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1.
Jpn J Infect Dis ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32115543

RESUMO

Dengue affects tropical and subtropical regions, including Guangdong province of China. Dengue cases have been reported almost every year in Shantou city in Guangdong province. To understand the molecular characteristics of dengue viruses (DENVs) isolated in Shantou, we performed a molecular epidemiological study based on envelope protein (E) gene of the DENVs isolated from the cases. Totally, 174 serum samples were collected from 174 dengue-suspected patients during 2015-2017. 33.9% (59/174) were diagnosed with dengue. Serotypes of DENVs were identified in 27 samples, 37% (10/27), 55.6% (15/27), 3.7% (1/27), 3.7% (1/27) were DENV-1, DENV-2 DENV-3 and DENV-4, respectively. Genotype Ⅰ and Ⅳ were detected in DENV-1 while only Cosmopolitan genotype was detected in DENV-2. The replacement of predominant serotype (genotype),which took place every year,implied that the dengue endemic in Shantou might be caused by imported infection rather than local circulation. Our results suggested that DENVs in Shantou were closely related to the strains circulating in Southeast Asian countries, which were possibly transmitted to Shantou through some relay point cities.

2.
J Clin Lab Anal ; : e23286, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32159262

RESUMO

BACKGROUND: Dynamic assessment of cerebrospinal fluid (CSF) is essential for diagnosis, treatment, and prognosis of tuberculous meningitis, one of the most severe forms of central nervous system (CNS) infection. CASE PRESENTATION: A 45-year-old man sought care as he developed confusion, clonic convulsion, and coma. Longitudinal, comprehensive analyses of cytological, biochemical, and microbial changes in CSF specimen were assessed for this patient. On day 1 of hospitalization, modified Ziehl-Neelsen staining of CSF identified positive acid-fast bacilli, cytological analysis revealed neutrophilic-predominant pleocytosis (neutrophils 77%), and adenosine deaminase (ADA) was substantially elevated. Therefore, tuberculous meningitis was diagnosed and first-line standard anti-tuberculosis treatment was initiated. Interestingly, after 7-day treatment, the patient was greatly improved, and CSF disclosed a dominant percentage of lymphocytes (82%) as well as macrophages engulfing Mycobacterium tuberculosis. Later, the dose of dexamethasone was reduced, large number of neutrophils (57%) was present and protein level was immediately elevated in CSF specimen, indicating a possible relapse of tuberculous meningitis. Since the clinical condition of the patient was not worsening, the patient was stick to reduced dose of dexamethasone and standard anti-tuberculosis agents. He was discharged from the hospital on day 34, with 1-year continuation standard anti-tuberculosis therapy, and was clinically resolved from tuberculous meningitis. CONCLUSION: Detailed analyses of cellular composition, biochemical results, and microbial tests of CSF specimen provide the physician direct evidence of the immune surveillance status during tuberculous meningitis, which facilitates early diagnosis, optimal treatment, and improved prognosis.

3.
Org Lett ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003213

RESUMO

Herein, novel host-guest properties between perethylated pillar[6]arene and four kinds of ferrocene derivatives were fully investigated. NMR titrations, 2D NOESY NMR spectroscopy, and ESI-MS are used to confirm that they indeed formed stable inclusion complexes. Two precious single-crystal structures were obtained and showed that ferrocene derivatives with different chemical structures exhibit different binding modes with perethylated pillar[6]arenes.

4.
Int Immunopharmacol ; 81: 106266, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32062079

RESUMO

BACKGROUND: Autologous hematopoietic stem cell transplantation is an effective therapeutic strategy for lymphoma patients. However, some patients have to give up receiving transplantation because of failing to obtain sufficient CD34+ cells yields. Therefore, we ex vivo expanded HSCs of lymphoma patients using UM171 to solve the problem of HSCs deficiency. METHODS: Mobilized peripheral blood-derived CD34+ cells from lymphoma patients were cultured for 10 days with or without UM171. The fold of cell expansion and the immunophenotype of expanded cells were assessed by flow cytometry. RNA-seq experiment was performed to identify the mechanism by which UM171 promoted HSCs expansion. RESULTS: UM171 treatment increased the proportion of CD34+ (68.97 ± 6.91%), CD34+ CD38- cells (44.10 ± 9.20%) and CD34+CD38-CD45RA-CD90+ LT-HSCs (3.05 ± 2.08%) compared to vehicle treatment (36.08 ± 11.14%, 18.30 ± 9.49% and 0.56 ± 0.45%, respectively). UM171 treatment led to an 85.08-fold increase in LT-HSC numbers relative to initial cells. Importantly, UM171 promoted expansion of LT-HSCs achieved 138.57-fold in patients with poor mobilization. RNA-seq data showed that UM171 upregulated expression of HSC-, mast cell-specific genes and non-canonical Wnt signaling related genes, and inhibited genes expression of erythroid, megakaryocyte and inflammatory mediated chemokine. CONCLUSIONS: Our study shows that UM171 can efficiently promote ex vivo expansion of HSCs from lymphoma patients, especially for poorly mobilizing patients. In terms of mechanism, UM171 upregulate HSC-specific genes expression and suppress erythroid and megakaryocytic differentiation, as well as activate non-classical Wnt signaling.

5.
Med Sci Monit ; 26: e920541, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32054823

RESUMO

BACKGROUND Multiple myeloma is featured by the proliferation of malignant plasma cell in bone marrow. We aimed to demonstrate the effects of valproic acid combined with GANT61 on multiple myeloma cell proliferation and clarify its mechanism. MATERIAL AND METHODS Multiple myeloma cells were exposed to valproic acid, GANT61, or the combination of valproic acid and GANT61, respectively. MTT assay was performed to detect the cell viability. Quantitative reverse transcriptase polymerase chain reaction and western blotting were used to detect mRNA and expression levels of proteins in Hedgehog signaling pathway. The Q-value of the combination regime was calculated to evaluate the drug combination effect. RESULTS Both valproic acid and GANT61 alone inhibited multiple myeloma cell proliferation in a dose-dependent manner compared to the control. In the presence of GANT61 or not, valproic acid inhibited multiple myeloma cell proliferation in a time-dependent manner. These 2 drugs had a synergistic effect at valproic acid concentration of ≥4 mM. Expression analysis showed that valproic acid significantly inhibited the expression levels of PTCH1, GLI1, and HES-1. GANT61 enhanced the inhibition of Hedgehog signaling pathway mediated by valproic acid. CONCLUSIONS GANT61 and valproic acid inhibited multiple myeloma cell proliferation synergistically by inhibiting the Hedgehog signaling pathway. The present study may provide a combination regime for the therapy of multiple myeloma.

6.
J Med Genet ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051257

RESUMO

BACKGROUND: Asthenoteratospermia, one of the most common causes for male infertility, often presents with defective sperm heads and/or flagella. Multiple morphological abnormalities of the sperm flagella (MMAF) is one of the common clinical manifestations of asthenoteratospermia. Variants in several genes including DNAH1, CEP135, CATSPER2 and SUN5 are involved in the genetic pathogenesis of asthenoteratospermia. However, more than half of the asthenoteratospermia cases cannot be explained by the known pathogenic genes. METHODS AND RESULTS: Two asthenoteratospermia-affected men with severe MMAF (absent flagella in >90% spermatozoa) from consanguineous families were subjected to whole-exome sequencing. The first proband had a homozygous missense mutation c.188G>A (p.Arg63Gln) of DZIP1 and the second proband had a homozygous stop-gain mutation c.690T>G (p.Tyr230*). Both of the mutations were neither detected in the human population genome data (1000 Genomes Project, Exome Aggregation Consortium) nor in our own data of a cohort of 875 Han Chinese control populations. DZIP1 encodes a DAZ (a protein deleted in azoospermia) interacting protein, which was associated with centrosomes in mammalian cells. Immunofluorescence staining of the centriolar protein Centrin1 indicated that the spermatozoa of the proband presented with abnormal centrosomes, including no concentrated centriolar dot or more than two centriolar dots. HEK293T cells transfected with two DZIP1-mutated constructs showed reduced DZIP1 level or truncated DZIP1. The Dzip1-knockout mice, generated by the CRSIPR-Cas9, revealed consistent phenotypes of severe MMAF. CONCLUSION: Our study strongly suggests that homozygous DZIP1 mutations can induce asthenoteratospermia with severe MMAF. The deficiency of DZIP1 induces sperm centrioles dysfunction and causes the absence of flagella.

7.
Neurosci Lett ; 720: 134749, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-31935433

RESUMO

OBJECTIVE: The aim of this study is to investigate the protective effects as well as the underlying molecular mechanisms of geniposide in APP/PS1 transgenic mice. METHOD: APP/PS1 mice were subjected to intragastric administration of geniposide (50 mg/kg/d) for 8 weeks (including a 2-week behavior test). The novel object recognition (NOR) and the Morris water maze (MWM) tests were used for behavioral assessments. Aß1-40 plaques in mice cortices and hippocampi are visualized with immunohistochemistical staining. ELISA was used to quantify the levels of soluble Aß1-40 and Aß1-42 in the hippocampus. Western blot was used to detect p-Akt/Akt, p-mTOR/mTOR and p-4E-BP1/4E-BP1 levels. The relative mRNA levels of Akt, mTOR and 4E-BP1 were quantified using real-time PCR (RT-PCR). RESULTS: Geniposide alleviated cognitive impairment by improving the ability of novel object exploration, spatial memory, and reduced the level of Aß in the brain of APP/PS1 mice. Geniposide possibly regulates mTOR-related proteins through modification of phosphorylation. Geniposide markedly lowered p-mTOR and p-Akt expressions while elevating p-4E-BP1 expression. Geniposide obviously reduced the relative mRNA levels of Akt and mTOR and increased the relative mRNA level of 4E-BP1. CONCLUSION: Geniposide is able to alleviate cognitive impairments and cerebral damage in APP/PS1 mice, with its neuroprotective effects likely mediated via modulation of the mTOR signaling pathway.

8.
Theor Appl Genet ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919537

RESUMO

Modern agriculture relies heavily on chemical fertilizers, especially in terms of cereal production. The excess application of fertilizers not only increases production cost, but also causes severe environmental problems. As one of the major cereal crops, rice (Oryza sativa L.) provides the staple food for nearly half of population worldwide, especially in developing countries. Therefore, improving rice yield is always the priority for rice breeding. Macronutrients, especially nitrogen (N) and phosphorus (P), are two most important players for the grain yield of rice. However, with economic development and improved living standard, improving nutritional quality such as micronutrient contents in grains has become a new goal in order to solve the "hidden hunger." Micronutrients, such as iron (Fe), zinc (Zn), and selenium (Se), are critical nutritional elements for human health. Therefore, breeding the rice varieties with improved nutrient use efficiency (NUE) is thought to be one of the most feasible ways to increase both grain yield and nutritional quality with limited fertilizer input. In this review, we summarized the progresses in molecular dissection of genes for NUE by reverse genetics on macronutrients (N and P) and micronutrients (Fe, Zn, and Se), exploring natural variations for improving NUE in rice; and also, the current genetic toolbox and future perspectives for improving rice NUE are discussed.

9.
J Exp Bot ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31974553

RESUMO

Due to its subtropical origin, rice (Oryza sativa L.) is sensitive to low-temperature stress. We report the identification of LOC_Os04g24110, annotated to encode the UDP-glycosyltransferase enzyme UGT90A1, as a gene associated with the low-temperature seedling survivability (LTSS) quantitative trait locus qLTSS4-1. Haplotype differences in the control region of OsUGT90A1 affecting differential expression in chilling tolerant and chilling sensitive rice accessions rather than differences in protein sequences correlate with chilling tolerance phenotypes. OsUGT90A1 expression is cold regulated, and its overexpression helps to maintain membrane integrity during cold stress and promotes leaf growth during stress recovery, correlating with reduced levels of reactive oxygen species due to increased antioxidant enzyme activities. Overexpression of OsUGT90A1 in Arabidopsis moreover improves freezing survival and salt stress tolerance, correlating with enhanced antioxidant enzyme activities. In rice, overexpression of OsUGT90A1 decreases while gene knockout increases root lengths of three-week-old seedlings, indicating that differential expression of this gene may affect phytohormone activities. Thus, higher OsUGT90A1 expression in chilling tolerant than chilling sensitive accessions helps maintain cell membrane integrity as an abiotic stress tolerance response mechanism to prepare plants to resume growth and development during stress recovery.

11.
Mol Hum Reprod ; 26(2): 80-87, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-31953539

RESUMO

Fertilization involves a series of molecular events immediately following egg-sperm fusion; Ca2+ oscillations are the earliest signaling event, and they initiate the downstream reactions including pronucleus formation. Successful human reproduction requires normal fertilization. In clinical IVF or ICSI attempts, some infertile couples suffer from recurrent fertilization failure. However, the genetic reasons for fertilization failure are largely unknown. Here, we recruited several couples diagnosed with fertilization failure even though their gametes are morphologically normal. Through whole-exome sequencing and Sanger sequencing, we identified biallelic mutations in gene-encoding phospholipase C zeta 1 (PLCZ1) in four independent males in couples diagnosed with fertilization failure. Western blotting showed that missense mutations decreased the level of PLCZ1 and that nonsense or frameshift mutations resulted in undetectable or truncated proteins. Expression of these mutations in mice significantly reduced the levels of oocyte activation. Artificial oocyte activation in patient oocytes could rescue the phenotype of fertilization failure and help establish pregnancy and lead to live birth. Our findings expand the spectrum of PLCZ1 mutations that are responsible for human fertilization failure and provide a potentially feasible therapeutic treatment for these patients.

12.
J Med Genet ; 57(3): 187-194, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31704776

RESUMO

BACKGROUND: Abnormal pronuclear formation during fertilisation and subsequent early embryonic arrest results in female infertility. In recent years, with the prevalence of assisted reproductive technology, a few genes have been identified that are involved in female infertility caused by abnormalities in oocyte development, fertilisation and embryonic development. However, the genetic factors responsible for multiple pronuclei formation during fertilisation and early embryonic arrest remain largely unknown. OBJECTIVE: We aim to identify genetic factors responsible for multiple pronuclei formation during fertilisation or early embryonic arrest. METHODS: Whole-exome sequencing was performed in a cohort of 580 patients with abnormal fertilisation and early embryonic arrest. Effects of mutations were investigated in HEK293T cells by western blotting and immunoprecipitation, as well as minigene assay. RESULTS: We identified a novel homozygous missense mutation (c.397T>G, p.C133G) and a novel homozygous donor splice-site mutation (c.546+5G>A) in the meiotic gene REC114. REC114 is involved in the formation of double strand breaks (DSBs), which initiate homologous chromosome recombination. We demonstrated that the splice-site mutation affected the normal alternative splicing of REC114, while the missense mutation reduced the protein level of REC114 in vitro and resulted in the loss of its function to protect its partner protein MEI4 from degradation. CONCLUSIONS: Our study has identified mutations in REC114 responsible for human multiple pronuclei formation and early embryonic arrest, and these findings expand our knowledge of genetic factors that are responsible for normal human female meiosis and fertility.

13.
Pulmonology ; 26(1): 18-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31412983

RESUMO

BACKGROUND: Asthma, a common chronic inflammatory disease, is treated with corticosteroid in most cases, but corticosteroid resistance in severe asthma patients seriously impairs the therapeutic effects. LncRNA-CASC7 inhibits cell proliferation and enhances drug sensitivity, but the molecular mechanisms of corticosteroid resistance in severe asthma are still unknown. METHODS: Airway smooth muscle cells (ASMCs) from healthy and severe asthmatic subjects were used in this study. The expression of CASC7 and miR-21 were modified by transfection with the pcDNA3.1-CASC7, miR-21 mimics and inhibitor. MTT assay was conducted to measure cell proliferation. ELISA assay was used to determine the secretion of CCL5, CCL11 and IL-6. The phosphorylation of glucocorticoid receptor (GR) and the PI3K/AKT signaling were assessed by western blotting assays. qRT-PCR was used to analyze the expression of CASC7, miR-21 and PTEN. Dual-luciferase reporter assay was used to assess the interaction among CASC7, miR-21 and PTEN. RESULTS: Compared with AMSCs from severe asthma patients, dexamethasone inhibited cytokines (CCL5, CCL11 and IL-6) and promoted the phosphorylation of GR more significantly in normal AMSCs. CASC7 expression was suppressed while miR-21 expression and AKT activity were promoted in ASMCs from severe asthma patients. CASC7 promoted PTEN expression via directly inhibiting miR-21 expression. Overexpression of CASC7 suppressed the PI3K/AKT signaling pathway and promoted the inhibition effects of dexamethasone on cell proliferation and cytokines secretion via targeting miR-21. CONCLUSION: CASC7 increased corticosteroid sensitivity by inhibiting the PI3K/AKT signaling pathway via targeting miR-21, which provided a promising potential target for designing novel therapeutic strategy for severe asthma.

14.
Ann Hum Genet ; 84(1): 46-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31495922

RESUMO

Intellectual disability (ID) describes a wide range of serious human diseases caused by defects in central nervous system development and function. Some mutant genes have been found to be associated with these diseases, but not all cases can be explained, thus suggesting that other disease-causing genes have not yet been discovered. Sialic acid is involved in a number of key biological processes, including embryo formation, nerve cell growth, and cancer cell metastasis, and very recently it has been suggested that N-acetylneuraminic acid synthase-mediated synthesis of sialic acid is required for brain and skeletal development. CMP-sialic acid synthetase (CMAS) is one of four enzymes involved in NeuNAc metabolism, as it catalyzes the formation of CMP-NeuNAc. Before the present study, no links between mutations in CMAS and incidences of human ID had been reported. In the current study, we recruited a recessive nonsyndromic ID pedigree with consanguineous marriage in which all patients have typical clinical manifestations of ID. We identified the NM_018686.3:c.563G > A (p.Arg188His) substitution in CMAS as being responsible for the disease in this family. Conservation analysis, structural prediction, and enzyme activity experiments demonstrated that (p.Arg188His) influences protein dimerization and alters CMAS enzyme activity. Our results offer a new orientation for future research and clinical diagnosis.

15.
Bioinformatics ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794005

RESUMO

MOTIVATION: RNA 5-methylcytosine (m5C) is a type of post-transcriptional modification that may be involved in numerous biological processes and tumorigenesis. RNA m5C can be profiled at single-nucleotide resolution by high-throughput sequencing of RNA treated with bisulfite (RNA-BisSeq). However, the exploration of transcriptome-wide profile and potential function of m5C in splicing remains to be elucidated due to lack of isoform level m5C quantification tool. RESULTS: We developed a computational package to quantify Epitranscriptomal RNA m5C at the transcript isoform level (named Episo). Episo consists of three tools, mapper, quant and Bisulfitefq, for mapping, quantifying, and simulating RNA-BisSeq data, respectively. The high accuracy of Episo was validated using an improved m5C-specific methylated RNA immunoprecipitation (meRIP) protocol, as well as a set of in silico experiments. By applying Episo to public human and mouse RNA-BisSeq data, we found that the RNA m5C is not evenly distributed among the transcript isoforms, implying the m5C may subject to be regulated at isoform level. AVAILABILITY: Episo is released under the GNU GPLv3+ license. The resource code Episo is freely accessible from https://github.com/liujunfengtop/Episo (with Tophat/cufflink) and https://github.com/liujunfengtop/Episo/tree/master/Episo_Kallisto (with Kallisto). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

16.
Front Genet ; 10: 1128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824559

RESUMO

The sex of Chinese tongue sole (Cynoglossus semilaevis) is determined by both genetic sex determination (GSD) and environmental sex determination (ESD), making it an ideal model to study the relationship between sex-determination and temperature. In the present study, transcriptomes of undifferentiated gonads from genetic females and males, as well as differentiated gonads from males, females, and pseudomales under high and normal temperature treatments were generated for comparative transcriptomic analysis. A mean of 68.24 M high-quality clean reads was obtained for each library. Differentially expressed genes (DEGs) between different sexes and environmental treatments were identified, revealing that the heat shock protein gene family was involved in the high temperature induced sex reversal. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were enriched in pseudomale and genetic female comparison included neuroactive ligand-receptor interaction, cortisol synthesis and secretion, and steroid hormone biosynthesis. Furthermore, weighted gene co-expression network analyses were conducted on all samples, and two modules were positive correlated with pseudomale under high temperature. An illustrated protein-protein interaction map of the module identified a hub gene, hsc70. These findings provide insights into the genetic network that is involved in sex determination and sexual differentiation, and improve our understanding of genes involved in sex reversal under high temperature.

17.
Am J Ophthalmol ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31887279

RESUMO

PURPOSE: To analyze matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and their molar ratios in the aqueous humor in previous APAC patients and their correlations with trabeculectomy outcomes. DESIGN: Prospective cohort study. METHODS: Aqueous humor samples were collected from a total of 78 eyes including 52 previous APAC eyes and 26 cataract eyes. TIMP-1, 2, 3, and 4 and MMP-1, 2, 3, 7, 8, 9, 12 and 13 analyte concentrations were measured using multiplexed immunoassays kits. Patient follow-up occurred at 1 week and 1, 3, 6, 12, and 18 months. RESULTS: In the previous APAC group, eleven MMP/TIMP molar ratios were significantly lower. APAC eyes were then followed for up to 18 months after trabeculectomy and divided into success (37 eyes) and failure (15 eyes) groups. Five out of the eleven molar ratios were significantly lower in the failure group than the success group. In multiple logistic regression analysis, failed filtration surgery was more likely in APAC eyes with lower MMP-2/TIMP-2 (P = 0.040, OR = 44.499) and MMP-13/TIMP-1 (P = 0.034, OR = 37.947) ratios. Previous APAC eyes were divided according to MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios. Compared to eyes with high ratios, eyes with low MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios had significantly higher failure rates. CONCLUSIONS: In previous APAC eyes, changes in MMP and TIMP levels resulted in MMP and TIMP imbalance. Lower MMP-2/TIMP-2 and MMP-13/TIMP-1 ratios in aqueous humor are risk factors for trabeculectomy failure. Modulating specific MMP/TIMP ratios may have potential clinical applications for filtration surgery.

18.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683567

RESUMO

The trans-resveratrol (RSV)-loaded silica aerogel (RLSA) was prepared by the sol-gel method, adding the drug during the aging process, solvent replacement and freeze drying. A series of characterizations showed that RSV stays in the silica aerogel in two ways. First, RSV precipitates due to minimal solubility in water during the solvent replacement process. After freeze drying, the solvent evaporates and the RSV recrystallizes. It can be seen from scanning electron microscope (SEM) and transmission electron microscope (TEM) images that the recrystallized RSV with micron-sized long rod-shaped is integrated with the dense silica network skeleton. Second, from small-angle X-ray scattering (SAXS) results, a portion of the RSV molecules is not crystallized and the size is extremely small. This can be attached to the primary and secondary particles of silica to enhance its network structure and inhibit shrinkage, which is why the volume and pore size of RLSA is larger. In addition, the diffusion of RSV in silica alcogel was studied by a one-dimensional model. The apparent diffusion coefficients of inward diffusion, outward diffusion and internal diffusion were calculated by fitting the time- and position-dependent concentration data. It was found that the outward diffusion coefficient (5.25 × 10-10 m2/s) is larger than the inward (2.93 × 10-10 m2/s), which is probably due to the interface effect. The diffusion coefficients obtained for different concentrations in the same process (inward diffusion) are found to be different. This suggests that the apparent diffusion coefficient obtained is affected by molecular adsorption.

19.
Am J Hum Genet ; 105(6): 1168-1181, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31735294

RESUMO

As a type of severe asthenoteratospermia, multiple morphological abnormalities of the flagella (MMAF) are characterized by the presence of immotile spermatozoa with severe flagellar malformations. MMAF is a genetically heterogeneous disorder, and the known MMAF-associated genes can only account for approximately 60% of human MMAF cases. Here we conducted whole-exome sequencing and identified bi-allelic truncating mutations of the TTC29 (tetratricopeptide repeat domain 29) gene in three (3.8%) unrelated cases from a cohort of 80 MMAF-affected Han Chinese men. TTC29 is preferentially expressed in the testis, and TTC29 protein contains the tetratricopeptide repeat domains that play an important role in cilia- and flagella-associated functions. All of the men harboring TTC29 mutations presented a typical MMAF phenotype and dramatic disorganization in axonemal and/or other peri-axonemal structures. Immunofluorescence assays of spermatozoa from men harboring TTC29 mutations showed deficiency of TTC29 and remarkably reduced staining of intraflagellar-transport-complex-B-associated proteins (TTC30A and IFT52). We also generated a Ttc29-mutated mouse model through the use of CRISPR-Cas9 technology. Remarkably, Ttc29-mutated male mice also presented reduced sperm motility, abnormal flagellar ultrastructure, and male subfertility. Furthermore, intracytoplasmic sperm injections performed for Ttc29-mutated mice and men harboring TTC29 mutations consistently acquired satisfactory outcomes. Collectively, our experimental observations in humans and mice suggest that bi-allelic mutations in TTC29, as an important genetic pathogeny, can induce MMAF-related asthenoteratospermia. Our study also provided effective guidance for clinical diagnosis and assisted reproduction treatments.

20.
Int Heart J ; 60(5): 1231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564710

RESUMO

An error appeared in the article entitled "Polysaccharides from Enteromorpha Prolifera Ameliorate Acute Myocardial Infarction in Vitro and in Vivo via Up-Regulating HIF-1α" by Zongqiu Wang, Zhihua Zhang, Jing Zhao, Chunming Yong, and Yongjun Mao (Vol. 60, No. 4, 964-973, 2019).The second affiliation of the authors on the bottom of page 964 should be replaced by "2Department of Vascular Surgery, The Affiliated Central Hospital of Qingdao University, Qingdao, China".

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