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1.
Semin Cancer Biol ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33812985

RESUMO

Ras proteins are small GTPases that participate in multiple signal cascades, regulating crucial cellular processes including cell survival, proliferation, and differentiation. Mutations or deregulated activities of Ras are frequently the driving force for oncogenic transformation and tumorigenesis. Posttranslational modifications play a crucial role in mediating the stability, activity, or subcellular localization/trafficking of numerous cellular regulators including Ras proteins. A series of recent studies reveal that Ras proteins are also regulated by sumoylation. All three Ras protein isoforms (HRas, KRas, and NRas) are modified by SUMO3. The conserved lysine42 appears to be the primary site for mediating sumoylation. Expression of KRasV12/R42 mutants compromised the activation of the Raf/MEK/ERK signaling axis, leading to a reduced rate of cell migration and invasion in vitro in multiple cell lines. Moreover, treatment of transformed pancreatic cells with a SUMO E2 inhibitor blocks cell migration in a concentration-dependent manner, which is associated with a reduced level of both KRas sumoylation and expression of mesenchymal cell markers. Furthermore, mouse xenograft experiments reveal that expression of a SUMO-resistant mutant appears to suppress tumor development in vivo. Combined, these studies indicate that sumoylation functions as an important mechanism in mediating the roles of Ras in cell proliferation, differentiation, and malignant transformation and that the SUMO-modification system of Ras oncoproteins can be explored as a new druggable target for various human malignancies.

2.
Am J Nephrol ; : 1-11, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823527

RESUMO

INTRODUCTION: Increasing evidence has demonstrated that loss of peritubular capillaries plays a critical role in renal interstitial fibrosis. Leucine-rich α2-glycoprotein-1 (LRG1) has been observed promoting angiogenesis in the ocular disease mouse model and myocardial infarction model. We aimed to explore the role of LRG1 in renal interstitial fibrosis. METHODS: We analyzed the expression of LRG1 in the plasma and kidney of CKD patients by ELISA and immunohistochemistry. Relationships between the expression of LRG1 in plasma and kidney and renal fibrosis and inflammation were analyzed. Tube formation assay was used to detect the angiogenesis in the human umbilical vein endothelial cell lines (HUVECs). And real-time PCR was used to detect the mRNA expression of LRG1, inflammatory factors, renal tubular injury indicators, pro-fibrotic cytokines, and CD31. We examined the effects of genetic ablation of LRG1 on renal fibrosis induced by unilateral ureteral obstruction (UUO) mice model at day 7. RESULTS: We demonstrated that the expression of LRG1 in renal tissues and plasma samples was upregulated in CKD patients. And the expression of LRG1 was elevated in human renal tubular epithelial cell line (HK-2) cells in response to the stimulation of TNF-α in vitro, and in kidney after UUO in vivo. The deficiency of the LRG1 gene aggravated renal fibrosis, inflammatory cells infiltration, and capillary rarefaction after UUO. In vitro, LRG1 promoted the tube formation of HUVEC cells. LRG1 inhibits fibronectin secretion induced by TGF-ß1 in HK-2 and overexpression of LRG1 in HK-2 cells decreased fibronectin secretion. CONCLUSION: LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.

3.
Fitoterapia ; 151: 104904, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33813000

RESUMO

Five new compounds (xuejieins A-E), including three new phenolic glycosides (1, 2, and 5) and two new flavonoids (10 and 11), together with six known compounds were isolated from the resins of Dracaena cochinchinensis (Chinese dragon's blood). The structures of the new compounds were confirmed by extensive spectroscopic methods and electronic circular dichroism (ECD) data analysis. Especially, the absolute configurations of the sugar moieties in compounds 1, 2, and 5 were clarified by GC analysis after acid hydrolysis. All isolated compounds have been tested for antifungal and wound healing promoting activities, The results showed that compound 9 shows significant antifungal activities against Botrytis cinerea, Magnaporthe grisea, Penicillium digitatum, and Sclerotinia sclerotiorum. In addition, compound 4 could significantly stimulate human keratinocytes (HaCAT) proliferation, mobility, and human umbilical vein vascular endothelial cells (HUVECs) tube formation at 40 µM.

4.
Nat Commun ; 12(1): 1540, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750785

RESUMO

The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.


Assuntos
Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Microambiente Tumoral/fisiologia , Linfócitos B , Fibroblastos , Regulação Neoplásica da Expressão Gênica , Humanos , Células Mieloides , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/imunologia , Fenótipo , Prognóstico , Intervalo Livre de Progressão , Análise de Sequência de RNA , Células Estromais , Linfócitos T , Microambiente Tumoral/imunologia
5.
Ecotoxicol Environ Saf ; 214: 112060, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33676052

RESUMO

OBJECTIVE: To study the association between ambient air pollutant exposure during the follicular phase and in vitro fertilization (IVF) outcomes. DESIGN: A single-center retrospective analysis. SETTING: Henan Province, China. PATIENTS: Patients (n = 6659) living in Zhengzhou, Henan Province in central China who underwent their first IVF cycle at the First Affiliated Hospital of Zhengzhou University between 2013 and 2019 were included for analysis. INTERVENTION: None. MAIN OUTCOME MEASURE: The relationships between PM2.5, PM10, and AQI (Air Quality Index) with IVF outcomes during the follicular phase (period I, 85 days before oocyte retrieval; period II, gonadotrophin start to oocyte retrieval). RESULTS: Compared with the bottom tertile, exposure to the top PM2.5 and PM10 tertiles during period I was associated with decreased clinical pregnancy (PM2.5: adjusted odds ratio [OR], 0.838%, and 95% confidence interval [CI], 0.723 and 0.971; PM10: adjusted OR, 0.818%, and 95% CI, 0.705 and 0.950), and decreased live birth rate (PM2.5: adjusted odds ratio [OR], 0.852%, and 95% confidence interval [CI], 0.736 and 0.987; PM10: adjusted OR, 0.850%, and 95% CI, 0.733 and 0.986), and exposure to the top PM2.5 tertile during period II adversely affected clinical pregnancy and the live birth rate (adjusted OR, 0.824%, and 95% CI, 0.711 and 0.955; adjusted OR, 0.817%, and 95% CI, 0.706 and 0.945). Compared with the bottom PM10 tertile, exposure to the middle PM10 tertile in period II showed decreased clinical pregnancies and live births (adjusted OR, 0.844; 95% CI, 0.729 and 0.978, adjusted OR, 0.846; 95% CI, 0.731 and 0.979). The PM10 level during period II of the follicular phase tend to adversely affect live birth rate, but the tendency did not reach significance (P = 0.051). CONCLUSION: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes. CAPSULE: Exposure to PM2.5 and PM10 before oocyte retrieval has an adverse effect on IVF outcomes.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Fertilização In Vitro/estatística & dados numéricos , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Feminino , Humanos , Masculino , Razão de Chances , Recuperação de Oócitos , Material Particulado/análise , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
6.
Bioorg Chem ; 110: 104781, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33677246

RESUMO

Forty-three quinolizidine alkaloids (1-43), including twelve new matrine-type ones, sophalodes A-L (1-7, 17, 19 and 28-30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1-4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction analysis, and quantum chemical calculation. In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30 µM, respectively. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, additional research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27 µM.

7.
Oncogene ; 40(14): 2596-2609, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33750895

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective against non-small cell lung cancer (NSCLC) with EGFR-activating mutations. The mechanisms underlying EGFR-TKI resistance are not fully understood. This study aimed to analyze the effects of seven EGFR ligands on EGFR-TKI sensitivity in NSCLC cells and patients. Cells with EGFR E746-A750del mutation were treated with recombinant EGFR ligands, and analyzed for cell viability, proliferation, and apoptosis. shRNA knockdown of endogenous Epiregulin (EREG) or overexpression of exogenous EREG and immunofluorescence experiments were carried out. Public gene expression datasets were used for tumor microenvironment and clinical assessment. Among the EGFR ligands, EREG significantly diminished cellular sensitivity to TKIs and was associated with decreased response to erlotinib in NSCLC patients. EREG induced AKT phosphorylation and attenuated TKI-induced cellular apoptosis in an ErbB2-dependent manner. EREG induced the formation of the EGFR/ErbB2 heterodimer regardless of gefitinib treatment. However, overexpression or knockdown of EREG in cancer cells had little impact on TKI sensitivity. Single-cell RNA sequencing data revealed that EREG was predominantly expressed in macrophages in the tumor microenvironment. In addition, EREG-enriched macrophage conditional medium induced EGFR-TKI resistance. These findings shed new light on the mechanism underlying EGFR-TKI resistance, and suggest macrophage-produced intratumoral EREG as a novel regulator and biomarker for EGFR-TKI therapy in NSCLC.

8.
Chem Biodivers ; 18(4): e2001066, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33656782

RESUMO

Three new matrine-type alkaloids, 8ß-hydroxyoxysophoridine (1), 9ß-hydroxysophoridine (2), 9ß-hydroxyisosophocarpine (3), together with one known analog, 11,12-dehydromatrine (4), were isolated from the seeds of Sophora alopecuroides L. The structures of new compounds were elucidated using extensive spectroscopic techniques including the experimental and calculated ECD data. The anti-inflammatory activities of all the isolates on NO production in RAW 264.7 cells stimulated by lipopolysaccharide were evaluated. Among them, 8ß-hydroxyoxysophoridine (1) showed a significant inhibitory effect with an IC50 value of 18.26 µM.

9.
Water Sci Technol ; 83(6): 1347-1356, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33767041

RESUMO

The rapid overcompensatory growth that appears when cyanobacteria are supplied with adequate resources after a period of resource deprivation might contribute to the occurrence of cyanobacterial blooms. We investigated the changing characteristics of overcompensatory growth and serine/threonine kinase (STK) genes expression of cyanobacterium Microcystis aeruginosa in response to light limitation. The results showed M. aeruginosa exhibited overcompensatory growth for 2 days after light recovery, during which the increase in growth was inversely related to light intensity. Expression of STK genes, such as spkD, was upregulated significantly at 0.5-4 h after light recovery (P < 0.05). To investigate the function of STK genes in the overcompensatory growth, M. aeruginosa spkD was heterologously expressed in Synechocystis. Transgenic Synechocystis exhibited greater and longer overcompensatory growth than wild-type Synechocystis after light recovery. Relative expression levels of STK genes in transgenic Synechocystis were significantly higher than those in wild-type Synechocystis at 24 h of light recovery (P < 0.05). Heterologous expression of Microcystis spkD might stimulate overcompensatory growth of Synechocystis by affecting its STK gene expression.


Assuntos
Proteínas de Bactérias , Synechocystis , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Serina , Synechocystis/genética , Synechocystis/metabolismo
10.
Front Immunol ; 12: 598799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746945

RESUMO

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , /terapia , Interleucina-6/sangue , Regulação para Cima , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , /epidemiologia , Criança , China/epidemiologia , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
11.
Ann Clin Lab Sci ; 51(1): 12-21, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33653776

RESUMO

Breast carcinoma (BC) ranks the second leading cause of cancer death in females. Alcohol is consistent risk factor for BC. The alcohol dehydrogenases (ADHs) family is associated with alcohol metabolism in vivo. However, whether ADHs can act as biomarkers for BC and the underlying mechanism of them affecting BC are unclear. In the present study, the expression levels, prognostic values, epigenetic and genetic alterations, and regulatory networks of ADHs were explored in BC using public online database. Among ADHs family, the expression level of ADH2 is remarkably decreased in the BC and high expression level of ADH2 is significantly associated with better overall survival in BC. Decreasing mRNA expression level of ADH2 is due to DNA hypermethylation in the promoter rather than genetic alterations. ADH2 strongly correlates with pathways in glycolysis/gluconeogenesis, fatty acid metabolism, and cytochrome P450 pathways in BC. Our finding provided novel insights into ADH2 in BC and implied that ADH2 could act as a novel biomarker for BC prognosis.

12.
Jpn J Ophthalmol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656708

RESUMO

PURPOSE: To compare the differences between cycloplegic and noncycloplegic refraction as well as associated factors in grade one students of primary schools, and explore the effectiveness of noncycloplegic refraction for refractive error screening. STUDY DESIGN: Cross-sectional study. METHODS: A school-based study of 1856 students was conducted in Lhasa, Tibetan Plateau, China. Cycloplegia was achieved with two drops of 1% cyclopentolate and 1 drop of Mydrin P at a 5-min interval. Autorefraction was performed under both cycloplegic and noncycloplegic conditions. Bland-Altman analysis, receiver operating characteristic curve analysis, univariate and multiple linear regression models were used for analysis. RESULTS: Of the 1856 children enrolled, 1830 (98.60%) completed all procedures. The average age was 6.83 ± 0.46 years. 965 (52.73%) children were boys and 1737 (94.92%) were Tibetan. Overall, there was a significant difference between cycloplegic and noncycloplegic SE of 0.90 ± 0.76D (P < 0.001). However, the intra-class coefficient correlation (ICC) for cylinder between these two methods was high (ICC = 0.941, 95% CI, 0.935-0.946). Larger differences between cycloplegic and noncycloplegic SE were associated with hyperopic RE and higher cylindrical value (P < 0.001). The prevalence of myopia, emmetropia and hyperopia with and without cycloplegia was (3.93% vs 14.59%), (9.95% vs 45.8%) and (86.21% vs 39.56%), respectively. Myopia, emmetropia and hyperopia based on noncycloplegic refraction was defined as SE ≤ - 0.625D, - 0.625 < SE ≤ 0D, and SE > 0D, respectively. CONCLUSIONS: Lack of cycloplegia leads to underestimation of hyperopia, with overestimation of myopia and emmetropia. Larger hyperopic refraction exhibited greater difference between cycloplegic and noncycloplegic refraction.

13.
Nanomaterials (Basel) ; 11(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668780

RESUMO

Silver vanadates (SVOs) have been widely investigated as cathode materials for high-performance lithium-ion batteries (LIBs). However, similar to most vanadium-based materials, SVOs suffer from structural collapse/amorphization and vanadium dissolution from the electrode into the electrolyte during the Li insertion and extraction process, causing poor electrochemical performance in LIBs. We employ ultrathin Al2O3 coatings to modify ß-AgVO3 (as a typical example of SVOs) by an atomic layer deposition (ALD) technique. The galvanostatic charge-discharge test reveals that ALD Al2O3 coatings with different thicknesses greatly affected the cycling performance. Especially, the ß-AgVO3 electrode with ~10 nm Al2O3 coating (100 ALD cycles) exhibits a high specific capacity of 271 mAh g-1, and capacity retention is 31%, much higher than the uncoated one of 10% after 100 cycles. The Coulombic efficiency is improved from 89.8% for the pristine ß-AgVO3 to 98.2% for Al2O3-coated one. Postcycling analysis by cyclic voltammetry (CV), cyclic voltammetry (EIS), and scanning electron microscopy (SEM) disclose that 10-nm Al2O3 coating greatly reduces cathode-electrolyte interphase (CEI) resistance and the charge transfer resistance in the ß-AgVO3 electrode. Al2O3 coating by the ALD method is a promising technique to construct artificial CEI and stabilize the structure of SVOs, providing new insights for vanadium-based electrodes and their energy storage devices.

14.
J Int Med Res ; 49(2): 300060520984915, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33641473

RESUMO

OBJECTIVE: To investigate the effectiveness and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) in post-extubation preterm infants. METHODS: This was a randomized, controlled trial. A total of 149 preterm infants aged between 25 to 34 weeks' gestational age with a birth weight of <1500 g who required invasive mechanical ventilation on admission were included. After extubation, they were randomized to the NHFOV group (n = 47), nasal intermittent positive pressure ventilation (NIPPV) group (n = 51), or nasal continuous positive airway pressure (NCPAP) group (n = 51). We compared the effectiveness and safety among these three groups. RESULTS: A total of 139 preterm infants finally completed the study. The reintubation rate was significantly lower in the NHFOV group than in the other groups. The duration of non-invasive ventilation and the length of hospital stay in the NHFOV and NIPPV groups were significantly shorter than those in the NCPAP group. The incidence of bronchopulmonary dysplasia in the NHFOV and NIPPV groups was significantly lower than that in the NCPAP group. The NHFOV group had significantly less nasal injury than the NCPAP group. CONCLUSION: As post-extubation respiratory support in preterm infants, NHFOV has a lower reintubation rate compared with NCPAP and NIPPV, without increasing the rate of complications.

15.
Nat Commun ; 12(1): 1458, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674589

RESUMO

Epitranscriptomic modifications can impact behavior. Here, we used Drosophila melanogaster to study N6-methyladenosine (m6A), the most abundant modification of mRNA. Proteomic and functional analyses confirm its nuclear (Ythdc1) and cytoplasmic (Ythdf) YTH domain proteins as major m6A binders. Assays of short term memory in m6A mutants reveal neural-autonomous requirements of m6A writers working via Ythdf, but not Ythdc1. Furthermore, m6A/Ythdf operate specifically via the mushroom body, the center for associative learning. We map m6A from wild-type and Mettl3 mutant heads, allowing robust discrimination of Mettl3-dependent m6A sites that are highly enriched in 5' UTRs. Genomic analyses indicate that Drosophila m6A is preferentially deposited on genes with low translational efficiency and that m6A does not affect RNA stability. Nevertheless, functional tests indicate a role for m6A/Ythdf in translational activation. Altogether, our molecular genetic analyses and tissue-specific m6A maps reveal selective behavioral and regulatory defects for the Drosophila Mettl3/Ythdf pathway.


Assuntos
Adenosina/análogos & derivados , Adenosina/metabolismo , Drosophila melanogaster/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Regiões 5' não Traduzidas , Adenosina/genética , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Feminino , Proteínas Nucleares/metabolismo , Proteômica , Estabilidade de RNA , RNA Mensageiro/metabolismo
16.
J Hazard Mater ; 414: 125389, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33677314

RESUMO

Despite the ubiquity of cypermethrin (CYP) stereoisomers in environment biota, the stereoisomeric selectivity of endocrine-disrupting potency of α-CYP, ß-CYP, and θ-CYP has not been well studied. In this study, dual-luciferase reporter gene assays were adopted to analyze their potential endocrine-disrupting effects via four receptors (ERα, GRα, MR and RXR). The results showed that α-CYP was antagonistic to ERα, GRα, and MR with RIC20 of 9.1 × 10-7, 7.6 × 10-7, and 1.0 × 10-6 M, respectively. ß-CYP exhibited only ERα-mediated agonistic activity with a REC20 of 2.1 × 10-6 M. None of the CYP stereoisomers interacted with RXR. Molecular docking indicated that α-CYP had the strongest binding capacity to GRα among the compounds. The expression levels of steroid hormone-related genes in human adrenocortical carcinoma (H295R) cells displayed that all three compounds inhibited the transcription of 3-ßHSD, indicating the block of turning cholesterol into different hormones. Both α-CYP and ß-CYP upregulated genes encoding estrogen- and aldosterone-forming enzymes including 17-ßHSD, CYP19, STAR, and CYP11B2. Mortality and malformation toxicity assays in zebrafish embryos revealed that the order of toxicity was α-CYP > ß-CYP > θ-CYP. Our results indicated that α-CYP may pose the strongest endocrine-disrupting effects. The data provided here will be helpful to systematically understand stereoisomeric selectivity in the endocrine-disrupting effects of cypermethrin.

17.
Inorg Chem ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739095

RESUMO

Trivalent praseodymium (Pr3+)-doped materials have been extensively used in high-resolution laser spectroscopy, owing to their outstanding conversion efficiencies of plentiful transitions in the visible laser region. However, to clarify the microstructure and energy transfer mechanism of Pr3+-doped host crystals is a challenging topic. In this work, the stable structures of Pr3+-doped yttrium orthoaluminate (YAlO3) have been widely searched based on the CALYPSO method. A novel monoclinic structure with the Pm group symmetry is successfully identified. The Pr3+ impurity can precisely occupy the Y3+ position and get incorporated into the YAlO3 (YAP) host crystal with a Pr3+ concentration of 6.25%. The result of the electronic band structure reveals a 3.62 eV band gap, which suggests a semiconductor character of YAP:Pr. Using our developed well-established parametrization matrix diagonalization (WEPMD) method, we have systematically analyzed the energy level scheme and proposed a set of newly improved parameters. Additionally, the energy transfer mechanism of YAP:Pr is clarified by deciphering the numerical electric dipole and magnetic dipole transitions. The popular red emission at 653 nm is assigned to the transition 3P0 → 3F2, while the transition 3P0 → 3H4 with a large branching ratio is predicted to be a good laser channel. Many promising emission lines for laser actions are also obtained in the visible light region. Our results not only provide important insights into the energy transfer mechanisms of rare-earth ion-doped materials but also pave the way for the implementation of new types of laser devices.

18.
Rare Metals ; : 1-9, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33679100

RESUMO

Owing to their high performance and earth abundance, copper sulfides (Cu2-x S) have attracted wide attention as a promising medium-temperature thermoelectric material. Nanostructure and grain-boundary engineering are explored to tune the electrical transport and phonon scattering of Cu2-x S based on the liquid-like copper ion. Here multiscale architecture-engineered Cu2-x S are fabricated by a room-temperature wet chemical synthesis combining mechanical mixing and spark plasma sintering. The observed electrical conductivity in the multiscale architecture-engineered Cu2-x S is four times as much as that of the Cu2-x S sample at 800 K, which is attributed to the potential energy filtering effect at the new grain boundaries. Moreover, the multiscale architecture in the sintered Cu2-x S increases phonon scattering and results in a reduced lattice thermal conductivity of 0.2 W·m-1·K-1 and figure of merit (zT) of 1.0 at 800 K. Such a zT value is one of the record values in copper sulfide produced by chemical synthesis. These results suggest that the introduction of nanostructure and formation of new interface are effective strategies for the enhancement of thermoelectric material properties. Supplementary Information: The online version of this article (10.1007/s12598-020-01698-6) contains supplementary material, which is available to authorized users.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33610681

RESUMO

FOXI1 plays a key role in the development of gastric cancer. However, the whole genome FOXI1 binding sites and its target genes are unclear. In the present study, we used ChIP-seq and RNA-seq technologies to identify the target gene of FOXI1. Firstly, ChIP-seq data showed that, 4476 unique peaks in the genome region were captured. Most of these binding peaks are located in introns or intergenic regions. We annotated all the peaks to the nearest gene and identified 404 genes as FOXI1 binding genes. KEGG and GO analysis showed that FOXI1 binding gene to be correlated with the cellular process, cell part, cell, binding, single-organism process. Further, we performed FOXI1-overexpressed RNA-seq experiment. We comprehensively analyzed the ChIP-seq and RNA-seq data and take the intersection of two databases, several genes were identified. ATF3 was selected from the intersection since ATF3 was the most enriched mRNA after FOXI1 overexpressed. ChIP-qPCR and luciferase report gene were used to validate that ATF3 was target gene of FOXI1. Intriguely, ATF3 protein was significantly downregulated after FOXI1 overexpressed. We found FOXI1 can also bind to the promoter of miR-590 and active it which directly target ATF3. The binding site between FOXI1 and miR-590 was verified by ChIP-qPCR and luciferase report gene, and the target relationship between miR-590 and ATF3 was confirmed by dual-luciferase reporter gene. In conclusion, our data identified the genome binding sites of FOXI1, and provide evidence that FOXI1 inhibits gastric cancer cell proliferation by activating miR-590/ATF3 axis.

20.
J Breath Res ; 15(1): 016017, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33586667

RESUMO

Exhaled breath analysis has emerged as a promising non-invasive method for diagnosing lung cancer (LC), whereas reliable biomarkers are lacking. Herein, a standardized and systematic study was presented for LC diagnosis, classification and metabolism exploration. To improve the reliability of biomarkers, a validation group was included, and quality control for breath sampling and analysis, comprehensive pollutants analysis, and strict biomarker screening were performed. The performance of exhaled breath biomarkers was shown to be excellent in diagnosing LC even in early stages (stage I and II) with surpassing 0.930 area under the receiver operating characteristic (ROC) curve (AUC), 90% of sensitivity and 88% of specificity both in the discovery and validation analyses. Meanwhile, in these two groups, diagnosing subtypes of LC attained AUCs over 0.930 and reached 1.00 in the two subtypes of adenocarcinomas. It is demonstrated that the metabolism changes in LC are possibly related to lipid oxidation, gut microbial, cytochrome P450 and glutathione S-transferase, and glutathione pathways change in LC progression. Overall, the reliable biomarkers contribute to the clinical application of breath analysis in screening LC patients as well as those in early stages.

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