Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
1.
Mol Genet Genomics ; 296(6): 1323-1335, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34609588

RESUMO

Sex form is one of the most important characteristics in papaya cultivation in which hermaphrodite is the preferable form. Self-pollination of H*-TSS No.7, an inbred line derived from a rare X chromosome mutant SR*, produced all-hermaphrodite progeny. The recessive lethal allele controlling the all-hermaphrodite phenomenon was proposed to be the recessive Germination suppressor (gs) locus. This study employed next-generation sequencing technology and genome comparison to identify the candidate Gs gene. One specific gene, monodehydroascorbate reductase 4 (MDAR4) harboring a unique polymorphic 3 bp deletion in H*-TSS No.7 was identified. The function of MDAR4 is known to be involved in the hydrogen peroxide (H2O2) scavenging pathway and is associated with seed germination. Furthermore, MDAR4 showed higher expression in the imbibed seeds than that in the dry seeds indicating its potential role in the seed germination. Perhaps this is the very first report providing the evidences that MDAR4 is the candidate of Gs locus in H*-TSS No.7. In addition, Gs allele-specific markers were developed which would be facilitated for breeding all-hermaphrodite lines.


Assuntos
Carica/genética , Cromossomos de Plantas/genética , Organismos Hermafroditas/genética , NADH NADPH Oxirredutases/genética , Genoma de Planta/genética , Germinação/genética , Peróxido de Hidrogênio/metabolismo , Polinização/genética , Polinização/fisiologia , Sementes/crescimento & desenvolvimento , Deleção de Sequência/genética
2.
Reprod Sci ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580843

RESUMO

High maternal serum estradiol (E2) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART).

3.
Leuk Lymphoma ; : 1-9, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587859

RESUMO

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has led to unprecedented results to date in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), yet its clinical application in elderly patients with R/R DLBCL remains somewhat limited. In this study, a total of 31 R/R DLBCL patients older than 65 years of age were enrolled and received humanized anti-CD19 CAR T-cell therapy. Patients were stratified into a fit, unfit, or frail group according to the comprehensive geriatric assessment (CGA). The fit group had a higher objective response (OR) rate (ORR) and complete response (CR) rate than that of the unfit/frail group, but there was no difference in the part response (PR) rate between the groups. The unfit/frail group was more likely to experience AEs than the fit group. The peak proportion of anti-CD19 CAR T-cells in the fit group was significantly higher than that of the unfit/frail group. The CGA can be used to effectively predict the treatment response, adverse events, and long-term survival.

4.
Top Curr Chem (Cham) ; 379(6): 37, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554348

RESUMO

Traditional drug discovery effectively contributes to the treatment of many diseases but is limited by high costs and long cycles. Quantitative structure-activity relationship (QSAR) methods were introduced to evaluate the activity of compounds virtually, which saves the significant cost of determining the activities of the compounds experimentally. Over the past two decades, many web tools for QSAR modeling with various features have been developed to facilitate the usage of QSAR methods. These web tools significantly reduce the difficulty of using QSAR and indirectly promote drug discovery. However, there are few comprehensive summaries of these QSAR tools, and researchers may have difficulty determining which tool to use. Hence, we systematically surveyed the mainstream web tools for QSAR modeling. This work may guide researchers in choosing appropriate web tools for developing QSAR models, and may also help develop more bioinformatics tools based on these existing resources. For nonprofessionals, we also hope to make more people aware of QSAR methods and expand their use.


Assuntos
Descoberta de Drogas , Internet , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade
5.
Front Mol Biosci ; 8: 670160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395520

RESUMO

N6-methyladenosine (m6A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m6A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m6A levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide m6A modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of m6A modifications during sepsis. Methylated lncRNAs and mRNAs were measured by m6A single-base site qPCR. The global m6A levels in left ventricle tissue were significantly decreased in the LPS group. While 27 transcripts (23 mRNAs and four lncRNAs) were hypermethylated, 46 transcripts (39 mRNAs and 7 lncRNAs) were hypomethylated in the LPS group. The mRNA expression of writers and readers was significantly decreased in the LPS group. The m6A modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in m6A modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to m6A modifications in cardiac tissue during sepsis, and m6A modifications might be promising therapeutic targets.

6.
Brief Bioinform ; 22(6)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34219140

RESUMO

Motif identification is among the most common and essential computational tasks for bioinformatics and genomics. Here we proposed a novel convolutional layer for deep neural network, named variable convolutional (vConv) layer, for effective motif identification in high-throughput omics data by learning kernel length from data adaptively. Empirical evaluations on DNA-protein binding and DNase footprinting cases well demonstrated that vConv-based networks have superior performance to their convolutional counterparts regardless of model complexity. Meanwhile, vConv could be readily integrated into multi-layer neural networks as an 'in-place replacement' of canonical convolutional layer. All source codes are freely available on GitHub for academic usage.

8.
J Dent Sci ; 16(3): 915-921, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34141105

RESUMO

Background/purpose: Effective regulation of the inflammatory process is essential for pulp repair and regeneration. Meloxicam has anti-inflammatory activity in systemic administration. The purpose of this study is to observe effects of topically applied meloxicam on inflamed pulp and to explore its potential value in the treatment of pulpitis. Materials and methods: The coronal pulp tissues of rat molars were stimulated with 10 mg/mL lipopolysaccharide (LPS group) and then treated with 500 µmol/L meloxicam (meloxicam group). The untreated pulp tissues were used as the control group. After 3 h of incubation in vitro, the gene expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in each group was detected by real-time RT-PCR. The pulp tissues of each group were randomly subcutaneously implanted into nude mice, and 500 µmol/L meloxicam was injected into the subcutaneous pocket of the meloxicam group. Haematoxylin eosin staining, Masson staining and immunohistochemical staining were performed on samples after 3 days and 4 weeks retrieval, respectively. Results: Compared with the LPS group, the mRNA expression levels of TNF-α and IL-6 of the meloxicam group were significantly reduced in vitro. The inflammatory response and cyclooxygenase-2 expression of the meloxicam group were decreased, and osteodentin-like tissue was generated in the pulp cross section of the meloxicam group in vivo. Conclusion: The topical application of meloxicam inhibits the inflammatory response of inflamed pulp and further promotes the formation of osteodentin-like tissues but fails to induce the formation of the pulp-dentin complex. Topically applied meloxicam has the potential to regulate pulp inflammation.

10.
ACS Appl Mater Interfaces ; 13(4): 5165-5175, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33480251

RESUMO

In this study, three polymer precursor conformations, dilute, semi-dilute, and concentrated, were used to fabricate carbon molecular sieving (CMS) membranes via a fixed carbonization protocol. The effects of the precursor conformation on the microstructure of the resultant CMS membranes were characterized by Raman analysis. Their ability to separate light gases, such as H2/CH4 and H2/N2, was assessed with a single-gas system. Additionally, a novel method was proposed to detect the cutoff size of the CMS membranes created in this study. The method combined high-resolution transmission electron microscopy (HR-TEM) and a focused ion beam (FIB) system. Finally, due to the semi-dilute solution's denser polymer chains and lack of severe polymer entanglement, highly graphited CMS membranes with excellent gas separation performance were successfully synthesized using a semi-dilute polyetherimide dope solution. Interlayer distances in the carbon matrix were visualized and measured using our novel probing tool (HR-TEM and FIB) and software. The CMS membrane fabricated with a semi-dilute dope exhibited the best gas separation performance of the tested membranes. It had the most ordered carbon sheet orientation and exhibited a superior selectivity of H2/CH4 = 293 with a hydrogen permeability of 1138.7 Barrer, far surpassing the reported permselectivity of other membranes. We believe that the high H2/CH4 selectivity presented here is unprecedented for CMS membranes reported in the literature.

11.
Reprod Sci ; 28(3): 785-793, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33211273

RESUMO

BNC1 is a transcription factor that is crucial for spermatogenesis and male fertility, although the underlying mechanism remains unclear. To study BNC1's specific role in spermatogenesis, we characterized a previously developed mouse model carrying a truncating mutation in Bnc1 (termed Bnc1+/tr for heterozygotes and Bnc1tr/tr for homozygotes) and found that the mutation decreased BNC1 protein levels and resulted in germ cell loss by apoptosis. Given that loss of functional Bnc1 is known to result in decreased expression of the spermatogenesis genes Ybx2 and Papolb, we aimed to explore whether and how BNC1 promotes transcription of Ybx2 and Papolb to mediate its role in spermatogenesis. We confirmed significant reduction in YBX2 and PAPOLB protein levels in testis tissue from Bnc1+/tr and Bnc1tr/tr males compared with wild-type mice (Bnc1+/+). Consistently, knockdown of Bnc1 led to downregulation of Ybx2 and Papolb in CRL-2196 cells in vitro. To investigate if BNC1 directly induces Ybx2 and Papolb gene expression, chromatin immunoprecipitation using mouse testicular tissue and luciferase reporter assays in HEK293 cells were used to identify functional binding of BNC1 to the Ybx2 and Papolb promoters at defined BNC1 binding sites. Taken together, this study reveals a mechanism for BNC1's role in spermatogenesis by directly binding to BNC1 binding elements in the promoter regions of both Ybx2 and Papolb and inducing transcription of these important spermatogenesis genes.

12.
Front Oncol ; 10: 544956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123466

RESUMO

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma. Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma. Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma.

13.
Appl Opt ; 59(24): 7338-7342, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32902500

RESUMO

We study the motion morphology, distance, and velocity of plasma and laser-induced shock waves induced by a millisecond-nanosecond (ms-ns) combined-pulse laser with different pulse delays on silicon. The laser shadowgraph method is used, and the phenomenon of double laser-induced shock waves has been found while the pulse delay is 1.2-1.8 ms. The controlling variable method is used to study this phenomenon, and it is found that it is mainly related to the ignition of the laser-supported absorption wave induced by the ms laser. Moreover, the plasma expansion velocity increases with the increase of pulse delay, the axial propagation distance of laser-induced shock waves increases monotonically with pulse delay, and the velocity of laser-induced shock waves decreases with the increase of pulse delay.

14.
Br J Cancer ; 123(7): 1154-1163, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32632148

RESUMO

BACKGROUND: Hepatitis B virus (HBV) has a crucial role in the progression of hepatocellular carcinoma (HCC). Tumour cells must develop anoikis resistance in order to survive before metastasis. This study aimed to investigate the mechanism of IQGAP1 in HBV-mediated anoikis evasion and metastasis in HCC cells. METHODS: IQGAP1 expression was detected by immunohistochemistry, real-time PCR and immunoblot analysis. Lentiviral-mediated stable upregulation or knockdown of IGAQP1, immunoprecipitation, etc. were used in function and mechanism study. RESULTS: IQGAP1 was markedly upregulated in HBV-positive compared with HBV-negative HCC cells and tissues. IQGAP1 was positively correlated to poor prognosis of HBV-associated HCC patients. IQGAP1 overexpression significantly enhanced the anchorage-independent growth and metastasis, whereas IQGAP1-deficient HCC cells are more sensitive to anoikis. Mechanistically, we found that HBV-induced ROS enhanced the association of IQGAP1 and Rac1 that activated Rac1, leading to phosphorylation of Src/FAK pathway. Antioxidants efficiently inhibited IQGAP1-mediated anoikis resistance and metastasis. CONCLUSIONS: Our study indicated an important mechanism by which upregulated IQGAP1 by HBV promoted anoikis resistance, migration and invasion of HCC cells through Rac1-dependent ROS accumulation and activation of Src/FAK signalling, suggesting IQGAP1 as a prognostic indicator and a novel therapeutic target in HCC patients with HBV infection.


Assuntos
Carcinoma Hepatocelular/patologia , Quinase 1 de Adesão Focal/fisiologia , Neoplasias Hepáticas/patologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas rac1 de Ligação ao GTP/fisiologia , Proteínas Ativadoras de ras GTPase/fisiologia , Quinases da Família src/fisiologia , Animais , Anoikis , Linhagem Celular Tumoral , Feminino , Hepatite B/complicações , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Transdução de Sinais/fisiologia
15.
Int J Clin Exp Pathol ; 13(3): 550-555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32269694

RESUMO

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare malignancy of epithelial origin. It involves a variety of histologic types and often has distant metastasis. ACC metastasis to the liver is rare and usually involves spread to other organs. CASE PRESENTATION: We report a case of liver metastasis from a submandibular gland adenoid cystic carcinoma 11 years after resection of tumor. The patient was admitted to our hospital due to a liver-occupying lesion found by abdominal B-ultrasound, CT and MRI. A metastasis was found only in the liver, and after discussion the patient was treated with surgery. This tumor was histologically consistent with the diagnostic criteria of ACC. The patient was followed up 24 months after surgery, and showed no recurrence in the liver parenchyma at the site of operation or other organs. CONCLUSIONS: ACC is a very rare tumor and its pathogenesis is not completely clear. There are few articles about the imaging findings of ACC in the liver, and so it was difficult for us to make a correct diagnosis in clinical practice. The diagnosis of ACC mainly relies on pathologic examination, so we summarize the correlation between imaging and pathology.

16.
Eur J Pharmacol ; 874: 172961, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32044322

RESUMO

The tyrosine kinase inhibitor (TKI) gefitinib exerts good therapeutic effect on NSCLC patients with sensitive EGFR-activating mutations. However, most patients ultimately relapse due to the development of drug resistance after 6-12 months of treatment. Here, we showed that a HIF-1α inhibitor, YC-1, potentiated the antitumor efficacy of gefitinib by promoting EGFR degradation in a panel of human NSCLC cells with wild-type or mutant EGFRs. YC-1 alone had little effect on NSCLC cell survival but significantly enhanced the antigrowth and proapoptotic effects of gefitinib. In insensitive NSCLC cell lines, gefitinib efficiently inhibited the phosphorylation of EGFR but not the downstream signaling of ERK, AKT and STAT3; however, when combined with YC-1 treatment, these signaling pathways were strongly impaired. Gefitinib treatment induced EGFR arrest in the early endosome, and YC-1 treatment promoted delayed EGFR transport into the late endosome as well as receptor degradation. Moreover, the YC-1-induced reduction of HIF-1α protein was associated with the enhancement of EGFR degradation. HIF-1α knockdown promoted EGFR degradation, showing synergistic antigrowth and proapoptotic effects similar to those of the gefitinib and YC-1 combination treatment in NSCLC cells. Our findings provide a novel combination treatment strategy with gefitinib and YC-1 to extend the usage of gefitinib and overcome gefitinib resistance in NSCLC patients.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/farmacologia , Indazóis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Endocitose/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos
17.
Chin Med J (Engl) ; 133(3): 301-309, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31929360

RESUMO

BACKGROUND: Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs. METHODS: Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses. RESULTS: Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity). CONCLUSION: Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Osteogênese/fisiologia , Semaforina-3A/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão/biossíntese , Engenharia Tecidual
18.
Drug Discov Today ; 25(1): 248-258, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705979

RESUMO

Undesirable pharmacokinetic (PK) properties or unacceptable toxicity are the main causes of the failure of drug candidates at the clinical trial stage. Since the concept of drug-likeness was first proposed, it has become an important consideration in the selection of compounds with desirable bioavailability during the early phases of drug discovery. Over the past decade, online resources have effectively facilitated drug-likeness studies in an economical and time-efficient manner. Here, we provide a comprehensive summary and comparison of current accessible online resources, in terms of their key features, application fields, and performance for in silico drug-likeness studies. We hope that the assembled toolbox will provide useful guidance to facilitate future in silico drug-likeness research.


Assuntos
Descoberta de Drogas , Produtos Biológicos , Bases de Dados Factuais , Humanos , Preparações Farmacêuticas/metabolismo , Farmacocinética
19.
J Mol Cell Biol ; 12(1): 71-83, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31065688

RESUMO

Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging. Genome-wide expression profiling and direct binding studies (by chromatin immunoprecipitation sequencing) with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10 (Klhl10), testis expressed 14 (Tex14), and spermatogenesis and centriole associated 1 (Spatc1). Moreover, biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like (TAF7L), a germ cell-specific paralogue of the transcription factor IID subunit TAF7, both in vitro and in testis, suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis. The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of BNC1, TAF7L, Y-box-binding protein 2 (YBX2), outer dense fiber of sperm tails 1 (ODF1), and glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) were significantly decreased in the testis of men with non-obstructive azoospermia. The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.


Assuntos
Senilidade Prematura/metabolismo , Azoospermia/metabolismo , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/metabolismo , Espermatogênese/genética , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Testículo/metabolismo , Fator de Transcrição TFIID/metabolismo , Fatores de Transcrição/deficiência , Fatores de Transcrição/metabolismo , Senilidade Prematura/genética , Animais , Azoospermia/genética , Azoospermia/patologia , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Transdução de Sinais/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Fatores de Transcrição/genética , Transfecção
20.
Huan Jing Ke Xue ; 40(7): 2967-2976, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854693

RESUMO

With the constraint that all six major pollutants in Nanjing must meet the air quality standards by 2030, on the basis of the 2015 emission inventory, the CMAQ air quality model was used to conduct PM2.5 sensitivity tests, and scenario analysis was used to predict the emission inventory and the air quality of four emission reduction scenarios were simulated. Finally, the total control index under the constraint of meeting the standards was obtained. The results show that primary particulate matter (PPM) reduction is the most effective at reducing the concentration of PM2.5 in the atmosphere, on the basis of emission reduction in surrounding areas, PPM emission reduction accounts for 88% of the total reduction of the annual average concentration of PM2.5, followed by NH3, NOx, SO2, and VOCs, which contribute to 10.3%, 5.5%, 3.2%, and 0.5%, respectively. Compared to 2015, the reduction ratios of the major pollutants are between 22% and 53%. Controlling the activity level is more effective for SO2, NH3 and CO emissions reduction, while there is still more opportunity for NOx and VOCs end treatment. When the emissions of SO2, NOx, PM10, PM2.5, BC, OC, CO, VOCs, and NH3 are controlled to 2.43×104, 8.47×104, 9.42×104, 3.74×104, 0.19×104, 0.30×104, 26.56×104, 13.08×104, and 1.50×104 t, respectively, it is expected that the levels of the six pollutants in Nanjing can meet the national ambient air quality level 2 standards.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...