Image1_Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis.JPEG

Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8+ T cells, CD4+ T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.</p

Image4_Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis.JPEG

Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8+ T cells, CD4+ T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.</p

Table1_Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis.xlsx

Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8+ T cells, CD4+ T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.</p

Image2_Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis.JPEG

Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8+ T cells, CD4+ T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.</p

Image3_Screening of ferroptosis-related genes with prognostic effect in colorectal cancer by bioinformatic analysis.JPEG

Colorectal cancer (CRC) remains a common malignant tumor of digestive tract with high incidence rate and high mortality in the worldwide. The current clinical treatments of CRC often fail to achieve satisfactory results. Searching for more effective prediction or prognosis biomarkers, or developing more targeted therapeutic schedule may help to improve the outcomes of CRC patients. Here, we tried to study the effect of ferroptosis-related genes on CRC prognosis and make it clearer that ferroptosis has connection with immune environment. First, we obtained gene expression data of CRC and normal tissues, as well as corresponding clinical data from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were intersected with ferroptosis-related gene set downloaded from FerrDb database, and 93 abnormally expressed ferroptosis-related genes were obtained. Then, these genes were analyzed for functional enrichment. Univariate Cox regression and multivariate Cox regression analyses were performed to establish prognostic model based on ferroptosis-related genes. In the process of exploring the correlation between prognostic genes and immune infiltration, we found that these genes were closely related to B cells, CD8+ T cells, CD4+ T cells, macrophages and other cells in CRC. In addition, we found a large proportion of plasma cells and macrophages in TCGA-COADREAD. Finally, a prognostic nomogram of ferroptosis-related genes was established, including age, sex, grade and other predicted values. To summary, we established a prognostic model of colorectal cancer (CRC) based on ferroptosis-related genes and further explored the relationship between these genes with immune microenvironment.</p

Soluble Silver Acetylide for the Construction and Structural Conversion of All-Alkynyl-Stabilized High-Nuclearity Homoleptic Silver Clusters

Silver acetylide complex [Ag­(ArCC)]_<i>n</i> (Ar = 3,5-di-<i>tert</i>-butylphenyl) with unprecedented high solubility in common organic solvents has been designed and synthesized. The high solubility is due to two bulky <i>tert</i>-butyl substituents on the phenyl ring. This feature is significant to construct and isolate single crystals of all-alkynyl-stabilized silver clusters, which are crucial to investigate the intrinsic binding interaction and coordination modes between Ag­(I) and ethynide ligands. Crystallization of [Ag­(ArCC)]_<i>n</i> under various conditions resulted in three high-nuclearity homoleptic silver acetylide clusters, namely, [Ag₂₁(ArCC)₂₀]­(OH) (<b>1</b>), [Ag₁₆(ArCC)₁₆] (<b>2</b>), and [Ag₁₅(ArCC)₁₅] (<b>3</b>). Complex <b>1</b> has a [Ag₂₁] cluster protected by twenty 3,5-di-<i>tert</i>-butyl-phenylethynide ligands. Complexes <b>2</b> and <b>3</b> have neutral [Ag₁₆] and [Ag₁₅] clusters, respectively. In addition to these homoleptic silver clusters, two new silver acetylides [Ag₂₀(ArCC)₁₆(CH₃COO)₄] (<b>4</b>) and [Ag₂₂(ArCC)₁₆(NO₃)₄(CH₃CH₂OH)₄]­(OH)₂ (<b>5</b>) were synthesized. The acetate and nitrate anions in these structures are more like counterions instead of acting as critical building blocks or templates for cluster assembly. These results illustrated the significance of 3,5-di-<i>tert</i>-butyl-phenylethynide ligands in the construction and stabilization of high-nuclearity silver clusters. Analysis of structures of <b>1</b>–<b>5</b> revealed several novel coordination modes between Ag­(I) and ethynide ligands, which contributed considerably to our knowledge of Ag­(I)–ethynide binding interactions

Table_1_Does abstaining from alcohol in high school moderate intervention effects for college students? Implications for tiered intervention strategies.pdf

Brief motivational intervention (BMI) and personalized feedback intervention (PFI) are individual-focused brief alcohol intervention approaches that have been proven efficacious for reducing alcohol use among college students and young adults. Although the efficacy of these two intervention approaches has been well established, little is known about the factors that may modify their effects on alcohol outcomes. In particular, high school drinking may be a risk factor for continued and heightened use of alcohol in college, and thus may influence the outcomes of BMI and PFI. The purpose of this study was to investigate whether high school drinking was associated with different intervention outcomes among students who received PFI compared to those who received BMI. We conducted moderation analyses examining 348 mandated students (60.1% male; 73.3% White; and 61.5% first-year student) who were randomly assigned to either a BMI or a PFI and whose alcohol consumption was assessed at 4-month and 15-month follow-ups. Results from marginalized zero-inflated Poisson models showed that high school drinking moderated the effects of PFI and BMI at the 4-month follow-up but not at the 15-month follow-up. Specifically, students who reported no drinking in their senior year of high school consumed a 49% higher mean number of drinks after receiving BMI than PFI at the 4-month follow-up. The results suggest that alcohol consumption in high school may be informative when screening and allocating students to appropriate alcohol interventions to meet their different needs.</p

Hypoxia-Targeting, Tumor Microenvironment Responsive Nanocluster Bomb for Radical-Enhanced Radiotherapy

Although ultrasmall metal nanoparticles (NPs) have been used as radiosensitizers to enhance the local damage to tumor tissues while reducing injury to the surrounding organs, their rapid clearance from the circulatory system and the presence of hypoxia within the tumor continue to hamper their further application in radiotherapy (RT). In this study, we report a size tunable nanocluster bomb with a initial size of approximately 33 nm featuring a long half-life during blood circulation and destructed to release small hypoxia microenvironment-targeting NPs (∼5 nm) to achieve deep tumor penetration. Hypoxic profiles of solid tumors were precisely imaged using NP-enhanced computed tomography (CT) with higher spatial resolution. Once irradiated with a 1064 nm laser, CT-guided, local photothermal ablation of the tumor and production of radical species could be achieved simultaneously. The induced radical species alleviated the hypoxia-induced resistance and sensitized the tumor to the killing efficacy of radiation in Akt-mTOR pathway-dependent manner. The therapeutic outcome was assessed in animal models of orthotopical breast cancer and pancreatic cancer, supporting the feasibility of our combinational treatment in hypoxic tumor management

DataSheet_1_Radiomics features based on internal and marginal areas of the tumor for the preoperative prediction of microsatellite instability status in colorectal cancer.docx

ObjectivesTo explore whether the preoperative CT radiomics can predict the status of microsatellite instability (MSI) in colorectal cancer (CRC) patients and identify the region with the most stable and high-efficiency radiomics features.MethodsThis retrospective study involved 230 CRC patients with preoperative computed tomography scans and available MSI status between December 2019 and October 2021. Image segmentation and radiomic feature extraction were performed as follows. First, slices with the maximum tumor area (region of interest, ROI) were manually contoured. Subsequently, each ROI was shrunk inward by 1, 2, and 3 mm, respectively, where the remaining ROIs were considered as the internal region of the tumor (named as IROI1, IROI2, and IROI3), and the shrunk regions were considered as marginal regions of the tumor (named as MROI1, MROI2, and MROI3). Finally, radiomics features were extracted from each of the ROI. The intraclass correlation coefficient and least absolute shrinkage and selection operator method were used to choose the most reliable and relevant features of MSI status. Clinical, radiomics, and combined clinical radiomics models have been established. Calibration curve and decision curve analyses (DCA) were generated to explore the correction effect and assess the clinical applicability of the above models, respectively.ResultsIn the testing cohort, the radiomics model based on IROI3 yielded the highest average area under the curve (AUC) value of 0.908, compared with the remaining radiomics models. Additionally, hypertension and N stage were considered as clinically independent factors of MSI status. The combined clinical radiomics model achieved excellent diagnostic efficacy (AUC: 0.928; sensitivity: 0.840; specificity: 0.867) in the testing cohort, as well as favorable calibration and clinical utility by calibration curve and DCA analyses.ConclusionsThe IROI3 model, which is based on a 3-mm shrink in the largest areas of the tumor, could noninvasively reflect the heterogeneity and genetic instability within the tumor. This suggests that it is an important biomarker for the preoperative prediction of MSI status. The model can extract more robust and effective radiomics features, which lays a foundation for the radiomics study of hollow organs, such as in CRC.</p

Anti-Fas Antibody Conjugated Nanoparticles Enhancing the Antitumor Effect of Camptothecin by Activating the Fas–FasL Apoptotic Pathway

Emerging evidence suggest that the introduction of Fas ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL-based therapeutic strategies. Herein, smart nanoparticles (NPs) with a sandwich structure were fabricated. These NPs consist of a matrix metalloproteinase (MMP) cleavable PEG outer layer, an anti-Fas antibody middle layer, and a camptothecin (CPT)-loaded inner core. They could accumulate at a tumor site by the enhanced permeability and retention (EPR) effect. The removable PEG layer protects the cytotoxic anti-Fas antibody from premature contact with normal tissues, thus avoiding the unexpected lethal side effect before they reach the tumor site. Due to the high level of MMP expressed by tumor cells inside the tumor tissue, these NPs would shed their PEG layers, resulting in the exposure of anti-Fas antibody to bind the Fas receptor and triggering the apoptosis of tumor cells. Results of Western blot confirmed that these NPs could mimic the function of activated cytotoxic lymphocyte (CTL) to activate the Fas–FasL apoptosis pathway of tumor cells. With the aid of CPT payload, these anti-Fas antibody conjugated NPs achieved a high tumor inhibition in the B16 allograft tumor animal model. The design of these NPs provides a method for delivering cytotoxic ligand to targeting tissue, which may be valuable in cancer therapy