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BACKGROUND: Atherosclerosis is a chronic inflammatory disease, in which macrophages determine the progression of atherosclerotic plaques. However, no studies have investigated how METTL3 (methyltransferase like 3) in macrophages affects atherosclerotic plaque formation in vivo. Additionally, whether Braf mRNA is modified by METTL3-dependent N6-methyladenosine (m6A) methylation remains unknown. METHODS: We analyzed single-cell sequencing data of atherosclerotic plaques in mice fed with a high fat diet for different periods. Mettl3fl/fl Lyz2cre Apoe-/- mice and littermate control Mettl3fl/fl Apoe-/- mice were generated and fed high fat diet for 14 weeks. In vitro, we stimulated peritoneal macrophages with ox-LDL (oxidized low-density lipoprotein) and tested the mRNA and protein expression levels of inflammatory factors and molecules regulating ERK (extracellular signal-regulated kinase) phosphorylation. To find METTL3 targets in macrophages, we performed m6A-methylated RNA immunoprecipitation sequencing and m6A-methylated RNA immunoprecipitation-qPCR. Further, point mutation experiments were used to explore m6A-methylated adenine. Using RNA immunoprecipitation assay, we explored m6A methylation-writing protein bound to Braf mRNA. RESULTS: In vivo, METTL3 expression in macrophages increased with the progression of atherosclerosis. Myeloid cell-specific METTL3 deletion negatively regulated atherosclerosis progression and the inflammatory response. In vitro, METTL3 knockdown or knockout in macrophages attenuated ox-LDL-mediated ERK phosphorylation rather than JNK (c-Jun N-terminal kinase) and p38 phosphorylation and reduced the level of inflammatory factors by affecting BRAF protein expression. The negative regulation of inflammation response caused by METTL3 knockout was rescued by overexpression of BRAF. In mechanism, METTL3 targeted adenine (39725126 in chromosome 6) on the Braf mRNA. Then, YTHDF1 could bind to m6A-methylated Braf mRNA and promoted its translation. CONCLUSIONS: Myeloid cell-specific Mettl3 deficiency suppressed hyperlipidemia-induced atherosclerotic plaque formation and attenuated atherosclerotic inflammation. We identified Braf mRNA as a novel target of METTL3 in the activation of the ox-LDL-induced ERK pathway and inflammatory response in macrophages. METTL3 may represent a potential target for the treatment of atherosclerosis.
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Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Placa Aterosclerótica/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Macrófagos/metabolismo , Inflamação/genética , Inflamação/prevenção & controle , Inflamação/metabolismo , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Apolipoproteínas E/metabolismoRESUMO
PURPOSE: In the contemporary workplace, enduring fatigue has become a standard for employees. This investigation assesses whether such working conditions exacerbate the depletion of employees' personal resources. The need for recovery serves as an indicator of the necessity to mitigate post-work fatigue. A high need for recovery signifies that employees must commence a new workday while already fatigued. METHODS: This research recruited two cohorts of nurses, categorized by a high need for recovery and a low need for recovery, to examine the correlation between work effort and hair cortisol concentrations in each group. RESULTS: Hair cortisol concentrations serve as a biological marker of cumulative cortisol secretion over a specific time frame, reflecting overall personal resource expenditure during this interval. Findings revealed a notable positive correlation between intrinsic work effort (over-commitment) and hair cortisol levels exclusively among nurses with a high need for recovery. CONCLUSION: These outcomes imply that active effort amidst fatigue may lead to excessive strain. This insight enriches the classic 'effort-recovery' model by illustrating how an employee' s personal volition can influence the accumulation of fatigue.
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The objective of this experiment was to evaluate the influence of nanoselenium (NANO-Se) addition on milk production, milk fatty acid synthesis, the development and metabolism regulation of mammary gland in dairy cows. Forty-eight Holstein dairy cows averaging 720 ± 16.8 kg of body weight, 66.9 ± 3.84 d in milk (dry matter intake [DIM]) and 35.2 ± 1.66 kg/d of milk production were divided into four treatments blocked by DIM and milk yields. Treatments were control group, low-Se (LSe), medium-Se (MSe) and high-Se (HSe) with 0, 0.1, 0.2 and 0.3 mg Se, respectively, from NANO-Se per kg dietary dry matter (DM). Production of energy- and fat-corrected milk (FCM) and milk fat quadratically increased (p < 0.05), while milk lactose yields linearly increased (p < 0.05) with increasing NANO-Se addition. The proportion of saturated fatty acids (SFAs) linearly decreased (p < 0.05), while proportions of monounsaturated fatty acids (MUFAs) linearly increased and polyunsaturated fatty acids (PUFAs) quadratically increased. The digestibility of dietary DM, organic matter (OM), crude protein (CP), neutral detergent fiber (NDF) and acid detergent fiber (ADF) quadratically increased (p < 0.05). Ruminal pH quadratically decreased (p < 0.01), while total VFA linearly increased (p < 0.05) with increasing NANO-Se addition. The acetic to propionic ratio decreased (p < 0.05) linearly due to the unaltered acetic molar percentage and a quadratical increase in propionic molar percentage. The activity of CMCase, xylanase, cellobiase and pectinase increased linearly (p < 0.05) following NANO-Se addition. The activity of α-amylase increased linearly (p < 0.01) with an increase in NANO-Se dosage. Blood glucose, total protein, estradiol, prolactin, IGF-1 and Se linearly increased (p < 0.05), while urea nitrogen concentration quadratically decreased (p = 0.04). Moreover, the addition of Se at 0.3 mg/kg from NANO-Se promoted (p < 0.05) mRNA and protein expression of PPARγ, SREBP1, ACACA, FASN, SCD, CCNA2, CCND1, PCNA, Bcl-2 and the ratios of p-ACACA/ACACA and BCL2/BAX4, but decreased (p < 0.05) mRNA and protein expressions of Bax, Caspase-3 and Caspase-9. The results suggest that milk production and milk fat synthesis increased by NANO-Se addition by stimulating rumen fermentation, nutrients digestion, gene and protein expressions concerned with milk fat synthesis and mammary gland development.
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Detergentes , Lactação , Feminino , Bovinos , Animais , Lactação/fisiologia , Detergentes/metabolismo , Detergentes/farmacologia , Digestão/fisiologia , Leite/metabolismo , Dieta/veterinária , Nutrientes , Suplementos Nutricionais , RNA Mensageiro/metabolismo , Rúmen/metabolismo , Ração Animal/análiseRESUMO
AIMS: Glioma patients are at high risk for postoperative delirium (POD), yet studies focusing on this population in general neurosurgical ward settings are limited. This paper investigates the incidence of POD and related risk factors in glioma patients hospitalized in general wards. DESIGN: Prospective observational study. METHODS: This prospective study included 133 adult glioma patients hospitalized in the general neurosurgery ward. In addition to collecting routine perioperative general clinical data, patients' psychological status was assessed preoperatively using the Hospital Anxiety and Depression Scale (HADS). POD was assessed within 3 days postoperatively using the Confusion of Consciousness Assessment method, twice daily. The incidence of POD was calculated, and risk factors were identified using logistic regression analysis. RESULTS: The incidence of POD in glioma patients admitted to the general ward was 31.6% (40/133). Multivariate regression revealed advanced age (age > 50 years), frontal lobe tumour, presence of preoperative anxiety or depression, retention of a luminal drain, postoperative pain, indwelling catheter these six factors were independent risk factors for the development of delirium in patients after surgery. CONCLUSION: In general ward settings, supratentorial glioma patients exhibit a high risk of POD. Critical risk factors include preoperative psychological conditions, as well as postoperative pain, drainage and catheterization. Rigorous preoperative evaluations, effective pain management strategies and the integration of humanistic care principles are essential in mitigating the risk of POD for glioma patients. RELEVANCE TO CLINICAL PRACTICE: In general ward settings, this study reveals the high occurrence of POD in glioma patients and identifies preoperative psychological states, age, tumour location and several postoperative factors as significant risk factors for POD, which provides a framework for targeted interventions. By integrating these insights into clinical practice, healthcare teams can better identify glioma patients at risk for POD and implement preventive measures, thereby enhancing recovery and overall care quality for glioma patients in general neurosurgical wards. REPORTING METHOD: This study adheres to the STROBE guidelines, ensuring a transparent and comprehensive reporting of the observational research methodology and results. PATIENT OR PUBLIC CONTRIBUTION: Patients involvement was limited to the provision of data through their participation in the study's assessments and the collection of clinical information. The study did not involve a direct patient or public contribution in the design, conduct, analysis, or interpretation of the data, nor in the preparation of the manuscript.
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Delírio , Glioma , Complicações Pós-Operatórias , Humanos , Estudos Prospectivos , Fatores de Risco , Feminino , Glioma/cirurgia , Glioma/psicologia , Masculino , Pessoa de Meia-Idade , Incidência , Delírio/epidemiologia , Delírio/etiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Adulto , Estudos de Coortes , Neoplasias Encefálicas/cirurgiaRESUMO
Biotin (BI) and cobalamin (CA) are essential for rumen propionate production and hepatic gluconeogenesis. The study evaluated the influence of BI or/and coated CA (CCA) on milk performance and nutrient digestion in cows. Sixty Holstein dairy cows were assigned in a 2 × 2 factorial arrangement and randomised block design to four groups. The factors were BI at 0 or 20 mg/day and CCA at 0 or 9 mg CA/day. Dry matter intake increased with BI addition but was unchanged with CCA supply. Addition of BI or CCA increased fat-corrected milk, milk fat and milk protein yields and feed efficiency. Moreover, lactose yield was increased by CCA addition. Dry matter, organic matter, crude protein and acid detergent fibre total-tract digestibility increased for BI or CCA supply. When CCA was supplemented, positive response of neutral detergent fibre digestibility to BI addition was enhanced. Supplementing BI did not affect pH, propionate content and acetate to propionate ratio, but increased total volatile fatty acids (VFA) and acetate contents. Supplementing CCA decreased pH and acetate to propionate ratio, but increased total VFA, acetate and propionate contents. Rumen protease and carboxymethyl-cellulase activities and fungi, bacteria and Butyrivibrio fibrisolvens numbers increased for BI or CCA supply. In addition, protozoa increased for BI addition, and protease activity and Prevotella ruminicola increased for CCA supply. When CCA was supplemented, positive responses of R. albus and Ruminobacter amylophilus numbers to BI addition were enhanced. Blood glucose concentration was unchanged with BI supply, but increased for CCA supply. Blood nonesterified fatty acids and ß-hydroxybutyrate contents reduced with BI or CCA supply. Supplementation with BI or CCA increased blood BI or CA content. The results showed that supplementing BI or/and CCA improved lactation performance and nutrient digestion, and CCA supply did not enhance the lactation performance response to BI supply.
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Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Biotina , Dieta , Digestão , Fermentação , Lactação , Rúmen , Vitamina B 12 , Animais , Bovinos/fisiologia , Feminino , Ração Animal/análise , Biotina/administração & dosagem , Biotina/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Digestão/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Lactação/efeitos dos fármacos , Lactação/fisiologia , Leite/química , Rúmen/efeitos dos fármacos , Rúmen/fisiologia , Vitamina B 12/farmacologia , Vitamina B 12/administração & dosagemRESUMO
The experiment investigated the impacts of FA on the proliferation of bovine mammary gland epithelial cells (BMECs) and to investigate the underlying mechanisms. Supplementation of 10 µM FA elevated the mRNA expression of proliferating cell nuclear antigen (PCNA), cyclin A2 and cyclin D1, and protein expression of PCNA and Cyclin A1. The mRNA and protein expression of B-cell lymphoma-2 (BCL2) and the BCL2 to BCL2 associated X 4 (BAX4) ratio elevated, while that of BAX, Caspase-3 and Caspase-9 reduced by FA. Both Akt and mTOR signaling pathways were activated by FA. Moreover, the stimulation of BMECs proliferation, the alteration of proliferative genes and protein expression, the change of apoptotic genes and protein expression, and the activation of mTOR signaling pathway caused by FA were obstructed by Akt inhibitor. Suppression of mTOR with Rapamycin reversed the FA-modulated promotion of BMECs proliferation and change of proliferous genes and protein expression, with no impact on mRNA or proteins expression related to apoptosis and FA-activated Akt signaling pathway. Supplementation of rumen-protected FA in cow diets evaluated milk yields and serum insulin-like growth factor-1 and estradiol levels. The results implied that the proliferation of BMECs was stimulated by FA through the Akt-mTOR signaling pathway.
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Glândulas Mamárias Animais , Proteínas Proto-Oncogênicas c-akt , Feminino , Bovinos , Animais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Glândulas Mamárias Animais/metabolismo , Serina-Treonina Quinases TOR/genética , Dieta/veterinária , Leite/metabolismo , Células Epiteliais/metabolismo , RNA Mensageiro/genética , Lactação/genética , Suplementos Nutricionais , Ácido Fólico/farmacologia , Ácido Fólico/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologiaRESUMO
Cell death-inducing DFFA-like effector C (CIDEC) is responsible for metabolic disturbance and insulin resistance, which are considered to be important triggers in the development of diabetic cardiomyopathy (DCM). To investigate whether CIDEC plays a critical role in DCM, DCM rat model was induced by a high-fat diet and a single injection of low-dose streptozotocin (27.5 mg/kg). DCM rats showed severe metabolic disturbance, insulin resistance, myocardial hypertrophy, interstitial fibrosis, ectopic lipid deposition, inflammation and cardiac dysfunction, accompanied by CIDEC elevation. With CIDEC gene silencing, the above pathophysiological characteristics were significantly ameliorated accompanied by significant improvements in cardiac function in DCM rats. Enhanced AMP-activated protein kinase (AMPK) α activation was involved in the underlying pathophysiological molecular mechanisms. To further explore the underlying mechanisms that CIDEC facilitated collagen syntheses in vitro, insulin-resistant cardiac fibroblast (CF) model was induced by high glucose (15.5 mmol/L) and high insulin (104 µU/mL). We observed that insulin-resistant stimulation dramatically raised CIDEC expression and promoted CIDEC nuclear translocation in CFs. Meanwhile, AMPKα2 was observed to distribute almost completely inside CF nucleus. The results further proved that CIDEC biochemically interacted and co-localized with AMPKα2 rather than AMPKα1 in CF nucleus, which provided a novel mechanism of CIDEC in promoting collagen syntheses. This study suggested that CIDEC gene silencing alleviates DCM via AMPKα signaling both in vivo and in vitro, implicating CIDEC may be a promising target for treatment of human DCM.
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Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Regulação da Expressão Gênica , Inativação Gênica , Proteínas/antagonistas & inibidores , Animais , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Resistência à Insulina , Masculino , Fosforilação , Proteínas/genética , Proteínas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The deposition and spreading of pesticide droplets on the surface of plants is a severe challenge to precise pesticide application, which directly affects the pesticide utilization rate and efficacy. Cotton harvest aids are widely used in machine-picked cotton but the effect of formulation and concentration on the droplet behavior and defoliation effect of cotton defoliants is not clear. To clarify the influence of formulation and concentration on the droplet behavior of cotton defoliants, four formulations (suspension concentrate (SC), water dispersible granule (WG), oil dispersion (OD), and wettable powder (WP)) of cotton defoliants were used to prepare different concentrations of harvest aid solutions, according to the spraying volume. The physicochemical properties, droplet impact, and spreading and deposition behavior were studied. The results indicated that the four kinds of harvest aids have good physicochemical properties and can be wet and spread on cotton leaves. The surface tension of the high-concentration harvest aid solution (the spraying volume was less than 1.2 L/667 m2) was increased, which increased the contact angle and reduced the adhesion tension, adhesion work, and the spreading area. Once the harvest aid solution systems impacted the cotton leaves, it could spread to the maximum in a short time (10 ms). The field experiment showed that the droplet spectrum of harvest aids changed slightly, the coefficient of variation (CV) did not exceed 50%, and the defoliation rate was better when the spraying volume was 1.5 L/667 m2. The correlation and principal component analysis showed that the spraying volume (concentration) and coverage were negatively correlated with the defoliation rate, while the viscosity, diffusion factor, and spreading rate were positively correlated with the defoliation rate. Overall, the use of appropriate spraying volume application in cotton fields can improve the performance of spray, increase the effective deposition and wetting spread of defoliants on cotton leaves, further reduce the dosage of defoliants, and improve pesticide utilization. These results can provide a theoretical basis for the scientific preparation and spraying of cotton harvest aid solutions.
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Praguicidas , Praguicidas/análise , Praguicidas/química , Folhas de Planta/química , Pós , Água , MolhabilidadeRESUMO
Coal burst prediction is an important research hotspot in coal mine production safety. This paper presents FDNet, which is a knowledge and data fusion-driven deep neural network for coal burst prediction. The main idea of FDNet is to extract explicit features based on the existing mine seismic physical model and utilize deep learning to automatically extract the implicit features of mine microseismic data. The key innovations of FDNet include an expert knowledge indicator selection method based on a subset search strategy, a mine microseismic data extraction method based on a deep convolutional neural network, and a feature deep fusion method of mine microseismic data based on an attention mechanism. We conducted a set of engineering experiments in Gaojiapu Coal Mine to evaluate the performance of FDNet. The results show that compared with the state-of-the-art data-driven machines and knowledge-driven methods, the prediction accuracy of FDNet is improved by 5% and 16%, respectively.
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Carvão Mineral , Redes Neurais de ComputaçãoRESUMO
As a tyrosine phosphatase, Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) serves as an inhibitor in PI3K-Akt pathway. In mammals, SHP2 can phosphorylate GSK3ß at Y216 site to control the expression of IFN. So far, the multiple functions of SHP2 have been reported in mammals. However, little is known about fish SHP2. In this study, we cloned and identified a grass carp (Ctenopharyngodon idellus) SHP2 gene (CiSHP2, MT373151). SHP2 is conserved among different vertebrates by amino acid sequences alignment and the phylogenetic tree analysis. CiSHP2 shared the closest homology with Danio rerio SHP2. Simultaneously, SHP2 was also tested in grass carp tissues and CIK (C. idellus kidney) cells. We found that it responded to poly I:C stimulation. CiSHP2 was located in the cytoplasm just as the same as those of mammals. Interestingly, it inhibited the phosphorylation level of GSK3ß in a non-contact manner. Meanwhile CiGSK3ß interacted with and directly phosphorylated CiTBK1. In addition, we found that CiSHP2 also reduced the phosphorylation level of CiTBK1 by CiGSK3ß, and then it depressed the expression of IFN I via GSK3ß-TBK1 axis. These results suggested that CiSHP2 was involved in CiGSK3ß and CiTBK1 activity but not regulated their transcriptional level. At the same time, we also found that CiSHP2 also influenced the activity of CiIRF3. Therefore, fish SHP2 inhibited IFN I expression through blocking GSK3ß-TBK1 signal axis.
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Carpas/imunologia , Proteínas de Peixes/imunologia , Glicogênio Sintase Quinase 3 beta/imunologia , Interferon Tipo I/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/imunologia , Sequência de Aminoácidos , Animais , Carpas/genética , Linhagem Celular , Proteínas de Peixes/genética , Fosforilação , Filogenia , Poli I-C/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genéticaRESUMO
BACKGROUND: To investigate the clinical characteristics and manifestations of older patients with coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, 566 patients with confirmed COVID-19 were enrolled and the clinical characteristics, laboratory findings, complications and outcome data were collected and analyzed. RESULTS: Among the 566 patients (median age, 61.5 years) with COVID-19, 267 (47.2%) patients were male and 307 (54.2%) were elderly. Compared with younger patients, older patients had more underlying comorbidities and laboratory abnormalities. A higher rate of acute respiratory distress syndrome (ARDS), acute cardiac injury and heart failure was observed in the older group as compared with younger and middle-aged groups, particularly those oldest-old patients had more multi-organ damage. Older patients with COVID-19 were more likely to suffer from acute cardiac injury in cases with preexistenting cardiovascular diseases, while there was no difference among the three groups when patients had no history of cardiovascular diseases. Older patients presented more severe with the mortality of 18.6%, which was higher than that in younger and middle-aged patients (P < 0.05). Multivariable analysis showed that age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were associated with death in older patients, while glucocorticoids might be harmful. CONCLUSIONS: Older patients, especially the oldest-old patients were more likely to exhibit significant systemic inflammation, pulmonary and extrapulmonary organ damage and a higher mortality. Advanced age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were independent predictors of death in older patients with COVID-19 and glucocorticoids should be carefully administered in older patients.
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Betacoronavirus , Infecções por Coronavirus/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico , Adulto , Idoso , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2 , Taxa de Sobrevida/tendênciasRESUMO
Ginsenoside Rd (GS-Rd), isolated from the Chinese traditional herbal medicine Panax ginseng, is used for the treatment of cardiovascular diseases, inflammation, different body pains, and trauma. Caspase-3 and Caspase-9 belong to cysteine aspartic acid specific protease (Caspase) family that plays an important role in apoptosis progression of cancers. In the present study, we investigated the anti-tumor effect of GS-Rd by MTT assay, colony formation assessment, flow cytometry, and Western blotting. Our results revealed that ginsenoside Rd significantly inhibits human gastric cancer (GC) growth and cell proliferation. Flow cytometer analysis showed that the GS-Rd could significantly induce apoptosis and arrest the G0/G1 phase in GC cells. Further, GS-Rd was found to increase the ratio of Bax/Bcl-2 and the expression of Caspase-3 and Caspase-9, respectively, and to decrease the expression of Cyclin D1. Taken together, our study suggests that GS-Rd significantly inhibits GC cell proliferation, induces cell apoptosis through increase the expression of Caspase-3, Caspase-9, and the ratio of Bax/Bcl-2. GS-Rd also induces cell cycle arrest at G0/G1 phase by down-regulation Cyclin D1. Thus, GS-Rd could serve as a lead to develop novel therapeutic agents to against human gastric cancer.
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Antineoplásicos Fitogênicos/uso terapêutico , Caspase 3/genética , Caspase 9/genética , Ginsenosídeos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Caspase 3/biossíntese , Caspase 9/biossíntese , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismoRESUMO
Senescence-associated secretory phenotype (SASP) plays a role in aging adipose tissue dysfunction by directly promoting chronic inflammation. The JNK/p53 pathway was reported as a potential mechanism that mediates SASP. In this study, we investigated the effects of L-carnitine, an inhibitor of the JNK/p53 pathway in adipose tissue SASP and dysfunction. Young and aging rat were given L-carnitine by gavage. Next, we detected the senescence, cytokines expression, chronic inflammation and insulin resistance of adipose tissue. Additionally, JNK/p53 pathway was estimated. Our results show a significant increase expression of SASP components in the adipose tissue of aging rats compared to young rats. Further, we found that infiltration of immune cells and the expression of pro-inflammatory cytokines were enhanced in aging adipose tissue while insulin signaling activity was reduced in aging adipose tissue. Interestingly, L-carnitine markedly reduced the expression of SASP factors. L-Carnitine could significantly reduce chronic inflammation, improving insulin resistance. Further, L-carnitine inhibited SASP by inhibiting JNK/p53 pathway. L-Carnitine inhibited SASP by JNK/p53 pathway and attenuated adipose tissue dysfunction of aging.
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Tecido Adiposo/metabolismo , Envelhecimento/fisiologia , Carnitina , Senescência Celular , Animais , Carnitina/metabolismo , Carnitina/farmacologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in several types of tumors including cervical cancer. Arginine methyltransferase inhibitor 1 (AMI-1) inhibits solid tumors by targeting PRMT5. However, the effect of AMI-1 on cervical cancer is still unknown. In this study, we provided the first evidence that AMI-1 reduced cervical cancer cell proliferation, colony formation and promoted cell apoptosis in vitro. Suppression of tumorigenicity was also confirmed in vivo. Mechanistic studies revealed that AMI-1 significantly reduced PRMT5 level in cells and mice xenografts model of cervical cancer. These results suggest that AMI-1 inhibits cervical cancer by type II PRMT5.
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Antineoplásicos/farmacologia , Naftalenossulfonatos/farmacologia , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Ureia/análogos & derivados , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fator de Iniciação 4E em Eucariotos/metabolismo , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína-Arginina N-Metiltransferases/metabolismo , Ureia/farmacologia , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A novel haloalkalitolerant, rod-shaped bacterium, designated strain YIM 4-4T, was isolated from the surface water of the Dugerno lake, a haloalkaline lake in Inner Mongolia. The taxonomy of strain YIM 4-4T was investigated by a polyphasic approach. Strain YIM 4-4T was Gram-stain-negative, strictly aerobic, non-motile and formed red colonies. Optimal growth conditions were 28 °C, pH 8.0-11.0 and 0.5-2 % NaCl. The major respiratory quinone was menaquinone-7 (MK-7). The polar lipid profile was composed predominantly of phosphatidylethanolamine, six unidentified polar lipids, one phospholipid and one aminolipid. The predominant cellular fatty acids (>5 %) were iso-C15 : 0, iso-C17 : 1I/anteiso-C17 : 1B, iso-C16 : 1G, iso-C17 : 0 3-OH, C16 : 1ω7c/C16 : 1ω6c and iso-C16 : 1. The genomic DNA G+C content was 43.0âmol%. 16S rRNA gene sequence analysis indicated that the members of the genera Cecembia, Fontibacter, Aquiflexum and Indibacter of the family Cyclobacteriaceae (phylum Bacteroidetes) were the most closely related, with 16S rRNA gene sequence similarities ranging from 93.6 to 94.2 %. Other members of the family Cyclobacteriaceae showed sequence similarities < 93.0 %. On the basis of phenotypic, chemotaxonomic and phylogenetic properties, strain YIM 4-4T represents a novel species of a new genus, for which the name Mongoliibacter ruber gen. nov., sp. nov. is proposed. The type strain is YIM 4-4T ( = CCTCC AB 2012966T = DSM 27929T).
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OBJECTIVES: The purpose of this study was to explore whether work strain (i.e., job demands and job control) and subjective need for recovery (NFR) after work are related to measured concentration of cumulative cortisol. METHODS: Participants were 43 teachers recruited from kindergarten. They self-reported their NFR, job demands and job control over the last month. NFR was measured with the NFR scale. Job demands and control were assessed with the Chinese version of the Job Content Questionnaire. Hair cortisol was used to represent cumulative cortisol excretion. Hair cortisol concentration (HCC) was measured with high-performance liquid chromatography-tandem mass spectrometry. RESULTS: No significant correlations were found between job demands or job control and HCC. NFR was significantly and inversely correlated with HCC (r = -0.41, p = 0.006). The inverse association between NFR and HCC remained significant when age and job demands and job control were controlled for (p = 0.02). CONCLUSIONS: The activity of the hypothalamic-pituitary-adrenal axis declines with the accumulation of NFR after working time.
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Docentes , Hidrocortisona/metabolismo , Doenças Profissionais/psicologia , Descanso/psicologia , Estresse Psicológico/fisiopatologia , Adulto , China , Feminino , Cabelo/química , Humanos , Pessoa de Meia-Idade , Doenças Profissionais/fisiopatologia , Autorrelato , Estresse Psicológico/metabolismo , Carga de Trabalho/psicologia , Local de Trabalho/psicologia , Adulto JovemRESUMO
BACKGROUND: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. MATERIAL AND METHODS: Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. RESULTS: By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples. CONCLUSIONS: We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Exoma , HumanosRESUMO
This article focuses on investigating the stability issue for recurrent neural networks (RNNs) with interval time-varying delays (TVDs) based on a flexible delay-dividing method with parameters, which are related to the delay derivative. First, an interval of delay is separated into parametric subintervals via the linear combination technique. Then, an establishment of Lyapunov-Krasovskii functional (LKF) is connected to the parameters, and a novel linear technology is suggested to dispose of integral terms in the derivatives of the constructed function. Finally, the validity and advantage of the inferred criteria are interpreted by the comparison of representative simulation examples.
RESUMO
Hydraulic fracturing technology is an effective way to develop tight sandstone reservoirs with low porosity and permeability. The tight sandstone reservoir is heterogeneous and the heterogeneity characteristics has an important influence on fracture propagation. To investigate hydraulic fracture performance in heterogeneous tight reservoir, the X-ray diffraction experiments are carried out, the Weibull distribution method and finite element method are applied to establish the uniaxial compression model and the hydraulic fracture propagation model of heterogeneous tight sandstone. Meanwhile, the sensitivity of different heterogeneity characterization factors and the multi-fracture propagation mechanism during hydraulic fracture propagation is analyzed. The results indicate that the pressure transfer in the heterogeneous reservoir is non-uniform, showing a multi-point initiation fracture mode. For different heterogeneity characterization factors, the heterogeneity characteristics based on elastic modulus are the most sensitive. The multi-fracture propagation of heterogeneous tight sandstone reservoir is different from that of homogeneous reservoir, the fracture propagation morphology is more complex. With the increase of stress difference, the fracture propagation length increases. With the increase of injection rate, the fracture propagation length increases. With the increase of cluster spacing, the propagation length of multiple fractures tends to propagate evenly. This study clarifies the influence of heterogeneity on fracture propagation and provides some guidance for fracturing optimization of tight sandstone reservoirs.
Assuntos
Fraturamento Hidráulico , Porosidade , Análise de Elementos Finitos , Modelos Teóricos , Difração de Raios X , PressãoRESUMO
Over the years, thrips have transitioned from a minor nuisance to a major problem, significantly impacting the yield and quality of cotton. Unmanned aerial vehicles (UAVs) for plant protection have emerged as an effective alternative to traditional pesticide spraying equipment. UAVs offer advantages such as avoiding crop damage and enhancing pesticide deposition on the plants and have become the primary choice for pesticide application in cotton fields. In this study, a 2-year field experiment found that the thrips population in a cotton field in Xinjiang, China, exhibited gradual growth during the early flowering phase, peaking in late July. The thrips population gradually shifted from the lower canopy to the upper canopy as the cotton flowers opened layer by layer. From 09:00 to 11:00 (GMT+8) and 19:00 to 21:00 (GMT+8), thrips mainly flew outside the flowers, while from 17:00 to 19:00 (GMT+8), they mostly inhabited the inner whorls of flowers. The insecticides 10% cyantraniliprole oil dispersion and 10% spinetoram suspension concentrate, sprayed by UAV, had the best control effect on thrips, with 80.51% and 79.22% control effect after 7 days of spraying, respectively. The optimal spraying time for 10% cyantraniliprole oil dispersion was 19:00 (GMT+8), and the control effect on thrips reached 91.16% at 7 days of spraying. During the cotton flowering period, thrips inhabited flowers in the evening and flew outside during the day. The best control effect on thrips was achieved with UAV-sprayed 10% cyantraniliprole oil dispersion at 19:00 (GMT+8).