Objective:
Our study aimed to observe and evaluate the clinical value of interleukin (IL)-11 in the serum and exhaled breath condensate of patients with non-small cell lung cancer (NSCLC).
Methods:
A ...total of 91 patients with NSCLC and 72 healthy volunteers were included in this study. IL-11 concentration was determined by ELISA, and the relationship between IL-11 expression in serum and exhaled breath condensate specimens, and the clinicopathological characteristics of patients with NSCLC were analyzed. The relationship between serum IL-11 expression and traditional tumor markers and inflammation indicators of NSCLC was also analyzed. The correlation between serum IL-11 and exhaled breath condensate IL-11 level was determined. The receiver operating characteristic curve was used to evaluate the diagnostic value of IL-11 and carcinoembryonic antigen single and combined detection for NSCLC. The published data from online databases were used to analyze the relationship between the expression of IL-11 and the prognosis of NSCLC.
Results:
IL-11 concentration in serum and exhaled breath condensate specimens of patients with NSCLC were significantly increased. IL-11 expression was positively correlated with lymph node metastasis, distant metastasis, tumor node metastasis stage, and tumor differentiation degree of NSCLC. The expression of IL-11 in serum was positively correlated with that in exhaled breath condensate specimens. IL-11 expression was closely related to that of neutrophil-to-lymphocyte ratio and carcinoembryonic antigen. The combination of serum IL-11 with exhaled breath condensate IL-11 and carcinoembryonic antigen showed significantly higher diagnostic value than any one marker alone. Besides, the high IL-11 expression was closely related to the poor prognosis of NSCLC.
Conclusion:
IL-11 can be used as a potential diagnostic and prognostic biomarker for NSCLC.
This study develops a urea-based homogeneous precipitation method to synthesize spherical carbonate precursors (Ni0.25Mn0.75CO3) for the Li-rich layered cathode material Li(Ni0.2Li0.2Mn0.6)O2. The ...structure and morphology of the precursor particles were tailored by controlling of urea concentration, reaction temperature and time. Combined with XRD, SEM, and particle size analysis, the optimized conditions for synthesizing desired stoichiometric Ni0.25Mn0.75CO3 were obtained. We also investigated the processes of nucleation and growth of precursors. The obtained spherical Li(Ni0.2Li0.2Mn0.6)O2 delivers discharge capacity of 237 mAh g−1 at the initial cycle and 253 mAh g−1 after 50 cycles.
•(NixMn1−xCO3) is prepared via a urea-based homogeneous precipitation method.•The work presents the optimized conditions for the preparation of carbonate precursor.•It gives the nucleation and growth mechanism process of carbonate precursors.•The obtained powders exhibit good cycling performance.
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the ...pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)- stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome. Key words: Acute lung injury; Macrophages; L-carnitine; Lipid accumulation; Anti-inflammation
Objective:
Lung cancer is one of the most common malignant tumors in humans. Finding a highly sensitive and specific marker is very important. This study investigated the clinical significance of ...epidermal growth factor in exhaled breath condensate and serum of patients with non-small cell lung cancer.
Methods:
From October 17, 2013, to June 5, 2017, exhaled breath condensate and blood samples from 155 patients with non-small cell lung cancer, 63 patients with benign pulmonary nodules, and 115 healthy controls were collected using a breath condenser. Each sample was analyzed by enzyme-linked immunosorbent assay.
Results:
Epidermal growth factor level in the exhaled breath condensate from the non-small cell lung cancer group (197.86 ± 60.67 pg/mL) was higher than that in the healthy group (124.75 ± 36.09 pg/mL), P < .05. Epidermal growth factor level in the exhaled breath condensate of the smoking group (208.85 ± 40.94 pg/mL) was higher than that of the nonsmoking group (185.52 ± 36.88 pg/mL), P < .05. Epidermal growth factor level in the exhaled breath condensate in phases III and IV of non-small cell lung cancer group (212.17 ± 35.41 pg/mL) was higher than that in phases I and II (173.91 ± 38.08 pg/mL), P < .05. Epidermal growth factor level in the exhaled breath condensate of the death group (241.05 ± 27.19 pg/mL) was higher than that of the survival group (188.75 ± 37.07 pg/mL), P < .05. The epidermal growth factor exhaled breath condensate levels were positively correlated with the serum epidermal growth factor levels with a correlation coefficient of 0.495 (P < .05). The sensitivity and specificity of epidermal growth factor exhaled breath condensate test were 80.0% and 89.6%, respectively.
Conclusion:
The detection of epidermal growth factor level in exhaled breath condensate exhibits is important in the diagnosis, disease monitoring, and prognosis of non-small cell lung cancer.
Recently, several molecular subtypes with different prognosis have been found in lung adenocarcinoma (LUAD). However, the characteristics of the ferroptosis molecular subtypes and the associated ...tumor microenvironment (TME) cell infiltration have not been fully studied in LUAD.
Using 1160 lung adenocarcinoma samples, we explored the molecular subtypes mediated by ferroptosis-related genes, along with the associated TME cell infiltration. The ferroptosis score was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to quantify the ferroptosis characteristics of a single tumor.
Three different molecular subtypes related to ferroptosis, with different prognoses, were identified in LUAD. Analysis of TME cell infiltration revealed immune heterogeneity among the three subtypes. Cluster A was characterized by immunosuppression and was associated with stromal activation. Cluster C was characterized by a large number of immune cells infiltrating the TME, promoting tumor immune response, and it was significantly enriched in immune activation-related signaling pathways. Relatively less infiltration of immune cells was a feature of cluster B. The ferroptosis score can predict tumor subtype, immunity and prognosis. A low ferroptosis score was characterized by immune activation and good prognosis, as seen in the cluster C subtype. Relative immunosuppression and poor prognosis were the characteristics of a high ferroptosis score, as seen in cluster A and B subtypes. At the same time, the anti-PD-1/L1 immunotherapy cohort demonstrated that a low ferroptosis score was associated with higher efficacy of immunotherapy.
The ferroptosis score is a promising biomarker that could be of great significance to determine the prognosis, molecular subtypes, TME cell infiltration characteristics and immunotherapy effects in patients with LUAD.
We report a method to eliminate the irreversible capacity of 0.4Li_2MnO_3·0.6LiNi_（0.5）Mn_（0.5）O_2（Li_（1.17）Ni_（0.25）Mn_（0.583）O_2） by decreasing lithium content to yield integrated layered-spinel ...structures.XRD patterns,High-resolution TEM image and electrochemical cycling of the materials in lithium cells revealed features consistent with the presence of spinel phase within the materials.When discharged to about 2.8 V,the spinel phase of LiM_2O_4（M=Ni,Mn） can transform to rock-salt phase of Li_2M_2O_4（M=Ni,Mn） during which the tetravalent manganese ions are reduced to an oxidation state of 3.0.So the spinel phase can act as a host to insert back the extracted lithium ions（from the layered matrix） that could not embed back into the layered lattice to eliminate the irreversible capacity loss and increase the discharge capacity.Their electrochemical properties at room temperature showed a high capacity（about 275 mAh g~（-1） at 0.1 C） and exhibited good cycling performance.
G protein-coupled receptor kinase 6 (GRK6) is expressed in various tissues and is involved in the development of several diseases including lung cancer. We previously reported that GRK6 is ...down-regulated in lung adenocarcinoma patients, which induces cell invasion and metastasis. However, further understanding of the role of GRK6 in lung adenocarcinoma is required. Here we explored the functional consequence of
inhibition in lung epithelial cells. Analysis of TCGA data was coupled with RNA sequencing (RNA-seq) in alveolar epithelial type II (ATII) cells following depletion of
with RNA interference (RNAi). Findings were validated in ATII cells followed by tissue microarray analysis. Pathway analysis suggested that one of the Hallmark pathways enriched upon GRK6 inhibition is 'Hallmark_Hypoxia' (FDR = 0.014). We demonstrated that
depletion induces HIF1α (hypoxia-inducible factor 1 alpha) levels and activity in ATII cells. The findings were further confirmed in lung adenocarcinoma samples, in which GRK6 expression levels negatively and positively correlate with HIF1α expression (
= 0.015) and VHL expression (
< 0.0001), respectively. Mechanistically, we showed the impact of GRK6 on HIF activity could be achieved
regulation of VHL levels. Taken together, targeting the HIF pathway may provide new strategies for therapy in GRK6-depleted lung adenocarcinoma patients.
We previously reported that the expression of G protein‐coupled receptor kinase 6 (GRK6) is significantly downregulated in lung adenocarcinoma (LADC) tissues, and low expression levels of GRK6 are ...correlated with poor survival prognosis. However, the specific regulatory mechanisms and functions of GRK6 in LADC remain unknown. Here, we report that GRK6 mRNA expression levels are downregulated in LADC tissues compared to those in matched adjacent non‐tumor tissues (P < 0.001). The promoter of the GRK6 gene was found to be hypermethylated in LADC tissues, and its methylation was correlated with both GRK6 expression and pathology grade. GRK6 promoter hypermethylation may predict shorter overall survival. Treatment with 5‐aza‐2′‐deoxycytidine significantly enhanced GRK6 gene expression. Four binding sites of CCAAT/enhancer‐binding protein‐α (C/EBPα) in the CpG island of the GRK6 gene promoter were predicted in silico, of which three sites were further confirmed by ChIP. Decreased binding of C/EBPα to binding sites 1, 3 and 4 of the GRK6 gene promoter was observed in LADC tissues. Inhibition of C/EBPα significantly inhibited GRK6 expression, while overexpression of C/EBPα significantly promoted GRK6 expression. In addition, overexpression of GRK6 significantly suppressed, while GRK6 knockdown promoted cell migration and invasion. Overexpression of GRK6 enhanced E‐cadherin expression and suppressed vimentin expression, and silencing of GRK6 had the opposite effects. Furthermore, ectopic expression of GRK6 significantly decreased matrix metalloproteinase (MMP) 2 and MMP7 protein expression levels. Our findings suggest that hypermethylation of the GRK6 gene promoter suppressed binding of C/EBPα, thereby contributing to the promotion of cell migration and invasion. The methylation status of the GRK6 promoter might be suitable for use as an epigenetic biomarker, and the C/EBPα–GRK6 signaling pathway may be a potential target for LADC.
Hypermethylation of the G protein‐coupled receptor kinase 6 (GRK6) gene promoter suppresses binding of C/EBPα in lung adenocarcinoma (LADC), thereby contributing to the promotion of cell migration and invasion. The methylation status of the GRK6 promoter might be suitable for use as an epigenetic biomarker, and the C/EBPα–GRK6 signaling pathway may be a potential target for LADC.
Tumor suppressor epigenetic silencing plays an important role in non-small cell lung cancer (NSCLC) development and progression. Previously, the expression of speckle-type POZ protein (SPOP) has been ...found to be significantly inhibited in NSCLC. Our research aimed to investigate the molecular mechanisms, clinical significance and epigenetic alteration of SPOP in NSCLC.
Bisulfite sequencing PCR and methylation-specific PCR were performed to test gene methylation. Chromatin immunoprecipitation (ChIP) was performed to detect transcription factor C/EBPα combinations and the promoter of the SPOP gene. Furthermore, we evaluated the effects of C/EBPα siRNA on SPOP expression, tumor cell migration and proliferation via MTT and Transwell assays in vitro and tumor growth in vivo. The relationship between the methylation status of the SPOP gene and clinicopathologic characteristics was investigated.
Hypermethylation was found in the CpG island of the SPOP gene promoter in NSCLC tissues, and this methylation was found to be correlated with SPOP expression. SPOP promoter methylation was associated with the pathology grade. The transcriptional activities were significantly inhibited by the hypermethylation of specific CpG sites within the SPOP gene promoter, while 5-aza-2'-deoxycytidine significantly increased SPOP gene expression. C/EBPα also played a key role in SPOP regulation. Five C/EBPα binding sites in the CpG island of the SPOP gene promoter were identified by ChIP. Inhibition of C/EBPα significantly reduced SPOP expression. SPOP mediated the C/EBPα-regulated suppression of invasion, migration and proliferation in vitro and tumor growth in vivo.
SPOP function and expression in NSCLS were regulated by DNA methylation and C/EBPα transcriptional regulation combination effects, indicating that the SPOP promoter methylation status could be utilized as an epigenetic biomarker and that the C/EBPα-SPOP signaling pathway could be a potential therapeutic target in NSCLC.
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Cognitive assessment plays a pivotal role in the early detection of cognitive impairment, particularly in the prevention and management of cognitive diseases such as Alzheimer’s and ...Lewy body dementia. Large-scale screening relies heavily on cognitive assessment scales as primary tools, with some low sensitivity and others expensive. Despite significant progress in machine learning for cognitive function assessment, its application in this particular screening domain remains underexplored, often requiring labor-intensive expert annotations.
This paper introduces a semi-supervised learning algorithm based on pseudo-label with putback (SS-PP), aiming to enhance model efficiency in predicting the high risk of cognitive impairment (HR-CI) by utilizing the distribution of unlabeled samples.
The study involved 189 labeled samples and 215,078 unlabeled samples from real world. A semi-supervised classification algorithm was designed and evaluated by comparison with supervised methods composed by 14 traditional machine-learning methods and other advanced semi-supervised algorithms.
The optimal SS-PP model, based on GBDT, achieved an AUC of 0.947. Comparative analysis with supervised learning models and semi-supervised methods demonstrated an average AUC improvement of 8% and state-of-art performance, repectively.
This study pioneers the exploration of utilizing limited labeled data for HR-CI predictions and evaluates the benefits of incorporating physical examination data, holding significant implications for the development of cost-effective strategies in relevant healthcare domains.
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