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1.
Eur J Med Res ; 29(1): 219, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576045

RESUMO

PURPOSE: Colorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment. METHODS: A consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments. RESULTS: Four distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells. CONCLUSIONS: Ion channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.


Assuntos
Neoplasias Colorretais , Canais Iônicos , Humanos , Canais Iônicos/genética , Nomogramas , Imunoterapia , Neoplasias Colorretais/genética , Prognóstico , Microambiente Tumoral
2.
Ying Yong Sheng Tai Xue Bao ; 35(1): 25-30, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511436

RESUMO

We systematically elaborated and compared the spatial scope and landscape changes of Horqin Grassland and Horqin Sand Land from their definitions and ranges. Horqin Grassland is an area with geographical units named after Mongolian tribes, but the boundary is unclear. Horqin Sand Land is also an area that borrows tribal names, but has independent topographic and geomorphic units, and clear boundaries. Horqin Grassland and Horqin Sand Land belong to two spatial regions that are both cross and different. The area and range of Horqin Grassland are larger than that of Horqin Sand Land which has obvious regional characteristics, and is a typical and research object area to study the development and restoration of aeolian desertification. Based on those cognition, we summarized the technologies and example models of comprehensive land management and desertification controlling over the years, and finally sorted out what should be focused on in the future to serve the annihilation war against desertification for Horqin Sand Land.


Assuntos
Conservação dos Recursos Naturais , Areia , Pradaria , China
3.
J Am Chem Soc ; 146(13): 9404-9412, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38504578

RESUMO

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable and potentially versatile approach is the coupling of a C-C bond through an outer-sphere mechanism, accompanied by the realization of enantiocontrol through cooperative catalysis; however, examples of such processes are yet to be identified. Herein, we present such a method for creating different compounds with quaternary stereocenters by photoredox/Fe/chiral primary amine triple catalysis. This approach facilitates the connection of an unactivated alkyl source with a tertiary alkyl moiety, which is also rare. The scalable process exhibits mild conditions, does not necessitate the use of a base, and possesses a good functional-group tolerance. Preliminary investigations into the underlying mechanisms have provided valuable insights into the reaction pathway.

4.
Fish Shellfish Immunol ; 148: 109503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479567

RESUMO

Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses and cell proliferation. However, the function of the PHBs in immune regulation has largely not been determined. In the present study, we identified PHB2 in the red swamp crayfish Procambarus clarkii. PHB2 was found to be widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge. PHB2 significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. Here, we observed that PHB2 promotes the nuclear translocation of STAT by binding to STAT. After blocking PHB2 or STAT with antibodies or interfering with PHB2 or STAT, the expression levels of the antiviral genes ß-thymosin (PcThy-4) and crustin2 (Cru2) decreased. The gene sequence of PHB2 was analyzed and found to contain a nuclear introgression sequence (NIS). After in vivo injection of PHB2 with deletion of NIS (rΔNIS-PHB2), the nuclear translocation of STAT did not change significantly compared to that in the control group. These results suggest that PHB2 promoted the nuclear translocation of STAT through NIS and mediated the expression of antiviral proteins to inhibit WSSV infection.


Assuntos
Timosina , Vírus da Síndrome da Mancha Branca 1 , Animais , Vírus da Síndrome da Mancha Branca 1/fisiologia , Astacoidea , Alimentos Marinhos , Antivirais
5.
Ear Nose Throat J ; : 1455613241230843, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411122

RESUMO

Objective: We examined the relationship between factors of middle ear conditions and the outcome of ossiculoplasty in chronic otitis media (COM) by measuring the improvement in the air-bone gap (ABG) and air conduction threshold (TAC). Methods: This retrospective study analyzed 76 patients (77 ears) who underwent ossiculoplasty from among 520 COM patients who underwent tympanoplasty based on the maximum preservation of the original ossicles. The reconstructed ossicular chain was performed by preserving or utilizing the remaining malleus in all cases with the presence of the malleus manubrium. Patients with eardrum adhesion, cholesteatoma, and cholesterol granuloma were defined as having a compromised middle ear condition (Group A), and those without as having an uncompromised middle ear condition (Group B). In each group, pure-tone audiometry was performed preoperatively and postoperatively, and improvements in the ABG and TAC were compared. The effects of the types of tympanoplasty and the method of ossiculoplasty (columella versus incus interposition) on postoperative ABG and TAC were also compared. Results: The postoperative ABG improvement in Group B was significantly higher than that in Group A [ß = 7.31, 95% confidence interval (CI) = 1.93-12.69, P < .05]. Type III minor columella tympanoplasty yielded significantly better results than type III major and type Vb tympanoplasty (ß = 11.42, 95% CI = 5.16-17.68, P < .01). There were no significant differences in the postoperative ABG or TAC between the reconstruction groups with and without preservation of malleus. Conclusions: Our results indicate that complex cases compromised by adhesions, cholesteatoma, and cholesterol granuloma have worse outcomes regarding hearing improvement and success rates, while those with intact stapes suprastructure have better outcomes. Malleus was maximally preserved in the patients of this study; however, this showed no significant prognostic benefit in hearing.

6.
CNS Neurosci Ther ; 30(2): e14567, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38421106

RESUMO

AIMS: This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation. METHODS: Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment. RESULTS: Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation. CONCLUSION: Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia.


Assuntos
Lesões Encefálicas Traumáticas , Hesperidina , Humanos , Microglia , Citrato (si)-Sintase/metabolismo , Citrato (si)-Sintase/farmacologia , Lisina/metabolismo , Ácido Cítrico/metabolismo , Ácido Cítrico/farmacologia , Doenças Neuroinflamatórias , Hesperidina/metabolismo , Hesperidina/farmacologia , Citratos , Lesões Encefálicas Traumáticas/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-38347690

RESUMO

Hyperspectral anomaly detection (HAD) aims to distinguish between the background and anomalies in a scene, which has been widely adopted in various applications. Deep neural network (DNN)-based methods have emerged as the predominant solution, wherein the standard paradigm is to discern the background and anomalies based on the error of self-supervised hyperspectral image (HSI) reconstruction. However, current DNN-based methods cannot guarantee correspondence between the background, anomalies, and reconstruction error, which limits the performance of HAD. In this article, we propose a novel gated transformer network for HAD (GT-HAD). Our key observation is that the spatial-spectral similarity in HSI can effectively distinguish between the background and anomalies, which aligns with the fundamental definition of HAD. Consequently, we develop GT-HAD to exploit the spatial-spectral similarity during HSI reconstruction. GT-HAD consists of two distinct branches that model the features of the background and anomalies, respectively, with content similarity as constraints. Furthermore, we introduce an adaptive gating unit to regulate the activation states of these two branches based on a content-matching method (CMM). Extensive experimental results demonstrate the superior performance of GT-HAD. The original code is publicly available at https://github.com/jeline0110/ GT-HAD, along with a comprehensive benchmark of state-of-the-art HAD methods.

8.
Front Oncol ; 14: 1335670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327746

RESUMO

Background: Being the most widely used biomarker for immunotherapy, the microsatellite status has limitations in identifying all patients who benefit in clinical practice. It is essential to identify additional biomarkers to guide immunotherapy. Aberrant DNA methylation is consistently associated with changes in the anti-tumor immune response, which can promote tumor progression. This study aims to explore immunotherapy biomarkers for colon cancers from the perspective of DNA methylation. Methods: The related data (RNA sequencing data and DNA methylation data) were obtained from The Cancer Genome Atlas (TCGA) and UCSC XENA database. Methylation-driven genes (MDGs) were identified through the Pearson correlation analysis. Unsupervised consensus clustering was conducted using these MDGs to identify distinct clusters of colon cancers. Subsequently, we evaluated the immune status and predicted the efficacy of immunotherapy by tumor immune dysfunction and exclusion (Tide) score. Finally, The Quantitative Differentially Methylated Regions (QDMR) software was used to identify the specific DNA methylation markers within particular clusters. Results: A total of 282 MDGs were identified by integrating the DNA methylation and RNA-seq data. Consensus clustering using the K-means algorithm revealed that the optimal number of clusters was 4. It was revealed that the composition of the tumor immune microenvironment (TIME) in Cluster 1 was significantly different from others, and it exhibited a higher level of tumor mutation burdens (TMB) and stronger anti-tumor immune activity. Furthermore, we identified three specific hypermethylation genes that defined Cluster 1 (PCDH20, APCDD1, COCH). Receiver operating characteristic (ROC) curves demonstrated that these specific markers could effectively distinguish Cluster 1 from other clusters, with an AUC of 0.947 (95% CI 0.903-0.990). Finally, we selected clinical samples for immunohistochemical validation. Conclusion: In conclusion, through the analysis of DNA methylation, consensus clustering of colon cancer could effectively identify the cluster that benefit from immunotherapy along with specific methylation biomarkers.

9.
J Inflamm Res ; 17: 655-667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328562

RESUMO

Purpose: The Nutritional Prognostic Score (NPS) is a composite indicator that effectively reflects the preoperative nutritional and inflammation status of patients. Its prognostic value has been extensively confirmed in various types of tumors. Our study aims to investigate the clinical implications of the NPS in the postoperative patients with cholangiocarcinoma (CCA). Patients and Methods: Data on clinicopathological characteristics were collected from CCA patients who underwent radical surgery between 2014 and 2019 at Harbin Medical University Cancer Hospital. NPS was calculated using relevant indicators to categorize the patients, and association of NPS with clinicopathological characteristics and survival outcomes were analyzed. To assess differences in survival rates between different groups, we utilized the Kaplan-Meier method. Independent prognostic risk factors were identified by Cox regression analysis. A CONomogram was created, and its accuracy in survival prediction was evaluated using receiver operating characteristic (ROC) curves. Independent verification was conducted in the validation group. Results: For this study, a cohort of 232 patients was enlisted and subsequently divided into training group (N=162) and validation group (N=70). An evident correlation was detected between NPS and preoperative malnutrition. Patients with higher NPS exhibited a worse overall survival (OS), with 5-year OS rates of 79.1%, 33.1%, and 10.6%. Multivariate analysis revealed that NPS was an independent risk factor for OS in resected CCA patients (P<0.001). The NPS-based Nomogram was developed to accurately assess the risk of patients. Conclusion: The NPS was identified as a significant risk factor that impacts the prognosis of patients with resected CCA. In order to improve prognosis management, the NPS-based Nomogram has been demonstrated to be a precise and efficient tool.

10.
J Orthop Surg Res ; 19(1): 116, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310246

RESUMO

BACKGROUND: Although prior observational studies indicate an association between cardiovascular diseases (CVDs) and frozen shoulder (FS), the potential causal relationship between them remains uncertain. This study aims to explore the genetic causal relationship between CVDs and FS using Mendelian randomization (MR). METHODS: Genetic variations closely associated with FS were obtained from the FinnGen Consortium. Summary data for CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), stroke, and ischemic stroke (IS), were sourced from several large-scale genome-wide association studies (GWAS). MR analysis was performed using inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW, as the primary MR analysis method, complemented by other sensitivity analyses, was utilized to validate the robustness of the results. Further reverse MR analysis was conducted to explore the presence of reverse causal relationships. RESULTS: In the forward MR analysis, genetically determined risk of stroke and IS was positively associated with FS (OR [95% CI] = 1.58 (1.23-2.03), P < 0.01; OR [95% CI] = 1.46 (1.16-1.85), P < 0.01, respectively). There was no strong evidence of an effect of genetically predicted other CVDs on FS risk. Sensitivity analyses confirmed the robustness of the results. In the reverse MR analysis, no causal relationships were observed between FS and various CVDs. CONCLUSION: The study suggests that stroke increases the risk of developing FS. However, further basic and clinical research is needed to substantiate our findings.


Assuntos
Bursite , Doenças Cardiovasculares , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética
11.
Mater Today Bio ; 24: 100915, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38188648

RESUMO

Objective: Abdominal wall hernias are common abdominal diseases, and effective hernia repair is challenging. In clinical practice, synthetic meshes are widely applied for repairing abdominal wall hernias. However, postoperative complications, such as inflammation and adhesion, are prevalent. Although biological meshes can solve this problem to a certain extent, they face the problems of heterogeneity, rapid degradation rate, ordinary mechanical properties, and high-cost. Here, a novel electrospinning mesh composed of polylactic acid and silk fibroin (PLA-SF) for repairing abdominal wall hernias was manufactured with good physical properties, biocompatibility and low production cost. Materials and methods: FTIR and EDS were used to demonstrate that the PLA-SF mesh was successfully synthesized. The physicochemical properties of PLA-SF were detected by swelling experiments and in vitro degradation experiments. The water contact angle reflected the hydrophilicity, and the stress‒strain curve reflected the mechanical properties. A rat abdominal wall hernia model was established to observe degradation, adhesion, and inflammation in vivo. In vitro cell mesh culture experiments were used to detect cytocompatibility and search for affected biochemical pathways. Results: The PLA-SF mesh was successfully synthesized and did not swell or degrade over time in vitro. It had a high hydrophilicity and strength. The PLA-SF mesh significantly reduced abdominal inflammation and inhibited adhesion formation in rat models. The in vitro degradation rate of the PLA-SF mesh was slower than that of tissue remodeling. Coculture experiments suggested that the PLA-SF mesh reduced the expression of inflammatory factors secreted by fibroblasts and promoted fibroblast proliferation through the TGF-ß1/Smad pathway. Conclusion: The PLA-SF mesh had excellent physicochemical properties and biocompatibility, promoted hernia repair of the rat abdominal wall, and reduced postoperative inflammation and adhesion. It is a promising mesh and has potential for clinical application.

12.
NPJ Aging ; 10(1): 4, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195699

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease worldwide, yet detection has remained largely based on surrogate serum biomarkers, elastography or biopsy. In this study, we used a total of 2959 participants from the UK biobank cohort and established the association of dual-energy X-ray absorptiometry (DXA)-derived body composition parameters and leveraged machine learning models to predict NAFLD. Hepatic steatosis reference was based on MRI-PDFF which has been extensively validated previously. We found several significant associations with traditional measurements such as abdominal obesity, as defined by waist-to-hip ratio (OR = 2.50 (male), 3.35 (female)), android-gynoid ratio (OR = 3.35 (male), 6.39 (female)) and waist circumference (OR = 1.79 (male), 3.80 (female)) with hepatic steatosis. Similarly, A Body Shape Index (Quantile 4 OR = 1.89 (male), 5.81 (female)), and for fat mass index, both overweight (OR = 6.93 (male), 2.83 (female)) and obese (OR = 14.12 (male), 5.32 (female)) categories were likewise significantly associated with hepatic steatosis. DXA parameters were shown to be highly associated such as visceral adipose tissue mass (OR = 8.37 (male), 19.03 (female)), trunk fat mass (OR = 8.64 (male), 25.69 (female)) and android fat mass (OR = 7.93 (male), 21.77 (female)) with NAFLD. We trained machine learning classifiers with logistic regression and two histogram-based gradient boosting ensembles for the prediction of hepatic steatosis using traditional body composition indices and DXA parameters which achieved reasonable performance (AUC = 0.83-0.87). Based on SHapley Additive exPlanations (SHAP) analysis, DXA parameters that had the largest contribution to the classifiers were the features predicted with significant association with NAFLD. Overall, this study underscores the potential utility of DXA as a practical and potentially opportunistic method for the screening of hepatic steatosis.

13.
Sensors (Basel) ; 24(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38257513

RESUMO

Aspect-based sentiment analysis is a fine-grained task where the key goal is to predict sentiment polarities of one or more aspects in a given sentence. Currently, graph neural network models built upon dependency trees are widely employed for aspect-based sentiment analysis tasks. However, most existing models still contain a large amount of noisy nodes that cannot precisely capture the contextual relationships between specific aspects. Meanwhile, most studies do not consider the connections between nodes without direct dependency edges but play critical roles in determining the sentiment polarity of an aspect. To address the aforementioned limitations, we propose a Structured Dependency Tree-based Graph Convolutional Network (SDTGCN) model. Specifically, we explore construction of a structured syntactic dependency graph by incorporating positional information, sentiment commonsense knowledge, part-of-speech tags, syntactic dependency distances, etc., to assign arbitrary edge weights between nodes. This enhances the connections between aspect nodes and pivotal words while weakening irrelevant node links, enabling the model to sufficiently express sentiment dependencies between specific aspects and contextual information. We utilize part-of-speech tags and dependency distances to discover relationships between pivotal nodes without direct dependencies. Finally, we aggregate node information by fully considering their importance to obtain precise aspect representations. Experimental results on five publicly available datasets demonstrate the superiority of our proposed model over state-of-the-art approaches; furthermore, the accuracy and F1-score show a significant improvement on the majority of datasets, with increases of 0.74, 0.37, 0.65, and 0.79, 0.75, 1.17, respectively. This series of enhancements highlights the effective progress made by the STDGCN model in enhancing sentiment classification performance.

14.
Open Life Sci ; 19(1): 20220806, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38283117

RESUMO

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

15.
J Biomater Appl ; 38(7): 858-865, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38165217

RESUMO

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.


Assuntos
Omento , Fator A de Crescimento do Endotélio Vascular , Ratos , Masculino , Animais , Omento/cirurgia , Ratos Sprague-Dawley , Reação a Corpo Estranho/etiologia , Inflamação/etiologia
16.
Geroscience ; 46(2): 1515-1526, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37648937

RESUMO

The identification of metabolic biomarkers for aging-related diseases and mortality is of significant interest in the field of longevity. In this study, we investigated the associations between nuclear magnetic resonance (NMR) metabolomics biomarkers and aging-related diseases as well as mortality using the UK Biobank dataset. We analyzed NMR samples from approximately 110,000 participants and used multi-head machine learning classification models to predict the incidence of aging-related diseases. Cox regression models were then applied to assess the relevance of NMR biomarkers to the risk of death due to aging-related diseases. Additionally, we conducted survival analyses to evaluate the potential improvements of NMR in predicting survival and identify the biomarkers most strongly associated with negative health outcomes by dividing participants into health, disease, and death groups for all age groups. Our analysis revealed specific metabolomics profiles that were associated with the incidence of age-related diseases, and the most significant biomarker was intermediate density lipoprotein cholesteryl (IDL-CE). In addition, NMR biomarkers could provide additional contributions to relevant mortality risk prediction when combined with conventional risk factors, by improving the C-index from 0.813 to 0.833, with 17 NMR biomarkers significantly contributing to disease-related death, such as monounsaturated fatty acids (MUFA), linoleic acid (LA), glycoprotein acetyls (GlycA), and omega-3. Moreover, the value of free cholesterol in very large HDL particles (XL-HDL-FC) in the healthy control group demonstrated significantly higher values than the disease and death group across all age groups. This study highlights the potential of NMR metabolomics profiling as a valuable tool for identifying metabolic biomarkers associated with aging-related diseases and mortality risk, which could have practical implications for aging-related disease risk and mortality prediction.


Assuntos
Bancos de Espécimes Biológicos , Humanos , Estudos Prospectivos , Estudos de Coortes , Espectroscopia de Ressonância Magnética , Biomarcadores , Envelhecimento
17.
J Environ Sci (China) ; 138: 607-625, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135424

RESUMO

In recent years, many cities have taken measures to reduce volatile organic compounds (VOCs), an important precursor of ozone (O3), to alleviate O3 pollution in China. 116 VOC species were measured by online and offline methods in the urban area of Jiaozuo from May to October in 2021 to analyze the compositional characteristics. VOC sources were analyzed by a positive matrix factorization (PMF) model, and the sensitivity of ozone generation was determined by ozone isopleth plotting research (OZIPR) simulation. The results showed that the average volume concentration of total VOCs was 30.54 ppbv and showed a bimodal feature due to the rush-hour traffic in the morning and at nightfall. The most dominant VOC groups were oxygenated VOCs (OVOCs, 29.3%) and alkanes (26.7%), and the most abundant VOC species were acetone and acetylene. However, based on the maximum incremental reactivity (MIR) method, the major VOC groups in terms of ozone formation potential (OFP) contribution were OVOCs (68.09 µg/m3, 31.5%), aromatics (62.90 µg/m3, 29.1%) and alkene/alkynes (54.90 µg/m3, 25.4%). This indicates that the control of OVOCs, aromatics and alkene/alkynes should take priority. Five sources of VOCs were quantified by PMF, including fixed sources of fossil fuel combustion (27.8%), industrial processes (25.9%), vehicle exhaust (19.7%), natural and secondary formation (13.9%) and solvent usage (12.7%). The empirical kinetic modeling approach (EKMA) curve obtained by OZIPR on O3 exceedance days indicated that the O3 sensitivity varied in different months. The results provide theoretical support for O3 pollution prevention and control in Jiaozuo.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Ozônio/análise , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , China , Alcenos , Alcinos
18.
Brain Res ; 1825: 148729, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38128810

RESUMO

Total sleep deprivation (TSD) negatively affects cognitive functions, especially vigilance attention, but studies on vigilance changes in terms of electroencephalography (EEG) microstates after TSD are limited. This study investigates the impact of TSD on vigilance attention, EEG microstates and its relationship. Thirty healthy adult males completed a psychomotor vigilance task (PVT) before, 24 h after, and 36 h after TSD while their EEG was recorded during rest. Microstate analysis revealed significant changes in the occurrence and contribution of microstate class B after TSD. Moreover, changes in the probability of transitioning between microstate classes A and D were observed, correlating with decreased vigilance. Specifically, a positive correlation was found between transitioning from class B to class C and vigilance, while a trend of negative correlation was observed between transitioning between classes A and D and vigilance. These findings indicate abnormal activity in the salience network and dorsal attention network following sleep deprivation. TSD impairs vigilance attention, as demonstrated by the effects on EEG microstate class B and the transitions between classes A and D. The study suggests its potential as an early warning indicator for predicting vigilance attention after sleep deprivation.


Assuntos
Eletroencefalografia , Privação do Sono , Adulto , Masculino , Humanos , Privação do Sono/complicações , Vigília , Cognição , Descanso , Encéfalo
19.
Eur J Pharmacol ; 964: 176272, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38110140

RESUMO

BACKGROUND: Postoperative abdominal adhesion (PAA) is a common postoperative complication. Clinically, various methods have been used to prevent the occurrence of PAA, such as drugs and physiotherapy; however, no satisfactory results have been obtained. Luteolin (LUT) is a natural flavonoid that reduces inflammation and acts as an antioxidant. This research aimed to examine the impact and mechanism of LUT in reducing PAA. METHODS: C57/BL6 mice were used in vivo experiments. PAA model was established using a brush friction method. Visual scoring and hematoxylin and eosin staining were used to score the severity of adhesions. Network pharmacology was used to infer potential targets and core pathways of LUT. Hydrogen peroxide (H2O2) was used to induce oxidative stress in vitro, while the reactive oxygen species (ROS) assay kit was used to evaluate oxidative stress levels. Western blotting, cell immunofluorescence, and multiple immunofluorescence assays were used to detect α-SMA, vimentin, E-cadherin, collagen I, or AKT phosphorylation level. Scratch assay was used to detect cell migration. RESULTS: LUT reduced the degree of PAA in mice. It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells. Network pharmacology analysis showed that LUT likely exerted anti-adhesion activity by regulating the PI3K-Akt signaling pathway. Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells. LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression. CONCLUSION: LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA. To this end, LUT has potential in PAA therapy.


Assuntos
Luteolina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Caderinas/metabolismo , Colágeno , Peróxido de Hidrogênio/farmacologia , Luteolina/farmacologia , Luteolina/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vimentina/metabolismo
20.
Inorg Chem ; 62(51): 21518-21527, 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38087775

RESUMO

The electro-driven extraction of uranium from fluorine-containing uranium wastewater is anticipated to address the challenge of separating fluoro-uranium complexes in conventional technologies. Herein, we developed hydroxy-rich cobalt-based oxides (CoOx) for electro-assisted uranium extraction from fluorine-containing wastewater. Relying on theoretical calculations and other spectral measurements, the hydroxy-rich CoOx nanosheets can enhance the affinity for uranium due to the existence of a substantial quantity of hydroxyl groups. Accordingly, the CoOx nanosheets exhibit outstanding U(VI) removal efficiency in the presence of fluorine ions. Through the utilization of X-ray absorption fine structure (XAFS), we confirm that hydroxy-rich CoOx nanosheets capture free uranyl ions to form a sturdy 2Oax-1U-3Oeq configuration, which can be achieved through electro-driven fluorine-uranium separation. Notably, for the first time, the whole reaction process of uranium species on the CoOx surface from the initial uranium single atom growth to uranium oxide nanosheets is monitored by aberration-corrected transmission electron microscopes (AC-TEM). This work provides a paradigm for the advancement of novel functional materials as electrocatalysts for uranium extraction, as well as a new approach for studying the evolution mechanism of uranium species.

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