Exploring the Mediation Effect of Metabolite Levels on the Association Between Gut Microbiota and HCC: A two-step, two-sample bidirectional Mendelian Randomization.

Background: Although the gut microbiota is one of the risk factors for liver cancer, it remains unclear whether the level of metabolites mediates this association. Methods: Utilizing summary data from genome-wide association studies (GWAS), we conducted a two-sample Mendelian Randomization (MR) analysis to explore the causal links between GM, metabolites, and HCC. A two-step MR analysis quantitatively assessed the effect of metabolite-mediated GM on HCC. Results: In our study, we demonstrated that Clostridium leptum was identified as a protective factor against HCC, with no evidence of reverse causality (Inverse-variance weighted [IVW], OR: 0.62 [95% CI, 0.42-0.91]; p = 0.016). Our study also found that the potential connection between the GM and HCC may be mediated by the level of metabolites. An increase of one standard deviation in C. leptum abundance led to a 38% decrease in HCC risk (OR: 0.62 [95% CI, 0.42-0.91]), with a 9% reduction in phosphoethanolamine (PE) levels (OR: 0.91 [95% CI: 0.84-0.99]). PE's mediation proportion was established as -6.725% (95% CI, 12.96% to -26.41%). Conclusion: Our results demonstrate that increasing specific GM abundance can lower HCC risk, mediated by PE levels. We offer new prevention and treatment targets for HCC by adjusting GM.

Gut Microbiota, Human Blood Metabolites, and Esophageal Cancer: A Mendelian Randomization Study.

BACKGROUND: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer (ESCA), yet the exact causal relationship remains unclear. PURPOSE: To investigate the potential causal relationship between the gut microbiota and ESCA with Mendelian randomization (MR) analysis. METHODS: Genome-wide association studies (GWASs) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) and 205 gut microbiota metabolic pathways conducted by the Dutch Microbiome Project (DMP) and a FinnGen cohort GWAS of esophageal cancer specified the summary statistics. To investigate the possibility of a mediation effect between the gut microbiota and ESCA, mediation MR analyses were performed for 1091 blood metabolites and 309 metabolite ratios. RESULTS: MR analysis indicated that the relative abundance of 10 gut microbial taxa was associated with ESCA but all the 12 gut microbiota metabolic pathways with ESCA indicated no statistically significant association existing. Two blood metabolites and a metabolite ratio were discovered to be mediating factors in the pathway from gut microbiota to ESCA. CONCLUSION: This research indicated the potential mediating effects of blood metabolites and offered genetic evidence in favor of a causal correlation between gut microbiota and ESCA.

Development and validation of a nomogram for predicting survival time and making treatment decisions for clinical stage IA NSCLC based on the SEER database.

Background: The aim of this study was to establish and validate a nomogram model for accurate prediction of patients' survival with T1aN0M0 none small cell lung cancer (NSCLC). Methods: The patients, diagnosed with the stage IA NSCLC from 2004-2015, were identified from the Surveillance, Epidemiology and End Results (SEER) database. The variables with a P-value < 0.05 in a multivariate Cox regression were selected to establish the nomogram. The discriminative ability of the model was evaluated by the concordance index (C-index). The proximity of the nomogram prediction to the actual risk was depicted by a calibration plot. The clinical usefulness was estimated by the decision curve analysis (DCA). Survival curves were made with Kaplan-Meier method and compared by Log-Rank test. Results: Eight variables, including treatment, age, sex, race, marriage, tumor size, histology, and grade were selected to develop the nomogram model by univariate and multivariate cox regression. The C-index was 0.704 (95% CI, 0.694-0.714) in the training set and 0.713 (95% CI, 0.697-0.728) in the test set, which performed significantly better than 8th edition AJCC TNM stage system (0.550, 95% CI, 0.408-0.683, P < 0.001). The calibration curve showed that the prediction ability of 3-years and 5-years survival rate demonstrated a high degree of agreement between the nomogram model and the actual observation. The DCA curves also proved that the nomogram-assisted decisions could improve patient outcomes. Conclusion: We established and validated a prognostic nomogram to predict 3-years and 5-years overall survival in stage IA NSCLC.

Predicting response to immunotherapy plus chemotherapy in patients with esophageal squamous cell carcinoma using non-invasive Radiomic biomarkers.

OBJECTIVES: To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. RESULTS: Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p < 0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility. CONCLUSIONS: The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.

MEOX2 serves as a novel biomarker associated with macrophage infiltration in oesophageal squamous cell carcinoma and other digestive system carcinomas.

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is a malignant tumour of the digestive system that is associated with high morbidity and mortality rates worldwide. With the increased use of immunotherapy in cancer treatment, there is an urgent need to elucidate the immune-related mechanisms in ESCC and other digestive system carcinomas. METHODS: In our study, single-sample gene set enrichment analysis (ssGSEA) was first performed to analyse the expression profile downloaded from the NCBI Gene Expression Omnibus (GEO) database. Then, via a series of bioinformatic analyses, including the Mann-Whitney test, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis and differentially expressed genes (DEGs) analysis, we identified target immunocytes and related genes. Finally, we validated the results with the TIMER database. RESULTS: Our analyses showed that the numbers of infiltrating macrophages were obviously higher in advanced stages in ESCC compared with other types of immunocytes. MEOX2 was identified as a biomarker correlated with macrophage infiltration in ESCC and other types of digestive system carcinomas. And MEOX2 expression was strongly associated with the mRNA expression of colony-stimulating factor 1 (CSF-1) and CSF-1 receptor (CSF-1R) in these kinds of carcinomas. CONCLUSION: We speculated that MEOX2 could facilitate macrophage infiltration via CSF-1/CSF-1R signalling in ESCC and other kinds of digestive system carcinomas, and MEOX2 might serve as a novel target in prospective tumour immunotherapies.

Stereotactic body radiation therapy for non-small cell lung cancer using the non-coplanar radiation of Cyberknife and Varian linac.

PURPOSE: This study aims to evaluate the planned dose of stereotactic body radiation therapy (SBRT) for treating early peripheral non-small cell lung cancer (NSCLC) using the non-coplanar radiation from Cyberknife and Varian linac. Moreover, this study investigates whether Cyberknife and Varian linac are qualified for non-coplanar radiation SBRT for treating early peripheral NSCLC, and which one is better for protecting organs at risk (OARs). METHODS: Retrospective analysis was performed based on the Cyberknife radiation treatment plans (RTPs) and Varian Eclipse RTPs of 10 patients diagnosed with early peripheral NSCLC. The dose distributions in the target and OARs were compared between the RTPs of Cyberknife and Varian Eclipse using Mim medical imaging software. RESULTS: For PTV, no significant difference in D98 and D95 between the Cyberknife and Eclipse was observed (t = -0.35, -1.67, P > 0.05). The homogeneity indexes (HIs) of Cyberknife plans are higher (t = 71.86, P < 0.05) than those of Eclipse plans. The V10, V15, V20, V25, V30 and Dmean of the lung with NSCLC and the V20 of the whole lung for Cyberknife were less than those for Eclipse (t = -4.73, -5.62, -7.75, -6.38, -6.89, -3.14, -7.09, respectively, P < 0.05). Cyberknife plans have smaller spinal cord Dmax, trachea Dmax, heart Dmax, chest wall Dmax (t = -2.49, -2.57, -3.71, -3.56, respectively, P < 0.05) and esophagus Dmax (t = -1.95, P > 0.05) than Varian Eclipse plans. CONCLUSION: To fulfill SBRT by non-coplanar radiation, Cyberknife is recommended for the institutions equipped with Cyberknife, while Varian linac can be applied for the institutions that have not adopted Cyberknife in clinical radiotherapy yet.

Effect of the Cationic Block Structure on the Characteristics of Sludge Flocs Formed by Charge Neutralization and Patching.

In this study, a template copolymer (TPAA) of (3-Acrylamidopropyl) trimethylammonium chloride (AATPAC) and acrylamide (AM) was successfully synthesized though ultrasonic-initiated template copolymerization (UTP), using sodium polyacrylate (PAAS) as a template. TPAA was characterized by an evident cationic microblock structure which was observed through the analyses of the reactivity ratio, Fourier transform infrared spectroscopy (FTIR), ¹H (13C) nuclear magnetic resonance spectroscopy (¹H (13C) NMR), and thermogravimetry/differential scanning calorimetry (TG/DSC). The introduction of the template could improve the monomer (AATPAC) reactivity ratio and increase the length and amount of AATPAC segments. This novel cationic microblock structure extremely enhanced the ability of charge neutralization, patching, and bridging, thus improving the activated sludge flocculation performance. The experiments of floc formation, breakage, and regrowth revealed that the cationic microblock structure in the copolymer resulted in large and compact flocs, and these flocs had a rapid regrowth when broken. Finally, the larger and more compact flocs contributed to the formation of more channels and voids, and therefore the specific resistance to filtration (SRF) reached a minimum.

Probing Carrier Transport and Structure-Property Relationship of Highly Ordered Organic Semiconductors at the Two-Dimensional Limit.

One of the basic assumptions in organic field-effect transistors, the most fundamental device unit in organic electronics, is that charge transport occurs two dimensionally in the first few molecular layers near the dielectric interface. Although the mobility of bulk organic semiconductors has increased dramatically, direct probing of intrinsic charge transport in the two-dimensional limit has not been possible due to excessive disorders and traps in ultrathin organic thin films. Here, highly ordered single-crystalline mono- to tetralayer pentacene crystals are realized by van der Waals (vdW) epitaxy on hexagonal BN. We find that the charge transport is dominated by hopping in the first conductive layer, but transforms to bandlike in subsequent layers. Such an abrupt phase transition is attributed to strong modulation of the molecular packing by interfacial vdW interactions, as corroborated by quantitative structural characterization and density functional theory calculations. The structural modulation becomes negligible beyond the second conductive layer, leading to a mobility saturation thickness of only ∼3 nm. Highly ordered organic ultrathin films provide a platform for new physics and device structures (such as heterostructures and quantum wells) that are not possible in conventional bulk crystals.