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1.
Artículo en Inglés | MEDLINE | ID: mdl-38832960

RESUMEN

CU traits, characterized by shallow affect, lack of fear, and absence of remorse, have been moderately associated with childhood maltreatment in a recent meta-analysis. However, the potential impact of brain structures remains undetermined. This paper examines the relationship between callous-unemotional (CU) traits, childhood maltreatment, and amygdala volumes. In this study, we used a region-of-interest (ROI) analysis to explore the interaction between the volumes of the amygdala, childhood maltreatment, and the manifestation of CU traits in adolescents diagnosed with conduct disorder (CD, N = 67), along with a comparison group of healthy-control youths (HCs, N = 89). The ROI analysis revealed no significant group differences in the bilateral amygdalar volumes. Significant positive correlation was discovered between all forms of child maltreatment (except for physical neglect) and CU traits across subjects. But the interaction of physical abuse and amygdala volumes was only significant within CD patients. Notably, a sensitivity analysis suggested that gender significantly influences these findings. These results contribute critical insights into the etiology of CU traits, emphasizing the need for customized clinical assessment tools and intervention strategies.

2.
Palliat Support Care ; : 1-7, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38736428

RESUMEN

OBJECTIVES: In Chinese culture, family members are the main decision maker on end-of-life (EoL) issues for patients with advanced cancer. Yet little is known about Chinese families' confidence in making EoL decisions and its associated factors. This study aims to investigate the status and associated factors of Chinese family members' confidence in making EoL decisions for patients with advanced cancer. METHODS: This cross-sectional study used a convenience sample of 147 family members of patients with stage III or stage IV cancer from a tertiary cancer center in Guangzhou, China. The questionnaires included demographic information of patients and their family members, patients' EoL preferences, and the Chinese version of the Family Decision-Making Self-Efficacy (FDMSE) Scale. RESULTS: A total of145 family members (98.64%) completed the questionnaires. The average score of FDMSE was 3.92 ± 0.53. A multiple regression analysis showed that the factors associated with FDMSE included patients' duration of disease, health insurance, participation in EoL decision-making, the expression of unfilled wishes, and family members' employment status. SIGNIFICANCE OF RESULTS: Chinese family members were not confident enough in making EoL decisions for patients with advanced cancer. It is recommended to develop cultural-tailored advanced care planning models to clarify patient preferences and to enhance the family members' self-efficacy in making EoL decisions with or for patients with advanced cancer.

3.
Heliyon ; 10(8): e29840, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681577

RESUMEN

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of lung cancer. Given the limited clinical benefits of immunotherapy in patients with non-small cell lung cancer (NSCLC), various predictors have been shown to significantly influence prognosis. However, no single predictor is adequate to forecast patients' survival benefit. Therefore, it's imperative to develop a prognostic model that integrates multiple predictors. This model would be instrumental in identifying patients who might benefit from ICIs. Retrospective analysis and small case series have demonstrated the potential role of these models in prognostic prediction, though further prospective investigation is required to evaluate more rigorously their application in these contexts. This article presents and summarizes the latest research advancements on immunotherapy prognostic models for NSCLC from multiple omics perspectives and discuss emerging strategies being developed to enhance the domain.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38324430

RESUMEN

Federated learning has recently been applied to recommendation systems to protect user privacy. In federated learning settings, recommendation systems can train recommendation models by collecting the intermediate parameters instead of the real user data, which greatly enhances user privacy. In addition, federated recommendation systems (FedRSs) can cooperate with other data platforms to improve recommendation performance while meeting the regulation and privacy constraints. However, FedRSs face many new challenges such as privacy, security, heterogeneity, and communication costs. While significant research has been conducted in these areas, gaps in the surveying literature still exist. In this article, we: 1) summarize some common privacy mechanisms used in FedRSs and discuss the advantages and limitations of each mechanism; 2) review several novel attacks and defenses against security; 3) summarize some approaches to address heterogeneity and communication costs problems; 4) introduce some realistic applications and public benchmark datasets for FedRSs; and 5) present some prospective research directions in the future. This article can guide researchers and practitioners understand the research progress in these areas.

5.
Nephron ; 148(4): 245-263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38142674

RESUMEN

INTRODUCTION: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) alleviates the progression of diabetic nephropathy by inhibiting inflammation and fibrosis. This study investigated how CASC2 impacts renal interstitial fibrosis (RIF) through regulating M1 macrophage (M1) polarization. METHOD: Nine-week-old mice underwent unilateral ureteral obstruction (UUO) establishment. Macrophages were induced toward M1 polarization using lipopolysaccharide (LPS) in vitro and cocultured with fibroblasts to examine how M1 polarization influences RIF. LnCeCell predicted that CASC2 interacted with myocyte enhancer factor 2 C (MEF2C), which was validated by dual-luciferase reporter assay. CASC2/MEF2C overexpression was achieved by lentivirus-expressing lncRNA CASC2 injection in vivo or CASC2 and MEF2C transfection in vitro. Renal injury was evaluated through biochemical analysis and hematoxylin-eosin/Masson staining. Macrophage infiltration and M1 polarization in the kidney and/or macrophages were detected by immunofluorescence, flow cytometry, and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR). Expressions of CASC2, MEF2C, and markers related to inflammation/M1/fibrosis in the kidney/macrophages/fibroblasts were analyzed by qRT-PCR, fluorescence in situ hybridization, enzyme-linked immunosorbent assay, and/or Western blot. RESULT: In the kidneys of mice, CASC2 was downregulated and macrophage infiltration was promoted time-dependently from days 3 to 14 post-UUO induction; CASC2 overexpression alleviated renal histological abnormalities, hindered macrophage infiltration and M1 polarization, downregulated renal function markers serum creatinine and blood urea nitrogen and inflammation/M1/fibrosis-related makers, and offset UUO-induced MEF2C upregulation. LncRNA CASC2 overexpression inhibited fibroblast fibrosis and M1 polarization in cocultured fibroblasts with LPS-activated macrophages. Also, CASC2 bound to MEF2C and inhibited its expression in LPS-activated macrophages. Furthermore, MEF2C reversed the inhibitory effects of lncRNA CASC2 overexpression. CONCLUSION: CASC2 alleviates RIF by inhibiting M1 polarization through directly downregulating MEF2C expression. CASC2 might represent a promising value of future investigations on treatment for RIF.


Asunto(s)
Nefropatías Diabéticas , Riñón/anomalías , ARN Largo no Codificante , Obstrucción Ureteral , Anomalías Urogenitales , Ratones , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regulación hacia Abajo , Factores de Transcripción MEF2/genética , Factores de Transcripción MEF2/metabolismo , Factores de Transcripción MEF2/farmacología , Lipopolisacáridos , Hibridación Fluorescente in Situ , Macrófagos/patología , Obstrucción Ureteral/genética , Obstrucción Ureteral/patología , Nefropatías Diabéticas/metabolismo , Fibrosis , Inflamación/genética , Inflamación/patología
6.
Pestic Biochem Physiol ; 197: 105654, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38072529

RESUMEN

Destruxin A, a non-ribosomal peptide toxin produced by Metarhizium, exhibits potent insecticidal activity by targeting various tissues, organs, and cells of insects. Our previous research has revealed that DA possesses the ability to bind to multiple proteins. In this study, we aimed to identify the most sensitive binding proteins of DA and investigate the physiological processes in which DA regulated. Through RNAi technology, we screened 22 binding proteins of DA in silkworm hemolymph. Among them, the juvenile hormone binding protein (JHBP), a hormone transport protein crucial for growth and development regulation, exhibited the highest sensitivity to DA. Subsequent experiments demonstrated that DA could inhibit the body weight gain of silkworm larvae, accelerate the pupation occurrence, and modulate the content of free juvenile hormone (JH) in the hemolymph. We also observed that DA could induce conformational changes in both the JHBP and the JHBP-JH binding complex. Notably, at low dosage, DA influenced the binding of JHBP to JH, while at high dosage, it irreversibly affected the binding of JHBP to JH. Molecular docking and point-mutant experiments suggested that DA might affect the N-arm of JHBP, which is responsible for JH binding. Additionally, we discovered that JHBP is widely distributed in various tissues of the silkworm, including the epidermis, gut, fat body, Malpighian tubule, gonad, muscle, trachea, and hemocyte. This study provides novel insights into the insecticidal mechanism of DA and enhances our understanding of the pathogenic process of Metarhizium.


Asunto(s)
Bombyx , Mariposas Nocturnas , Animales , Hormonas Juveniles/farmacología , Hormonas Juveniles/metabolismo , Simulación del Acoplamiento Molecular , Proteínas Portadoras/química , Mariposas Nocturnas/metabolismo , Bombyx/metabolismo , Proteínas de Insectos/metabolismo
8.
Analyst ; 149(1): 148-160, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37987554

RESUMEN

Extrachromosomal circular DNA (eccDNA) was discovered several decades ago, but little is known about its function. With the development of sequencing technology, several library preparation methods have been developed to elucidate the biogenesis and function of eccDNA. However, different treatment methods have certain biases that can lead to their erroneous interpretation. To address these issues, we compared the performance of different library preparation methods. Our investigation revealed that the utilization of rolling-circle amplification (RCA) and restriction enzyme linearization of mitochondrial DNA (mtDNA) significantly enhanced the efficiency of enriching extrachromosomal circular DNA (eccDNA). However, it also introduced certain biases, such as an unclear peak in ∼160-200 bp periodicity and the absence of a typical motif pattern. Furthermore, given that RCA can lead to a disproportionate change in copy numbers, eccDNA quantification using split and discordant reads should be avoided. Analysis of the genomic and elements distribution of the overall population of eccDNA molecules revealed a high correlation between the replicates, and provided a possible stability signature for eccDNA, which could potentially reflect different cell lines or cell states. However, we found only a few eccDNA with identical junction sites in each replicate, showing a high degree of heterogeneity of eccDNA. The emergence of different motif patterns flanking junctional sites in eccDNAs of varying sizes suggests the involvement of multiple potential mechanisms in eccDNA generation. This study comprehensively compares and discusses various essential approaches for eccDNA library preparation, offering valuable insights and practical advice to researchers involved in characterizing eccDNA.


Asunto(s)
ADN Circular , ADN , ADN Circular/genética , ADN/genética , Cromosomas , Genoma , Biblioteca de Genes
9.
Neurobiol Learn Mem ; 205: 107834, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37757954

RESUMEN

Neurofeedback (NF) is a promising method to self-regulate human brain activity for cognition enhancement. Due to the unclear results of alpha NF training on working memory updating as well as the impact of feedback modality on NF learning, this study aimed to understand further the underlying neural mechanism of alpha NF training effects on working memory updating, where the NF learning was also compared between visual and auditory feedback modalities. A total of 30 participants were assigned to Visual NF, Auditory NF, and Control groups. Working memory updating was evaluated by n-back (n =2,3) tasks before and after five alpha upregulation NF sessions. The result showed no significant difference in NF learning performance between the Visual and Auditory groups, indicating that the difference in feedback modality did not affect NF learning. In addition, compared to the control group, the participants who achieved successful NF learning showed a significant increase in n-back behavioral performance and P3a amplitude in 2-back and a significant decrease in P3a latency in 3-back. Our results in n-back further suggested that successful alpha NF training might improve updating performance in terms of the behavioral and related event-related potential (ERP) measures. These findings contribute to the understanding of the effect of alpha training on memory updating and the design of NF experimental protocol in terms of feedback modality selection.


Asunto(s)
Memoria a Corto Plazo , Neurorretroalimentación , Humanos , Memoria a Corto Plazo/fisiología , Neurorretroalimentación/métodos , Neurorretroalimentación/fisiología , Electroencefalografía/métodos , Potenciales Evocados/fisiología , Aprendizaje/fisiología
10.
Comput Biol Med ; 165: 107394, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37678134

RESUMEN

As the main technology to solve data islands and mine data value, federated learning has been widely researched and applied, and more and more federated learning platforms are emerging. The federated learning platform organizes users, devices and data to collaborate in a crowdsourcing manner and complete specific federated learning tasks. This paper designs the shortest path core-selection incentive mechanism by combining the VCG auction mechanism and the core concept of cooperative games. This mechanism solves the problems of overpayment, false-name attack, and deviation from the core of the VCG mechanism, and saves the expenditure of the federated learning task issuer. It adopts the VCG-nearest principle in the core selection, so that the federated learning task participants get rewards as close as possible to the outcome of VCG mechanism. This mechanism can guarantee four economic attributes: incentive compatibility, individual rationality, alliance rationality, and maximization of social efficiency. Medical experimental results illustrate the effectiveness of the mechanism.


Asunto(s)
Aprendizaje , Motivación , Humanos , Gastos en Salud
11.
J Fungi (Basel) ; 9(9)2023 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-37755048

RESUMEN

Mycopesticides are living preparations that use fungal cells, such as spores and hyphae, as active ingredients. They mainly include mycoinsecticides, mycofungicides, mycoherbicides and nematophagous fungi. The utilization of fungi for controlling agricultural pests can be traced back to approximately 1880, when entomopathogenic fungi were initially employed for this purpose. However, it was not until 1965 that the world's first mycopesticide, Beauveria bassiana, was registered as Boverin® in the former Soviet Union. In past decades, numerous novel mycopesticides have been developed for their lower R&D costs, as well as the environmentally friendly and safe nature. In this review, we investigated the mycopesticides situation of registration in USA, EU, China, Canada and Australia. Superisingly, it was found that the registered mycopesticides are extremely raised in recent years. Currently, the insecticides, fungicides (nematocides) and herbicides were respectively registered 27, 53 and 8 fungal strains. This paper also analyzes the main problems currently faced by mycopesticides and offers suggestions for their future development.

12.
Sci Rep ; 13(1): 10951, 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37414877

RESUMEN

In this work, we investigate the yield criterion of nanoporous materials by using homogenization approach and Steigmann-Ogden surface model. The representative volume element is proposed as an infinite matrix containing a tiny nanovoid. The matrix is incompressible, rigid-perfectly plastic, von Mises materials and nanovoids are dilute and equal in size. First, the constitutive of microscopic stress and microscopic strain rate is established based on the flow criterion. Secondly, according to the Hill's lemma, the relationship between the macroscopic equivalent modulus and the microscopic equivalent modulus is established by homogenization approach. Thirdly, the macroscopic equivalent modulus containing the Steigmann-Ogden surface model including surface parameters, porosity and nanovoid radius is derived from the trial microscopic velocity field. Finally, an implicit macroscopic yield criterion for nanoporous materials is developed. For surface modulus, nanovoids radius and porosity studies are developed through extensive numerical experiments. The research results in this paper have reference significance for the design and manufacture of nanoporous materials.

13.
Brain Sci ; 13(5)2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37239297

RESUMEN

Resting-state functional magnetic resonance imaging (fMRI) with graph theoretical modeling has been increasingly applied for assessing whole brain network topological organization, yet its reproducibility remains controversial. In this study, we acquired three repeated resting-state fMRI scans from 16 healthy controls during a strictly controlled in-laboratory study and examined the test-retest reliability of seven global and three nodal brain network metrics using different data processing and modeling strategies. Among the global network metrics, the characteristic path length exhibited the highest reliability, whereas the network small-worldness performed the poorest. Nodal efficiency was the most reliable nodal metric, whereas betweenness centrality showed the lowest reliability. Weighted global network metrics provided better reliability than binary metrics, and reliability from the AAL90 atlas outweighed those from the Power264 parcellation. Although global signal regression had no consistent effects on the reliability of global network metrics, it slightly impaired the reliability of nodal metrics. These findings provide important implications for the future utility of graph theoretical modeling in brain network analyses.

14.
Eur Child Adolesc Psychiatry ; 32(1): 193-203, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34635947

RESUMEN

There may be distinct conduct disorder (CD) etiologies and neural morphologies in adolescents with high callous unemotional (CU) traits versus low CU traits. Here, we employed surface-based morphometry methods to investigate morphological differences in adolescents diagnosed with CD [42 with high CU traits (CD-HCU) and 40 with low CU traits (CD-LCU)] and healthy controls (HCs, N = 115) in China. Whole-brain analyses revealed significantly increased cortical surface area (SA) in the left inferior temporal cortex and the right precuneus, but decreased SA in the left superior temporal cortex in the CD-LCU group, compared with the HC group. There were no significant cortical SA differences between the CD-HCU and the HC groups. Compared to the CD-HCU group, the CD-LCU group had a greater cortical thickness (CT) in the left rostral middle frontal cortex. Region-of-interest analyses revealed significant group differences in the right hippocampus, with CD-HCU group having lower right hippocampal volumes than HCs. We did not detect significant group differences in the amygdalar volume, however, the right amygdalar volume was found to be a significant moderator of the correlation between CU traits and the proactive aggression in CD patients. The present results suggested that the manifestations of CD differ between those with high CU traits versus low CU traits, and underscore the importance of sample characteristics in understanding the neural substrates of CD.


Asunto(s)
Trastorno de la Conducta , Humanos , Adolescente , Trastorno de la Conducta/diagnóstico por imagen , Trastorno de la Conducta/psicología , Imagen por Resonancia Magnética/métodos , Amígdala del Cerebelo/diagnóstico por imagen , Encéfalo , Emociones
15.
Cancer Med ; 12(1): 236-255, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35650714

RESUMEN

This meta-analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine-based regimens for colorectal cancer (CRC) in term of tumor. The eight electronic databases including Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals (CQVIP), and Wanfang Database were systematically searched for eligible studies from their inception to March 2021. Thirty-nine randomized controlled trials were involved in this study, and all the data were analyzed by Review Manager 5.3 (Nordic Cochran Centre, Copenhagen, Denmark) and R 4.0.5 software. The meta-analyses suggested that TCMs in combination with capecitabine-based regimens increased objective response rate (ORR) in the palliative treatment of CRC (risk ratio [RR], 1.35 [1.17, 1.55], I2  = 0%), disease control rate (DCR) (RR, 1.22 [1.12, 1.32], I2  = 3%), and quality of life (QOL) (RR, 1.71 [1.44, 2.03], I2  = 0%), with decreased risks of myelosuppression, anemia, thrombocytopenia, liver/renal dysfunction, neurotoxicity, nausea/vomiting, neutropenia, diarrhea, leukopenia, improved the peripheral lymphocyte, reduced the expression of tumor markers, and related factors. Further sensitivity analysis of specific plant-based TCMs found that dangshen, fuling, and gancao had significantly higher contributions to the results of the RR. The results show that capecitabine-based chemotherapy combined with TCM in the treatment of CRC increases the efficiency of ORR and DCR, reduces chemotherapeutic agents-associated adverse reactions, and improves their life quality as compared with chemotherapy alone, but further randomized and large sample of studies are needed.


Asunto(s)
Neoplasias Colorrectales , Medicamentos Herbarios Chinos , Neutropenia , Humanos , Medicina Tradicional China/métodos , Capecitabina/efectos adversos , Calidad de Vida , Medicamentos Herbarios Chinos/efectos adversos , Neutropenia/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
J Nephrol ; 36(2): 397-406, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36574208

RESUMEN

BACKGROUND: IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, especially in young Asian adults. Long RNA H19 is associated with renal pathologies, such as renal cell injury; however, a connection between serum H19 expression and kidney disease progression has not been demonstrated. METHOD: Our cohort consisted of 204 patients with IgAN. Serum H19 levels were determined with reverse-transcription quantitative polymerase between 1 May, 2014 and 1 May, 2015. H19 levels were log-transformed and categorical variables were categorized according to cutoff points of a ROC curve. Restricted cubic spline and generalized estimating equation analyses were performed to determine the association between serum H19 and kidney disease progression. RESULTS: H19 expression was significantly downregulated in patients with IgAN compared to healthy controls. Restricted cubic spline analyses showed that the relationship was negatively and linearly correlated (P for nonlinearly = 0.256). After adjusting for other potential clinical, pathologic, and treatment factors, H19 was found to be a protective factor for prognosis in IgAN (HR, 0.52; 95% CI 0.32-0.84; P = 0.008). ROC curve analysis showed that the clinical value of lncRNA H19 with CKD and area under the ROC curve was 0.746 (95% CI 0.663-0.829; P < 0.001) of the clinical prognostic value of H19. Serum restricted cubic spline analyses showed that the relationship was negatively and linearly correlated (P for non-linearly = 0.256). H19 > 0.097 in patients in IgAN was associated with a reduction of the risk of kidney progression by approximately 70% within 5 years compared to H19≤0.097 (HR, 0.30;95% CI 0.12-0.74; P = 0.009). CONCLUSION: H19 is an independent protective factor, and a high level of H19 often indicates better renal outcome within 5 years.


Asunto(s)
Glomerulonefritis por IGA , ARN Largo no Codificante , Insuficiencia Renal Crónica , Adulto , Humanos , Glomerulonefritis por IGA/patología , ARN Largo no Codificante/genética , Riñón/patología , Pronóstico , Progresión de la Enfermedad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología
17.
Environ Sci Pollut Res Int ; 30(5): 11798-11810, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36097311

RESUMEN

Whole-genome sequencing of pathogenic bacteria Stenotrophomonas maltophilia from a less polluted environment of permafrost can help understand the intrinsic resistome of both antibiotics and metals. This study aimed to examine the maximum minimum inhibitory concentration (MIC) of both antibiotics and metals, as well as antibiotic resistance genes and metal resistance genes annotated from whole-genome sequences. The permafrost S. maltophilia was sensitive to ciprofloxacin, tetracycline, streptomycin, and bacitracin, and resistant to chloramphenicol, trimethoprim-sulfamethoxazole, erythromycin, Zn2+, Ni2+, Cu2+, and Cr6+, with a lower maximum MIC, compared with clinical S. maltophilia. The former strain belonged to the lower antibiotic resistance gene (ARG) and metal resistance gene (MRG) clusters compared with the latter ones. The permafrost strain contained no or only one kind of ARG or MRG on a single genomic island, which explained the aforementioned lower maximum MIC and less diversity of ARGs or MRGs. The result indicated that the co-occurrence of antibiotic and metal resistance was due to a certain innate ability of S. maltophilia. The continuous human use of antibiotics or metals induced selective pressure, resulting in higher MIC and more diverse ARGs and MRGs in human-impacted environments.


Asunto(s)
Infecciones por Bacterias Gramnegativas , Hielos Perennes , Stenotrophomonas maltophilia , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Tibet , Pruebas de Sensibilidad Microbiana
18.
Front Oncol ; 12: 1025397, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36387195

RESUMEN

Background: The heterogeneity of tumor tissue is one of the reasons for the poor effect of tumor treatment, which is mainly affected by the tumor immune microenvironment and metabolic reprogramming. But more research is needed to find out how the tumor microenvironment (TME) and metabolic features of colon adenocarcinoma (COAD) are related. Methods: We obtained the transcriptomic and clinical data information of COAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering analysis was used to identify different molecular subtypes, identify differentially expressed genes (DEGs) associated with immune-and metabolism-related genes (IMRGs) prognosis. Univariate and multivariable Cox regression analysis and Lasso regression analysis were applied to construct the prognostic models based on the IMRG risk score. The correlations between risk scores and TME, immune cell infiltration, and immune checkpoint genes were investigated. Lastly, potential appropriate drugs related to the risk score were screened by drug sensitivity analysis. Results: By consensus clustering analysis, we identified two distinct molecular subtypes. It was also found that the multilayered IMRG subtypes were associated with the patient's clinicopathological characteristics, prognosis, and TME cell infiltration characteristics. Meanwhile, a prognostic model based on the risk score of IMRGs was constructed and its predictive power was verified internally and externally. Clinicopathological analysis and nomogram give it better clinical guidance. The IMRG risk score plays a key role in immune microenvironment infiltration. Patients in the high-risk groups of microsatellite instability (MSI) and tumor mutational burden (TMB) were found to, although with poor prognosis, actively respond to immunotherapy. Furthermore, IMRG risk scores were significantly associated with immune checkpoint gene expression. The potential drug sensitivity study helps come up with and choose a chemotherapy treatment plan. Conclusion: Our comprehensive analysis of IMRG signatures revealed a broad range of regulatory mechanisms affecting the tumor immune microenvironment (TIME), immune landscape, clinicopathological features, and prognosis. And to explore the potential drugs for immunotherapy. It will help to better understand the molecular mechanisms of COAD and provide new directions for disease treatment.

19.
Cells ; 11(19)2022 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-36230944

RESUMEN

OBJECTIVES: N6-methylladenosine (m6A) modification has not been fully studied in atherosclerosis. The objectives of this study were to investigate differentially expressed m6A methylated peaks and mRNAs, along with the regulatory role of methyltransferase 3 (METTL3) in pathological processes of atherosclerosis. METHODS: The pathological models of human coronary artery smooth muscle cells (HCASMCs) were induced in vitro. The differentially expressed mRNAs and m6A peaks were identified by RNA-Seq and meRIP-Seq. The potential mechanisms were analyzed via bioinformatic assays. Methylases expression was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) in HCASMCs, and by immunohistochemical assays in 40 human coronary arteries. The knockdown of METTL3 expression in cells was performed by siRNA transfection, and cell proliferation and migration were detected after transfection. RESULTS: We identified 5121 m6A peaks and 883 mRNAs that were expressed differentially in the pathological processes of HCASMCs. Bioinformatic analyses showed that the different m6A peaks were associated with cell growth and cell adhesion, and the 883 genes showed that the extracellular matrix and PI3K/AKT pathway regulate the processes of HCASMCs. Additionally, 10 hub genes and 351 mRNAs with differential methylation and expression levels were found. METTL3 was upregulated in the arteries with atherosclerotic lesions and in the proliferation and migration model of HCASMCs, and pathological processes of HCASMCs could be inhibited by the knockdown of METTL3. The mechanisms behind regulation of migration and proliferation reduced by siMETTL3 are concerned with protein synthesis and energy metabolism. CONCLUSIONS: These results revealed a new m6A epigenetic method to regulate the progress of atherosclerosis, which suggest approaches for potential therapeutic interventions that target METTL3 for the prevention and treatment of coronary artery diseases.


Asunto(s)
Aterosclerosis , Metiltransferasas , Adenosina/análogos & derivados , Adenosina/metabolismo , Aterosclerosis/genética , Línea Celular Tumoral , Humanos , Metiltransferasas/genética , Metiltransferasas/metabolismo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño
20.
Appl Psychophysiol Biofeedback ; 47(3): 223-229, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35691974

RESUMEN

Attention plays an important role in children's development and learning, and neurofeedback training (NFT) has been proposed as a promising method to improve attention, mainly in population with attention problems such as attention deficit hyperactivity disorder. However, whether this approach has a positive effect on attention in normal developing children has been rarely investigated. This pilot study conducted ten sessions of alpha/theta ratio (ATR) NFT on eight primary students in school environment, with two to three sessions per week. The results showed inter-individual difference in NFT learning efficacy that was assessed by the slope of ATR over training sessions. In addition, the attention performance was significantly improved after NFT. Importantly, the improvement of attention performance was positively correlated with the NFT learning efficacy. It thus highlighted the need for optimizing ATR NFT protocol for the benefits on attention at the individual level. Future work can employ a double-blind placebo-controlled design with larger sample size to validate the benefits of ATR NFT for attention in normal developing children.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Neurorretroalimentación , Trastorno por Déficit de Atención con Hiperactividad/terapia , Niño , Método Doble Ciego , Electroencefalografía/métodos , Humanos , Neurorretroalimentación/métodos , Proyectos Piloto
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