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Malignant tumors are among the most important causes of death worldwide. The pathogenesis of a malignant tumor is complex and has not been fully elucidated. Studies have shown that such pathogenesis is related to abnormal cell cycle progression. The expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors as well as functions of the cell cycle checkpoints determine whether the cell cycle progression is smooth. Cell-cycle-targeting drugs have the advantages of high specificity, low toxicity, low side effects, and low drug resistance. Identifying drugs that target the cell cycle and applying them in clinical treatments are expected to promote chemotherapeutic developments against malignant tumors. This article aims to review drugs targeted against the cell cycle and their action mechanisms.
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Trace elements generally contaminate wild fish, particularly in megacities, necessitating guided consumption practices. This study investigated the bioaccumulation of trace elements in wild fish from Chongqing City in June 2021. We evaluated their contamination and associated health risks to establish consumption guidance based on fish size. Our results indicate that the concentrations of Zn, Pb, Cr, and As were relatively high, with some fish exceeding the maximum residue limits. Herbivorous and pelagic fish generally exhibited lower bioaccumulation of most trace elements, except for Cr and As, which were higher in pelagic species. The contamination indices (Pi) for Cr, Pb and As were consistently above 0.2, indicating widespread contamination. The most contaminated fish typically measured around 19 cm in length and weighed approximately 90 g. Only the maximum target hazard quotients (THQ) for As, Cr, and Hg exceeded 1, with a notably high ratio of THQ(As) > 1, highlighting concerns over arsenic contamination. The THQ(As) remained below 1 for adults across all fish species, whereas for children, species such as Onychostoma sima, Pseudohemiculter dispar, and Parabramis pekinensis exceeded this threshold. Fish safe for adult consumption generally measured 13 cm in length and weighed 20 g, and for children, 16 cm and 25 g. Consequently, selecting larger fish is likely to reduce the consumption of contaminated fish, thereby decreasing health risks to the public. The centralization of contaminated fish with high risk in specific size range confirmed fish size could be used to gauge the contamination and health risk of fish.
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Bioacumulação , Peixes , Contaminação de Alimentos , Oligoelementos , Poluentes Químicos da Água , Animais , Peixes/metabolismo , China , Oligoelementos/análise , Humanos , Contaminação de Alimentos/análise , Medição de Risco , Poluentes Químicos da Água/análise , Cidades , Monitoramento Ambiental/métodos , Tamanho Corporal , CriançaRESUMO
Public sector employment in China has exhibited pronounced non-cyclical characteristics, with a recruiting scale and wage level showing limited responsiveness to economic fluctuations. The allure of civil service jobs in China has seen a significant resurgence post-COVID-19, with an observable increase in demand among educated job seekers for stable government positions amid growing economic uncertainties. This study investigates the implications of public sector employment rigidity on macroeconomic stability using a dynamic stochastic general equilibrium (DSGE) model integrated with search and matching (S&M) theory. Simulations incorporating alternative government job policies reveal that non-cyclical public employment exacerbates macroeconomic cyclical fluctuations. The low elasticity of public sector wages with respect to corporate wages fosters stable expectations among workers regarding the future value of government jobs, increasing the perceived value of the current state of unemployment. This leads job seekers to voluntarily remain unemployed, reducing labor supply to firms. Meantime, it preserves workers' bargaining power with firms, reinforcing wage stickiness and undermining the stabilizing role of price adjustments in employment. Hypothetical scenario analyses indicate that adopting a pro-cyclical wage policy for the public sector can mitigate the obstacles of wage cuts for firms, stimulate the creation of new jobs during economic downturns, and consequently reduce the magnitude and duration of rising unemployment rates. In contrast, maintaining a non-cyclical public sector wage may not prevent a continuous rise in unemployment or a worsening economic situation, even with expanded sector recruitment. This finding holds significant relevance in the context of the post-COVID era characterized by an economic slump and employment tension, providing theoretical support for establishing a transparent and flexible wage adjustment mechanism in the public sector that is linked to market conditions.
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COVID-19 , Emprego , Setor Público , Salários e Benefícios , China , Humanos , Setor Público/economia , COVID-19/epidemiologia , COVID-19/economia , Modelos Econômicos , Simulação por Computador , SARS-CoV-2 , DesempregoRESUMO
Background: Colorectal cancer (CRC) is commonly assessed by computed tomography (CT), but the associated radiation exposure is a major concern. This study aimed to quantitatively and qualitatively compare the image quality of virtual non-contrast (VNC) images reconstructed from arterial and portal venous phases with that of true non-contrast (TNC) images in patients with CRC to assess the potential of TNC images to replace VNC images, thereby reducing the radiation dose. Methods: A total of 69 patients with postoperative pathologically confirmed CRC at the West China Hospital of Sichuan University between May 2022 and April 2023 were enrolled in this cross-sectional study. The CT protocol included the acquisition of TNC images, arterial and portal venous phase images; the VNC images were reconstructed from the two postcontrast phase images. Several parameters, including the CT attenuation value, absolute attenuation error, imaging noise [standard deviation (SD)], signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), were measured in multiple abdominal structures for both the TNC and VNC images. Two blinded readers assessed the subjective image quality using a five-point scale. Interobserver agreement was evaluated using interclass correlation coefficients (ICCs). The paired t-test and Wilcoxon signed-rank test were used to compare the objective and subjective results between the TNC and VNC images. Individual measurements of radiation doses for the TNC scan and contrast scan protocols were recorded. Results: A total of 2,070 regions of interest (ROIs) of the 69 patients were analyzed. Overall, the VNC images exhibited significantly lower attenuation values and SD values than the TNC images in all tissues, except for the abdominal aorta, portal vein, and spleen. The mean absolute attenuation errors between the VNC and TNC images were all less than 10 Hounsfield units (HU). The percentages of absolute attenuation errors less than 5 and 10 HU in the VNC images from the arterial phase (VNCa) were 78.99% and 97.97%, respectively, while those from the portal venous phase (VNCp) were 81.59% and 96.96%, respectively. The absolute attenuation errors between the TNC and VNCa images were smaller than those between the TNC and VNCp images for tumors [VNCaerror: 2.77, interquartile range (IQR) 1.77-4.22; VNCperror: 3.27, IQR 2.68-4.30; P=0.002]. The SNR values and CNR values in the VNC images were significantly higher than those in the TNC images for all tissues, except for the portal vein and spleen. The image quality was rated as excellent (represented by a score of 5) in the majority of the TNC and VNC images; however, the VNC images scored lower than the TNC images. Eliminating the TNC phase resulted in a reduction of approximately 37.99% in the effective dose (ED). Conclusions: The VNC images provided accurate CT attenuation, good image quality, and lower radiation doses than the TNC images in CRC, and the VNCa images showed minimal differences in the CT attenuation of the tumors.
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Metal-organic frameworks (MOFs) are composite crystalline materials created through the coordination of metal ions and organic ligands. MOFs have attracted extensive attention in the biomedical field based on the advantages of internal porosity, customizable porosity, and facile surface modification. This review examines the utilization of MOFs in drug delivery systems, focusing on the research progress from the aspects of coloading drug systems, intelligent responsive carriers, biological macromolecule stabilizers, self-driving micro/nanomotors, and multifunctional living carriers. In addition, the current challenges the research faces are also discussed. The review aims to provide a reference for the further application of MOFs as advanced drug delivery systems.
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Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Humanos , Portadores de Fármacos/química , Porosidade , AnimaisRESUMO
We have prepared a highly active and stable copper-doped nickel electrocatalyst. Cu/Ni-doped MFI-type protozeolite layered nanoclusters electrodes have a large electrochemically active surface area (ECSA) and good HER activity, as well as excellent durability. The addition of Cu greatly increases hydrogen evolution reaction (HER) activity under acidic conditions. At the same time, the in situ grown Cu2+1O provides some activity, and in addition, the interface constructed between Cu and Ni further generates sufficient electrochemically active surface area. The activated Cu/Ni-doped MFI-type layered nanoclusters required only a 385 mV overpotential to generate 10 mA cm-2, demonstrating efficient and stable activity with potential practical applications.
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A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.
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Coarse cereals have been promoted for their health benefits, and sourdough is used to improve their steamed bread sensory acceptance. However, grains vary in dough physiochemical properties and steamed bread-making performance. This study investigated the effects of yeast and sourdough fermentation on the biochemical, textural, and flavor properties of dough and steamed bread of eight grain types. Results indicated that sourdough dough had a lower pH and higher total titrable acidity compared with yeast group. The texture of sourdough-steamed bread was significantly improved with reduced hardness and enhanced springiness. Microstructure revealed that sourdough resulted in starch surface corrosion and less amylopectin recrystallization. Aldehydes, alcohols, and esters are more dominant in sourdough group than yeast group. Foxtail millet and sorghum steamed breads exhibited the highest performances in texture, flavor, and sensory evaluation. This could provide a theoretical basis for producing coarse cereal products with desirable quality.
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Pão , Grão Comestível , Fermentação , Farinha , Paladar , Pão/análise , Farinha/análise , Grão Comestível/química , Amido/química , Manipulação de Alimentos/métodos , Humanos , Concentração de Íons de Hidrogênio , Vapor , Amilopectina/química , Sorghum/química , Culinária/métodosRESUMO
The utilization of byproducts from foxtail millet polishing can reduce food loss and waste. Thus, it is necessary to know the chemical compounds from the millet and the segregation of the layers. The nutrients including minerals were compared among the husk, bran, and millet, and a LC-MS metabolomics analysis was also performed among them. The results showed that the protein, crude fat and 4 fatty acids, seven minerals, the nitrogen-containing compounds and phenolic acids were at much higher levels in the bran part than the husk and millet, whereas the husk only contained higher levels of dietary fibre, and some minerals. The millet section, as the edible part, contained the lowest level of chemical constituents. It illustrated that the bran part contained more functional and nutritional components than the millet and husk part. Therefore, the bran of the foxtail millet should be a food resources instead of wasting.
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OBJECTIVES: To investigate the effect of motion-compensated reconstruction (MCR) algorithm on improving the image quality of coronary computed tomography angiography (CCTA) using second-generation dual-layer spectral detector computed tomography (DLCT), and to evaluate the influence of heart rate (HR) on the motion-correction efficacy of this algorithm. MATERIALS AND METHODS: We retrospectively enrolled 127 patients who underwent CCTA for suspected coronary artery disease using second-generation DLCT. We divided the patients into two subgroups according to their average HR during scanning: the "HR < 75 bpm" group and the "HR ≥ 75 bpm" group. All images were reconstructed by the standard (STD) algorithm and MCR algorithm. Subjective image quality (4-point Likert scale), interpretability, and objective image quality between the STD and MCR in the whole population and within each subgroup were compared. RESULTS: MCR showed significantly higher Likert scores and interpretability than STD on the per-segment (3.58 ± 0.69 vs. 2.82 ± 0.93, 98.4% vs. 91.9%), per-vessel (3.12 ± 0.81 vs. 2.12 ± 0.74, 96.3% vs. 78.7%) and per-patient (2.57 ± 0.76 vs. 1.62 ± 0.55, 90.6% vs. 59.1%) levels (all p < 0.001). In the analysis of HR subgroups on a per-vessel basis of interpretability, significant differences were observed only in the right coronary artery in the low HR group, whereas significant differences were noted in three major coronary arteries in the high HR group. For objective image quality assessment, MCR significantly improved the SNR (13.22 ± 4.06 vs. 12.72 ± 4.06) and the contrast-to-noise ratio (15.84 ± 4.82 vs. 15.39 ± 4.38) compared to STD (both p < 0.001). CONCLUSION: MCR significantly improves the subjective image quality, interpretability, and objective image quality of CCTA, especially in patients with higher HRs. CLINICAL RELEVANCE STATEMENT: The motion-compensated reconstruction algorithm of the second-generation dual-layer spectral detector computed tomography is helpful in improving the image quality of coronary computed tomography angiography in clinical practice, especially in patients with higher heart rates. KEY POINTS: Motion artifacts from cardiac movement affect the quality and interpretability of coronary computed tomography angiography (CCTA). This motion-compensated reconstruction (MCR) algorithm significantly improves the image quality of CCTA in clinical practice. Image quality improvement by using MCR was more significant in the high heart rate group.
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High-density lipoprotein (HDL) is a group of small, dense, and protein-rich lipoproteins that play a role in cholesterol metabolism and various cellular processes. Decreased levels of HDL and HDL dysfunction are commonly observed in individuals with type 2 diabetes mellitus (T2DM), which is also associated with an increased risk for cardiovascular disease (CVD). Due to hyperglycemia, oxidative stress, and inflammation that develop in T2DM, HDL undergoes several post-translational modifications such as glycation, oxidation, and carbamylation, as well as other alterations in its lipid and protein composition. It is increasingly recognized that the generation of HDL modifications in T2DM seems to be the main cause of HDL dysfunction and may in turn influence the development and progression of T2DM and its related cardiovascular complications. This review provides a general introduction to HDL structure and function and summarizes the main modifications of HDL that occur in T2DM. Furthermore, the potential impact of HDL modifications on the pathogenesis of T2DM and CVD, based on the altered interactions between modified HDL and various cell types that are involved in glucose homeostasis and atherosclerotic plaque generation, will be discussed. In addition, some perspectives for future research regarding the T2DM-related HDL modifications are addressed.
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Diabetes Mellitus Tipo 2 , Lipoproteínas HDL , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Lipoproteínas HDL/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Processamento de Proteína Pós-TraducionalRESUMO
Drought is one of the non-biological stresses that affect the growth and development of plants globally, especially Lagenaria siceraria plants. As a common nitric oxide (NO) donor, sodium nitroprusside plays a significant role in enhancing the resistance of plants to non-biological stresses. In this study, 'Yayao' (L. siceraria) was selected as the material through which to investigate the mitigating effects of different concentrations of sodium nitroprusside on L. siceraria plants under moderate drought stress. The results showed that a concentration of 0.25 mmol·L-1 sodium nitroprusside had the best mitigation effect on drought stress in L. siceraria plants. Under this condition, the plant height and leaf dry weight and fresh weight increased by 12.21%, 21.84%, and 40.48%. The photosynthetic parameters were significantly improved, and the fluorescence parameters Fo and Fm were reduced by 17.04% and 7.80%, respectively. The contents of soluble sugar and proline increased by 35.12% and 44.49%, respectively. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) increased by 51.52%, 164.11%, and 461.49%, respectively. The content of malondialdehyde (MDA) decreased by 34.53%, which alleviated the damage caused by reactive oxygen species. Additionally, sodium nitroprusside promoted the expression of genes related to antioxidant enzymes (SOD, CAT, and POD). Overall, this analysis indicates that an appropriate concentration of sodium nitroprusside can enhance the drought tolerance of L. siceraria plants through multiple aspects and alleviate the harm caused by drought stress.
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Selecting appropriate adjuvants is crucial for developing an effective vaccine. However, studies on the immune responses triggered by different adjuvants in COVID-19 inactivated vaccines are scarce. Herein, we evaluated the efficacy of Alum, CpG HP021, Alum combined with CpG HP021 (Alum/CpG), or MF-59 adjuvants with COVID-19 inactivated vaccines in K18-hACE2 mice, and compared the different immune responses between K18-hACE2 and BALB/c mice. In K18-hACE2 mice, the Alum/CpG group produced a 6.5-fold increase in anti-receptor-binding domain (RBD) IgG antibody titers compared to the Alum group, and generated a comparable level of antibodies even when the antigen amount was reduced by two-thirds, possibly due to the significant activation of germinal center (GC) structures in the central region of the spleen. Different adjuvants induced a variety of binding antibody isotypes. CpG HP021 and Alum/CpG were biased towards Th1/IgG2c, while Alum and MF-59 were biased toward Th2/IgG1. Cytokines IFN-γ, IL-2, and TNF-α were significantly increased in the culture supernatants of splenocytes specifically stimulated in the Alum/CpG group. The antibody responses in BALB/c mice were similar to those in K18-hACE2 mice, but with lower levels of neutralizing antibodies (NAbs). Notably, the Alum/CpG-adjuvanted inactivated vaccine induced a higher number of T cells secreting IFN-γ and IL-2, increased the percentage of effector memory T (TEM) cells among CD8+ T cells, and effectively protected K18-hACE2 mice from Delta variant challenge. Our results showed that Alum/CpG complex adjuvant significantly enhanced the immune response to inactivated COVID-19 antigens and could induce a long-lasting immune response.
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Adjuvantes Imunológicos , Adjuvantes de Vacinas , Compostos de Alúmen , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunoglobulina G , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Animais , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Camundongos , Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Adjuvantes de Vacinas/administração & dosagem , Feminino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia , Citocinas/imunologia , HumanosRESUMO
Objective: To monitor post-vaccination antibody production, neutralizing activity, and their dynamics over time in people living with HIV (PLWH). Methods: We collected sera from 147 PLWH and 94 healthy controls after vaccination at different time points and examined changes in antibody levels and neutralizing activity using enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay. Results: IgG levels were substantially increased in both PLWH and healthy controls after the booster injection. Antibody levels decreased significantly in both PLWH and controls five months after the booster injection. However, the rate of decrease was not significantly different between the two groups. The generated antibodies demonstrated protective efficacy against the wild-type SARS-CoV-2 strain, but very low protection against the mutant strains. Furthermore, the protection decreased over time. The vaccine was less effective in PLWH with <200/µl CD4 T cells. During the SARS-CoV-2 recovery period, participants had substantially increased serum antibody levels and protective efficacy compared with those who received the booster. Conclusion: Both PLWH and controls demonstrated comparable antibody production ability. Vaccines and booster development against SARS-CoV-2 mutant strains should be prioritized in PLWH, especially in those with low CD4 counts.
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Purpose: To evaluate the capability of dual-layer detector spectral CT (DLCT) quantitative parameters in conjunction with clinical variables to detect malignant lesions in cytologically indeterminate thyroid nodules (TNs). Materials and methods: Data from 107 patients with cytologically indeterminate TNs who underwent DLCT scans were retrospectively reviewed and randomly divided into training and validation sets (7:3 ratio). DLCT quantitative parameters (iodine concentration (IC), NICP (IC nodule/IC thyroid parenchyma), NICA (IC nodule/IC ipsilateral carotid artery), attenuation on the slope of spectral HU curve and effective atomic number), along with clinical variables, were compared between benign and malignant cohorts through univariate analysis. Multivariable logistic regression analysis was employed to identify independent predictors which were used to construct the clinical model, DLCT model, and combined model. A nomogram was formulated based on optimal performing model, and its performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis. The nomogram was subsequently tested in the validation set. Results: Independent predictors associated with malignant TNs with indeterminate cytology included NICP in the arterial phase, Hashimoto's Thyroiditis (HT), and BRAF V600E (all p < 0.05). The DLCT-clinical nomogram, incorporating the aforementioned variables, exhibited superior performance than the clinical model or DLCT model in both training set (AUC: 0.875 vs 0.792 vs 0.824) and validation set (AUC: 0.874 vs 0.792 vs 0.779). The DLCT-clinical nomogram demonstrated satisfactory calibration and clinical utility in both training set and validation set. Conclusion: The DLCT-clinical nomogram emerges as an effective tool to detect malignant lesions in cytologically indeterminate TNs.
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BACKGROUND: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. CASE PRESENTATION: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation. CONCLUSIONS: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.
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Cardiomiopatia Dilatada , Complexo de Carney , Insuficiência Cardíaca , Neoplasias Cardíacas , Transplante de Coração , Mixoma , Humanos , Cardiomiopatia Dilatada/cirurgia , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/diagnóstico por imagem , Masculino , Complexo de Carney/genética , Complexo de Carney/diagnóstico , Complexo de Carney/cirurgia , Complexo de Carney/complicações , Adulto , Mixoma/complicações , Mixoma/cirurgia , Mixoma/diagnóstico por imagem , Mixoma/diagnóstico , Mixoma/genética , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/genética , Resultado do Tratamento , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genéticaRESUMO
Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. These results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting.
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Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments. Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the anti-inflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL. Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1ß (IL1ß), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1ß and IL-6, suppress mRNA expression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65 translocation in TNF-α stimulated MH7A cells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/ß (IKKα/ß), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells. Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL.
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A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.
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Foxtail millet and sourdough are used to make foxtail millet sourdough steamed bread to improve the flavor and taste. Compared with the conventional freeze-thaw treatment (CFT), the effect of magnetic field-assisted freeze-thaw treatment (MFT) on the storage quality of foxtail millet sourdough and steamed bread is explored. The results showed that compared with CFT, MFT shortened the phase transition time of dough; decreased the water loss rate, the water mobility, and the freezable water content; increased the fermentation volume; stabilized the rheological properties; and minimized the damage of freezing and thawing to the secondary structure and microstructure of the gluten. In addition, an analysis of the specific volume, texture, surface color, and texture structure showed that MFT was beneficial to slowing the deterioration of the steamed bread texture. Finally, MFT effectively inhibited the growth and recrystallization of ice crystals during freezing and thawing, improving the quality of millet dough and steamed bread.