简介：AbstractObjective:To elucidate the epidermal melanocyte distribution according to sex, age, and body part with the goal of providing benchmark data for the diagnosis and therapeutic effect evaluation of pigmentary skin diseases.Methods:Epidermal melanocytes and keratinocytes were assessed using direct immunofluorescence staining, and the melanocyte density and epidermal thickness were calculated. The obtained data were statistically analyzed using SPSS Version 20.0 software. An independent-samples t test was used to compare the data between two groups, while data among three or more groups were compared by one-way analysis of variance. Data correlations were evaluated using Pearson correlation analysis.Results:Melanocytes were uniformly distributed among the keratinocytes in the basal layer, and the average ratio of melanocytes to keratinocytes was 1:7. Among them, the ratio in males was 1:6.5 and that in females was 1:7.4, with no significant difference (P= 0.127). The melanocyte density gradually declined as age increased; the ratio was 1:5.8 before 50 years of age without an obvious downtrend. The average melanocyte density was 1:7.9 within 51 to 65 years of age and 1:8.5 at >65 years of age, and the difference was statistically significant (P < 0.01). Obvious differences were found in the melanocyte density among different body parts; in descending order, these densities were as follows: face (1:4.0) >neck (1:5.1) >hip (1:5.7) >upper limb (1:7.4) >lower limb (1:8.3) >lower back (1:9.2) >thorax and abdomen (1:9.9). The melanocyte density was not related to the epidermal thickness.Conclusion:The melanocyte density showed a declining trend with age and significantly changed after 50 years of age. The melanocyte density was associated with body part; specifically, the density in the face, neck, and hip was higher than that in the limbs and torso. However, the melanocyte density was not associated with sex or epidermal thickness.

简介：AbstractInnate lymphoid cells (ILCs) are a group of lymphocytes without diversified antigen receptors encoded by gene rearrangement on T and B cells. ILCs, which are tissue-resident innate immune cells, expressed particularly in the mucosa or the barrier surface, contribute to the formation of lymphoid organs, the maintenance of tissue homeostasis, and the regulation of antimicrobial defenses. It has been recently reported that ILCs were enriched at the maternal-fetal interface. During a successful pregnancy, the maternal immune system must tolerate a fetus as an allograft. With the new defined of ILCs, a number of studies have shown that three types of ILCs are involved in embryonic development and pregnancy maintenance as well as the occurrence and development of pregnancy-related complications. This article reviews the types and roles of ILCs in normal pregnancy and pregnancy-related diseases.

简介：AbstractLong noncoding RNAs (lncRNAs) have recently been discovered and are increasingly recognized as vital components of modern molecular biology. Accumulating evidence shows that lncRNAs have emerged as important mediators in diverse biological processes such as cell differentiation, pluripotency, and tumorigenesis, while the function of lncRNAs in the field of normal and malignant hematopoiesis remains to be further elucidated. Here, we widely reviewed recent advances and summarize the characteristics and basic mechanisms of lncRNAs and keep abreast of developments of lncRNAs within the field of normal and malignant hematopoiesis. Based on gene regulatory networks at different levels of lncRNAs participation, lncRNAs have been shown to regulate gene expression from epigenetics, transcription and post transcription. The expression of lncRNAs is highly cell-specific and critical for the development and activation of hematopoiesis. Moreover, we also summarized the role of lncRNAs involved in hematological malignancies in recent years. LncRNAs have been found to play an emerging role in normal and malignant hematopoiesis, which may provide novel ideas for the diagnosis and therapeutic targets of hematological diseases in the foreseeable future.

简介：AbstractBackground:Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown.Methods:Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed.Results:Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 downregulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 downregulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9).Conclusions:Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

简介：AbstractBackground:Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.Methods:Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s t test.Results:Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).Conclusion:These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.

简介：AbstractBackground:Normal tension glaucoma (NTG) is a less pressure-dependent type of glaucoma with characteristic optic neuropathy. Recently, the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree. We intended to compare dynamic corneal response parameters (DCRs) among patients with primary open-angle glaucoma with normal tension or hypertension and controls. The correlations between DCRs and known risk factors for glaucoma were also analyzed.Methods:In this cross-sectional study, 49 NTG subjects, 45 hypertension glaucoma (HTG) subjects, and 50 control subjects were enrolled. We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG, HTG, and control groups. We also analyzed the correlations between DCRs and known risk factors for glaucoma (eg, central corneal thickness [CCT], intraocular pressure [IOP], etc).Results:The maximum inverse concave radius (NTG: 0.18 [0.17, 0.20] mm-1; control: 0.17 [0.16, 0.18] mm-1; P= 0.033), deformation amplitude ratio of 2 mm (DAR 2 mm, NTG: 4.87 [4.33, 5.39]; control: 4.37 [4.07, 4.88]; P < 0.001), and DAR 1 mm (NTG: 1.62 [1.58, 1.65]; control: 1.58 [1.54, 1.61]; P < 0.001) were significantly higher in NTG than in the controls. The integrated radius (IR, NTG: 8.40 ± 1.07 mm-1; HTG: 7.64 ± 1.31 mm-1; P = 0.026) and DAR 2 mm (NTG: 4.87 [4.33, 5.39]; HTG: 4.44 [4.12, 5.02]; P < 0.007) were significantly higher, whereas the stiffness parameter at the first applanation (SP-A1, NTG: 91.23 [77.45, 107.45]; HTG: 102.36 [85.77, 125.12]; P = 0.007) was lower in NTG than in HTG. There were no significant differences in the DCRs between HTG and control groups (P > 0.05). In the univariate and multivariate analyses, some of the DCRs, such as IR, were negatively correlated with CCT and IOP, whereas SP-A1 was positively correlated with CCT and IOP.Conclusions:The cornea was more deformable in NTG than in HTG or controls. There were no significant differences in corneal deformability between HTG and controls. The cornea was more deformable with the thinner cornea and lower IOP.

简介：AbstractBackground:Prenatal evaluation of fetal lung maturity (FLM) is a challenge, and an effective non-invasive method for prenatal assessment of FLM is needed. The study aimed to establish a normal fetal lung gestational age (GA) grading model based on deep learning (DL) algorithms, validate the effectiveness of the model, and explore the potential value of DL algorithms in assessing FLM.Methods:A total of 7013 ultrasound images obtained from 1023 normal pregnancies between 20 and 41 + 6 weeks were analyzed in this study. There were no pregnancy-related complications that affected fetal lung development, and all infants were born without neonatal respiratory diseases. The images were divided into three classes based on the gestational week: class I: 20 to 29 + 6 weeks, class II: 30 to 36 + 6 weeks, and class III: 37 to 41 + 6 weeks. There were 3323, 2142, and 1548 images in each class, respectively. First, we performed a pre-processing algorithm to remove irrelevant information from each image. Then, a convolutional neural network was designed to identify different categories of fetal lung ultrasound images. Finally, we used ten-fold cross-validation to validate the performance of our model. This new machine learning algorithm automatically extracted and classified lung ultrasound image information related to GA. This was used to establish a grading model. The performance of the grading model was assessed using accuracy, sensitivity, specificity, and receiver operating characteristic curves.Results:A normal fetal lung GA grading model was established and validated. The sensitivity of each class in the independent test set was 91.7%, 69.8%, and 86.4%, respectively. The specificity of each class in the independent test set was 76.8%, 90.0%, and 83.1%, respectively. The total accuracy was 83.8%. The area under the curve (AUC) of each class was 0.982, 0.907, and 0.960, respectively. The micro-average AUC was 0.957, and the macro-average AUC was 0.949.Conclusions:The normal fetal lung GA grading model could accurately identify ultrasound images of the fetal lung at different GAs, which can be used to identify cases of abnormal lung development due to gestational diseases and evaluate lung maturity after antenatal corticosteroid therapy. The results indicate that DL algorithms can be used as a non-invasive method to predict FLM.

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简介：AbstractBackground:Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells.Methods:We generated Zbtb46fl/fl and Zbtb46fl/flMx1-Cre mice. The deletion of Zbtb46 in Zbtb46fl/flMx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46fl/fl and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.Results:The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46fl/fl littermates (Zbtb46fl/flvs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46fl/flMx1-Cre mice was similar to those from Zbtb46fl/fl control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation.Conclusion:Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.

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