAST software, respectively. Expression of gene in different development stages of zebrafish embryos was detected by hybridization. The -EGFP-pCS recombinant plasmids were microinjected into zebrafish embryos, and fluorescence was observed under a fluorescence microscope. The expression of G6pd protein at 24, 48 and 72 hour post fertilization (hpf) zebrafish embryos was detected by Western blotting; the enzyme activity of G6pd at 24, 48 and 72 hpf zebrafish embryos was detected by modified G6pd quantitative ratio method.@*RESULTS@#: The G6pd protein similarity of zebrafish and human was 88%, and that of zebrafish and mouse was 87%. The results of hybridization showed that the gene was mainly expressed in the hematopoietic tissues of zebrafish; the results observed after microinjection of -EGFP-pCS recombinant plasmid were consistent with the results of hybridization. At 24, 48 and 72 hpf, the relative expression levels of G6pd protein in zebrafish embryos were 1.44±0.03, 1.47±0.05, and 1.54±0.02, respectively(>0.05); the G6pd enzyme activity levels were 1.74±0.17, 1.75±0.12, 1.71±0.22, respectively (>0.05).@*CONCLUSIONS@#: The study has observed the expression of gene and G6pd protein, and G6pd enzyme activity in zebrafish embryos at different development phases, which provides a reference for the establishment of a zebrafish G6PD deficiency model.

AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination / 神经科学通报·英文版

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.

Role of Tbx20 gene in the development of cardiac valves / 中华医学遗传学杂志

Cardiac valves are highly organized yet delicate structures that ensure unidirectional blood flow through the cardiac chambers and large vessels. Disturbed development of cardiac valves can lead to aberrant heart formation and function which account for approximately one third of congenital heart diseases. The formation of cardiac valves is a dynamic process accomplished by a series of complex events including lineage determination and cell proliferation, differentiation and migration. This paper reviews current knowledge about the role of Tbx20 gene in the development of cardiac valves, which include functional diversities of Tbx20 at various stages of cardiac valve development, its interaction with other signaling pathways, and genetic network involved in endocardial development.

Nr2e1 Downregulation Is Involved in Excess Retinoic Acid-induced Developmental Abnormality in the Mouse Brain / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality.</p><p><b>METHODS</b>The mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells. In addition, the regulation of Nr2e1 expression by RA was also determined in vitro.</p><p><b>RESULTS</b>Nr2e1 expression was significantly downregulated in the brain and NSCs of RA-treated mouse embryos, and knockdown of Nr2e1 affected the proliferation of NSCs in vitro. In addition, a similar expression pattern of Nr2e1 and RA receptor (RAR) α was observed after treatment of NSCs with different concentrations of RA.</p><p><b>CONCLUSION</b>Our study demonstrated that Nr2e1 could be regulated by RA, which would aid a better understanding of the mechanism underlying RA-induced brain abnormality.</p>