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1.
Artigo em Inglês | MEDLINE | ID: mdl-34632698

RESUMO

This study investigates if genetic factors could contribute to the high rate of mood disorders reported in a U.S. community known to have a restricted early founder population (confirmed here through runs of homozygosity analysis). Polygenic scores (PGSs) for eight common diseases, disorders, or traits, including psychiatric disorders, were calculated in 274 participants (125 mood disorder cases) who each reported three or four grandparents born in the community. Ancestry-matched controls were selected from the UK Biobank (UKB; three sets of N = 1,822 each). The mean PGSs were significantly higher in the community for major depression PRS (p = 2.1 × 10-19 , 0.56 SD units), bipolar disorder (p = 2.5 × 10-15 , 0.56 SD units), and schizophrenia (p = 3.8 × 10-21 , 0.64 SD units). The PGSs were not significantly different between the community participants and UKB controls for the traits of body mass index, Type 2 diabetes, coronary artery disease, and chronotype. The mean PGSs for height were significantly lower in the community sample compared to controls (-0.21 SD units, p = 1.2 × 10-5 ). The results are consistent with enrichment of polygenic risk factors for psychiatric disorders in this community.

2.
J Alzheimers Dis ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34602483

RESUMO

BACKGROUND: The associations between sleep characteristics and cognition are complicated. Alzheimer's disease (AD) pathologies have been proven to be associated with sleep characteristics. OBJECTIVE: We aimed to investigate the associations between sleep characteristics and cognitive function and examine the roles of AD pathologies in modulating the association of sleep duration with cognition. METHODS: A total of 974 participants who had measurements of cerebrospinal fluid (CSF) amyloid-ß (Aß), phosphorylated tau (P-tau), total tau proteins (T-tau), cognitive function, and sleep characteristics were included from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Linear regression analyses were utilized to explore the associations of sleep characteristics with cognition. Non-linear regression analyses were utilized to explore the associations of sleep habits with cognition. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition. RESULTS: The Pittsburgh Sleep Quality Index (PSQI) total score was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score (p = 0.0176). Long latency (p = 0.0054) and low efficiency (p = 0.0273) were associated with cognitive impairment. Habitual nap behavior was associated with lower MoCA scores (p = 0.0045). U-shaped associations were observed between sleep habits (bedtime and nocturnal sleep duration) and cognition. A causal mediation analysis indicated that P-tau/Aß 42 mediated the association of sleep duration with cognition. CONCLUSION: These findings showed sleep characteristics were associated with cognitive functions. Sleep habits (duration, bedtime) had U-shaped associations with cognition. AD core pathologies might partially mediate the influence of sleep duration on cognitive impairments.

3.
J Neurol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605986

RESUMO

OBJECTIVES: Our aim is to investigate the associations of sleep disorders with cerebrospinal fluid (CSF) α-synuclein (α-syn) in healthy controls (HCs), and patients with prodromal and early Parkinson's disease (PD). METHODS: We included a total of 575 individuals, consisting of 360 PD individuals, 46 prodromal PD individuals, and 169 HCs. Multiple linear regression models and linear mixed-effects models were used to investigate the associations of sleep disorders with baseline and longitudinal CSF α-syn. Associations between the change rates of sleep disorders and CSF α-syn were further investigated via multiple linear regression models. RESULTS: In PD, probable Rapid-eye-movement sleep Behavior Disorder (pRBD) (ß = - 0.1199; P = 0.0444) and RBD sub-items, such as aggressive dreams (ß = - 0.1652; P = 0.0072) and hurting bed partner (ß = - 0.2468; P = 0.0010), contributed to lower CSF α-syn. The association between aggressive dreams and lower CSF α-syn further survived Bonferroni correction (P < 0.0036). In prodromal PD, dream-enacting (a specific RBD behavior) was significantly associated with decreased CSF α-syn during the follow-up (ß = - 0.0124; P = 0.0237). HCs with daytime sleepiness when inactive-sitting in public places (ß = - 0.0033; P = 0.0135) showed decreased CSF α-syn. Furthermore, increased possibilities of daytime sleepiness when sitting and reading contributed to a greater decrease of CSF α-syn in HCs (ß = - 196.8779; P = 0.0433). CONCLUSIONS: Sleep disorders were associated with decreased CSF α-syn. Sleep management may be important for disease monitoring and preventing the progression of α-syn pathology.

4.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638970

RESUMO

Cardiovascular disease (CVD) is a common disease caused by many factors, including atherosclerosis, congenital heart disease, heart failure, and ischemic cardiomyopathy. CVD has been regarded as one of the most common diseases and has a severe impact on the life quality of patients. The main features of CVD include high morbidity and mortality, which seriously threaten human health. SUMO proteins covalently conjugate lysine residues with a large number of substrate proteins, and SUMOylation regulates the function of target proteins and participates in cellular activities. Under certain pathological conditions, SUMOylation of proteins related to cardiovascular development and function are greatly changed. Numerous studies have suggested that SUMOylation of substrates plays critical roles in normal cardiovascular development and function. We reviewed the research progress of SUMOylation in cardiovascular development and function, and the regulation of protein SUMOylation may be applied as a potential therapeutic strategy for CVD treatment.

5.
Chemosphere ; 288(Pt 1): 132390, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34600013

RESUMO

The nitrogen removal characteristics, physicochemical properties, and microbial community composition of four different anaerobic ammonium oxidation (anammox) sludge morphologies were investigated. The morphologies considered in this study, namely suspended sludge (Rs), biofilm (Rm), granular sludge (Rg), and encapsulated biomass (Re), were prepared from floc sludge. The results show that Re exhibited the maximum anammox activity, followed by Rg, Rm, and Rs. Additionally, the anammox contribution rate was higher in Rg and Re. The higher extracellular polymer content in Rg promoted sludge accumulation, and tryptophan was observed in Rm and Rg, which was replaced by humic acids in Rs. Re showed the largest specific surface area, hydrophobicity and strength, and its good structure ensured enrichment of anammox bacteria (AnAOB). In terms of the microbial community, the functional bacterium Candidatus Kuenenia accounted for the highest proportion in Rm (39.27%), but the presence of both anaerobic and aerobic regions led to increased community complexity with more nitrifying bacteria. In contrast, Rg and Re had a more specific microbial community. In addition, denitrifying bacteria tended to grow in Rs, while nitrifying bacteria were retained in Rm. The AnAOB were more likely to be enriched in sludge aggregates (both Rm and Rg) and carriers (Re). Through correlation analysis, the potential relationship involving bacterial flora evolution of each sample was clarified. Finally, the structural models of different morphologies of sludge were proposed. This study deepens the understanding of various anammox sludge morphologies as well as provides useful information for the cultivation of AnAOB and further application of anammox.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34525929

RESUMO

BACKGROUND: Wilms tumor (WT) is the most common primary renal malignancy in children. Autophagy plays dual roles in the promotion and suppression of various cancers. OBJECTIVE: The goal of our study was to develop a novel autophagy-related gene (ARG) prognostic nomogram for WT. METHODS: The Cancer Genome Atlas (TCGA) database was used. We screened the expression profiles of ARGs in 136 WT patients. The differentially expressed prognostic ARGs were evaluated by multivariate Cox regression analysis and survival analysis. A novel prognostic nomogram based on the ARGs and clinical characteristics was established using multivariate Cox regression analysis. RESULTS: First, 69 differentially expressed ARGs were identified in WT patients. Then, multivariate Cox regression analysis was used to determine 4 key prognostic ARGs (CC3CL1, ERBB2, HIF-α and CXCR4) in WT. According to their ARG expression levels, the patients were clustered into high- and low-risk groups. Next, survival analysis indicated that high-risk patients had significantly poorer overall survival than low-risk patients. The results of functional enrichment analysis suggested that autophagy may play a tumor-suppressive role in the initiation of WT. Finally, a prognostic nomogram with a Harrell's concordance index (C-index) of 0.841 was used to predict the survival probability of WT patients by integrating clinical characteristics and the 4-ARG signature. The calibration curve indicated its excellent predictive performance. CONCLUSION: In summary, the ARG signature could be a promising biomarker for monitoring the outcomes of WT. We established a novel nomogram based on the ARG signature, which accurately predicts the overall survival of WT patients.

7.
J Stroke Cerebrovasc Dis ; 30(11): 106071, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34482123

RESUMO

OBJECTIVE: To validate, update, and extend the role of RNF213 p.R4810K (G>A) for predicting the phenotype of moyamoya disease (MMD) patients and explore the different effects on pediatric and adult groups. METHODS: A total of 2,877 patients conducted from 2004 to 2018 were included. Review Manage 5.3 and SPSS 20.0 were applied to complete all statistical analyses. Information on age at onset, sex, initial symptom, family history and complications were obtained via retrospective chart review. Angiographic records were evaluated. RESULTS: In China, geographic proximity to Korea or Japan may affect the carrying rate of RNF213 p.R4810K. The proportion of patients with the following characteristics was significantly higher (P <0.017) in the GA than in the GG group: female, age at onset < 18 years, infarct after transient ischemic attack, family history of MMD, and posterior cerebral artery involvement. For pediatric patients, GA showed more cerebral hemorrhage (CH) (odds ratios (ORs) [95% confidence intervals (CIs)] = 3.99 (1.61-9.88), P = 0.003), more patients were in the Suzuki early and intermediate stage (P = 0.001; P = 0.001, respectively), while for the adult group, GA indicated more female (OR [95% CIs] = 1.43 [1.15-1.79], P = 0.001), fewer patients with diabetes (0.58 [0.38-0.86], P = 0.007) and intermediate Suzuki stage (P = 3.70 × 10-4). CONCLUSIONS: The incidence and carrying rates of RNF213 p.R4810K in various regions for Chinese MMD patients were obviously different. RNF213 p.R4810K has different predictive effects on phenotypes of pediatric and adult patients.

8.
Rev Cardiovasc Med ; 22(3): 895-901, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565088

RESUMO

Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009-1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037-2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018-2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.

9.
Sci Total Environ ; 803: 149754, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34496344

RESUMO

The immobilized carrier was prepared with complete anaerobic ammonia oxidation granular sludge (AnGS) and crushed AnGS, respectively. We evaluated the effects of granular form and continuous temperature changes on nitrogen removal by immobilized anaerobic ammonium oxidation (anammox) filler. The results showed that the rate of nitrogen removal of crushed and encapsulated AnGS was 20% higher than that of direct encapsulated AnGS. However, the latter had higher thresholds of tolerance to Fe2+ and Cu2+. In addition, the immobilization reduced the activation energy of anammox. Above 12.5 °C, the immobilized filler was efficient at removing nitrogen removal through the dual adjustment of temperature-hydraulic retention time. From 12.5 °C to 23 °C, the temperature had a greater influence on the nitrogen removal effect than the HRT. In contrast, HRT had a dominant influence from 23 °C to 32 °C. Anammox activity was severely inhibited below 12.5 °C. High-throughput sequencing analysis showed that the community structure migrated with the changes in temperature. The anammox functional bacteria Candidatus Kuenenia (18.31-39.73%) were the dominant genus at medium and high temperatures, and it was replaced by Chryseobacterium (24.19%) at 8.5 °C. In addition, an RDA analysis showed that Candidatus Brocadia was more adaptable to low temperatures than Candidatus Kuenenia. In addition, Bellilinea was more sensitive to temperature than Candidatus Kuenenia. Thus, the temperature could be appropriately lowered to avoid overbreeding. The results of this study optimized the operation of an anammox immobilized system and promote its further application.

10.
Interv Neuroradiol ; : 15910199211039689, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515559

RESUMO

BACKGROUND: Anterior communicating artery aneurysms are the second most common type of intracranial aneurysm and have a high incidence of rupture. Intraprocedural rupture can lead to a high mortality and morbidity rate, representing a major challenge in emergency endovascular treatment of ruptured anterior communicating artery aneurysms. METHODS: We performed a retrospective review of 344 consecutive patients with emergency endovascular treatment of ruptured anterior communicating artery aneurysms. Patients were grouped into intraprocedural rupture and non-intraprocedural rupture groups according to whether intraprocedural rupture occurred. Demographic and clinical factors, vessel-related factors and therapy-related factors were compared between the two groups. RESULTS: Intraprocedural rupture occurred in 11 patients (3.2%). Univariate analysis showed that hypertension, the occurrence of vasospasm, aneurysm size, aneurysm angle and a high aspect ratio value were significantly associated with intraprocedural rupture (P < 0.05). Multivariate analysis showed that hypertension odds ratio (OR, 9.799; P = 0.007), the occurrence of vasospasm (OR, 10.121; P = 0.002) and a high aspect ratio value (OR, 10.571; P = 0.006) were independent risk factors for intraprocedural rupture. CONCLUSIONS: A history of hypertension, the occurrence of vasospasm and a high aspect ratio value are independent risk factors for intraprocedural rupture among patients with ruptured anterior communicating artery aneurysms.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34474652

RESUMO

The aim of the current study was to explore possible connections between manganese exposure and the prevalence of cardiovascular disease (CVD) in older US adults. The relationship between serum manganese levels and CVD was explored in 2427 people aged 60 years and over using data from the National Health and Nutrition Examination Survey (NHANES) (2011-2018). Multivariate linear regression analysis was performed to investigate associations between CVD risk factors and serum manganese concentration. The relationship between manganese levels and the prevalence of CVD was probed using generalized linear models and restricted cubic spline curves. Stratified subgroup analysis was subsequently constructed to rule out spurious interactions between variables and manganese. Compared with the lowest quartile, the modified odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the manganese quartiles were 0.71 (OR: 0.51; CI: 1.00), 0.70 (0.50, 0.99), and 0.49 (0.34, 0.72). In the full adjusted model, a prominent negative relationship was observed between serum manganese concentration and CVD. A restricted cubic spline curve was used to show a nonlinear negative relationship between manganese concentration and CVD. In summary, manganese levels are negatively correlated with the risk of CVD in a nation-wide study of older US adults.

12.
Sci Total Environ ; 798: 149375, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375262

RESUMO

In this study, real-time measurement of Volatile Organic Compounds (VOCs) was conducted at an urban site in Changzhou, a typical corridor city in the Yangtze River Delta (YRD) region in China, by Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) during 2019 China International Import Expo (CIIE) episode. An improved method based on Air Quality Index (AQI) value is applied to identify polluted and clean periods. Diurnal pattern of VOC levels revealed elevated photochemical reactivity during polluted periods. Five VOC sources were identified by Positive Matrix Factorization (PMF) model, including secondary formation (22.71 ± 12.33%), biogenic (21.50% ± 11.76%), solvent usage (20.50 ± 10.07%), vehicle exhaust (18.32 ± 8.32%), and industrial process and fuel usage (16.96 ± 13.21%). The mean contribution of vehicular exhaust was 10.84% higher during the nighttime than the daytime under polluted days. The biogenic source contributed more during clean periods, while the secondary formation presented the opposite. Spatial analysis displayed that the VOC concentration was higher in the S and SSE. In terms of the regional transport, short-distance air masses from the northeast and the south within the YRD region led to high VOC levels and biogenic VOC derived from the ocean might affect the entire region. Stringent emission control policies enforced over the YRD for 2019 CIIE provided an excellent opportunity to determine the source-receptor response. As joint control area, the VOC level of Changzhou exhibited a substantial reduction and the VOC amounts emitted by solvent usage showed the biggest decrease (-58%). The findings of this study highlight the superiority of high time-resolved data in identifying the dynamic variation pattern (with the change of time and wind) of VOC levels and emission intensities.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Compostos Orgânicos Voláteis/análise
13.
Epigenomics ; 13(15): 1187-1203, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34382410

RESUMO

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

14.
Environ Pollut ; 290: 117984, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34455299

RESUMO

Continuous tightening emission standards (ESs) facilitate the reduction of organic gas emissions from gasoline vehicles. Correspondingly, it is essential to update the emissions and chemical speciation of total organic gases (TOGs), including volatile organic compounds (VOCs), intermediate volatility organic compounds (IVOCs), CH4, and unidentified non-methane hydrocarbons (NMHCs) for assessing the formation of ozone and secondary organic aerosol (SOA). In this study, TOG and speciation emissions from 12 in-use light-duty gasoline vehicle (LDGV) exhausts, covering the ESs from China II to China V, were investigated on a chassis dynamometer under the Worldwide Harmonized Light-duty Test Cycle (WLTC) in China. The results showed that the most effectively controlled subgroup in TOG emissions from LDGVs was VOCs, followed by the unidentified NMHCs and IVOCs. The mass fraction of VOCs in TOGs also reduced from 61 ± 9% to 46 ± 18% while the IVOCs gently increased from 2 ± 0.4% to 8 ± 4% along with the more stringent ESs. For the VOC subsets, the removal efficiency of oxygenated VOCs (OVOCs) was lower than those of other VOC subsets in the ESs from China IV to V, suggesting the importance of OVOC emission controls for relatively new LDGVs. The IVOC emissions were mainly subject to the ESs, then driving cycles and fuel use. The formation potentials of ozone and SOA from LDGVs decreased separately 96% and 90% along with the restricted ESs from China II-III to China IV. The major contributor of SOA formation transformed from aromatics in the VOC subsets for China II-III vehicles to IVOCs for China IV/V vehicles, highlighting that IVOC emissions from LDGVs are also needed more attentions to control in future.

15.
Clin Interv Aging ; 16: 1541-1553, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447245

RESUMO

Objective: Percutaneous coronary intervention (PCI) is one of the most effective treatments for acute coronary syndrome (ACS). However, the need for postoperative revascularization remains a major problem in PCI. This study was to develop and validate a nomogram for prediction of revascularization after PCI in patients with ACS. Methods: A retrospective observational study was conducted using data from 1083 patients who underwent PCI (≥6 months) at a single center from June 2013 to December 2019. They were divided into training (70%; n = 758) and validation (30%; n = 325) sets. Multivariate logistic regression analysis was used to establish a predictive model represented by a nomogram. The nomogram was developed and evaluated based on discrimination, calibration, and clinical efficacy using the concordance statistic (C-statistic), calibration plot and decision curve analysis (DCA), respectively. Results: The nomogram was comprised of ten variables: follow-up time (odds ratio (OR): 1.01; 95% confidence interval (CI): 1.00-1.03), history of diabetes mellitus (OR: 1.83; 95% CI: 1.25-2.69), serum creatinine level on admission (OR: 0.99; 95% CI: 0.98-1.00), serum uric acid level on admission (OR: 1.005; 95% CI: 1.002-1.007), lipoprotein-a level on admission (OR: 1.0021; 95% CI: 1.0013-1.0029), low density lipoprotein cholesterol level on re-admission (OR: 1.33; 95% CI: 0.10-0.47), the presence of chronic total occlusion (OR: 3.30; 95% CI: 1.93-5.80), the presence of multivessel disease (OR: 4.48; 95% CI: 2.85-7.28), the presence of calcified lesions (OR: 1.63; 95% CI: 1.11-2.39), and the presence of bifurcation lesions (OR: 1.82; 95% CI: 1.20-2.77). The area under the receiver operating characteristic curve values for the training and validation sets were 0.765 (95% CI: 0.732-0.799) and 0.791 (95% CI: 0.742-0.830), respectively. The calibration plots showed good agreement between prediction and observation in both the training and validation sets. DCA also demonstrated that the nomogram was clinically useful. Conclusion: We developed an easy-to-use nomogram model to predict the risk of revascularization after PCI in patients with ACS. The nomogram may provide useful assessment of risk for subsequent treatment of ACS patients undergoing PCI.

16.
Theranostics ; 11(16): 7640-7657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335955

RESUMO

Background: Since primary prostate cancer (PCa) can advance to the life-threatening metastatic PCa, exploring the molecular mechanisms underlying PCa metastasis is crucial for developing the novel targeted preventive strategies for decreasing the mortality of PCa. RNA N6-methyladenosine (m6A) is an emerging regulatory mechanism for gene expression and its specific roles in PCa progression remains elusive. Methods: Western blotting, quantitative real-time PCR and immunohistochemical analyses were used to detect target gene expression in PCa cells in vitro and prostate tissues from patients. RNA immunoprecipitation was conducted to analyze the specific binding of mRNA to the target protein. Migration and invasion assays were used to assess the migratory capacities of cancer cells. The correlation between target gene expression and survival rate of PCa patients was analyzed based the TCGA database. Results: We found that total RNA N6-methyladenosine (m6A) modification levels were markedly upregulated in human PCa tissues due to increased expression of methyltransferase like 3 (METTL3). Further studies revealed that the migratory and invasive capacities of PCa cells were markedly suppressed upon METTL3 knockdown. Mechanistically, METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells. Conclusions: Our findings highlight the role of METTL3 in modulating invasion and metastasis of PCa cells, providing insight into promising therapeutic strategies for hindering PCa progressing to deadly metastases.


Assuntos
Metiltransferases/genética , Neoplasias da Próstata/metabolismo , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica/fisiologia , Humanos , Masculino , Metiltransferases/metabolismo , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Proteases Específicas de Ubiquitina/genética
17.
Artigo em Inglês | MEDLINE | ID: mdl-34374478

RESUMO

Heterostructured catalysts show outstanding performance in electrochemical reactions owing to their beneficial interfacial properties. However, the rational design of heterostructured catalysts with the desired interfacial properties and charge-transfer characteristics is challenging. Herein, we developed a SrMn3 O6-x -SrMnO3 (SMOx -SMO) heterostructure through epitaxial growth, which demonstrated excellent electrocatalyst performance for the oxygen reduction reaction (ORR). The formation of high-valence Mn3+/4+ is beneficial for promoting a positive shift in the position of the d-band center, thereby optimizing the adsorption and desorption of ORR intermediates on the heterojunction surface and resulting in improved catalytic activity. When SMOx -SMO was applied as an air-electrode catalyst in a rechargeable zinc-air battery, a high output voltage and power density was achieved, with performance comparable to a battery prepared with Pt/C-IrO2 air-electrode catalysts, albeit with much better cycling stability.

18.
J Med Virol ; 93(11): 6210-6219, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34260071

RESUMO

To investigate the role of miR-4301 in rotavirus (RV)-infected Caco-2 cells. In this experiment, RNAs of RV-infected Caco-2 cells were extracted, and the high-throughput second-generation sequencing was performed to detect the expression profiles of host microRNAs (miRNAs). Synthetic miRNA mimics and inhibitors were examined (quantitative polymerase chain reaction [qPCR], crystalline violet, immunofluorescence and electron microscopy) to evaluate the effect on RV replication. Target genes of miR-4301 were predicted by software analysis. The expression of target genes was evaluated by qPCR and Western blot after transfected with miRNA inhibitor/mimic, and crystalline violet and qPCR were used to detect the downregulation effects of target genes on RV replication. By transfecting miRNA inhibitors/mimics and detecting downstream target genes, the mechanism of miRNA affecting RV replication was analyzed. There were 78 known miRNAs with significant differential expression, including 39 upregulated miRNAs and 39 downregulated miRNAs. The results showed that miR-4301 exerted a key role in enhancing RV replication. PPP1R3D protein which can inhibit RV replication was predicted as the target gene of miR-4301 by software analysis. While upregulating miR-4301 by RV, the expression of PPP1R3D and glycogen synthase (GS) is suppressed. For the first time, the effect of miR-4301 on RV infection, and its influence on GS was investigated. Specifically, RV inhibits host cell glycogen synthesis to utilize the host intracellular glucose for promoting its own replication.

19.
Bioengineered ; 12(1): 3503-3515, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34233591

RESUMO

Gestational diabetes mellitus (GDM) increases the risk of fetal heart malformations, though little is known about the mechanism of hyperglycemia-induced heart malformations. Thus, we aimed to reveal the global landscape of miRNAs and mRNAs in GDM-exposed fetoplacental arterial endothelial cells (dAECs) and establish regulatory networks for exploring the pathophysiological mechanism of fetal heart malformations in maternal hyperglycemia. Gene Expression Omnibus (GEO) datasets were used, and identification of differentially expressed miRNAs (DEMs) and genes (DEGs) in GDM was based on a previous sequencing analysis of dAECs. A miRNA-mRNA network containing 20 DEMs and 65 DEGs was established using DEMs altered in opposite directions to DEGs. In an in vivo study, we established a streptozotocin-induced pregestational diabetes mellitus (PGDM) mouse model and found the fetal cardiac wall thickness in different regions to be dramatically increased in the PGDM grouValidation of DEMs and DEGs in the fetal heart showed significantly upregulated expression of let-7e-5p, miR-139-5p and miR-195-5p and downregulated expression of SGOL1, RRM2, RGS5, CDK1 and CENPA. In summary, we reveal the miRNA-mRNA regulatory network related to fetal cardiac development disorders in offspring, which may shed light on the potential molecular mechanisms of fetal cardiac development disorders during maternal hyperglycemia.

20.
Nat Plants ; 7(8): 1026-1036, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34267359

RESUMO

The ancient gymnosperm genus Taxus is the exclusive source of the anticancer drug paclitaxel, yet no reference genome sequences are available for comprehensively elucidating the paclitaxel biosynthesis pathway. We have completed a chromosome-level genome of Taxus chinensis var. mairei with a total length of 10.23 gigabases. Taxus shared an ancestral whole-genome duplication with the coniferophyte lineage and underwent distinct transposon evolution. We discovered a unique physical and functional grouping of CYP725As (cytochrome P450) in the Taxus genome for paclitaxel biosynthesis. We also identified a gene cluster for taxadiene biosynthesis, which was formed mainly by gene duplications. This study will facilitate the elucidation of paclitaxel biosynthesis and unleash the biotechnological potential of Taxus.


Assuntos
Antineoplásicos/metabolismo , Vias Biossintéticas/genética , Genoma de Planta , Paclitaxel/biossíntese , Análise de Sequência , Taxus/genética , Taxus/metabolismo , Evolução Molecular , Plantas Medicinais/genética , Plantas Medicinais/metabolismo
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