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1.
Cancer Inform ; 23: 11769351231180789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617569

RESUMO

Background: Alternative polyadenylation (APA) plays a vital regulatory role in various diseases. It is widely accepted that APA is regulated by APA regulatory factors. Objective: Whether APA regulatory factors affect the prognosis of renal cell carcinoma remains unclear, and this is the main topic of this study. Methods: We downloaded the transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database. We used the Lasso regression system to construct an APA model for analyzing the relationship between common APA regulatory factors and renal cell carcinoma. We also validated our APA model using independent GEO datasets (GSE29609, GSE76207). Results: It was found that the expression levels of 5 APA regulatory factors (CPSF1, CPSF2, CSTF2, PABPC1, and PABPC4) were significantly associated with tumor gene mutation burden (TMB) score in renal clear cell carcinoma, and the risk score constructed using the expression level of 5 key APA regulatory factors could be used to predict the outcome of renal clear cell carcinoma. The TMB score is associated with the remodeling of the immune microenvironment. Conclusions: By identifying key APA regulatory factors in renal cell carcinoma and constructing risk scores for key APA regulatory factors, we showed that key APA regulators affect prognosis of renal clear cell carcinoma patients. In addition, the risk score level is associated with TMB, indicating that APA may affect the efficacy of immunotherapy through immune microenvironment-related genes. This helps us better understand the mRNA processing mechanism of renal clear cell carcinoma.

2.
World J Psychiatry ; 14(3): 409-420, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38617988

RESUMO

BACKGROUND: Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis (MHD) that significantly affect their quality of life (QOL). High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD. Currently, there is limited research on how social support mediates the relationship between dysphoria, despondency, and overall QOL in patients undergoing MHD. It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD, ultimately enhancing their overall QOL. AIM: To investigate the mediating role of social support in relationships between dysphoria, despondency, and QOL among patients undergoing MHD. METHODS: Participants comprised 289 patients undergoing MHD, who were selected using a random sampling approach. The Social Support Rating Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and QOL Scale were administered. Correlation analysis was performed to examine the associations between social support, dysphoria, despondency, and QOL in patients undergoing MHD. To assess the mediating impact of social support on dysphoria, despondency, and QOL in patients undergoing MHD, a bootstrap method was applied. RESULTS: Significant correlations among social support, dysphoria, despondency, and quality in patients undergoing MHD were observed (all P < 0.01). Dysphoria and despondency negatively correlated with social support and QOL (P < 0.01). Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD (P < 0.05). The direct effect of dysphoria on QOL was statistically significant (P < 0.05). Social support mediated the relationship between dysphoria and QOL, and this mediating effect was significant (P < 0.05). Similarly, the direct effect of despondency on QOL was significant (P < 0.05). Moreover, social support played a mediating role between despondency and QOL, with a significant mediating effect (P < 0.05). CONCLUSION: These findings suggest that social support plays a significant mediating role in the relationship between dysphoria, despondency, and QOL in patients undergoing MHD.

3.
Nat Struct Mol Biol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632360

RESUMO

The Pyrococcus horikoshii amino acid transporter GltPh revealed, like other channels and transporters, activity mode switching, previously termed wanderlust kinetics. Unfortunately, to date, the basis of these activity fluctuations is not understood, probably due to a lack of experimental tools that directly access the structural features of transporters related to their instantaneous activity. Here, we take advantage of high-speed atomic force microscopy, unique in providing simultaneous structural and temporal resolution, to uncover the basis of kinetic mode switching in proteins. We developed membrane extension membrane protein reconstitution that allows the analysis of isolated molecules. Together with localization atomic force microscopy, principal component analysis and hidden Markov modeling, we could associate structural states to a functional timeline, allowing six structures to be solved from a single molecule, and an inward-facing state, IFSopen-1, to be determined as a kinetic dead-end in the conformational landscape. The approaches presented on GltPh are generally applicable and open possibilities for time-resolved dynamic single-molecule structural biology.

4.
Fitoterapia ; 175: 105956, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604261

RESUMO

ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism, and abnormally high expression of ACLY occurs in many diseases, including cancers, dyslipidemia and cardiovascular diseases. ACLY inhibitors are prospective treatments for these diseases. However, the scaffolds of ACLY inhibitors are insufficient with weak activity. The discovery of inhibitors with structural novelty and high activity continues to be a research hotpot. Acanthopanax senticosus (Rupr. & Maxim.) Harms is used for cardiovascular disease treatment, from which no ACLY inhibitors have ever been found. In this work, we discovered three novel ACLY inhibitors, and the most potent one was isochlorogenic acid C (ICC) with an IC50 value of 0.14 ± 0.04 µM. We found dicaffeoylquinic acids with ortho-dihydroxyphenyl groups were important features for inhibition by studying ten phenolic acids. We further investigated interactions between the highly active compound ICC and ACLY. Thermal shift assay revealed that ICC could directly bind to ACLY and improve its stability in the heating process. Enzymatic kinetic studies indicated ICC was a noncompetitive inhibitor of ACLY. Our work discovered novel ACLY inhibitors, provided valuable structure-activity patterns and deepened knowledge on the interactions between this targe tand its inhibitors.

5.
Psych J ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618755

RESUMO

The phenomenon of familial clustering in depression is well established, yet the mechanisms by which depression is transmitted within families remain poorly understood. In the current study, we investigate the familial genetic and environmental transmission of depression by incorporating data from both adolescent twins and their parents. A total of 987 twin families were recruited from the Beijing Twin Study. Depression assessments were conducted for both adolescents and their parents. Twins' depression was assessed through reports from both the twins themselves and their parents, while parental depression was assessed by parental self-report. We employed a nuclear twin family model to examine genetic and environmental influences on adolescent depression. Our results, based on both self- and parent-report, demonstrate significant additive and dominant genetic influences on depression. We also found mild yet significant sibling environmental influences, while familial environmental influences were absent. Notably, parent-reported depression showed higher heritability but lower unique environmental influences compared with self-reported depression. These results highlight the important role of genetic transmission and sibling environmental transmission in explaining depression. Our study delineates the underlying mechanism of familial transmission in depression and can inform early treatments to halt transmission during adolescence.

6.
Huan Jing Ke Xue ; 45(5): 2926-2938, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629554

RESUMO

With the rapid urbanization and industrialization, heavy metal contamination in urban soil and surface dust has received particular attention due to its negative effects on the eco-environment and human health. Contamination and spatio-temporal characteristics, contamination sources, and source apportionment methods, as well as the ecological and health risks of heavy metals in urban soil and surface dust were reviewed. The knowledge gaps in current research and prospects of future works were proposed. Four key points were presented, including improving the research on the interaction mechanism of heavy metals in urban soil and surface dust under complex conditions, enriching verification methods to improve the source apportionment reliability of anthropogenic metals by receptor models, strengthening the research on chemical forms of heavy metals from different sources and their short-term accumulation processes in surface dust, and raising the credibility of ecological and health risk forecast of heavy metals by integrating the improved exposure parameters and chemical forms.

7.
Front Oncol ; 14: 1345190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571508

RESUMO

Introduction: Tumor treating fields (TTFields) have earned substantial attention in recent years as a novel therapeutic approach with the potential to improve the prognosis of glioblastoma (GBM) patients. However, the impact of TTFields remains a subject of ongoing debate. This study aimed to offer real-world evidence on TTFields therapy for GBM, and to investigate the clinical determinants affecting its efficacy. Methods: We have reported a retrospective analysis of 81 newly diagnosed Chinese GBM patients who received TTFields/Stupp treatment in the Second Affiliated Hospital of Zhejiang University. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Cox regression models with time-dependent covariates were utilized to address non-proportional hazards and to assess the influence of clinical variables on PFS and OS. Results: The median PFS and OS following TTFields/STUPP treatment was 12.6 months (95% CI 11.0-14.1) and 21.3 months (95% CI 10.0-32.6) respectively. Long-term TTFields treatment (>2 months) exhibits significant improvements in PFS and OS compared to the short-term treatment group (≤2 months). Time-dependent covariate COX analysis revealed that longer TTFields treatment was correlated with enhanced PFS and OS for up to 12 and 13 months, respectively. Higher compliance to TTFields (≥ 0.8) significantly reduced the death risk (HR=0.297, 95%CI 0.108-0.819). Complete surgical resection and MGMT promoter methylation were associated with significantly lower risk of progression (HR=0.337, 95% CI 0.176-0.643; HR=0.156, 95% CI 0.065-0.378) and death (HR=0.276, 95% CI 0.105-0.727; HR=0.249, 95% CI 0.087-0.710). Conclusion: The TTFields/Stupp treatment may prolong median OS and PFS in GBM patients, with long-term TTFields treatment, higher TTFields compliance, complete surgical resection, and MGMT promoter methylation significantly improving prognosis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38563809

RESUMO

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

9.
Heliyon ; 10(7): e28386, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560250

RESUMO

Background: Immune escape remains a major challenge in the treatment of malignant tumors. Here, we studied the mechanisms underlying immune escape in the tumor microenvironment and identified a potential therapeutic target. Methods: Pathological specimens from patients with liver cancer, soft tissue sarcoma, and liver metastasis of colon cancer were subjected to immunohistochemistry analysis to detect the expression of programmed death-1 (PD-1) in the tumor microenvironment (TME). Additionally, the expression of regulatory T cells (Tregs) and long non-coding RNAs (lncRNAs), such as highly upregulated in liver cancer (HULC) was evaluated by fluorescence in situ hybridization, and the relationship between HULC, Treg cells, and PD-1 was determined. The animals were divided into H22 hepatic carcinoma and S180 sarcoma groups. Each group was divided into Foxp3-/-C57BL/6J and C57BL/6J mice. Thereafter, mice were inoculated with 0.1 ml S180 sarcoma cells or 0.1 ml H22 hepatoma cells, at a concentration of 1 × 107/ml. The number of splenic CD4+CD25+Foxp3+ T cells was detected by flow cytometry, and serum interleukin-10 (IL-10) and transforming growth factor ß1 (TGF-ß1) levels were detected using a Luminex liquid suspension chip. Expression of PD-1, fork head box P3 (Foxp3), and HULC in the TME, were analyzed and the therapeutic effect of inhibiting the lncRNA HULC-Treg-PD-1 axis in malignant tumors was determined. Results: High expression of lncRNA HULC promotes the proliferation of Treg cells and increases PD-1 expression in the tumor microenvironment. The HULC-Treg-PD-1 axis plays an immunosuppressive role and promotes the proliferation of malignant tumors. Knocking out the Foxp3 gene can affect the HULC-Treg-PD-1 axis and reduce PD-1, IL-10, and TGF-ß1 expression to control the growth of malignant tumors. Conclusion: The lncRNA HULC-Treg-PD-1 axis promotes the growth of malignant tumors. This axis could be modulated to reduce PD-1, IL-10, and TGF-ß1 expression and the subsequent immune escape. The inhibition of immune escape in the tumor microenvironment can be achieved by controlling the LncRNA HULC-Treg-PD-1 axis.

10.
J Nat Prod ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38603577

RESUMO

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

11.
J Diabetes ; 16(4): e13543, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584150

RESUMO

OBJECTIVE: To summarize the clinical characteristics and imaging manifestations of patients with nonketotic hyperglycemic hemichorea (NH-HC) and to explore the possible pathogenesis, diagnosis. and treatment of the disease in order to improve the understanding of this disease and avoid misdiagnosis. METHODS: Retrospective analysis was performed on the case data of five patients with NH-HC admitted to our hospital in recent years. The patients were treated in the department of endocrinology, department of neurology, and department of neurosurgery in our hospital, respectively. Meanwhile, relevant literatures were consulted for further learning. RESULTS: NH-HC is usually presented as a triad of nonketotic hyperglycemia, lateral chorea, and typical imaging manifestations of head magnetic resonance imaging or computed tomography, but the clinical manifestations are not the same, and imaging features may also be different, presenting a diversified trend in clinical practice. All five patients were given glucose-lowering drugs and improved with or without combination of drugs to control symptoms of chorea. CONCLUSION: NH-HC is a rare complication of diabetes, characterized by hyperglycemia and hemichorea. How to identify the extreme situation and make fast judgment is a top priority. Timely and correct control of blood glucose is the key to the treatment, and when necessary, application of dopamine receptor antagonists in patients with combination therapy can accelerate improvement of the clinical symptoms. The prognosis of NH-HC is good, the clinician should strengthen comprehensive understanding of this disease to avoid missed diagnosis or misdiagnosis and enable patients to get more timely and effective treatment.


Assuntos
Coreia , Diabetes Mellitus , Hiperglicemia , Humanos , Coreia/diagnóstico por imagem , Coreia/etiologia , Coreia/tratamento farmacológico , Estudos Retrospectivos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Imageamento por Ressonância Magnética/efeitos adversos
12.
Sci Rep ; 14(1): 8154, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589524

RESUMO

To study the aerodynamic performance and wind-induced response of carbon fiber-reinforced polymer (CFRP) cables, CFRP cable was designed by replacing a steel cable in a tied arch bridge based on stiffness, strength and area equivalent criteria, respectively. The aerodynamic performance and wind-induced response of CFRP cable and steel cable were studied and compared by computational fluid dynamics (CFD) model. Based on the computational results, optimal cable replacement criterion was proposed for CFRP cable to replace steel cable. In addition, surface modification was conducted by engrooving vertical symmetric (VS), vertical asymmetric (VA) and helical symmetric (HS) V-shaped grooves to improve the aerodynamic performance and wind-induced response of CFRP cable. Results showed that CFRP cables exhibited inferior aerodynamic performance and wind-induced response in most cases. However, CFRP cable based on stiffness equivalent criterion exhibited better aerodynamic performance and wind-induced vibration properties compared to the other two cable replacement criteria, thus is regarded as the optimal substitute for steel cable. In addition, HS grooves generated symmetric disturbances and caused approximately equivalent boundary layer separation delays uniformly and continuously along the cable length, thus exhibiting better effect in decreasing the reverse flow region, the maximum negative flow velocity, the vortex shedding frequency and the wind-induced vibration amplitude of CFRP cable. Hence, the stiffness equivalent criterion combined with surface modification with HS V-shaped grooves was proposed to replace steel cable with CFRP cable. This study can provide insights into the aerodynamic performance and wind-induced response of CFRP cable and instructions for cable replacement practice.

13.
BMC Genomics ; 25(1): 378, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632523

RESUMO

OBJECTIVE: This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. METHODS: Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. RESULTS: All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77-84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. CONCLUSION: SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Pandemias , Genômica , China , Aminoácidos , Nucleotídeos
15.
Environ Res ; 252(Pt 2): 118821, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615793

RESUMO

How microzooplanktonic ciliate adaptative strategies differ across diatom bloom and non-diatom bloom areas in the Arctic Ocean remains poorly documented. To address this gap, two different situations were categorized in the Arctic Ocean at summer 2023: diatom bloom stations (DBS) (genus Thalassiosira, chain-like) and non-diatom bloom stations (nDBS). Total abundance of ciliate at 3 m and 25 m in DBS was 2.8 and 1.8 folds higher than in nDBS, respectively. Aloricate ciliates were singled out in both DBS and nDBS, whilst their average abundance and biomass of large size-fraction (>50 µm) in former were 4.5-5.6 folds higher than in latter. Regarding tintinnids, high abundance of Ptychocylis acuta (Bering Strait species) mainly occurred at DBS, coupled with distribution of co-occurring Pacific-origin species Salpingella sp.1, collectively suggested a strong intrusion of Pacific Inflow during summer 2023. Additionally, presence of high abundance of Acanthostomella norvegica and genus Parafavella in nDBS might indicate the trajectory of the Transpolar Drift. Alternatively, tintinnids can serve as credible bioindicators for either monitoring currents or evaluating microzooplankton Borealization. Average abundance of total ciliate within 15-135 µm body-size spectrum in DBS was higher than nDBS. Moreover, spearman's rank correlation between biotic and abiotic analysis revealed that temperature and dissolved oxygen at DBS determined tintinnid species richness and ciliate total abundance, respectively. The results clearly demonstrate that remarkable divergences in large size-fraction of ciliate abundance between DBS and nDBS validate their irreplaceable role in controlling phytoplankton outbreak and associated biological processes in polar seas.

16.
Molecules ; 29(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611807

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved into a dangerous pathogen resistant to beta-lactam antibiotics (BLAs) and has become a worrisome superbug. In this study, a strategy in which shikimic acid (SA), which has anti-inflammatory and antibacterial activity, is combined with BLAs to restart BLA activity was proposed for MRSA treatment. The synergistic effects of oxacillin combined with SA against oxacillin resistance in vitro and in vivo were investigated. The excellent synergistic effect of the oxacillin and SA combination was confirmed by performing the checkerboard assay, time-killing assay, live/dead bacterial cell viability assay, and assessing protein leakage. SEM showed that the cells in the control group had a regular, smooth, and intact surface. In contrast, oxacillin and SA or the combination treatment group exhibited different degrees of surface collapse. q-PCR indicated that the combination treatment group significantly inhibited the expression of the mecA gene. In vivo, we showed that the combination treatment increased the survival rate and decreased the bacterial load in mice. These results suggest that the combination of oxacillin with SA is considered an effective treatment option for MRSA, and the combination of SA with oxacillin in the treatment of MRSA is a novel strategy.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Animais , Camundongos , Ácido Chiquímico/farmacologia , Monobactamas , 60693 , Oxacilina/farmacologia
17.
J Agric Food Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598771

RESUMO

Intramuscular fat (IMF) plays a crucial role in enhancing meat quality, enriching meat flavor, and overall improving palatability. In this study, Single-cell RNA sequencing was employed to analyze the longissimus dorsi (LD) obtained from Guangdong small-ear spotted pigs (GDSS, with high IMF) and Yorkshire pigs (YK, with low IMF). GDSS had significantly more Fibro/Adipogenic Progenitor (FAPs), in which the CD9 negative FAPs (FAPCD9-) having adipogenic potential, as demonstrated by in vitro assays using cells originated from mouse muscle. On the other hand, Yorkshire had more fibro-inflammatory progenitors (FIPs, marked with FAPCD9+), presenting higher expression of the FBN1-Integrin α5ß1. FBN1-Integrin α5ß1 could inhibit insulin signaling in FAPCD9-, suppressing adipogenic differentiation. Our results demonstrated that fat-type pigs possess a greater number of FAPCD9-, which are the exclusive cells in muscle capable of differentiating into adipocytes. Moreover, lean-type pigs exhibit higher expression of FBN1-Integrin α5ß1 axis, which inhibits adipocyte differentiation. These results appropriately explain the observed higher IMF content in fat-type pigs.

18.
Acad Radiol ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599906

RESUMO

RATIONALE AND OBJECTIVES: To explore and externally validate habitat-based radiomics for preoperative prediction of epidermal growth factor receptor (EGFR) mutations in exon 19 and 21 from MRI imaging of non-small cell lung cancer (NSCLC)-originated brain metastasis (BM). METHODS: A total of 170, 62 and 61 patients from center 1, center 2 and center 3, respectively were included. All patients underwent contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans. Radiomics features were extracted from the tumor active (TA) and peritumoral edema (PE) regions in each MRI slice. The most important features were selected by the least absolute shrinkage and selection operator regression to develop radiomics signatures based on TA (RS-TA), PE (RS-PE) and their combination (RS-Com). Receiver operating characteristic (ROC) curve analysis was performed to access performance of radiomics models for both internal and external validation cohorts. RESULTS: 10, four and six most predictive features were identified to be strongly associated with the EGFR mutation status, exon 19 and exon 21, respectively. The RSs derived from the PE region outperformed those from the TA region for predicting the EGFR mutation, exon 19 and exon 21. The RS-Coms generated the highest performance in the primary training (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.955 vs. 0.946 vs. 0.928), internal validation (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.879 vs. 0.819 vs. 0.882), external validation 1 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.830 vs. 0.825 vs. 0.822), and external validation 2 (AUCs, RS-EGFR-Com vs. RS-exon 19-Com vs. RS-exon 21-Com, 0.812 vs. 0.818 vs. 0.800) cohort. CONCLUSION: The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

19.
Front Endocrinol (Lausanne) ; 15: 1370457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633753

RESUMO

Introduction: Serum Klotho (S-Klotho) is a transmembrane protein holds pivotal roles in anti-aging. The Dietary Inflammation Index (DII), a meticulously dietary tool, quantifies the inflammatory potential of an individual's diet. The existing research strongly suggests that a low DII diet plays a significant role in delaying aging and reducing aging-related symptoms in males. Testosterone could potentially act as a mediating intermediary between DII and S-Klotho. However, this aspect remains unexplored. This study aims to investigate the potential causal link of testosterone between DII and S-Klotho in males. Methods: We utilized data from National Health and Nutrition Examination Survey (NHANES) which focused on male participants from 2013-2016. Mediation analyses were used to investigate the effects of testosterone (TT), free testosterone (FT), and free androgen index (FAI) on the DII-S-Klotho relationship, using three modes adjusting for covariates. Results: Mediation analysis unveiled a significant inverse correlation between DII and S-Klotho levels (model 1: c = -14.78, p = 0.046). The interaction between DII and S-Klotho was modulated by TT in model 1 (ab = -1.36; 95% CI: -5.59, -0.55; p = 0.008), but lost significance after adjustments (model 2: ab = -0.39; 95% CI: -4.15, 1.66; p = 0.378; model 3: ab = -0.59; 95% CI: -4.08, 2.15; p = 0.442). For FT, the mediating impact was not statistically significant (model 1: ab = 0.43; 95% CI: -0.51, 5.44; p = 0.188; model 2: ab = 0.72; 95% CI: -0.26, 5.91; p = 0.136; model 3: ab = 0.84; 95% CI: -0.02, 8.06; p = 0.056). Conversely, FAI consistently influenced the DII-S-Klotho relationship (model 1: ab = 2.39; 95% CI: 0.69, 9.42; p = 0.002), maintaining significance after adjustments (model 2: ab = 3.2; 95% CI: 0.98, 11.72; p = 0.004; model 3: ab = 3.15; 95% CI: 0.89, 14.51; p = 0.026). Discussion: This study observed no mediating influence of TT or FT on the correlation between DII and S-Klotho after covariate control. Remarkably, FAI continued to significantly mediate the DII-S-Klotho connection even following covariate adjustment, although its significance in males warrants careful consideration.


Assuntos
Dieta , Testosterona , Masculino , Humanos , Inquéritos Nutricionais , Envelhecimento , Inflamação
20.
Stress Health ; : e3404, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635165

RESUMO

The way individuals handle daily stressors can significantly influence their mental health. Those who struggle with emotion regulation are especially vulnerable to the negative effects of stress. This study explored the role of catastrophizing, a maladaptive emotion regulation strategy, in shaping the relationships between daily stress responses and depressive symptoms. A total of 75 healthy college students participated in the study. We adopted an Ecological Momentary Assessment protocol over 14 consecutive days to capture the day-to-day dynamics of stress reactivity and recovery. Our findings indicate that individuals with higher levels of catastrophizing exhibited increased daily stress reactivity and delayed daily stress recovery, consequently raising their likelihood of experiencing amplified depressive symptoms. In contrast, those with lower levels of catastrophizing did not experience the same negative effects of increased daily stress reactivity on their mental health. These results enhance understanding of how real-life stressors contribute to the development of mental health issues and underscore the importance of adaptive emotion regulation for improved overall health and well-being.

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