Myeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB.

The pathogenesis of thyroid dysgenesis (TD) is not well understood. Here, using a combination of single-cell RNA and spatial transcriptome sequencing, we identify a subgroup of NF-κB-activated thyrocytes located at the center of thyroid tissues in postnatal mice, which maintained a partially mesenchymal phenotype. These cells actively protruded out of the thyroid primordium and generated new follicles in zebrafish embryos through continuous tracing. Suppressing NF-κB signaling affected thyrocyte migration and follicle formation, leading to a TD-like phenotype in both mice and zebrafish. Interestingly, during thyroid folliculogenesis, myeloid cells played a crucial role in promoting thyrocyte migration by maintaining close contact and secreting TNF-α. We found that cebpa mutant zebrafish, in which all myeloid cells were depleted, exhibited thyrocyte migration defects. Taken together, our results suggest that myeloid-derived TNF-α-induced NF-κB activation plays a critical role in promoting the migration of vertebrate thyrocytes for follicle generation.

Diagnosis and genetic analysis of a case with Bardet-Biedl syndrome caused by compound heterozygous mutations in the BBS12 gene.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.

Transcriptome sequencing reveals a lncRNA-mRNA interaction network in extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease. METHODS: High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro. RESULTS: Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. CONCLUSION: These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.

The relationship between maternal serum prenatal screening combined with epidemiological study and early onset preeclampsia.

OBJECTIVE: To explore the major risk factors and early prediction methods in the pathogenesis of early onset preeclampsia through combining prenatal screening markers and epidemiological characteristics. METHODS: Prenatal screening was performed in second trimester using enzyme-linked immunosorbent assay in 1,011 gravidas and epidemiological correlation factors were got by telephone with prospective cohort study. Predictive model of early onset preeclampsia was established and evaluated by single and multiple factor logistic analysis in 30 cases of preeclampsia and 867 cases of normal gravidas. RESULTS: As compared with the control group, the maternal serum level of human chorionic gonadotropin (hCG) in second trimester of patients with early onset preeclampsia elevated significantly (P < 0.001). Pregestational BMI ≥ 24 kg/m(2) (OR = 3.649, 95 % CI 1.600-8.321, P = 0.002), history of hypertension, diabetes and nephritis (OR = 55.724, 95 % CI 8.223-377.614, P < 0.001), family history of hypertension (OR = 6.777, 95 % CI 2.917-15.742, P < 0.001), and risk coefficient for trisomy 21 (OR = 3.688, 95 % CI 1.013-13.429, P = 0.048) were major risk factors of early onset preeclampsia. The sensitivity and specificity of predictive model were 70.0 and 75.1 %, when cutoff point was 0.249. The diagnostic accuracy of the logistic model was better than hCG. CONCLUSIONS: In order to early prevent the onset and development of EOPE, it is necessary to strengthen pregestational and prenatal care for women in these aspects including pregestational BMI ≥ 24 kg/m(2), history of hypertension, diabetes, nephritis, family history of hypertension, and high risk for trisomy 21 syndrom.

Atmospheric-pressure microplasma in dielectrophoresis-driven bubbles for optical emission spectroscopy.

The manipulation of bubbles and the ignition of microplasma within a 200 nL bubble at atmospheric pressure and in an inert silicone oil environment were achieved. Driven by dielectrophoresis (DEP), bubble generation, transportation, mixing, splitting, and expelling were demonstrated. This process facilitated the preparation of various bubbles with tuneable gas compositions. Different gas bubbles, including air, argon (Ar), helium (He), and Ar/He mixtures, were manipulated and ignited to the plasma state by dielectric barrier discharge (DBD) within a 50 µm-high gap between parallel plates. Moving and splitting the atmospheric-pressure microplasma in different gas bubbles were achieved by DEP. The excited light of the microplasma was recorded by an optical spectrometer for the optical emission spectroscopy (OES) analyses. The characteristic peaks of air, Ar, and He were observed in the DEP-driven microplasma. With the capability to manipulate bubbles and microplasma, this platform could be used for gas analyses in the future.