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The noradrenaline transporter has a pivotal role in regulating neurotransmitter balance and is crucial for normal physiology and neurobiology1. Dysfunction of noradrenaline transporter has been implicated in numerous neuropsychiatric diseases, including depression and attention deficit hyperactivity disorder2. Here we report cryo-electron microscopy structures of noradrenaline transporter in apo and substrate-bound forms, and as complexes with six antidepressants. The structures reveal a noradrenaline transporter dimer interface that is mediated predominantly by cholesterol and lipid molecules. The substrate noradrenaline binds deep in the central binding pocket, and its amine group interacts with a conserved aspartate residue. Our structures also provide insight into antidepressant recognition and monoamine transporter selectivity. Together, these findings advance our understanding of noradrenaline transporter regulation and inhibition, and provide templates for designing improved antidepressants to treat neuropsychiatric disorders.
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Antidepressivos , Microscopia Crioeletrônica , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Norepinefrina , Multimerização Proteica , Humanos , Antidepressivos/química , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Apoproteínas/química , Apoproteínas/metabolismo , Apoproteínas/ultraestrutura , Ácido Aspártico/química , Ácido Aspártico/metabolismo , Sítios de Ligação , Colesterol/metabolismo , Colesterol/química , Modelos Moleculares , Norepinefrina/metabolismo , Norepinefrina/química , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/química , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/ultraestrutura , Ligação Proteica , Especificidade por SubstratoRESUMO
Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.
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DNA Glicosilases , Cardiomiopatias Diabéticas , Resistência à Insulina , Animais , DNA Glicosilases/metabolismo , DNA Glicosilases/genética , DNA Glicosilases/deficiência , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Camundongos , Masculino , PPAR gama/metabolismo , Glucose/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Modelos Animais de Doenças , Glicólise , Humanos , Camundongos Endogâmicos C57BLRESUMO
Fringe projection profilometry (FPP) faces significant challenges regarding calibration difficulty and stitching error accumulation when operating across scenes ranging from tens to hundreds of meters. This Letter presents a calibration-free 3D measurement method by integrating a binocular vision of a FPP scanner with a wide field-of-view (FoV) vision that constructs global benchmarks to unify local 3D scanning and global 3D stitching, which is adaptable to arbitrarily large-scale scenes. A posterior global optimization model is then established to determine the reconstruction parameters and stitching poses simultaneously at each scanning node with adaptively distributed benchmarks. Consequently, the integrated vision measurement system not only eliminates the large-scale pre-calibration and stitching error accumulation but also overcomes system structural instability during moving measurement. With the proposed method, we achieved 3D measurements with an accuracy of 0.25 mm and a density of 0.5 mm for over 50-m-long scenes.
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We demonstrate the InGaN/GaN-based monolithic micro-pyramid white (MPW) vertical LED (VLED) grown on (-201)-oriented ß-Ga2O3 substrate by selective area growth. The transmission electron microscopy (TEM) reveals an almost defect-free GaN pyramid structure on (10-11) sidewalls, including stacked dual-wavelength multi-quantum wells (MQWs). From the electroluminescence (EL) spectra of the fabricated MPW VLED, a white light emission with a high color rendering index (CRI) of 97.4 is achieved. Furthermore, the simulation shows that the light extraction efficiency (LEE) of the MPW VLED is at least 4 times higher compared with the conventional planar LED. These results show that the MPW VLED grown on ß-Ga2O3 has great potential for highly efficient phosphor-free white light emission.
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BACKGROUND: Early screening and detection of lung cancer is essential for the diagnosis and prognosis of the disease. In this paper, we investigated the feasibility of serum Raman spectroscopy for rapid lung cancer screening. METHODS: Raman spectra were collected from 45 patients with lung cancer, 45 with benign lung lesions, and 45 healthy volunteers. And then the support vector machine (SVM) algorithm was applied to build a diagnostic model for lung cancer. Furthermore, 15 independent individuals were sampled for external validation, including 5 lung cancer patients, 5 benign lung lesion patients, and 5 healthy controls. RESULTS: The diagnostic sensitivity, specificity, and accuracy were 91.67%, 92.22%, 90.56% (lung cancer vs. healthy control), 92.22%,95.56%,93.33% (benign lung lesion vs. healthy) and 80.00%, 83.33%, 80.83% (lung cancer vs. benign lung lesion), repectively. In the independent validation cohort, our model showed that all the samples were classified correctly. CONCLUSION: Therefore, this study demonstrates that the serum Raman spectroscopy analysis technique combined with the SVM algorithm has great potential for the noninvasive detection of lung cancer.
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Neoplasias Pulmonares , Análise Espectral Raman , Máquina de Vetores de Suporte , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Análise Espectral Raman/métodos , Estudos de Casos e Controles , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Detecção Precoce de Câncer/métodos , Adulto , Sensibilidade e Especificidade , Algoritmos , Biomarcadores Tumorais/sangueRESUMO
BACKGROUND: Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship. METHODS: For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes. RESULTS: We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02-2.55, P = 4.07 × 10-2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53-0.89, P = 5.74 × 10-3) and CD19 (OR = 0.59, 95%CI = 1.02-2.55, P = 4.07 × 10-2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01-1.09, P = 1.19 × 10-2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00-1.08, P = 2.83 × 10-2). CONCLUSIONS: Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Análise da Randomização Mendeliana , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias Renais/genética , Estudo de Associação Genômica AmplaRESUMO
The retinopathy of prematurity (ROP) can cause serious clinical consequences and, fortunately, it is remediable while the time window for treatment is relatively narrow. Therefore, it is urgent to screen all premature infants and diagnose ROP degree timely, which has become a large workload for pediatric ophthalmologists. We developed a retinal image-free procedure using small amount of blood samples based on the plasma Raman spectrum with the machine learning model to automatically classify ROP cases before medical intervention was performed. Statistical differences in infrared Raman spectra of plasma samples were found among the control, mild (ZIIIS1), moderate (ZIIIS2 & ZIIS1), and advanced (ZIIS2) ROP groups. With the different wave points of Raman spectra as the inputs, the outputs of our support vector machine showed that the area under the curves in the receiver operating characteristic (AUC) were 0.763 for the pair comparisons of the control with the mild groups, 0.821 between moderate and advanced groups (ZIIS2), while more than 90% in comparisons of the other four pairs: control vs. moderate (0.981), control vs. advanced (0.963), mild vs. moderate (0.936), and mild vs. advanced (0.953), respectively. Our study could advance principally the ROP diagnosis in two dimensions: the moderate ROPs have been classified remarkably from the mild ones, which leaves more time for the medical treatments, and the procedure of Raman spectrum with a machine learning model based on blood samples can be conveniently promoted to those hospitals lacking of the pediatric ophthalmologists with experience in reading retinal images.
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Retinopatia da Prematuridade , Telemedicina , Recém-Nascido , Lactente , Humanos , Criança , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/terapia , Sensibilidade e Especificidade , Telemedicina/métodos , Algoritmos , Aprendizado de Máquina , Idade GestacionalRESUMO
A cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols with ortho-naphthoquinone methides (o-NQMs), which were in situ-generated from enynones, has been established in the presence of silver/Brønsted acid cocatalysts. In the reaction pathway, the key o-NQM intermediates were formed through Ag(I)-catalyzed cyclization of enynones, while the indole-based carbocation intermediates were generated via Brønsted acid-catalyzed dehydration of 2-indolylmethanols. By this approach, a wide range of seven-membered cyclohepta[b]indoles were synthesized in good yields with high efficiency under mild reaction conditions, which serves as a useful strategy toward constructing indole-fused seven-membered rings. Moreover, the catalytic asymmetric version of this (4 + 3) cycloaddition has been realized under the cooperative catalysis of Ag(I) with chiral phosphoric acid, which offered chiral cyclohepta[b]indole with a good enantioselectivity (75% ee). This work not only represents the first cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols but also provides a good example for o-NQM-involved cycloadditions, which will contribute to the chemistry of 2-indolylmethanols and enrich the research contents of cooperative catalysis.
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This research evaluated the hepatopancreas, intestine, and muscle transcriptome alternation of Macrobrachium rosenbergii, and to confirm the relative glycerophospholipid, cytochrome P450 system, and fatty acid metabolism gene expression in sediments containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) of 60 ng/sediment (g) and 700 ng/sediment (g) for 90 days of culture. Transcriptome analysis revealed that the TCDD sediment affected the hepatopancreatic metabolism of xenobiotics in M. rosenbergii via the cytochrome P450 system, drug metabolism-other enzymes, drug metabolism-cytochrome P450, chemical carcinogenesis, and lysosome function. Intestinal analysis also showed a similar phenomenon, but this finding was not observed in the muscle tissue. qPCR analysis indicated that the expression levels of APTG4, LPGAT1, ACHE, GPX4, ECHS1, ATP5B, FABP, and ACC in the hepatopancreatic and intestinal tissues decreased, but those in the muscle tissues did not. In summary, TCDD sediment induced tissue metabolism, especially in the hepatopancreas and intestine. TCDD sediment mainly affected the digestive enzyme gene expression with concentration. These results indicated that the presence of TCDD in the sediment played a major role in the hepatopancreatic and intestinal metabolism system of M. rosenbergii.
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Palaemonidae , Dibenzodioxinas Policloradas , Animais , Hepatopâncreas/metabolismo , Perfilação da Expressão Gênica , Água Doce , Músculos/metabolismo , Transcriptoma , Intestinos , Sistema Enzimático do Citocromo P-450/metabolismoRESUMO
p-Sulfonatocalix[n]arenes (SCnA) have demonstrated great potential for drug encapsulation through host-guest complexation to improve solubility, stability, and bioavailability. In this study, the solubilization effect of SCnA (n = 4, 6, 8) on 95 active compounds derived from traditional Chinese medicine (TCM) was investigated. Based on the significant solubilization effect on alkaloids, SC6A/SC8A and 76 alkaloids were selected as the host and guest, respectively, to determine the binding constant by competitive fluorescence titration. LASSO regression was adopted to investigate the mechanism of the complex of SCnA with alkaloids. The binding constant of alkaloids-SC6A and alkaloids-SC8A was related to the alkaloid alkalinity. Also, the electronegativity, polarization, first ionization potential, hydrogen bond potential, the molecular size, and shape of alkaloids are critical properties to determine alkaloids-SC6A binding constant as well as electronegativity, polarization, hydrophobicity, and the molecular size and shape of alkaloids play an important role for the alkaloids-SC8A binding constant.
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Alcaloides , Medicina Tradicional Chinesa , Alcaloides/químicaRESUMO
Herein, a visual and luminescent dual-mode (colorimetric and fluorometric) method for the detection of P-phenylenediamine (PPD) in hair dye was successfully established based on cerium-nitrogen co-doped carbon dots (Ce, N-CDs) that displayed remarkable luminescence and peroxidase activity. Ce, N-CDs catalyzed H2O2 to produce superoxide anion, which then oxidized the colorless 3,3,5,5-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB), capable of quenching the fluorescence through fluorescence resonance energy transfer (FRET) between Ce, N-CDs and oxTMB. The reducing properties of PPD could reduce oxTMB back to TMB, leading to a decrease in the absorption intensity of oxTMB and a fluorescence recovery of Ce, N-CDs. As a result, the quantitative detection of PPD could be achieved by measuring the absorption values of oxTMB and the fluorescence signal of Ce, N-CDs. The detection limits for PPD were calculated as 0.36 µM and 0.10 µM for colorimetry and fluorimetry, respectively. Furthermore, smartphone application (ColorPicker) capable of measuring the RGB value of the color was utilized in the detection system, facilitating on-site quantitative detection. This approach effectively shortens the detection time and simplifies the operation, offering a powerful and convenient tool for real-time monitoring of PPD.
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PURPOSE: Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL. METHODS: We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP. RESULTS: There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect. CONCLUSION: This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.
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Paralisia Cerebral , Sistema Glinfático , Leucomalácia Periventricular , Criança , Recém-Nascido , Humanos , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico por imagem , Paralisia Cerebral/patologia , Leucomalácia Periventricular/complicações , Leucomalácia Periventricular/diagnóstico por imagem , Leucomalácia Periventricular/patologia , Sistema Glinfático/patologia , Estudos Retrospectivos , Mãos/patologiaRESUMO
Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: -13.36% [-22.74%, -2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.
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Síndrome Coronariana Aguda , Metais , MicroRNAs , Humanos , Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/genética , MicroRNAs/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Estudos Prospectivos , Incidência , Idoso , Metais/sangue , China/epidemiologia , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/sangue , AdultoRESUMO
BACKGROUND: To examine the safety and efficacy of ZelanteDVT™ catheter rheolytic thrombectomy in the treatment of patients with iliac vein stent thrombosis. METHODS: A retrospective analysis method was conducted by means of collecting the data of 32 patients who had completed the treatment of iliac vein stent thrombosis with ZelanteDVT catheter rheolytic thrombectomy from March 2019 to March 2023. Data on clinical characteristics, technical success, clinical success, complications, and early follow-up were analyzed. RESULTS: The technical success rates were 100%, intraoperatively, in which 22 cases were improved to thrombus clearance Grade II (50-90%), 10 were Grade III (>90%). There were 21 cases treated with subsequent catheter-directed thrombolysis, and the average urokinase administration of (120.90 ± 29.63)∗10Ë4 units. The clinical success rates were 100% and the swelling of the affected limbs were significantly improved, a significant difference in the pre/postoperative between-thigh circumference difference [(5.16 ± 1.08) vs. (1.75 ± 0.84), P < 0.000]. The pre/postoperative Venous Clinical Severity Score was [(12.94 ± 1.70) vs. (7.44 ± 1.31), P < 0.000]. No serious complications occurred during the perioperative period. The postoperative and 12-month stent patency rate was 100.00% (32/32) and 71.88% (23/32), respectively. CONCLUSIONS: The ZelanteDVT catheter rheolytic thrombectomy seems to have a promising application prospect for the treatment of patients with iliac vein stent thrombosis.
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Veia Ilíaca , Stents , Trombectomia , Grau de Desobstrução Vascular , Trombose Venosa , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/fisiopatologia , Veia Ilíaca/cirurgia , Resultado do Tratamento , Trombectomia/efeitos adversos , Trombectomia/instrumentação , Idoso , Trombose Venosa/terapia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/fisiopatologia , Fatores de Tempo , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/efeitos adversos , Adulto , Dispositivos de Acesso Vascular , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Terapia Trombolítica/efeitos adversosRESUMO
Cellular senescence is an important factor leading to pulmonary fibrosis. Deficiency of 8-oxoguanine DNA glycosylase (OGG1) in mice leads to alleviation of bleomycin (BLM)-induced mouse pulmonary fibrosis, and inhibition of the OGG1 enzyme reduces the epithelial mesenchymal transition (EMT) in lung cells. In the present study, we find decreased expression of OGG1 in aged mice and BLM-induced cell senescence. In addition, a decrease in OGG1 expression results in cell senescence, such as increases in the percentage of SA-ß-gal-positive cells, and in the p21 and p-H2AX protein levels in response to BLM in lung cells. Furthermore, OGG1 promotes cell transformation in A549 cells in the presence of BLM. We also find that OGG1 siRNA impedes cell cycle progression and inhibits the levels of telomerase reverse transcriptase (TERT) and LaminB1 in BLM-treated lung cells. The increase in OGG1 expression results in the opposite phenomenon. The mRNA levels of senescence-associated secretory phenotype (SASP) components, including IL-1α, IL-1ß, IL-6, IL-8, CXCL1/CXCL2, and MMP-3, in the absence of OGG1 are obviously increased in A549 cells treated with BLM. Interestingly, we demonstrate that OGG1 binds to p53 to inhibit the activation of p53 and that silencing of p53 reverses the inhibition of OGG1 on senescence in lung cells. Additionally, the augmented cell senescence is shown in vivo in OGG1-deficient mice. Overall, we provide direct evidence in vivo and in vitro that OGG1 plays an important role in protecting tissue cells against aging associated with the p53 pathway.
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DNA Glicosilases , Guanina/análogos & derivados , Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Pulmão/metabolismo , Senescência Celular , DNA Glicosilases/genética , DNA Glicosilases/metabolismoRESUMO
To establish a new method for detecting crystal violet (CV), a harmful dye, herein, a genre of novel biomass carbon dots (CDs) was synthesized via a microwave method and employed as a fluorescent probe, in which water spinach and polyethylene glycol (PEG) performed as raw materials. Based on the inner filter effect (IFE) between the luminescent CDs and CV, the blue emission of this probe at 430 nm could be quenched by CV. Hence, a new strategy was proposed to selectively determine CV in aquaculture ambient. Moreover, under the optimal experiment conditions, this method showed a good linearity between the concentration of CV (c) and fluorescence quenching rate (ΔF/F0) in the concentration range of 4-200 µmol/L with the corresponding correlation coefficient (r) and the detection limit of 0.997 and 710 nmol/L, respectively. With advantages of environmental protectivity, sensitivity, affordability, and user-friendliness, the facilely fabricated CDs could be successfully applied in detecting CV in aquaculture samples, providing a technical foundation for monitoring the pollution of CV and ensuring the quality and safety of aquatic products.
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Biomassa , Carbono , Corantes Fluorescentes , Violeta Genciana , Micro-Ondas , Pontos Quânticos , Violeta Genciana/química , Carbono/química , Pontos Quânticos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Espectrometria de Fluorescência , Fluorescência , Polietilenoglicóis/químicaRESUMO
Ulcerative colitis (UC) is one of the most prevalent inflammatory bowel diseases and poses a serious threat to human health. Currently, safe and effective preventive measures are unavailable. In this study, the protective effects of asiaticoside (AS) on dextran sodium sulfate (DSS)-induced colitis in mice and the underlying molecular mechanism were investigated. In this experiment, colitis was induced in mice with DSS. Subsequently, the role of AS in colitis and its underlying mechanisms were examined using H&E staining, immunofluorescence staining, western blot, Elisa, FMT, and other assays. The results showed that AS significantly attenuated the related symptoms of DSS-induced colitis in mice. In addition, AS inhibited the activation of signaling pathways TLR4/NF-κB and MAPK reduced the release of inflammatory factors, thereby attenuating the inflammatory response in mice. AS administration also restored the permeability of the intestinal barrier by increasing the levels of tight junction-associated proteins (claudin-3, occludin, and ZO-1). In addition, AS rebalanced the intestinal flora of DSS-treated mice by increasing the diversity of the flora. AS can alleviate DSS-induced ulcerative colitis in mice by maintaining the intestinal barrier, thus inhibiting the signaling pathways TLR4/NF-κB and MAPK activation, reducing the release of inflammatory factors, and regulating intestinal microecology.
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Colite Ulcerativa , Colite , Triterpenos , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , NF-kappa B , Receptor 4 Toll-Like , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , ColoRESUMO
PURPOSE: Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). MATERIALS AND METHODS: The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. RESULTS: The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. CONCLUSION: This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.
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Cânula , Traqueostomia , Humanos , Contagem de Colônia Microbiana , Estudos Cross-Over , Detergentes , ÁguaRESUMO
BACKGROUND: Emerging evidence suggests that the long head of the biceps (LHBT) may play a role in stabilizing the glenohumeral joint, and this has led to controversy around the efficacy of biceps tenotomy for superior labral anterior and posterior (SLAP) lesions. Therefore, the aim of this finite element analysis (FEA) study was to determine the stress absorption and humeral head translation restriction effects of the LHBT within the glenohumeral joint during the late cocking and deceleration phases of overhead throwing with a view to resolving the controversy around tenotomy. METHODS: Eight FEA models were created using computed tomography and magnetic resonance imaging data from normal glenohumeral joints. The models represented four LHBT conditions: uninjured, subpectoral tenodesis, tenotomy, and type II SLAP lesions. The late cocking and deceleration phases of the overhead throwing were simulated for each model. The impacts of the four LHBT conditions on glenohumeral joint stress absorption and humeral head displacement restriction were studied based on 1) stress and related distributions on the cartilage, labrum, capsule, and LHBT and 2) humeral head translation variation. RESULTS: The FEA analysis showed that the magnitude of the contact stress on the articular cartilage, labrum, and capsule was the lowest in the uninjured models, followed by the subpectoral tenodesis, tenotomy, and type II SLAP lesion models. Humeral head translation was the most restricted in the subpectoral tenodesis models, followed by the tenotomy and type II SLAP lesion models. CONCLUSION: Finite element analysis demonstrated that the LHBT plays a significant role in stress absorption and displacement restriction in the late cocking and deceleration phases of overhead throwing. Subpectoral tenodesis of the LHBT exhibited lesser amount of stress and humeral head translation than those of tenotomy, thereby making it a better option for patients who engage in overhead throwing.
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To compare and analyze the molecular mechanisms of adipose deposition in subcutaneous fat (SAF)and intramuscular fat (IMF) tissues in Ningxiang pigs, differential gene expression profiles in SAF and IMF tissues of Ningxiang pigs were identified and analysed using RNA-seq technology. Six healthy 250-day-old male Ningxiang pigs with similar body weights (approximately 85 kg) of intraspecific individuals were selected as experimental material and samples of SAF and IMF tissues were collected. Differential genes associated with fat deposition and lipid metabolism were obtained by sequencing two adipose tissue transcriptomes and performing GO (Gene Ontology) functional annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. To verify the reliability of the sequencing results, six differential genes were randomly selected to validate using qRT-PCR. The results showed that we identified 2406 DEGs, with 1422 up-regulated and 984 down-regulated genes in two tissues. GO functional annotation analysis revealed that the differentially expressed genes were mainly involved in lipid metabolism related pathways, such as steroid biosynthesis, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and autophagy pathway. KEGG pathway enrichment showed that the differentially expressed genes were mainly enriched in the biological processes related to lipid binding, fatty acid metabolism, glycol ester metabolism, lipid biosynthesis and other biological processes related to lipid metabolism. Genes related to lipid metabolism, such as TCAP, NR4A1, ACACA, LPL, ELOVL6, DGAT1, PRKAA1, ATG101, TP53INP2, FDFT1, ACOX1 and SCD were identified by bioinformatic analyses and verified by qRT-PCR. Our results indicated that these genes may play important roles in the regulation of fat deposition and metabolism in the SAF and IMF tissue, providing the further mechanistic investigation of fat deposition in Ningxiang pigs.