Association of High Body Mass Index in Early Life With the Development of Colorectal Cancer.

SIGNIFICANCE: This study on the relationship between early life high BMI and the development of CRC reveals the role of high BMI during childhood and adolescence in the occurrence and progression of CRC. It suggests the importance of restoring normal weight or reducing weight in individuals with high BMI early in life for the prevention of colorectal cancer.

RHOF activation of AKT/ß-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance.

Acute myeloid leukemia (AML) is a clonal malignancy originating from leukemia stem cells, characterized by a poor prognosis, underscoring the necessity for novel therapeutic targets and treatment methodologies. This study focuses on Ras homolog family member F, filopodia associated (RHOF), a Rho guanosine triphosphatase (GTPase) family member. We found that RHOF is overexpressed in AML, correlating with an adverse prognosis. Our gain- and loss-of-function experiments revealed that RHOF overexpression enhances proliferation and impedes apoptosis in AML cells in vitro. Conversely, genetic suppression of RHOF markedly reduced the leukemia burden in a human AML xenograft mouse model. Furthermore, we investigated the synergistic effect of RHOF downregulation and chemotherapy, demonstrating significant therapeutic efficacy in vivo. Mechanistically, RHOF activates the AKT/ß-catenin signaling pathway, thereby accelerating the progression of AML. Our findings elucidate the pivotal role of RHOF in AML pathogenesis and propose RHOF inhibition as a promising therapeutic approach for AML management.

Investigation of Fe-Ni Battery/Module for Grid Service Duty Cycles.

Iron-nickel (Fe-Ni) batteries are renowned for their durability and resilience against overcharging and operating temperatures. However, they encounter challenges in achieving widespread adoption for energy storage applications due to their low efficiency and the need for regular maintenance and electrolyte replacement, which adds to maintenance costs. This study evaluates and demonstrates the capabilities of Fe-Ni batteries for participating in grid energy storage applications. Stable performance was observed frequency regulation (FR) testing at 100% and 50% state of charge (SOC)s, while at 50% SOC, there was a 14% increase in efficiency compared to 100% SOC. Although 25% SOC achieved higher efficiency, limited cyclability was observed due to reaching the discharge cutoff voltage. Optimal SOC selection, battery monitoring, maintenance, and appropriate charging strategies of Fe-Ni batteries seem to be crucial for their FR applications. Fe-Ni batteries exhibit stable peak shaving (PS) results, indicating their suitability and reliability under various load conditions for PS testing. Extended cycling tests confirm their potential for long-term grid-scale energy storage, enhancing their appeal for PS and FR applications.

Correlation between hemoglobin and the risk of common malignant tumors: a 1999-2020 retrospective analysis and causal association analysis.

BACKGROUND: The role of hemoglobin (HGB) in common malignant tumors remains unclear. METHODS: A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve. RESULTS: High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05). CONCLUSION: High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.

The causal relationship between COVID-19 and ten esophageal diseases: a study utilizing Mendelian randomization.

Background: Clinical signs of dysphagia, pancreatic achalasia, and esophagitis have been reported in patients with COVID-19. However, the causal relationship between COVID-19 and esophageal diseases is not clear. Therefore, we utilized Mendelian randomization to explore the potential association between COVID-19 and esophageal diseases. Methods: The summary statistics for a Genome-wide association study (GWAS) were obtained from The COVID-19 Host Genetics Initiative, encompassing four types of COVID-19 as exposure: severe COVID-19, hospitalized COVID-19 versus ambulatory COVID-19, hospitalized COVID-19 versus uninfected, and confirmed COVID-19. Additionally, summary statistics for ten esophageal diseases as outcomes were sourced from the GWAS Catalog and FinnGen databases. Univariate Mendelian randomization (MR) analysis was utilized to thoroughly investigate and validate the potential causal association between COVID-19 and various esophageal conditions, including esophageal varices, Barrett's esophagus, esophagitis, esophageal obstruction, esophageal ulcer, esophageal perforation, gastroesophageal reflux, congenital esophageal malformations, benign esophageal tumors, and esophageal adenocarcinoma. Results: An inverse variance-weighted (IVW) model was utilized for univariate Mendelian randomization (MR) analysis, which revealed that genetic liability in patients with confirmed COVID-19 was associated with esophageal obstruction (OR [95% CI]: 0.5275458 [0.2822400-0.9860563]; p-value = 0.0450699). Furthermore, a suggestive causal association was found between genetic liability and a reduced risk of benign esophageal tumors (OR [95% CI]: 0.2715453 [0.09368493-0.7870724]; p-value = 0.0163510), but with a suggestively increased risk of congenital esophageal malformations (OR [95% CI]: 6.959561 [1.1955828-40.51204]; p-value = 0.03086835). Additionally, genetic liability in hospitalized COVID-19 patients, compared to non-hospitalized COVID-19 patients, was suggestively associated with an increased risk of esophagitis (OR [95% CI]: 1.443859 [1.0890568-1.914252]; p-value = 0.01068201). The reliability of these causal findings is supported by Cochran's Q statistic and the MR-Egger intercept test. Conclusion: The results of this study suggest the existence of a causal relationship between COVID-19 and esophageal diseases, highlighting differing risk effects of COVID-19 on distinct esophageal conditions.

GTSE1: A potential prognostic and diagnostic biomarker in various tumors including lung adenocarcinoma.

OBJECTIVE: This research was aimed to comprehensively investigate the expression levels, diagnostic and prognostic implications, and the relationship with immune infiltration of G2 and S phase-expressed-1 (GTSE1) across 33 tumor types, including lung adenocarcinoma (LUAD), through gene expression profiling. METHODS: GTSE1 mRNA expression data together with clinical information were acquired from Xena database of The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene Expression Omnibus (GEO) database for this study. The Wilcoxon rank-sum test was used to detect differences in GTSE1 expression between groups. The ability of GTSE1 to accurately predict cancer status was evaluated by calculating the area under the curve (AUC) value for the receiver operating characteristic curve. Additionally, we investigated the predictive value of GTSE1 in individuals diagnosed with neoplasms using univariate Cox regression analysis as well as Kaplan-Meier curves. Furthermore, the correlation between GTSE1 expression and levels of immune infiltration was assessed by utilizing the Tumor Immune Estimate Resource (TIMER) database to calculate the Spearman rank correlation coefficient. Finally, the pan-cancer analysis findings were validated by examining the association between GTSE1 expression and prognosis among patients with LUAD. RESULTS: GTSE1 exhibited significantly increased expression levels in a wide range of tumor tissues in contrast with normal tissues (p < 0.05). The expression of GTSE1 in various tumors was associated with clinical features, overall survival, and disease-specific survival (p < 0.05). In immune infiltration analyses, a strong correlation of the level of immune infiltration with the expression of GTSE1 was observed. Furthermore, GTSE1 demonstrated good discriminative and diagnostic value for most tumors. Additional experiments confirmed the relationship between elevated GTSE1 expression and unfavorable prognosis in individuals diagnosed with LUAD. These findings indicated the crucial role of GTSE1 expression level in influencing the development and immune infiltration of different types of tumors. CONCLUSIONS: GTSE1 might be a potential biomarker for the prognosis of pan-cancer. Meanwhile, it represented a promising target for immunotherapy.

Stress granule-localized USP8 potentiates cGAS-mediated type I interferonopathies through deubiquitination of DDX3X.

Cyclic GMP-AMP synthase (cGAS) undergoes liquid-liquid phase separation (LLPS) to trigger downstream signaling upon double-stranded DNA (dsDNA) stimulation, and the condensed cGAS colocalizes with stress granules (SGs). However, the molecular mechanism underlying the modulation of cGAS activation by SGs remains elusive. In this study, we show that USP8 is localized to SGs upon dsDNA stimulation and potentiates cGAS-stimulator of interferon genes (STING) signaling. A USP8 inhibitor ameliorates pathological inflammation in Trex1-/- mice. Systemic lupus erythematosus (SLE) databases indicate a positive correlation between USP8 expression and SLE. Mechanistic study shows that the SG protein DDX3X promotes cGAS phase separation and activation in a manner dependent on its intrinsic LLPS. USP8 cleaves K27-linked ubiquitin chains from the intrinsically disordered region (IDR) of DDX3X to enhance its condensation. In conclusion, we demonstrate that USP8 catalyzes the deubiquitination of DDX3X to facilitate cGAS condensation and activation and that inhibiting USP8 is a promising strategy for alleviating cGAS-mediated autoimmune diseases.

Targeted delivery of HSP90 inhibitors for efficient therapy of CD44-positive acute myeloid leukemia and solid tumor-colon cancer.

Heat shock protein 90 (HSP90) is overexpressed in numerous cancers, promotes the maturation of numerous oncoproteins and facilitates cancer cell growth. Certain HSP90 inhibitors have entered clinical trials. Although less than satisfactory clinical effects or insurmountable toxicity have compelled these trials to be terminated or postponed, these results of preclinical and clinical studies demonstrated that the prospects of targeting therapeutic strategies involving HSP90 inhibitors deserve enough attention. Nanoparticulate-based drug delivery systems have been generally supposed as one of the most promising formulations especially for targeting strategies. However, so far, no active targeting nano-formulations have succeeded in clinical translation, mainly due to complicated preparation, complex formulations leading to difficult industrialization, incomplete biocompatibility or nontoxicity. In this study, HSP90 and CD44-targeted A6 peptide functionalized biomimetic nanoparticles (A6-NP) was designed and various degrees of A6-modification on nanoparticles were fabricated to evaluate targeting ability and anticancer efficiency. With no excipients, the hydrophobic HSP90 inhibitor G2111 and A6-conjugated human serum albumin could self-assemble into nanoparticles with a uniform particle size of approximately 200 nm, easy fabrication, well biocompatibility and avoidance of hepatotoxicity. Besides, G2111 encapsulated in A6-NP was only released less than 5% in 12 h, which may avoid off-target cell toxicity before entering into cancer cells. A6 peptide modification could significantly enhance uptake within a short time. Moreover, A6-NP continues to exert the broad anticancer spectrum of Hsp90 inhibitors and displays remarkable targeting ability and anticancer efficacy both in hematological malignancies and solid tumors (with colon tumors as the model cancer) both in vitro and in vivo. Overall, A6-NP, as a simple, biomimetic and active dual-targeting (CD44 and HSP90) nanomedicine, displays high potential for clinical translation.

A machine learning approach to predicting vascular calcification risk of type 2 diabetes: A retrospective study.

BACKGROUND: Recently, patients with type 2 diabetes mellitus (T2DM) have experienced a higher incidence and severer degree of vascular calcification (VC), which leads to an increase in the incidence and mortality of vascular complications in patients with T2DM. HYPOTHESIS: To construct and validate prediction models for the risk of VC in patients with T2DM. METHODS: Twenty-three baseline demographic and clinical characteristics were extracted from the electronic medical record system. Ten clinical features were screened with least absolute shrinkage and selection operator method and were used to develop prediction models based on eight machine learning (ML) algorithms (k-nearest neighbor [k-NN], light gradient boosting machine, logistic regression [LR], multilayer perception [(MLP], Naive Bayes [NB], random forest [RF], support vector machine [SVM], XGBoost [XGB]). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, and precision. RESULTS: A total of 1407 and 352 patients were retrospectively collected in the training and test sets, respectively. Among the eight models, the AUC value in the NB model was higher than the other models (NB: 0.753, LGB: 0.719, LR: 0.749, MLP: 0.715, RF: 0.722, SVM: 0.689, XGB:0.707, p < .05 for all). The k-NN model achieved the highest sensitivity of 0.75 (95% confidence interval [CI]: 0.633-0.857), the MLP model achieved the highest accuracy of 0.81 (95% CI: 0.767-0.852) and specificity of 0.875 (95% CI: 0.836-0.912). CONCLUSIONS: This study developed a predictive model of VC based on ML and clinical features in type 2 diabetic patients. The NB model is a tool with potential to facilitate clinicians in identifying VC in high-risk patients.

Prognostic value of PAX8 in small cell lung cancer.

Objectives: Small cell lung cancer (SCLC) shows poor prognosis since it metastasizes widely at early stage. Paired box gene (PAX) 8 is a transcriptional factor of PAX family, of which the expression in lung cancer is a controversial issue, and its prognostic value of PAX8 in SCLC is still unclear. Materials and methods: Overall, 184 subjects who were pathologically diagnosed with SCLC were enrolled in the study. Immunohistochemical analysis of PAX8 and Ki-67 were performed. The correlations between PAX8 expression and clinical features or Ki-67 index were further analyzed. Subsequently, an analysis of the association between PAX8, stage, Ki-67 status, and overall survival (OS) were performed in 169 subjects with follow-up information. Results: PAX8 was positive in 53.8% (99/184) SCLC specimens. The positive rate is significantly higher in extensive-stage specimens (61.0%) than in limited-stage specimens (45.24%). PAX8 expression is positively correlated with Ki-67 index (P = 0.001) while negatively correlated with OS (HR = 3.725, 95% CI 1.943-7.139, P＜0.001). In combination groups, the PAX8 negative and limited stage group had the most promising OS. Conclusion: PAX8 expression rate in SCLC specimens is not low. It has prognostic value in small cell lung cancer.

A novel prognostic signature of coagulation-related genes leveraged by machine learning algorithms for lung squamous cell carcinoma.

Coagulation-related genes (CRGs) have been demonstrated to be essential for the development of certain tumors; however, little is known about CRGs in lung squamous cell carcinoma (LUSC). In this study, we adopted CRGs to construct a coagulation-related gene prognostic signature (CRGPS) using machine learning algorithms. Using a set of 92 machine learning integrated algorithms, the CRGPS was determined to be the optimal prognostic signature (median C-index = 0.600) for predicting the prognosis of an LUSC patient. The CRGPS was not only superior to traditional clinical parameters (e.g., T stage, age, and gender) and its commutative genes but also outperformed 19 preexisting prognostic signatures for LUSC on predictive accuracy. The CRGPS score was positively correlated with poor prognoses in patients with LUSC (hazard ratio > 1, p < 0.05), indicating its suitability as a prognostic marker for this disease. The CRGPS was observed to be inversely correlated with the degree of infiltration of natural killer cells. For some tumors, patients with lower CRGPS scores are more likely to experience enhanced immunotherapy effects (area under the curve = 0.70), which implies that the CRGPS can potentially predict immunotherapy efficacy. A high CRGPS score is predictive of an LUSC patient being sensitive to several drugs. Collectively, these findings indicate that the CRGPS may be a reliable indicator of the prognoses of patients with LUSC and may be useful for the clinical management of such patients.

Phosphonate-based iron complex for a cost-effective and long cycling aqueous iron redox flow battery.

A promising metal-organic complex, iron (Fe)-NTMPA2, consisting of Fe(III) chloride and nitrilotri-(methylphosphonic acid) (NTMPA), is designed for use in aqueous iron redox flow batteries. A full-cell testing, where a concentrated Fe-NTMPA2 anolyte (0.67 M) is paired with a Fe-CN catholyte, demonstrates exceptional cycling stability over 1000 charge/discharge cycles, and noteworthy performances, including 96% capacity utilization, a minimal capacity fade rate of 0.0013% per cycle (1.3% over 1,000 cycles), high Coulombic efficiency and energy efficiency near 100% and 87%, respectively, all achieved under a current density of 20 mA·cm-². Furthermore, density functional theory unveils two potential coordination structures for Fe-NTMPA2 complexes, improving the understanding between the ligand coordination environment and electron transfer kinetics. When paired with a high redox potential Fe-Dcbpy/CN catholyte, 2,2'-bipyridine-4,4'-dicarboxylic (Dcbpy) acid and cyanide (CN) ligands, Fe-NTMPA2 demonstrates a notably elevated cell voltage of 1 V, enabling a practical energy density of up to 9 Wh/L.

MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma.

OBJECTIVE: This study sought to explore the clinical value of matrix metalloproteinases 12 (MMP12) in multiple cancers, including lung adenocarcinoma (LUAD). METHODS: Using >10,000 samples, this retrospective study demonstrated the first pan-cancer analysis of MMP12. The expression of MMP12 between cancer groups and their control groups was analyzed using Wilcoxon rank-sum tests. The clinical significance of MMP12 expression in multiple cancers was assessed using receiver operating characteristic curves, Kaplan-Meier curves, and univariate Cox analysis. A further LUAD-related analysis based on 4565 multi-center and in-house samples was performed to verify the findings regarding MMP12 in pan-cancer analysis partly. RESULTS: MMP12 mRNA is highly expressed in 13 cancers compared to their controls, and the MMP12 protein level is elevated in some of these cancers (e.g., colon adenocarcinoma) (P < .05). MMP12 expression makes it feasible to distinguish 21 cancer tissues from normal tissues (AUC = 0.86). A high MMP12 expression is a prognosis risk factor in eight cancers, such as adrenocortical carcinoma (hazard ratio >1, P < .05). The elevated MMP12 expression is also a prognosis protective factor in breast-invasive carcinoma and colon adenocarcinoma (hazard ratio <1, P < .05). Some pan-cancer findings regarding MMP12 are verified in LUAD-MMP12 expression is upregulated in LUAD at both the mRNA and protein levels (P < .05), has the potential to distinguish LUAD with considerable accuracy (AUC = .91), and plays a risk prognosis factor for patients with the disease (P < .05). CONCLUSIONS: MMP12 is highly expressed in most cancers and may serve as a novel biomarker for the prediction and prognosis of numerous cancers.

Clinical significance and prospective mechanism of increased CDKN2A expression in small cell lung cancer.

BACKGROUND: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. METHODS: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan-Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. RESULTS: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. CONCLUSION: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.

The distribution and enrichment characteristics of rare earth elements between coals and coal ashes from four coal-fired power plants.

Coal and coal ash (slag and fly ash) have emerged as important potential sources for rare earth elements (REY). The distribution and enrichment of REY during coal combustion from coal-fired power plants are of great significance for the recovery of REY. In this study, the concentration of REY in coal and coal ash from four coal-fired power plants in China was determined using microwave digestion-inductively coupled plasma mass spectrometry. The distribution and enrichment characteristics of REY in coal and coal ash were studied. The coal ash contains 310-683 µg g-1 of REY, and the proportion of critical REY was greater than 30%, which is higher than the extraction concentration (300 µg g-1) recommended by the United States Department of Energy, indicating significant REY recovery potential. The concentration of REY in coal was positively correlated with ash yield, which could be explained by the fact that REY are mainly distributed in minerals. Coal and coal ash show similar REY distribution patterns, indicating that REY were not fractionated during the coal combustion. In addition, the enrichment coefficient of REY in fly ash was greater than that in slag, which revealed that REY were mainly enriched in fly ash. Therefore, the REY in fly ash has more recycling potential.

Prediction of lymph node metastasis of lung squamous cell carcinoma by machine learning algorithm classifiers.

BACKGROUND: Lymph node metastasis (LNM) is an essential factor affecting the prognosis of patients with lung squamous cell carcinoma (LUSC), as well as a critical consideration for the choice of treatment strategy. Exploring effective methods for predicting LNM in LUSC may benefit clinical decision making. MATERIALS AND METHODS: We used data collected from the Surveillance, Epidemiology, and End Results (SEER) database to develop machine learning algorithm classifiers, including boosted trees (BTs), based on the primary clinical parameters of patients to predict LNM in LUSC. Training on a large-sample training cohort (n = 8,063) allowed for the construction of several concise classifiers for LNM prediction in LUSC, which were then validated using test and in-house cohorts (n = 2,017 and 57, respectively). RESULTS: The six classifiers established in this research enabled distinction between patients with and without LNM. Among these classifiers, the BT classifier was the top performer, with accuracy, F1 scores, precision, recall, sensitivity, and specificity values of 0.654, 0.621, 0.654, 0.592, 0.592, and 0.711, respectively. The precision recall (PR) and receiver operating characteristic (ROC) (with area under the curve = 0.714) curves also supported this result, which was validated by the in-house cohort. Notably, the tumor stage was a critical factor in determining LNM in patients with LUSC. CONCLUSIONS: The use of classifiers, especially the BT classifier, may serve as a useful tool for improving clinical precision and individualized treatment of patients with LUSC.

CDK6 is a novel predictive and prognosis biomarker correlated with immune infiltrates in multiple human neoplasms, including small cell lung carcinoma.

The roles of cyclin-dependent kinase 6 (CDK6) in various cancers, including small cell lung carcinoma (SCLC), remain unclear. Here, 111,54 multi-center samples were investigated to determine the expression, clinical significance, and underlying mechanisms of CDK6 in 34 cancers. The area under the curve (AUC), Cox regression analysis, and the Kaplan-Meier curves were used to explore the clinical value of CDK6 in cancers. Gene set enrichment analysis and correlation analysis were performed to detect potential CDK6 mechanisms. CDK6 expression was essential in 24 cancer cell types. Abnormal CDK6 expression was observed in 14 cancer types (e.g., downregulated in breast invasive carcinoma; p < 0.05). CDK6 allowed six cancers to be distinguished from their controls (AUC > 0.750). CDK6 expression was a prognosis marker for 13 cancers (e.g., adrenocortical carcinoma; p < 0.05). CDK6 was correlated with several immune-related signaling pathways and the infiltration levels of certain immune cells (e.g., CD8+ T cells; p < 0.05). Downregulated CDK6 mRNA and protein levels were observed in SCLC (p < 0.05, SMD = - 0.90). CDK6 allowed the identification of SCLC status (AUC = 0.91) and predicted a favorable prognosis for SCLC patients (p < 0.05). CDK6 may be a novel biomarker for the prediction and prognosis of several cancers, including SCLC.

ITGB4 Serves as an Identification and Prognosis Marker Associated with Immune Infiltration in Small Cell Lung Carcinoma.

Integrin beta 4 (ITGB4) is a vital factor for numerous cancers. However, no reports regarding ITGB4 in small cell lung carcinoma (SCLC) have been found in the existing literature. This study systematically investigated the expression and clinical value of ITGB4 in SCLC using multi-center and large-sample (n = 963) data. The ITGB4 expression levels between SCLC and control tissues were compared using standardized mean difference and Wilcoxon rank-sum test. The clinical significance of the gene in SCLC was observed using Cox regression and Kaplan-Meier curves. ITGB4 is overexpressed in multiple cancers and represents significant value in distinguishing among cancer samples (AUC = 0.91) and predicting the prognoses (p < 0.05) of patients with different cancers. In contrast, decreased ITGB4 mRNA expression was determined in SCLC (SMD < 0), and this finding was further confirmed at protein levels using in-house specimens (p < 0.05). This decrease in expression may be attributed to the regulatory role of estrogen receptor 1. ITGB4 may participate in the progression of SCLC by affecting several signaling pathways (e.g., tumor necrosis factor signaling pathway) and a series of immune cells (e.g., dendritic cells) (p < 0.05). The gene may serve as a potential marker for predicting the disease status (AUC = 0.97) and prognoses (p < 0.05) of patients with SCLC. Collectively, ITGB4 was identified as an identification and prognosis marker associated with immune infiltration in SCLC.

Elevated profiles of peripheral Th22, Th17, Th2 cells, and decreased percentage of Th1 cells in breast cancer patients.

BACKGROUND: Th22 subset is a particular type of CD4+ T helper cells subset. Our study aimed to explore the expression level of circulating Th22, Th17, Th1, and Th2 cells and the possible mechanism of these cells in breast cancer (BC) with different pathological features. METHODS: Our study enrolled 43 newly diagnosed BC patients and 30 healthy controls. Frequencies of peripheral Th22, Th17, Th1, and Th2 cells were tested by flow cytometry. Concentrations of IL-22 cytokine in plasma were examined by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was done to test aromatic hydrocarbon receptor (AHR) and RAR-associated orphan receptor C (RORC) gene expression. RESULTS: Frequencies of Th22, Th17, Th2 subsets, and the plasma IL-22 level was obviously higher in the BC patients. A positive correlation between Th22 frequency and IL-22 concentration in plasma was detected in BC patients. Furthermore, the percentage of Th22, Th2 subsets in peripheral blood of HER2 positive BC was higher than that in HER2 negative BC patients. A negative correlation between Th1 subset and Ki-67% as well as a positive correlation between Th2 subset and Ki-67% was found in BC patients. The proportion of Th1 cells in BC patients was significantly lower than that of the control group. Expression of AHR and RORC transcription factors were also observed to be upregulated in the BC patients. Furthermore, Th22 cells were positively correlated with BC tumor stage and clinical outcomes. The BC patients with a higher percentage of Th22, Th17, Th1 cells or a lower percentage of Th1 cells showed a decreased trend of survival rate. CONCLUSION: Th22, Th17, Th1, and Th2 subsets may play an essential role in BC patients. Th22, Th17, Th1, and Th2 cells may have potential significance to be used as clinical markers in BC patients with different molecular classification. Th22 cells may have potential value in BC patients' outcomes prediction, providing clinical value.

Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse.

Background: The pathogenesis of recurrent pelvic organ prolapse (POP) is currently unclear. Therefore, developing targeted preventive measures is difficult. This study identified potential key pathways, crucial genes, comorbidities, and therapeutic targets associated with the occurrence and development of recurrent POP. Methods: The original microarray data GSE28660, GSE53868, and GSE12852 were downloaded from the GEO database. Identification and validation of differentially expressed genes (DEGs) and hub genes associated with recurrent POP were performed using R software and cytoHubba of Cytoscape. Protein-protein interaction (PPI) networks were constructed using the STRING tool and visualized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were effectively performed using DAVID platforms. In addition, the NetworkAnalyst platform was used to explore and visualize the miRNA-hub gene network, TF-hub gene network, hub gene-disease network, and hub gene-drug/chemical network. Results: A total of 110 DEGs and 6 hub genes (ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE) were identified in this study. These genes were primarily enriched in the PPAR, AMPK, and adipocytokine, non-alcoholic fatty liver disease, and signaling pathways related to glycerol metabolism. Moreover, 96 miRNAs and 97 TFs were identified to as being associated with recurrent POP. These genes were closely linked to adipocyte metabolism and distribution, energy metabolism, and the longevity regulatory pathway. In addition, 192 diseases or chronic complications were potentially related to the recurrence of POP, including diabetes, hypertension, obesity, inflammatory diseases, and chronic obstructive pulmonary disease. Furthermore, 954 drugs or compounds were shown to have therapeutic potential for recurrent POP, and the most critical target drugs were dexamethasone, bisphenol A, efavirenz, 1-methyl-3-isobutylxanthine, and estradiol. Conclusions: The results of this study revealed that ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE as potential hub genes associated with recurrent POP, and these hub genes may aid in the understanding of the mechanism underlying POP recurrence and the development of potential molecular drugs.