Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
1.
Polymers (Basel) ; 16(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38931998

RESUMO

With the swift progress of the electronics industry, discarded circuit boards have become an important source of non-degradable waste. In this work, discarded epoxy resin was collected as a precursor to prepare activated carbon (AC) through stepwise carbonization/activation methods. The rough carbon materials with a certain graphite and amorphous structure reveal the multiple oxygen-containing groups on their surface. In the process of studying the adsorption of methyl orange by activated carbon, it is found that the adsorption is in accordance with the quasi-secondary kinetic model, and equilibrium adsorption amounts can reach 41.051 mg/g. The adsorption isotherm of AC is more in line with the Langmuir model, and the saturation adsorption amount at three different temperatures is 23.137 mg/g, 30.358 mg/g, and 37.202 mg/g, respectively. The enthalpy (ΔH) is 17.30 KJ/mol in the adsorption process, which indicates that is a physical process with heat-absorbing capabilities. This work is of great significance with regard to the recycling of waste to reduce pollution and in terms of gaining economic benefits.

2.
Front Pharmacol ; 15: 1385330, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860164

RESUMO

Liver fibrosis occurs in response to chronic damage and inflammation to the liver. Leaving untreated, it can lead to decreased liver function and can eventually progress to cirrhosis, a more advanced and irreversible state of liver damage. Clinical investigations showed that chronic liver disease associated with neurological symptoms including anxiety, depression, and cognitive decline. However, few therapeutic options are available for treating liver and related brain pathologies simultaneously. In this study, we aim to find therapeutic candidates that target the liver-brain axis. Gossypetin, a flavonoid from sedum, shows promising capability in treating liver and brain pathologies in CCl4-induced mouse model. Short term of gossypetin administration is sufficient to ameliorate impaired liver function and pre-existing liver fibrosis, suppress MKK3/6-p38 MAPK and p53 activation, and abolish the activation of hepatic stellate cells and Kupffer cells. Although we observe no neuronal loss in the brain of mice with liver fibrosis, we do observe astrogliosis and microglial activation in certain brain regions, especially the hippocampus. Brief gossypetin administration also shows potential in alleviating neuroinflammation in these regions. These results suggest that gossypetin can target the liver-brain axis and be a promising candidate for treating chronic liver fibrosis patients with neurological symptoms.

3.
J Leukoc Biol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478636

RESUMO

Melanoma, caused by malignant melanocytes, is known for its invasiveness and poor prognosis. Therapies are often ineffective due to their heterogeneity and resistance. Bacillus Calmette-Guérin (BCG), primarily a tuberculosis vaccine, shows potential in treating melanoma by activating immune responses. In this study, data from The Cancer Genome Atlas and the NCBI GEO database were utilized to determine pivotal differentially expressed genes (DEGs) such as DSC2, CXCR1, BOK, and CSTB, which are significantly upregulated in BCG treated blood samples and are strongly associated with the prognosis of melanoma. We employ tools like edgeR and ggplot2 for functional and pathway analysis and develop a prognostic model using LASSO Cox regression analysis to predict patient survival. A notable finding is the correlation between BCG-related genes and immune cell infiltration in melanoma, highlighting the potential of these genes as both biomarkers and therapeutic targets. Additionally, the study examines genetic alterations in these genes and their impact on the disease. This study highlights the necessity of further exploring BCG-related genes for insights into melanoma pathogenesis and treatment enhancement, suggesting that BCG's role in immune activation could offer novel therapeutic avenues in cancer treatment.

4.
Environ Sci Technol ; 58(8): 3800-3811, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38350025

RESUMO

The growing global water crisis necessitates sustainable desalination solutions. Conventional desalination technologies predominantly confront environmental issues such as high emissions from fossil-fuel-driven processes and challenges in managing brine disposal during the operational stages, emphasizing the need for renewable and environmentally friendly alternatives. This study introduces and assesses a bioinspired, solar-driven osmosis desalination device emulating the natural processes of mangroves with effective contaminant rejection and notable productivity. The bioinspired solar-driven osmosis (BISO) device, integrating osmosis membranes, microporous absorbent paper, and nanoporous ceramic membranes, was evaluated under different conditions. We conducted experiments in both controlled and outdoor settings, simulating seawater with a 3.5 wt % NaCl solution. With a water yield of 1.51 kg m-2 h-1 under standard solar conditions (one sun), the BISO system maintained excellent salt removal and accumulation resistance after up to 8 h of experiments and demonstrated great cavitation resistance even at 58.14 °C. The outdoor test recorded a peak rate of 1.22 kg m-2 h-1 and collected 16.5 mL in 8 h, showing its practical application potential. These results highlight the BISO device's capability to address water scarcity using a sustainable approach, combining bioinspired design with solar power, presenting a viable pathway in renewable-energy-driven desalination technology.


Assuntos
Membranas Artificiais , Purificação da Água , Purificação da Água/métodos , Água , Água do Mar , Osmose , Cloreto de Sódio
5.
Angew Chem Int Ed Engl ; 63(14): e202319100, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38335151

RESUMO

Residual lead iodide (PbI2) is deemed to a double-edged sword in perovskite film as small amounts of PbI2 are beneficial to the photovoltaic performance, but excessive will cause degradation of photovoltaic performance and stability. Herein, an in situ repair strategy has been developed by introducing amine-releasable mediator (methylammonium pyridine-2-carboxylic, MAPyA) to eliminate over-residual PbI2 and regulate the crystal quality of perovskite film. Notably, MAPyA can be partially decomposed into methylamine (MA) gas and pyridine-2-carboxylic (PyA) during high temperature annealing. The released MA can locally form liquid intermediate phase, facilitating the reconstruction of perovskite microcrystals and residual PbI2. Moreover, the leftover PyA is confirmed to effectively passivate the uncoordinated lead ions in final perovskite film. Based upon this, superior perovskite film with optimized crystal structure and holistic negligible PbI2 is acquired. The assembled device realizes outstanding efficiency of 24.06 %, and exhibits a remarkable operational stability that maintaining 87 % of its origin efficiency after continuous illumination for 1480 h. And the unencapsulated MAPyA-treated devices present significant uplift in humidity stability (maintaining ~93 % of the initial efficiency over 1500 h, 50-60 % relative humidity). Furthermore, the further optimization of this strategy with nanoimprint technology proves its superiority in the amplificative preparation for perovskite films.

6.
Environ Pollut ; 344: 123395, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266697

RESUMO

Overexposure to manganese (Mn) can lead to neurotoxicity, the underlying mechanisms remain incompletely understood. Circular RNAs (circRNAs) have emerged as important regulators in various biological processes. It is plausible that circRNAs may be involved in the biological mechanisms underlying Mn caused neurotoxicity. Here, circRest was downregulated in Mn-exposed mouse neuroblastoma cells (N2a cells) by RNA sequencing and quantitative real-time PCR. When circRest was overexpressed, it led to an increase in cell viability and a decrease in apoptosis following Mn exposure. Conversely, silencing circRest resulted in opposite effects in N2a cells. Further investigation revealed that circRest acts as a mmu-miR-6914-5p sponge, and mmu-miR-6914-5p could bind and inhibit Ephb3, thereby promoting apoptosis in N2a cells. This was confirmed through RNA antisense purification and dual luciferase reporter assays. Additionally, the circRest/mmu-miR-6914-5p/Ephb3 axis may influence memory and learning in mice following Mn exposure. In conclusion, our study uncovers a novel mechanism by which circRest may attenuate Mn caused neurotoxicity via the mmu-miR-6914-5p/Ephb3 axis.


Assuntos
MicroRNAs , RNA Circular , Animais , Camundongos , Apoptose , Sequência de Bases , Proliferação de Células , Manganês , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
7.
Food Chem Toxicol ; 184: 114322, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38056821

RESUMO

Manganese (Mn) is an essential micronutrient in maintaining homeostasis in the human body, while excessive Mn exposure can lead to neurological disorders. To investigate whether there is an association between elevated ROS and pyroptosis caused by Mn exposure using both in vitro and in vivo models. We exposed BV2 and N2a, which represent microglial cells and Neuroblastoma cells in the brain, respectively, to different concentrations of Mn for 24 h. Following Mn exposure, we assessed cell morphology, levels of lactate dehydrogenase, and cellular ROS levels. C57BL/6 male mice were exposed to 0-100 mg/kg MnCl2·4H2O for 12 weeks through gavage. The expression level of pyroptosis proteins including caspase3 and GSDME in the hippocampus was examined. We found that Mn exposure resulted in elevated levels of cellular ROS and protein expression of Caspase3 and GSDME in both N2a and BV2 cells. The pyroptosis levels were blunted by either inhibiting Caspase3 expression or ROS production. In the in vivo model, protein levels of Caspase3 and GSDME also increased dependent of Mn concentrations. These findings suggested that neuronal pyroptosis induced by Mn exposure may occur through the ROS-stimulated Caspase3-GSDME pathway. Moreover, utilizing inhibitors targeting Caspase3 or ROS may provide protection against Mn-induced toxicity.


Assuntos
Manganês , Piroptose , Camundongos , Animais , Masculino , Humanos , Manganês/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais
8.
Angew Chem Int Ed Engl ; 63(1): e202315233, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37990773

RESUMO

Eliminating the undesired photoinstability of excess lead iodide (PbI2 ) in the perovskite film and reducing the energy mismatch between the perovskite layer and heterogeneous interfaces are urgent issues to be addressed in the preparation of perovskite solar cells (PVSCs) by two-step sequential deposition method. Here, the 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4 ) is employed to convert superfluous PbI2 to more robust 1D EMIMPbI3 which can withstand lattice strain, while forming an interfacial dipole layer at the SnO2 /perovskite interface to reconfigure the interfacial energy band structure and accelerate the charge extraction. Consequently, the unencapsulated PVSCs device attains a champion efficiency of 24.28 % with one of the highest open-circuit voltage (1.19 V). Moreover, the unencapsulated devices showcase significantly improved thermal stability, enhanced environmental stability and remarkable operational stability accompanied by 85 % of primitive efficiency retained over 1500 h at maximum power point tracking under continuous illumination.

9.
ACS Appl Mater Interfaces ; 15(43): 50047-50057, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856877

RESUMO

Immunomodulation therapies have attracted immense interest recently for the treatment of immune-related diseases, such as cancer and viral infections. This new wave of enthusiasm for immunomodulators, predominantly revolving around cytokines, has spurred emerging needs and opportunities for novel immune monitoring and diagnostic tools. Considering the highly dynamic immune status and limited window for therapeutic intervention, precise real-time detection of cytokines is critical to effectively monitor and manage the immune system and optimize the therapeutic outcome. The clinical success of such a rapid, sensitive, multiplex immunoanalytical platform further requires the system to have ease of integration and fabrication for sample sparing and large-scale production toward massive parallel analysis. In this article, we developed a nanoplasmonic bioink-based, label-free, multiplex immunosensor that can be readily "written" onto a glass substrate via one-step calligraphy patterning. This facile nanolithography technique allows programmable patterning of a minimum of 3 µL of nanoplasmonic bioink in 1 min and thus enables fabrication of a nanoplasmonic microarray immunosensor with 2 h simple incubation. The developed immunosensor was successfully applied for real-time, parallel detection of multiple cytokines (e.g., interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß)) in immunomodulated macrophage samples. This integrated platform synergistically incorporates the concepts of nanosynthesis, nanofabrication, and nanobiosensing, showing great potential in the scalable production of label-free multiplex immunosensing devices with superior analytical performance for clinical applications in immunodiagnostics and immunotherapy.


Assuntos
Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Ressonância de Plasmônio de Superfície/métodos , Monitorização Imunológica , Imunoensaio/métodos , Citocinas/análise
10.
Ren Fail ; 45(2): 2251592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37732400

RESUMO

Research on the relationship between the weight-adjusted skeletal muscle mass index and all-cause mortality is rare, and even rarer is the relationship between the creatinine/body weight (Cre/BW) ratio and all-cause mortality. Therefore, this study aimed to investigate the relationship between the Cre/BW ratio and mortality in individuals with normal renal function. This prospective study used data from the National Health and Nutrition Examination Survey (NHANES) database. A Cox hazard model was used to analyze the relationship between the Cre/BW ratio and mortality risk. In total, 45,459 participants were included, of which 49.97% were women, with an average age of 45.68 ± 18.08 years. The incidence of all-cause mortality was 10.9% among these participants during the median (interquartile range) follow-up of 9.6 (5.2, 14.2) years. After adjusting for all covariates, a U-shaped relationship was found between the Cre/BW ratio and all-cause mortality (P for nonlinearity <0.001), with the lowest risk observed at Cre/BW ratios (×100) between 0.821 and 0.987. In the threshold effect analysis, the Cre/BW ratio (×100) had a threshold value of 0.96. When the Cre/BW ratio (×100) was <0.96, all-cause mortality was negatively associated with the Cre/BW ratio (×100) (0.63 (0.41, 0.97)). In contrast, when the Cre/BW ratio (×100) was ≥0.96, the higher Cre/BW ratio was associated with a greater hazard ratio of all-cause mortality (1.67 (1.41, 1.97)). In conclusion, we report a U-shaped relationship between the Cre/BW ratio and all-cause mortality. Controlling the Cre/BW ratio within a certain range may reduce the risk of all-cause mortality.


Assuntos
Estudos de Coortes , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Creatinina , Inquéritos Nutricionais , Estudos Prospectivos , Peso Corporal
11.
Planta ; 258(3): 65, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566145

RESUMO

MAIN CONCLUSION: Ectopic expression of Camellia oleifera Abel. gibberellin 20-oxidase 1 caused a taller phenotype, promoted secondary cell wall deposition, leaf enlargement, and early flowering, and reduced chlorophyll and anthocyanin accumulation and seed enlargement phenotype in Arabidopsis. Plant height and secondary cell wall (SCW) deposition are important plant traits. Gibberellins (GAs) play important roles in regulating plant height and SCWs deposition. Gibberellin 20-oxidase (GA20ox) is an important enzyme involved in GA biosynthesis. In the present study, we identified a GA synthesis gene in Camellia oleifera. The total length of the CoGA20ox1 gene sequence was 1146 bp, encoding 381 amino acids. Transgenic plants with CoGA20ox1 had a taller phenotype; a seed enlargement phenotype; promoted SCWs deposition, leaf enlargement, and early flowering; and reduced chlorophyll and anthocyanin accumulation. Genetic analysis showed that the mutant ga20ox1-3 Arabidopsis partially rescued the phenotype of CoGA20ox1 overexpression plants. The results showed that CoGA20ox1 participates in the growth and development of C. oleifera. The morphological changes in CoGA20ox1 overexpressed plants provide a theoretical basis for further exploration of GA biosynthesis and analysis of the molecular mechanism in C. oleifera.


Assuntos
Arabidopsis , Camellia , Arabidopsis/metabolismo , Camellia/genética , Camellia/metabolismo , Antocianinas/metabolismo , Expressão Ectópica do Gene , Giberelinas/metabolismo , Plantas Geneticamente Modificadas/genética , Parede Celular/metabolismo , Clorofila/metabolismo , Regulação da Expressão Gênica de Plantas
12.
Eur J Pharm Sci ; 189: 106531, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37479045

RESUMO

Hypertensive nephropathy (HTN) is a common complication of hypertension. Although various agents for treatment of hypertension exert significant effects, there is currently no effective treatment for hypertensive nephropathy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin (DAPA), are a new class of hypoglycemic agents shown to improve the prognosis of patients with chronic kidney disease and diabetes mellitus. However, the mechanisms underlying the protective effects of DAPA remain unclear. RNA-sequencing (RNA-Seq)-based computational analysis was conducted to explore the transcriptomic changes to spontaneously hypertensive rats (SHRs) treated with DAPA for 8 weeks. Differentially expressed genes in SHRs were related to dysregulation of lipid metabolism, oxidation-reduction reaction, immunity and inflammation in HTN. Transcriptome analysis showed that 8 weeks of DAPA therapy exerted protective effects on the renal tissues of SHRs through the lysosomal, phagosomal, and autophagic pathways. VENN diagram analysis identified Zinc finger and BTB domain-containing 20 (Zbtb20) as the potential target of DAPA therapy. Consistent with the RNA-Seq findings, real-time quantitative PCR and immunohistochemical analyses revealed increased expression of Zbtb20 in the renal tissues of SHRs, whereas expression was decreased following 8 weeks of DAPA administration. The results of this study clarified the transcriptome signature of HTN and the beneficial effects of DAPA on renal tissues by alleviating dysregulation of metabolic processes and reducing inflammation.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Inibidores do Transportador 2 de Sódio-Glicose , Ratos , Animais , Ratos Endogâmicos SHR , Transcriptoma , Transportador 2 de Glucose-Sódio/genética , Transportador 2 de Glucose-Sódio/metabolismo , RNA-Seq , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/genética , Inflamação , Glucose , Sódio
13.
ACS Appl Mater Interfaces ; 15(23): 27732-27741, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37261449

RESUMO

The transport, distribution, and mixing of microfluidics often require additional instruments, such as pumps and valves, which are not feasible when operated in point-of-care (POC) settings. Here, we present a simple microfluidic pathogen detection system known as Rotation-Chip that transfers the reagents between wells by manually rotating two concentric layers without using external instruments. The Rotation-Chip is fabricated by a simple computer numerical control (CNC) machining process and is capable of carrying out 60 multiplexed reactions with a simple 30 or 60° rotation. Leveraging superhydrophobic coating, a high fluid transport efficiency of 92.78% is achieved without observable leaking. Integrated with an intracellular fluorescence assay, an on-chip detection limit of 1.8 × 106 CFU/mL is achieved for ampicillin-resistant Escherichia coli (E. coli), which is similar to our off-chip results. We also develop a computer vision method to automatically distinguish positive and negative samples on the chip, showing 100% accuracy. Our Rotation-Chip is simple, low-cost, high-throughput, and can display test results with a single chip image, making it ideal for various multiplexing POC applications in resource-limited settings.


Assuntos
Escherichia coli , Sistemas Automatizados de Assistência Junto ao Leito , Rotação , Computadores , Interações Hidrofóbicas e Hidrofílicas , Dispositivos Lab-On-A-Chip
14.
Diab Vasc Dis Res ; 20(3): 14791641231173617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37209031

RESUMO

BACKGROUND: Insulin Resistance (IR) are associated with Hypertension (HTN). Triglyceride glucose-body mass index (TyG-BMI) is a readily available and clinically significant indicator of IR. This study aimed to investigate whether TyG-BMI is independently associated with HTN. METHODS: A total of 15,464 patients with normal blood glucose from 2004 to 2016 participated in this study. Participants were divided into four groups using the quartile method: TyG-BMI below 153.1, between 153.1 and 174.2, between 174.2 and 199.3, and over 199.3. The covariates included age, sex, BMI, WC, HDL-C, TC, TG, HbA1c, FPG, ALT, AST, GGT, SBP, DBP, smoking status, alcohol consumption, and exercise habits. RESULTS: The average age was 43.7 ± 8.9 years, and 45.4% were men. The prevalence of HTN was 6.2% (964/15464) of the population. TyG-BMI remained significantly associated with HTN after multivariate adjustment for TyG-BMI as a continuous variable (adjusted OR = 2.87, 95% CI: 1.90-4.34). Each 10-unit rise in TyG-BMI (continuous variable) was linked to a 31% increase in the prevalence of HTN (adjusted OR = 1.31, 95% CI: 1.25-1.37). In the subgroup analysis stratified by age, sex, waist circumference, and smoking status, the association between TyG-BMI and HTN were stable. CONCLUSION: In this study, TyG-BMI was highly correlated with HTN, but more experiments and different populations are needed to verify this.


Assuntos
Hipertensão , Resistência à Insulina , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Glucose , Índice de Massa Corporal , Estudos Transversais , Triglicerídeos , Glicemia , Japão/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia
15.
Adv Mater ; 35(33): e2301852, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37087113

RESUMO

The two-step sequential deposition process is demonstrated as a reliable technology for the fabrication of efficient perovskite solar cells (PVSCs). However, the complete conversion of dense PbI2 to perovskite in planar PVSCs is tough without mesoporous titanium dioxide as support. Herein, multifunctional capsules consisting of zeolitic imidazolate framework-8 (ZIF-8) encapsulant and formamidinium iodide (FAI) are introduced between tin oxide (SnO2 ) and lead iodide (PbI2 ) layer. Intriguingly, the capsule dopant interlayer benefits the formation of porous PbI2 film due to the porous nanostructure of ZIF-8 that is favorable for the subsequent intercalation reaction. Furthermore, the constituent of the perovskite precursor in ZIF-8 pores can convert into the crystal nuclei of perovskite by reacting with PbI2 first, thereby promoting further perovskite crystallization. Significantly, the incorporation of ZIF-8 can enhance the resistance of perovskite against UV illumination due to down-conversion effect. Consequently, the modified device achieves a champion power conversion efficiency (PCE) of 24.08% and displays enhanced UV stability, which can sustain 83% of its original PCE under 365 nm UV illumination for 300 h. Moreover, the unencapsulated device maintains 90% of initial PCE after 1500 h storage in dark ambient conditions with a relative humidity range of 50%-70%.

16.
J Med Chem ; 66(9): 6218-6238, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-36880691

RESUMO

Nowadays, small-molecule drugs have become an indispensable part of tumor immunotherapy. Accumulating evidence has indicated that specifically blocking PGE2/EP4 signaling to induce robust antitumor immune response represents an attractive immunotherapy strategy. Herein, a 2H-indazole-3-carboxamide containing compound 1 was identified as a EP4 antagonist hit by screening our in-house small-molecule library. Systematic structure-activity relationship exploration leads to the discovery of compound 14, which displayed single-nanomolar EP4 antagonistic activity in a panel of cell functional assays, high subtype selectivity, and favorable drug-like profiles. Moreover, compound 14 profoundly inhibited the up-regulation of multiple immunosuppression-related genes in macrophages. Oral administration of compound 14, either as monotherapy or in combination with an anti-PD-1 antibody, significantly impaired tumor growth via enhancing cytotoxic CD8+ T cell-mediated antitumor immunity in a syngeneic colon cancer model. Thus, these results demonstrate the potential of compound 14 as a candidate for developing novel EP4 antagonists for tumor immunotherapy.


Assuntos
Neoplasias do Colo , Indazóis , Receptores de Prostaglandina E Subtipo EP4 , Humanos , Neoplasias do Colo/patologia , Imunoterapia , Prostaglandinas , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Transdução de Sinais , Indazóis/química , Indazóis/farmacologia
17.
Front Cardiovasc Med ; 10: 1068562, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818333

RESUMO

Introduction: Atrial fibrillation (AF) is prone to heart failure and stroke. Early management can effectively reduce the stroke rate and mortality. Current clinical guidelines screen high-risk individuals based solely on age, while this study aims to explore the possibility of other AF risk predictors. Methods: A total of 18,738 elderly people (aged over 60 years old) in Chinese communities were enrolled in this study. The baseline characteristics were mainly based on the diagnosis results of electrocardiogram (ECG) machine during follow up, accompanied by some auxiliary physical examination basic data. After the analysis of both independent and combined baseline characteristics, AF risk predictors were obtained and prioritized according to the results. Independent characteristics were studied from three aspects: Chi-square test, Mann-Whitney U test and Cox univariate regression analysis. Combined characteristics were studied from two aspects: machine learning models and Cox multivariate regression analysis, and the former was combined with recursive feature elimination method and voting decision. Results: The resulted optimal combination of risk predictors included age, atrial premature beats, atrial flutter, left ventricular hypertrophy, hypertension and heart disease. Conclusion: Patients diagnosed by short-time ECG machines with the occurrence of the above events had a higher probability of AF episodes, who are suggested to be included in the focus of long-term ECG monitoring or increased screening density. The incidence of risk predictors in different age ranges of AF patients suggests differences in age-specific patient management. This can help improve the detection rate of AF, standardize the management of patients, and slow down the progression of AF.

18.
ISA Trans ; 136: 663-675, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36443119

RESUMO

Error entropy is a well-known learning criterion in information theoretic learning (ITL), and it has already been applied to a wide range of fields. However, the shape of error entropy cannot be changed freely since its kernel function is the Gaussian kernel function, which causes the error entropy-based algorithm to handle only some specific kinds of noises. Benefiting from the property that the generalized Gaussian kernel function is free to adjust its shape, a novel Kalman-type filter algorithm based on the generalized minimum error entropy (GMEEKF) criterion is derived. Moreover, the mean error behavior, mean square error behavior, and computational complexity of the GMEEKF algorithm are analyzed. Finally, several simulations and experiments are performed to demonstrate the performance of the GMEEKF algorithm in comparison with the existing Kalman-type filter algorithms.

19.
Front Pharmacol ; 13: 989636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324689

RESUMO

Left atrial remodeling, characterized by enlargement and hypertrophy of the left atrium and increased fibrosis, was accompanied by an increased incidence of atrial fibrillation. While before morphological changes at the early stage of hypertension, how overloaded hypertension influences the transcriptomic profile of the left atrium remains unclear. Therefore, RNA-sequencing was performed to define the RNA expressing profiles of left atrium in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats as a control group. We also compared the changes in the RNA expression profiles in SHRs treated with an angiotensin receptor blocker (ARB) and angiotensin receptor-neprilysin inhibitor (ARNI) to assess the distinct effects on the left atrium. In total, 1,558 differentially expressed genes were found in the left atrium between WKY rats and SHRs. Bioinformatics analysis showed that these mRNAs could regulate upstream pathways in atrial remodeling through atrial fibrosis, inflammation, electrical remodeling, and cardiac metabolism. The regulated transcripts detected in the left atrial tissue in both the ARB-treated and ARNI-treated groups were related to metabolism. In contrast to the ARB-treated rates, the transcripts in ARNI-treated rats were mapped to the cyclic guanosine monophosphate-protein kinase G signaling pathway.

20.
Cell Death Dis ; 13(11): 1004, 2022 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-36437247

RESUMO

Blocked cellular differentiation is a critical pathologic hallmark of acute myeloid leukemia (AML). Here, we showed that genetic activation of the orphan GPCR GPR132 significantly induced cell differentiation of AML both in vitro and in vivo, indicating that GPR132 is a potential trigger of myeloid differentiation. To explore the therapeutic potential of GPR132 signaling, we screened and validated a natural product 8-gingerol (8GL) as a GPR132 agonist. Notably, GPR132 activation by 8GL promoted differentiation and reduced colony formation in human AML cell lines with diverse genetic profiles. Mechanistic studies revealed that 8GL treatment inhibits the activation of the mammalian target of rapamycin (mTOR), a regulator of AML cell differentiation blockade, via activating GPR132-Gs-PKA pathway. We further showed that the combination of 8GL and an mTOR inhibitor synergistically elicited AML cell differentiation in vitro. Importantly, 8GL alone or in combination with an mTOR inhibitor remarkably impaired tumor growth and extended mouse survival in an AML xenograft model accompanied by enhanced cell differentiation. Notably, genetic or pharmacological activation of GPR132 triggered the differentiation of human primary AML cells. In summary, this study demonstrated that activation of orphan GPR132 represents a potential strategy for inducing myeloid differentiation in AML patients.


Assuntos
Diferenciação Celular , Leucemia Mieloide Aguda , Receptores Acoplados a Proteínas G , Animais , Humanos , Camundongos , Proteínas de Transporte/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Mamíferos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...