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Magnaporthe oryzae is a rice blast pathogen that seriously threatens rice yield. Benzovindiflupyr is a succinate dehydrogenase inhibitor (SDHI) fungicide that effectively controls many crop diseases. Benzovindiflupyr has a strong inhibitory effect on M. oryzae; however, control of rice blast by benzovindiflupyr and risk of resistance to benzovindiflupyr are not well studied in this pathogen. In this study, six benzovindiflupyr-resistant strains were obtained by domestication induced in the laboratory. The MoSdhBH245D mutation was the cause of M. oryzae resistance to benzovindiflupyr, which was verified through succinate dehydrogenase (SDH) activity assays, molecular docking, and site-specific mutations. Survival fitness analysis showed no significant difference between the benzovindiflupyr-resistant and parent strains. Positive cross-resistance to benzovindiflupyr and other SDHIs and negative cross-resistance to azoxystrobin were observed. Therefore, the risk of benzovindiflupyr resistance in M. oryzae might be medium to high. It should be combined with other classes of fungicides (tebuconazole and azoxystrobin) to slow the development of resistance.
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Farmacorresistência Fúngica , Fungicidas Industriais , Mutação , Succinato Desidrogenase , Succinato Desidrogenase/genética , Succinato Desidrogenase/antagonistas & inibidores , Fungicidas Industriais/farmacologia , Farmacorresistência Fúngica/genética , Doenças das Plantas/microbiologia , Magnaporthe/efeitos dos fármacos , Magnaporthe/genética , Simulação de Acoplamento Molecular , Oryza/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Estrobilurinas/farmacologia , AscomicetosRESUMO
FMS-like receptor tyrosine kinase 3 (Flt3) expression was reported to increase in the heart in response to pathological stress, but the role of Flt3 activation and its underlying mechanisms remain poorly elucidated. This study was designed to investigate the role of Flt3 activation in sympathetic hyperactivity-induced cardiac hypertrophy and its mechanisms through autophagy and mitochondrial dynamics. In vivo, cardiac hypertrophy was established by subcutaneous injection of isoprenaline (6 mg/kg·day) in C57BL/6 mice for 7 consecutive days. The Flt3-ligand intervention was launched 2 h prior to isoprenaline each day. In vitro, experiments of cardiomyocyte hypertrophy, autophagy, and mitochondrial dynamics were performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that the expression level of Flt3 protein was significantly increased in the hypertrophic myocardium provoked by isoprenaline administration. Flt3-ligand intervention alleviated isoprenaline-induced cardiac oxidative stress, hypertrophy, fibrosis, and contractile dysfunction. Isoprenaline stimulation impaired autophagic flux in hypertrophic mouse hearts, supported by the accumulation of LC3II and P62 proteins, while Flt3-ligand restored the impairment of autophagic flux. Flt3 activation normalized the imbalance of mitochondrial fission and fusion in the hearts of mice evoked by isoprenaline as evidenced by the neutralization of elevated mitochondrial fission markers and reduced mitochondrial fusion markers. In NRCMs, Flt3-ligand treatment attenuated isoprenaline-stimulated hypertrophy, which was abolished by a Flt3-specific blocker AC220. Activating Flt3 reversed isoprenaline-induced autophagosome accumulation and impairment of autophagic flux probably by enhancing SIRT1 expression and consequently TFEB nuclear translocation. Flt3 activation improved the imbalance of mitochondrial dynamics induced by isoprenaline in NRCMs through the SIRT1/P53 pathway. Activation of Flt3 mitigated ISO-stimulated hypertrophy probably involves the restoration of autophagic flux and balance of mitochondrial dynamics. Therefore, activation of Flt3 attenuates isoprenaline-induced cardiac hypertrophy in vivo and in vitro, the potential mechanism probably attributes to SIRT1/TFEB-mediated autophagy promotion and SIRT1/P53-mediated mitochondrial dynamics balance. These findings suggest that activation of Flt3 may be a novel target for protection against cardiac remodeling and heart failure during sympathetic hyperactivity.
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Dinâmica Mitocondrial , Tirosina Quinase 3 Semelhante a fms , Ratos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Isoproterenol/toxicidade , Sirtuína 1 , Ligantes , Proteína Supressora de Tumor p53 , Autofagia , Miócitos Cardíacos , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controleRESUMO
Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its ability to overcome critical limitations, including low tissue-penetration depth and phototoxicity in photodynamic therapy (PDT). Biogenic metal oxide nanoparticles (NPs) have been used as anti-cancer drugs due to their biocompatibility properties with most biological systems. Here, sonosensitizer MWO4-PEG NPs (M = Fe Mn Co Ni) were synthesized as inhibitors to activation-induced cytidine deaminase (AID), thus neutralizing the extensive carcinogenesis of AID in diffuse large B-cell lymphoma (DLBCL). The physiological properties of these nanomaterials were examined using transmission electron microscopy (TEM). The inhibition of NPs to AID was primarily identified by the affinity interaction prediction between reactive oxygen species (ROS) and AID through molecular dynamics and molecular docking technology. The cell apoptosis and ROS generation in US-triggered NPs treated DLBCL cells (with high levels of AID) were also detected to indicate the sonosensitivity and toxicity of MWO4-PEG NPs to DLBCL cells. The anti-lymphoma studies using DLBCL and AID-deficient DLBCL cell lines indicated a concentration-dependent profile. The synthesized MWO4-PEG NPs in this study manifested good sonodynamic inhibitory effects to AID and well treatment for AID-positive hematopoietic cancers.
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Linfoma Difuso de Grandes Células B , Nanopartículas Metálicas , Nanopartículas , Terapia por Ultrassom , Humanos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Óxidos , Polietilenoglicóis/uso terapêuticoRESUMO
Background and objective: Depression is a widespread mental health condition that can impact both mental and physical well-being. Prior research has shown that high levels of copper in the blood and low levels of folate are linked to depression. This study aimed to explore whether serum folate levels, independently or in combination with serum copper levels, associated with the risk of depression. Methods: Data from participants aged 18-80 years in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016 were analyzed to examine the role of trace elements. Depression was assessed using the nine-item Patient Health Questionnaire (PHQ-9). Logistic regression analyses were employed to evaluate the main effect of serum copper and folate levels on depression. Three indices, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze the interaction effect. Results: Among the 4,847 participants selected for this study, 429 (8.9%) had PHQ-9 scores above 10, which we defined as having depressive symptoms. After adjusting for all confounding factors, higher serum copper levels [≥15.5 vs. <15.5 µmol/L, odds ratio (OR): 1.54; 95% confidence intervals (CI): 1.18-2.11] and folate deficiency (folate ≥53.7 vs. <53.7 µmol/L, OR: 1.44; 95% CI: 1.21-2.10) were associated with an increased risk of depression. Patients with both higher serum copper levels and folate deficiency (OR: 2.11; 95% CI: 1.43-3.14) had the highest risk of depression than other levels. High copper levels and low folate levels are associated with the occurrence of depression symptoms, and there may be a synergistic effect between them (SI: 1.65; 95% CI: 1.49-4.76), with this interaction accounting for 19% of depression cases (API: 0.19; 95% CI: 0.01-0.54). Conclusion: There may be a synergistic interaction between high copper levels and low folate levels associated with increasing risk of depression. Further population-based interventional studies are needed to confirm whether folic acid supplementation is effective in preventing depression in individuals with high blood copper levels.
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Background: The segmentation of prostates from transrectal ultrasound (TRUS) images is a critical step in the diagnosis and treatment of prostate cancer. Nevertheless, the manual segmentation performed by physicians is a time-consuming and laborious task. To address this challenge, there is a pressing need to develop computerized algorithms capable of autonomously segmenting prostates from TRUS images, which sets a direction and form for future development. However, automatic prostate segmentation in TRUS images has always been a challenging problem since prostates in TRUS images have ambiguous boundaries and inhomogeneous intensity distribution. Although many prostate segmentation methods have been proposed, they still need to be improved due to the lack of sensibility to edge information. Consequently, the objective of this study is to devise a highly effective prostate segmentation method that overcomes these limitations and achieves accurate segmentation of prostates in TRUS images. Methods: A three-dimensional (3D) edge-aware attention generative adversarial network (3D EAGAN)-based prostate segmentation method is proposed in this paper, which consists of an edge-aware segmentation network (EASNet) that performs the prostate segmentation and a discriminator network that distinguishes predicted prostates from real prostates. The proposed EASNet is composed of an encoder-decoder-based U-Net backbone network, a detail compensation module (DCM), four 3D spatial and channel attention modules (3D SCAM), an edge enhancement module (EEM), and a global feature extractor (GFE). The DCM is proposed to compensate for the loss of detailed information caused by the down-sampling process of the encoder. The features of the DCM are selectively enhanced by the 3D spatial and channel attention module. Furthermore, an EEM is proposed to guide shallow layers in the EASNet to focus on contour and edge information in prostates. Finally, features from shallow layers and hierarchical features from the decoder module are fused through the GFE to predict the segmentation prostates. Results: The proposed method is evaluated on our TRUS image dataset and the open-source µRegPro dataset. Specifically, experimental results on two datasets show that the proposed method significantly improved the average segmentation Dice score from 85.33% to 90.06%, Jaccard score from 76.09% to 84.11%, Hausdorff distance (HD) score from 8.59 to 4.58 mm, Precision score from 86.48% to 90.58%, and Recall score from 84.79% to 89.24%. Conclusions: A novel 3D EAGAN-based prostate segmentation method is proposed. The proposed method consists of an EASNet and a discriminator network. Experimental results demonstrate that the proposed method has achieved satisfactory results on 3D TRUS image segmentation for prostates.
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As a rapidly developing information technology in recent years, the metaverse has significantly transformed how we live, learn, and work. In order to accelerate the use of metaverse technology and promote users' acceptance of the metaverse, this study constructs an integrated model based on flow theory and use and satisfaction theory, to further explore the factors affecting users' acceptance of the metaverse. A total of 265 valid questionnaires were obtained through a situational questionnaire survey. Considering the limitations of a single analysis technique, we use two methods to analyze the data. Among them, the symmetric PLS-SEM method is mainly used to analyze the effects of single variables, while the asymmetric fsQCA method is used to analyze the combined effects of variables. The PLS-SEM results manifest that flow experience, perceived risk, and personal innovation directly influence users' acceptance of the metaverse, while perceived cost has no effect. Simultaneously, interactivity, presence, and social presence indirectly affect users' acceptance of the metaverse, while informativeness and enjoyment have no indirect effect. Significantly, fsQCA unveiled five configurations resulting in a high user acceptance of the metaverse, as well as six configurations leading to a negative acceptance. The complementary findings from PLS-SEM and fsQCA offer valuable insights for both theoretical understanding and practical implementation.
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Glyphosate is a widely used broad-spectrum herbicide in agriculture and horticulture to control a variety of weeds and undesirable plants. However, the excessive use of glyphosate has raised a number of environmental and human health concerns. It is urgent to develop tools to detect glyphosate. Herein, a novel dual-signal probe CCU-Cu2+ was designed and synthesized on the basis of CCU. CCU exhibited excellent selectivity and great sensitivity for Cu2+ which were based on both fluorescence "turn-off" reaction and comparative color visualisation methods. Due to the strong chelating ability of glyphosate on Cu2+, the CCU-Cu2+ complex was applied to glyphosate detection in practical samples. The experimental results in vitro showed that the CCU-Cu2+ complex was highly selective and rapid, with a low detection limit (1.6 µM), and could be recognised by the naked eye in the detection of glyphosate. Based on the excellent properties of the CCU-Cu2+ complex, we also constructed a smartphone-assisted detection sensing system for glyphosate detection, which has the advantages of precision, sensitivity, and high interference immunity. Moreover, the CCU-Cu2+ complex was also successfully employed for exogenous glyphosate imaging in living cells. These characteristics demonstrated that CCU-Cu2+ holds significant potential for detection and imaging of glyphosate in bio-systems.
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Cobre , Corantes Fluorescentes , Glicina , Glifosato , Herbicidas , Glicina/análogos & derivados , Glicina/química , Corantes Fluorescentes/química , Humanos , Cobre/química , Cobre/análise , Herbicidas/análise , Herbicidas/química , Limite de Detecção , Espectrometria de Fluorescência/métodos , Imagem Óptica/métodos , Contaminação de Alimentos/análise , Smartphone , Análise de Alimentos/métodosRESUMO
Background: Alzheimer's disease (AD) is an age-related neurodegenerative disease that is clinically characterized by progressive cognitive decline. Glucagon-like peptide-1 (GLP-1) is a hormone that belongs to the incretin family and is released in response to nutrient intake. It plays a role in maintaining metabolic homeostasis and has been suggested to be involved in maintaining the brain microenvironment. However, the role of GLP-1 in AD pathogenesis has not been fully illustrated. Objective: This study aims to investigate the clinical relevance of GLP-1 in AD and the effects of GLP-1 in amyloid-ß (Aß) metabolism in vitro. Methods: In this study, 39 AD patients and 120 cognitively intact controls were included. Plasma levels of GLP-1 were measured using ELISA. SH-SY5Y cells overexpressing human amyloid precursor protein (APP) were treated with GLP-1. Western blot analysis was used to assess the effects of GLP-1 on the metabolism of Aß. Results: Plasma GLP-1 levels were decreased with aging. Plasma GLP-1 levels were lower in AD patients in comparison with healthy older adults. Plasma GLP-1 levels were positively associated with Mini-Mental State Examination scores but negatively associated with plasma pTau181 levels. GLP-1 dose-dependently increased the area fraction of mitochondrial staining in vitro. Furthermore, GLP-1 dose-dependently promoted the α-cleavage of APP, thus reducing the generation of Aß. Conclusions: GLP-1 has neuroprotective effects in AD, and therefore the decrease in GLP-1 levels during aging might contribute to the development of AD.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Peptídeo 1 Semelhante ao Glucagon , Humanos , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Doença de Alzheimer/sangue , Masculino , Idoso , Feminino , Biomarcadores/sangue , Peptídeos beta-Amiloides/sangue , Cognição/fisiologia , Idoso de 80 Anos ou mais , Precursor de Proteína beta-Amiloide/sangue , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Proteínas tau/sangue , Testes de Estado Mental e Demência , Envelhecimento/sangueRESUMO
Acute kidney injury (AKI) is one of the most important lethal factors for patients admitted to intensive care units (ICUs), and timely high-risk prognostic assessment and intervention are essential to improving patient prognosis. In this study, a stacking model using the MIMIC-III dataset with a two-tier feature selection approach was developed to predict the risk of in-hospital mortality in ICU patients admitted for AKI. External validation was performed using separate MIMIC-IV and eICU-CRD. The area under the curve (AUC) was calculated using the stacking model, and features were selected using the Boruta and XGBoost feature selection methods. This study compares the performance of a stacking model using two-tier feature selection with a model using single-tier feature selection (XGBoost: 85; Boruta: 83; two-tier: 0.91). The predictive effectiveness of the stacking model was further validated by using different datasets (Validation 1: 0.83; Validation 2: 0.85) and comparing it with a simpler model and traditional clinical scores (SOFA: 0.65; APACH IV: 0.61). In addition, this study combined interpretable techniques and causal inference to analyze the causal relationship between features and predicted outcomes.
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Injúria Renal Aguda , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Humanos , Injúria Renal Aguda/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Área Sob a Curva , Fatores de RiscoRESUMO
The clinic application of doxorubicin (DOX) is severely limited by its severe cardiotoxicity. Tripartite motif-containing protein 16 (TRIM16) has E3 ubiquitin ligase activity and is upregulated in cardiomyocytes under pathological stress, yet its role in DOX-induced cardiotoxicity remains elusive. This study aims to investigate the role and mechanism of TRIM16 in DOX cardiotoxicity. Following TRIM16 overexpression in hearts with AAV9-TRIM16, mice were intravenously administered DOX at a dose of 4 mg/kg/week for 4 weeks to assess the impact of TRIM16 on doxorubicin-induced cardiotoxicity. Transfection of OE-TRIM16 plasmids and siRNA-TRIM16 was performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that DOX challenge elicited a significant upregulation of TRIM16 proteins in cardiomyocytes. TRIM16 overexpression efficiently ameliorated cardiac function while suppressing inflammation, ROS generation, apoptosis and fibrosis provoked by DOX in the myocardium. TRIM16 knockdown exacerbated these alterations caused by DOX in NRCMs. Mechanistically, OE-TRIM16 augmented the ubiquitination and degradation of p-TAK1, thereby arresting JNK and p38MAPK activation evoked by DOX in cardiomyocytes. Furthermore, DOX enhanced the interaction between p-TAK1 and YAP1 proteins, resulting in a reduction in YAP and Nrf2 proteins in cardiomyocytes. OE-TRIM16 elevated YAP levels and facilitated its nuclear translocation, thereby promoting Nrf2 expression and mitigating oxidative stress and inflammation. This effect was nullified by siTRIM16 or TAK1 inhibitor Takinib. Collectively, the current study elaborates that upregulating TRIM16 mitigates DOX-induced cardiotoxicity through anti-inflammation and anti-oxidative stress by modulating TAK1-mediated p38 and JNK as well as YAP/Nrf2 pathways, and targeting TRIM16 may provide a novel strategy to treat DOX-induced cardiotoxicity.
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Cardiotoxicidade , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Ratos , Apoptose , Cardiotoxicidade/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/toxicidade , Inflamação/metabolismo , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Depression is a common mental disease, accompanied by anxiety and persistent depression. Endophilin A1 (EPA1) is a brain-specific protein enriched in synaptic terminals that is primarily expressed in the central nervous system. It has been reported that EPA1 is involved in neurotransmitter release, which indicates that the protein may be involved in depression. However, it is unclear whether EPA1 is implicated in the development of depression. METHODS: The mice depression model was established by chronic unpredicted mild stress (CUMS). Depression-like behaviors were detected by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST) and open-field test (OFT). Neuronal histopathology was applied by hematoxylin and eosin stain (H&E), and Nissl stain. EPA1, NLRP1 inflammatory complexes, NADPH oxidase2 (NOX2), synaptic-related protein expression of the mice were tested by western blot. Immunofluorescence was applied to detect the expression of EPA1 and ROS in mice hippocampus. EPA1 knockdown was performed by an adeno-associated virus (AAV) vector containing EPA1-shRNA-EGFP infusion. RESULT: CUMS exposure induced depressive-like behaviors and increased the expression of EPA1 in the hippocampus. Knockdown hippocampal EPA1 ameliorated CUMS-induced depressive-like behaviors, decreased calcium (Ca2+) overload, decreased ROS generation and NOX2 expression, inhibited NLRP1 inflammasome-driven neuroinflammation, and restored the levels of BDNF, PSD95, GAP-43, SYN, and MAP-2 in the hippocampus. CONCLUSION: EPA1 contributes to CUMS induced depressive-like behaviors and the mechanism may be related to NLRP1 inflammasome-driven inflammatory response, regulating calcium ion homeostasis and ROS generation, and alleviating synaptic function damage. This indicated that EPA1 may participate in the occurrence and development of depression.
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Depressão , Inflamassomos , Animais , Camundongos , Comportamento Animal , Cálcio/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Inflamassomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Psicológico/metabolismoRESUMO
BACKGROUND: It has been reported that metformin use may reduce the risk of thyroid cancer, but existing studies have generated inconsistent results. The purpose of this study was to investigate such association between metformin use and the risk of thyroid cancer. METHODS: Studies of metformin use for the risk of thyroid cancer were searched in Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Database, Wanfang Data, and Chinese Scientific Journals Database (VIP) from the establishment date to December 2022. Newcastle-Ottawa scale is adopted for assessing the methodological quality of included studies, and the inter-study heterogeneity was assessed by using the I-squared statistic. Combined odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated through either fixed-effects or random-effects model according to the heterogeneity. Besides, subgroup analyses, sensitivity analyses and test for publication bias were conducted. RESULTS: Five studies involving 1,713,528 participants were enrolled in the qualitative and quantitative synthesis. The result of the meta-analyses showed that metformin use was associated with a statistically significant lower risk of thyroid cancer (pooled OR = 0.68, 95% CI = 0.50-0.91, P = 0.011). Moreover, in the subgroup analysis, we found that the use of metformin may also aid in the prevention of thyroid cancer in Eastern population (pooled OR = 0.55, 95% CI = 0.35-0.88, P = 0.012) rather than Western population (pooled OR = 0.89, 95% CI = 0.52-1.54, P = 0.685). Sensitivity analysis suggested the results of this meta-analyses were relatively stable. No publication bias was detected. CONCLUSION: Metformin use is beneficial for reducing the risk of thyroid cancer. For further investigation, more well-designed studies are still needed to elucidate the association between metformin use and the risk of thyroid cancer.
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Metformina , Neoplasias da Glândula Tireoide , Humanos , Metformina/uso terapêutico , Risco , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/prevenção & controle , ChinaRESUMO
BACKGROUND: Endophilin A1 (EPA1) is encoded by the SH3GL2 gene, and SH3GL2 was designated as a Parkinson's disease (PD) risk locus by genome-wide association analysis, suggesting that EPA1 may be involved in the occurrence and development of PD. OBJECTIVE: To investigate the role of EPA1 in lipopolysaccharide (LPS)-induced PD model mice. METHODS: The mice PD model was prepared by injecting LPS into the substantia nigra (SN), and the changes in the behavioral data of mice in each group were observed. The damage of dopaminergic neurons, activation of microglia, and reactive oxygen species (ROS) generation were detected by immunofluorescence method; calcium ion concentration was detected by calcium content detection kit; EPA1 and inflammation and its related indicators were detected by western blot method. EPA1 knockdown was performed by an adeno-associated virus vector containing EPA1-shRNA-eGFP infusion. RESULTS: LPS-induced PD model mice developed behavioral dysfunction, SN dopaminergic nerve damage, significantly increased calcium ion, calpain 1, and ROS production, activated NLRP1 inflammasome and promoted pro-inflammatory cell release, and SN EPA1 knockdown improves behavioral disorders, alleviates dopaminergic neuron damage, reduces calcium, calpain 1, ROS generation, and blocks NLRP1 inflammasome-driven inflammatory responses. CONCLUSION: The expression of EPA1 in the SN of LPS-induced PD model mice was increased, and it played a role in promoting the occurrence and development of PD. EPA1 knockdown inhibited the NLRP1 inflammasome activation, decreased the release of inflammatory factors and ROS generation, and alleviated dopaminergic neuron damage. This indicated that EPA1 may participating in the occurrence and development of PD.
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Doença de Parkinson , Animais , Camundongos , Cálcio/metabolismo , Calpaína/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Estudo de Associação Genômica Ampla , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Substância Negra/metabolismoRESUMO
Background: It has been reported that the use of glucocorticoids may be able to improve clinical pregnancy rates in patients receiving in vitro fertilization and embryo transfer (IVF-ET). The purpose of this study was to investigate the association between glucocorticoid use and clinical pregnancy rate in IVF-ET patients. Methods: This study has been registered on the International Register of Prospective Systems Evaluation (PROSPERO) (ID: CRD42022375427). A thorough and detailed search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted to identify eligible studies up to October 2022. Quality assessment was conducted on the modified Jadad Scoring Scale and Newcastle-Ottawa Scale, and the inter-study heterogeneity was estimated by Q test and I2 test. Combined hazard ratios with 95% CI were calculated using random effects or fixed effects models based on heterogeneity. Meanwhile, Begg's and Egger's tests were used to detect the existence of publication bias, the leave-one-out method was used for sensitivity analysis and multiple subgroup analyses were conducted. Results: Seventeen studies involving 3056 IVF-ET cycles were included. We found that glucocorticoid use was associated with a higher IVF-ET pregnancy rate (OR = 1.86, 95% CI = 1.27-2.74, P = 0.002). In the subgroup analysis, studies of different regions and different study types all showed similar results that glucocorticoid is beneficial to improve the clinical pregnancy rate of patients with IVF-ET, and patients with positive autoantibodies and patients receiving IVF-ET multiple times also showed the same results. However, there was no significant change in clinical pregnancy rates in the seven studies with negative autoantibodies and in the seven studies with initial IVF-ET treatment. The results of the 12 medium-acting glucocorticoids and 4 long-acting glucocorticoids were also generally consistent with each other. There was no statistical difference in subgroup analysis of whether patients had endometriosis or not. Conclusion: Appropriate use of glucocorticoids is beneficial for improving the clinical pregnancy rate in women receiving IVF-ET, but this result still needs to be verified by more high-quality and large sample size randomized controlled trials (RCTs).
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BACKGROUND: Participation in colonoscopies is an essential aspect of endoscopic training. The purpose of this study was to explore the impact of fellow/trainee participation on colonoscopy outcomes. METHODS: This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). From database inception to July 2022, studies investigating fellow involvement and colonoscopy outcomes were searched across Cochrane library, PubMed, and other databases. The random-effects model was applied to generate more conservative estimates. Sensitive analysis was conducted to explore whether the result would depend on a particular study. Egger's test and Begg's test were used to estimate the potential for publication bias. RESULTS: Seventeen studies including 30,062 participants were included. We found that fellow/trainee involvement enhanced the overall rates of adenoma detection and polyp detection (OR = 1.26, 95% CI = 1.14-1.40, p < 0.001; OR = 1.29, 95% CI = 1.02-1.63, p = 0.020, respectively). The mean number of adenoma/polyps per colonoscopy was also higher with fellow/trainee participation (MD = 0.12, 95% CI = 0.08-0.17, p < 0.001; MD = 0.15, 95% CI = 0.02-0.28, p = 0.020, respectively). CONCLUSION: In addition to its educational purpose, fellow or trainee involvement is associated with beneficial effects on colonoscopy outcomes.
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Adenoma , Colonoscopia , Humanos , Animais , Ratos , Revisões Sistemáticas como Assunto , Colonoscopia/educação , Colonoscopia/métodos , Adenoma/diagnóstico , Hospitais de EnsinoRESUMO
Background: Gestational hypertension (GH) is a common disease that seriously threatens the safety and health of pregnant women and their newborns. Physical exercise (PE) is widely recognized as a health maintenance method and it has numerous benefits. Studies on the association between PE and the risk of GH in obese and overweight pregnant women have generated controversial findings. This updated meta-analysis was performed to reassess the effects of PE on GH. Methods: The articles from inception to April 2022, presenting studies investigating exercise intervention and pregnancy outcomes were explored across several online databases. Heterogeneity among the included studies was estimated and tested by Q test and I 2 statistic. Risk ratios (RRs) and 95% confidence intervals (CI) were calculated through either random-effect or fixed-effect models. Subgroup analyses, sensitivity analyses, and publication bias diagnoses were also conducted. Results: Twelve with 1,649 subjects were included. PE was associated with a reduced risk of GH in obese and overweight pregnant women (Pooled RR = 0.58, 95% CI = 0.42-0.81, P = 0.001; I 2 = 24.3%). Subgroup analysis found significant trends amongst Eastern countries (RR = 0.59, 95% CI = 0.36-0.96, P = 0.033). Sensitivity analysis suggested the results were stable. No publication bias was detected based on Begg's test and Egger's test. Conclusion: PE was associated with reduced risk of GH in obese and overweight pregnant women, especially in Eastern countries. More well-designed studies are still needed to further elaborate on these associations. Systematic review registration: CRD42022326183.
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Hipertensão Induzida pela Gravidez , Sobrepeso , Exercício Físico , Feminino , Humanos , Recém-Nascido , Obesidade/complicações , Sobrepeso/terapia , Gravidez , GestantesRESUMO
BACKGROUND: Proton pump inhibitor use was reported to potentially provide benefits to prevent diabetes mellitus. This study aims to investigate the association between proton pump inhibitor use and the risk of developing diabetes mellitus. METHODS: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021238481). A systematic literature search was conducted to identify eligible studies up to February 2021. Quality assessment was conducted according to Jadad Scoring Scale and Newcastle-Ottawa Scale. The heterogeneity among studies was tested and estimated by Q test and I2. Pooled hazard ratio with 95% CI was calculated using the random-effects or fixed-effects model depending on the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also performed. RESULTS: Eight studies including 850 019 participants were included. We found that proton pump inhibitor use was associated with a statistically non-significant increased risk of diabetes mellitus (pooled hazard ratio was 1.06, 95% CI = 0.89-1.28, P = .50). In subgroup analysis, 5 studies conducted in North America confirmed the overall result; however, one study conducted in Europe demonstrated a statistically significant increased risk, while one study in Asia revealed a statistically significant decreased risk. CONCLUSION: Proton pump inhibitor use is not associated with either increased or decreased risk of diabetes mellitus. However, more well- designed studies focusing on proton pump inhibitor use and the risk of diabetes mellitus, especially among populations with different backgrounds, are still needed.
Assuntos
Diabetes Mellitus , Inibidores da Bomba de Prótons , Diabetes Mellitus/epidemiologia , Humanos , Imunoterapia , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de RiscoRESUMO
Aim: The aim of this study was to investigate the association of miR-1275 rs16759, IGF2BP1 rs11079850 and IGF2BP3 rs34414305 with hepatocellular carcinoma (HCC) risk. Materials & methods: Genotyping of the rs16759 and rs11079850 was performed using a Taqman assay and genotyping of the rs34414305 was performed using PCR. Relative expression of miR-1275, IGF2BP1 and IGF2BP3 was examined using quantitative PCR. Results: Comparison of the rs16759GG, CG/GG and CC genotype showed an increased risk of HCC. When comparing G with C allele, a significantly increased risk of HCC was also found. The rs16759, rs11079850 and rs34414305 had combined the interactive effects on the carcinogenesis of HCC. Moreover, the rs34414305 Del/ATT-Del/Del carriers displayed lower levels of IGF2BP3. Conclusion: The rs16759, rs11079850 and rs34414305 may singly and interactively contribute to carcinogenesis of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Circular single-stranded DNA (c-ssDNA) has significant applications in DNA detection, the development of nucleic acid medicine, and DNA nanotechnology because it shows highly unique features in mobility, dynamics, and topology. However, in most cases, the efficiency of c-ssDNA preparation is very low because polymeric byproducts are easily formed due to intermolecular reaction. Herein, we report a one-pot ligation method to efficiently prepare large c-ssDNA. By ligating several short fragments of linear single-stranded DNA (l-ssDNA) in one-pot by using T4 DNA ligase, longer l-ssDNAs intermediates are formed and then rapidly consumed by the cyclization. Since the intramolecular cyclization reaction is much faster than intermolecular polymerization, the formation of polymeric products is suppressed and the dominance of intramolecular cyclization is promoted. With this simple approach, large-sized single-stranded c-ssDNAs (e.g., 200-nt) were successfully synthesized in high selectivity and yield.
RESUMO
With the aim of exploring and modulating the interfacial charge kinetics, a ternary g-C3N4/Ag/BiVO4 was constructed with excellent photocatalytic performance and preferable stability toward H2 evolution in absence of cocatalyst. Both density functional theory (DFT) and experimental results implied that the type II g-C3N4/BiVO4 composite can be switched to Z-scheme via Ag nanoparticles as the electron shuttle. The optimal photocatalytic H2 yield rate achieved for g-C3N4/Ag/BiVO4 was 57.4⯵mol·g-1·h-1, being far surpassed the H2 harvest rate of g-C3N4/BiVO4, Ag/g-C3N4 and g-C3N4, which is 2.9, 14.8 and 1.7⯵mol·g-1·h-1, respectively. The apparent quantum efficiency of g-C3N4/Ag/BiVO4 photocatalyst was also determined to be 1.23%. Besides, the photocatalytic performance of g-C3N4/Ag/BiVO4 well preserved over 5 runs in 50â¯h. The improved H2 production performance is considered as the consequence of promoted segregation of photoexcited charge carriers and SPR effects of Ag nanoparticles. In combination with photocurrent measurement, examination of active species and DFT calculation, it is found that Ag nanoparticles as an electron mediator can highly promote the Z-scheme carrier migration that electrons come from conduction band of BiVO4 will quickly assemble with the photo-induced holes from valence band of g-C3N4, leaving electrons in the conduction band of g-C3N4 and holes in valence band of BiVO4 that could greatly enhance the charge separation efficiency.