Kinetic Resolution of N-Allylic Pyrazoles via Photoexcited Chiral Copper Complex-Catalyzed Alkene E → Z Isomerization.

Herein, we present an efficient and practical kinetic resolution (KR) of racemic allylic pyrazoles utilizing photoexcited chiral-copper-complex-mediated alkene E → Z isomerization. This method enables the synthesis of both enantioenriched E- and Z-allylic pyrazoles, achieving enantiomeric excesses (e.e.) of up to 97% and selectivity factors (S factors) as high as 217. Remarkably, the method's ability to furnish allylic pyrazoles with the Z-configuration, which is notably arduous to obtain under thermodynamic control, underscores the transformative potential of this synthetic protocol.

Identification and analysis of prognostic metabolic characteristics in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a highly lethal gastrointestinal malignancy. The five-year survival rate of metastatic colorectal cancer remains low, at 14 percent. Numerous publications have suggested a role for peroxisome proliferator-activated receptors (PPARs) in malignancy. Recent studies have shown that PPARs, as nuclear transcription factors, may serve as potential targets for the treatment of metabolic syndrome tumors and their associated complications. However, the molecular mechanism has not been thoroughly investigated. Hence, in order to enhance the prediction of personalized medicine for PPAR-associated modulators in malignancy treatment, a timely review becomes essential. Utilizing TCGA-COAD expression profile data and patient overall survival (OS) information, this study systematically conducted investigations to identify and develop Hub stem cell-related diagnostic and prognostic identification models, aiming to enhance the multi-gene markers for COAD. Utilizing the differential expression profiles of stem cell-related genes, an 11-gene (SLC27A4, CPT1C, CPT1B, CPT2, CYP4A11, FABP3, FABP7, AQP7, MMP1, ACOX1, ANGPTL4) diagnostic and prognostic model was developed. This model demonstrated precise diagnostic and prognostic capabilities and holds the potential to characterize the clinicopathologic features of COAD. Univariate and multivariate Cox proportional hazards regression analyses were conducted to ascertain the independent factors influencing OS outcomes in COAD. The results revealed that CPT1B, SLC27A4, and FABP3 were identified as independent risk prognostic factors for OS in COAD, whereas ACOX1 and CPT2 served as independent protective prognostic factors. The hub genes associated with PPARs were identified through the differential expression of contrast agent COAD and normal tissues. Finally, the investigation of variations in immune infiltration and the analysis of relevant biological pathways validate the prognostic significance of the independent post-factors within this molecular model. This research aims to provide references for comprehending the mechanism of post-transcriptional regulation of COAD and molecular therapy.

Comprehensive analysis and experimental verification of the mechanism of action of T cell-mediated tumor-killing related genes in Colon adenocarcinoma.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract. A new prognostic scoring model for colon adenocarcinoma (COAD) is developed in this study based on the genes involved in tumor cell-mediated killing of T cells (GSTTKs), accurately stratifying COAD patients, thus improving the current status of personalized treatment. METHOD: The GEO and TCGA databases served as the sources of the data for the COAD cohort. This study identified GSTTKs-related genes in COAD through single-factor Cox analysis. These genes were used to categorize COAD patients into several subtypes via unsupervised clustering analysis. The biological pathways and tumor microenvironments of different subgroups were compared. We performed intersection analysis between different subtypes to obtain intersection genes. Single-factor Cox regression analysis and Lasso-Cox analysis were conducted to establish clinical prognostic models. Two methods are used to assess the accuracy of model predictions: ROC and Kaplan-Meier analysis. Next, the prediction model was further validated in the validation cohort. Differential immune cell infiltration between various risk categories was identified via single sample gene set enrichment analysis (ssGSEA). The COAD model's gene expression was validated via single-cell data analysis and experiments. RESULT: We established two distinct GSTTKs-related subtypes. Biological processes and immune cell tumor invasion differed significantly between various subtypes. Clinical prognostic models were created using five GSTTKs-related genes. The model's risk score independently served as a prognostic factor. COAD patients were classified as low- or high-risk depending on their risk scores. Patients in the low-risk category recorded a greater chance of surviving. The outcomes from the validation cohort match those from the training set. Risk scores and several tumor-infiltrating immune cells were strongly correlated, according to ssGSEA. Single-cell data illustrated that the model's genes were linked to several immune cells. The experimental results demonstrated a significant increase in the expression of HOXC6 in colon cancer tissue. CONCLUSION: Our research findings established a new gene signature for COAD. This gene signature helps to accurately stratify the risk of COAD patients and improve the current status of individualized care.

Identification of biomarkers of renal ischemia-reperfusion injury by bioinformatics analysis and single-cell sequencing analysis combined with in vivo validation.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a serious clinical complication of kidney injury. This research dealt with investigating the hub genes and pathways associated with renal IRI. METHODS: The transcriptome expression dataset of mouse renal ischemia samples (GSE39548) was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were filtered by R software for key genes utilized for gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene enrichment analysis (GSEA). The gene co-expression network was developed by WGCNA analysis to screen important modules. Hub genes from the intersection of DEGs and WGCNA were subjected to protein-protein interaction (PPI) network. The biomarkers obtained by SVM-REF and LASSO algorithm were validated by other datasets and subjected to GSEA analysis. The expression of biomarkers in renal IRI was detected by qRT-PCR and subjected to single-cell analysis. RESULTS: A total of 157 DEGs were discovered. Biological function analysis depicted that the DEGs were primarily involved in cytokine-cytokine receptor interaction, as well as the signaling pathways IL-17, MAPK, and TNF. The intersection of DEGs and the genes obtained by WGCNA analysis yielded 149 hubs genes. Based on SVM-REF and LASSO algorithm, cyp1a1 and pdk4 were determined as potential biomarkers in individuals with renal ischemia and showed good diagnostic value. qRT-PCR results depicted that cyp1a1 and pdk4 were significantly up-regulated in renal ischemia mice (P < 0.05). Finally, the single-cell analysis identified the expression of Cyp1a1 and Pdk4 in mice kidney tissue. CONCLUSION: cyp1a1 and pdk4 were identified to play important roles in renal IRI. This research provides a new perspective and basis for studying the pathogenesis of renal IRI and developing new treatments.

Effect of continuous aerobic exercise on endothelial function: A systematic review and meta-analysis of randomized controlled trials.

Background: Current research suggests that continuous aerobic exercise can be effective in improving vascular endothelial function, while the effect between different intensities and durations of exercise is unclear. The aim of this study was to explore the effect of different durations and intensities of aerobic exercise on vascular endothelial function in different populations. Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: 1) randomized controlled trials (RCTs); 2) including both an intervention and control group; 3) using flow-mediated dilation (FMD) as the outcome measure; and 4) testing FMD on the brachial artery. Results: From 3,368 search records initially identified, 41 studies were eligible for meta-analysis. There was a significant effect of continuous aerobic exercise on improving flow-mediated dilation (FMD) [weighted mean difference (WMD), 2.55, (95% CI, 1.93-3.16), p < 0.001]. Specifically, moderate-intensity [2.92 (2.02-3.825), p < 0.001] and vigorous-intensity exercise [2.58 (1.64-3.53), p < 0.001] significantly increased FMD. In addition, a longer duration [<12 weeks, 2.25 (1.54-2.95), p < 0.001; ≥12 weeks, 2.74 (1.95-3.54), p < 0.001], an older age [age <45, 2.09 (0.78-3.40), p = 0.002; 45 ≤ age <60, 2.25 (1.49-3.01), p < 0.001; age ≥60, 2.62 (1.31-3.94), p < 0.001], a larger basal body mass index (BMI) [20 < BMI < 25, 1.43 (0.98-1.88), p < 0.001; 25 ≤ BMI < 30, 2.49 (1.07-3.90), p < 0.001; BMI ≥ 30, 3.05 (1.69-4.42), p < 0.001], and a worse basal FMD [FMD < 4, 2.71 (0.92-4.49), p = 0.003; 4 ≤ FMD < 7, 2.63 (2.03-3.23), p < 0.001] were associated with larger improvements in FMD. Conclusion: Continuous aerobic exercise, especially moderate-intensity and vigorous-intensity aerobic exercise, contributed to improving FMD. The effect of continuous aerobic exercise on improving FMD was associated with duration and participant's characteristics. Specifically, a longer duration, an older age, a larger basal BMI, and a worse basal FMD contributed to more significant improvements in FMD. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=341442], identifier [CRD42022341442].

Dual-mode optical thermometer based on fluorescence intensity ratio of Eu3+/Mn4+ co-doping zinc titanate phosphors.

Zinc titanate phosphors containing Eu3+/ Mn4+ as active ions were synthesized by using the solid-state method. XRD patterns of the powders confirmed that the samples were a mixture of cubic Zn2TiO4 and hexagonal ZnTiO3 phases. The luminous intensity of ZTO: Eu3+phosphors and ZTO: Mn4+ phosphors both increased with the increase of doping concentration, reaching the maximum at 2 mol% Eu3+ and 0.3 mol% Mn4+, respectively. In the photoluminescence spectra of ZTO: Eu3+(2 mol%) phosphors with different Mn4+ doping amounts excited at 465 nm, the emission spectra revealed the characteristic peaks of Eu3+ with low Mn4+ content, and with the Mn4+ content increasing, the emission spectra contained both Mn4+ and Eu3+ luminescence peaks. In the variable temperature spectra, the relative sensitivity of the samples was improved with the concentration of Mn4+ increasing and achieved the maximum value of 3.2 %/K.

Virtual versus jaw simulation in inlay preparation preclinical teaching: a randomised controlled trial.

BACKGROUND: To investigate the effect of virtual simulation systems on the teaching of inlay experiments and to guide the experimental teaching of tooth preparation. METHODS: Participants in their second semester of the junior year were selected to carry out the unified teaching and evaluation of dental preparation theory. The age varied from 18 to 22 years (19.96 ± 0.70) and the participants were randomly divided into four groups (n = 19) with a similar male-to-female ratio following CONSORT guidelines, including a jaw simulation model training group (Group J), a virtual simulation system training group (Group V), a jaw model training first followed by a virtual system training group (Group J-V), and a virtual system followed by a jaw model training group (Group V-J). The inlay tooth preparation assessment was performed on the extracted teeth. The data were analysed according to the assessment scores by a senior clinician. The subjective feelings of the students towards the system were evaluated using questionnaires. RESULTS: The second theoretical scores of Group V-J (63.5 ± 2.89) and Group J-V (60.5 ± 3.25) were higher than those of Group V (57.5 ± 3.13) and Group J (58.0 ± 3.67). The experimental scores of Groups J-V and V-J (62.79 ± 2.84; 64.00 ± 2.85) were higher than those of Groups V and J (56.05 ± 3.39; 55.74 ± 2.53). The questionnaire survey illustrated that most students preferred the digital virtual simulation system (perfect assessment: 91.3%, accuracy: 82.6%, satisfaction: 52.2%). CONCLUSION: Virtual simulation training can facilitate the teaching effect of tooth preparation in inlay experiments, and the teaching mode of Group V-J was the best. Therefore, this teaching mode is to be popularised.

Synergistic Radiosensitization Mediated by Chemodynamic Therapy via a Novel Biodegradable Peroxidases Mimicking Nanohybrid.

Purpose: Reactive oxygen species (ROS) are practically essential in radiotherapy to damage cancer cells; however, they are always inadequate for some malignant entities. Here, we designed a biodegradable mesoporous silica decorated with hemin and glucose oxidase (GOD@Hemin-MSN) to generate a chemodynamic therapy in order to enhance the killing capacity of radiotherapy. Methods: Mesoporous silica, as an outstanding drug carrier, can deliver hemin and glucose oxidase to the tumor site. With high level of metabolism activity, cancer cells are abundant in glucose, which can be oxidized into H2O2 by glucose oxidase (GOD) on site. The generated H2O2 is subsequently converted into intracellular ROS, especially hydroxyl radical within the tumor microenvironment, by hemin, which has mimetic peroxidase properties. By this means, the ROS can be supplemented or enriched to facilitate the killing of tumor cells. Results: The chemodynamic therapy induced by GOD@Hemin-MSN produced quantities of ROS, which compensated for their inadequacy as a result of radiotherapy, and exhibited remarkable antitumor efficacy, with a tumor inhibition rate of 91.5% in A549 tumor-bearing mice. Conclusion: This work has validated GOD@Hemin-MSN as a radiosensitizer in chemodynamic therapy, which showed biocompatibility and potential for translational application.

Camptothecin Delivery via Tumor-Derived Exosome for Radiosensitization by Cell Cycle Regulation on Patient-Derived Xenograft Mice.

Purpose: While radiotherapy remains the leading clinical treatment for many tumors, its efficacy can be significantly hampered by the insensitivity of cells in the S phase of the cell cycle to such irradiation. Methods: Here, we designed a highly targeted drug delivery platform in which exosomes were loaded with the FDA-approved anti-tumor drug camptothecin (CPT) which is capable of regulating cell cycle. The utilized exosomes were isolated from patient tumors, enabling the personalized treatment of individuals to ensure better therapeutic outcomes. Results: This exosome-mediated delivery strategy was exhibited robust targeted to patient-derived tumor cells in vitro and in established patient-derived xenograft models. By delivering CPT to tumor cells, this nanoplatform was able to decrease cell cycle arrest in the S phase, increasing the frequency of cells in the G1 and G2/M phases such that they were more radiosensitive. Conclusion: This therapeutic approach was able to substantially enhance the sensitivity of patient-derived tumors to ionizing radiation, thereby improving the overall efficacy of radiotherapy without the need for a higher radiation dose.

Mn2+ ions substitution inducing improvement of optical performances in ZnAl2O4: Cr3+ phosphors: Energy transfer and ratiometric optical thermometry.

Zn1-xMnxAl2O4:0.1 mol% Cr3+ (0.04≤x≤0.16) phosphors with single spinel phase were synthesized by using sol-gel method and the structure, optical and temperature sensing performances were reported herein. The results of X-ray photoelectron spectra indicate that the inversion defects related to octahedral Zn are reduced and the crystal field surrounding Al changes with Mn2+ doping in ZnAl2O4 lattices. Mn2+/Cr3+ co-doped ZnAl2O4 nanophosphors reveal a green emission band assigned to Mn2+ and a series of red emission peaks assigned to Cr3+, respectively. With the concentration of Mn2+ increasing, the intensity of zero phonon line (R line) assigned to Cr3+ increases, reaching the maximum at the optimal Mn2+ concentration of x=0.14. The energy transfer from Mn2+ to Cr3+ is confirmed with the energy transfer efficiency of 83%. The separation between 2E(eg) and 2E(tg) of Cr3+ is enlarged due to Mn2+ dopants giving rise to a change of crystal field. The luminous intensity ratio between two separated emission peaks at 685 nm (R3) and 689 nm (R2) reveals an obvious temperature dependence. The relative sensitivity changes from 3.7 %K-1 to 0.25 %K-1 with the temperature increasing from 80 K to 310 K, which is much larger than that of ZnAl2O4:Cr3+ nanophosphors without Mn2+, indicating its good application prospect in optical thermometry.

SCAMP4 is a novel prognostic marker and correlated with the tumor progression and immune infiltration in glioma.

BACKGROUND: Glioma is the most prevalent brain tumor with high mortality and morbidity and the prognosis of patients remains very poor. Glioma therapy is largely limited by the extraordinary invasive capability in glioma and the lack of valuable biomarkers of LGG and GBM. So it is urgent and important for us to identify valuable biomarkers to treat glioma patients. SCAMP4 (Secretory Carrier-Associated Membrane Protein 4) has not been reported to be linked to cancer prognostic or any treatments. METHODS: We analyzed the role of SCAMP4 in LGG and GBM via the publicly available CGGA (The Chinese Glioma Atlas) and TCGA (The Cancer Genome Atlas) databases. The correlations between SCAMP4 and the immune cells were analyzed by applying CIBERSORT and TIMER, while R was utilized in the analysis of the statistical data. RESULTS: Our results indicated that SCAMP4 which is correlated to age, stage, grade and tumor status and may be a promising independent prognostic factor in LGG and GBM. Meanwhile, the expression of SCAMP4 is closely associated with some tumor-infiltrating immune cells such as Monocytes, NK cells activated, Macrophages, Mast cells resting and so on. Furthermore, during the in-depth analysis of the integrated correlations, we also find that isocitrate dehydrogenase 1 (IDH1) and SCAMP4 shared similar prognostic values. CONCLUSIONS: Together with all these findings, the identification of SCAMP4 as a new biomarker could elucidate how the immune microenvironment influence the glioma development. With further analysis, SCAMP4 may be a predictor for glioma prognosis.

The low expression of NUP62CL indicates good prognosis and high level of immune infiltration in lung adenocarcinoma.

A primary factor in tumor morbidity and mortality, lung adenocarcinoma (LUAD) is known to be a major subtype of lung cancer, having the lowest survival rate among all other cancers. Using The Cancer Genome Atlas (TCGA) database the relationship between the immune infiltrate and the NUP62CL was explored and the value of the NUP62CL expression in the prognosis and diagnosis LUAD was examined. Using the logistic regression and the Wilcoxon signed-rank test the relationship between the NUP62CL and the clinico-pathological features was analyzed. There was a significant correlation between the clinical stage (p = 0.005), the N (p = 0.004), and the decreased expression of NUP62CL. The prognosis of LUAD with high NUP62CL expression was revealed to be worse than that with low NUP62CL expression (p < 0.001) by the Kaplan-Meier survival analysis. The potentiality of NUP62CL to be a significant factor of prognosis for LUAD was indicated by the analyses of the multivariate and the univariate Cox regression models. In LUAD, the crucial role of recombination and maintenance of telomere as a significant pathway for NUP62CL was suggested by the Gene Set Enrichment Analysis (GSEA). To analyze the correlation between the genes and the tumor infiltrating immune cells the CIBERSORT was used. Moreover the positive correlation with the NUP62CL expression in LUAD of the infiltration level of the tumor infiltrating B lymphocytes and memory CD4+ T cells was exhibited by CIBERSORT. Therefore, NUP62CL may be a new valuable prognostic indicator for LUAD.

Development of a Prognostic Model for Ovarian Cancer Patients Based on Novel Immune Microenvironment Related Genes.

Ovarian cancer (OV) has become the most lethal gynecological cancer. However, its treatment methods and staging system are far from ideal. In the present study, taking the advantage of large-scale public cohorts, we extracted a list of immune-related prognostic genes that differentially expressed in tumor and normal ovarian tissues. Importantly, an individualized immune-related gene based prognostic model (IPM) for OV patients were developed. Furthermore, we validated our IPM in Gene Expression Omnibus (GEO) repository and compared the immune landscape and pathways between high-risk and low-risk groups. The results of our study can serve as an important model to identify the immune subset of patients and has potential for use in immune therapeutic selection and patient management.

Genetic Epidemiology of Medication Safety and Efficacy Related Variants in the Central Han Chinese Population With Whole Genome Sequencing.

Medication safety and efficacy-related pharmacogenomic research play a critical role in precision medicine. This study comprehensively analyzed the pharmacogenomic profiles of the central Han Chinese population in the context of medication safety and efficacy and compared them with other global populations. The ultimate goal is to improve medical treatment guidelines. We performed whole-genome sequencing in 487 Han Chinese individuals and investigated the allele frequencies of pharmacogenetic variants in 1,731 drug response-related genes. We identified 2,139 (81.18%) previously reported variants in our population with annotations in the PharmGKB database. The allele frequencies of these 2,139 clinical-related variants were similar to those in other East Asian populations but different from those in other global populations. We predicted the functional effects of nonsynonymous variants in the 1,731 pharmacogenes and identified 1,281 novel and 4,442 previously reported deleterious variants. Of the 1,281 novel deleterious variants, five are common variants with an allele frequency >5%, and the rest are rare variants with an allele frequency <5%. Of the 4,442 known deleterious variants, the allele frequencies were found to differ from those in other populations, of which 146 are common variants. In addition, we found many variants in non-coding regions, the functions of which require further investigation. This study compiled a large amount of data on pharmacogenomic variants in the central Han Chinese population. At the same time, it provides insight into the role of pharmacogenomic variants in clinical medication safety and efficacy.

Development and Validation of a Clinical Prognostic Model Based on Immune-Related Genes Expressed in Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent and terminal subtype of RCC. Reliable markers associated with the immune response are not available to predict the prognosis of patients with ccRCC. We exploited the extensive number of ccRCC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository to perform a comprehensive analysis of immune-related genes (IRGs). Methods: Based on TCGA data, we incorporated IRGs and their expression profiles of 72 normal and 539 ccRCC samples. Univariate Cox analysis was used to evaluate the relationship between overall survival (OS) and IRGs expression. The Lasso Cox regression model identified prognostic genes used to establish a clinical immune prognostic model. The TF-IRG network was used to study the potential molecular mechanisms of action and properties of ccRCC-specific IRGs. Multivariate Cox analysis established a clinical prognostic model of IRGs. Results: We found a significant correlation among 15 differentially expressed IRGs with the OS of patients with ccRCC. Gene function enrichment analysis showed that these IRGs are significantly associated with response to receptor ligand activity. Lasso Cox regression analysis identified 10 genes with the greatest prognostic value. A clinical prognostic model based on six IRGs, which performed well for predicting prognosis, revealed significant associations of patients' survival with age, sex, stage, tumor, node, and metastasis. Moreover, these findings reflect the infiltration of tumors by various immune cells. Conclusion: We identified six clinically significant IRGs and incorporated them into a clinical prognostic model with great significance for monitoring and predicting prognosis of ccRCC.

SYT16 is a prognostic biomarker and correlated with immune infiltrates in glioma: A study based on TCGA data.

BACKGROUND: Glioma is the most lethal primary brain tumor. Lower-grade glioma (LGG) is the crucial pathological type of Glioma. Immune-infiltration of the tumor microenvironment positively associated with overall survival in LGG. SYT16 is a gene has not been reported in cancer. We assess the role of SYT16 in LGG, via the publicly available TCGA database. METHODS: Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of SYT16 in LGG. We evaluated the influence of SYT16 on survival of LGG patients by survival module. Then, datasets of LGG were downloaded from TCGA. The correlations between the clinical information and SYT16 expression were analyzed using logistic regression. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival. we also explore the correlation between SYT16 and cancer immune infiltrates using CIBERSORT and correlation module of GEPIA. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of SYT16 Expression and Immune Infiltration Level in LGG and to explore cumulative survival in LGG. RESULTS: The univariate analysis using logistic regression, indicated that increased SYT16 expression significantly correlated with the tumor grade. Moreover, multivariate analysis revealed that the up-regulated SYT16 expression is an independent prognostic factor for good prognosis. Specifically, SYT16 expression level has significant negative correlations with infiltrating levels of B cell, CD4+ T cells, Macrophages, Neutrophils and DCs in LGG. In addition, GSEA identified ingle organism behavior, gated channel activity, cognition, transporter complex and ligand gated channel activity  in Gene Ontology (GO) were differentially enriched in the high SYT16 expression phenotype pathway. Neuroactive ligand receptor interaction, calcium signaling pathway, long term potentiation, type II diabetes mellitus and long term depression were identified as differentially enriched  pathway in Kyoto Encyclopedia of Genes and Genomes (KEGG). CONCLUSION: SYT16 is a Prognostic Biomarker and Correlated with Immune Infiltrates in LGG.

Low expression of RGL4 is associated with a poor prognosis and immune infiltration in lung adenocarcinoma patients.

Lung adenocarcinoma (LUAD) is a frequently diagnosed histologic subtype with increasing morbidity and mortality. RalGDS-Like 4 (RGL4) has not been reported to be associated with cancer risk, prognosis, immunotherapy or any other treatments. We perform a bioinformatics analysis on data downloaded from the Cancer Genome Atlas (TCGA)-LUAD, and we find that low expression of RGL4 is accompanied by worse outcomes and prognosis in LUAD patients. As a promising predictor, the potential influence and mechanisms of RGL4 on overall survival are worth exploring. Moreover, RGL4 expression is significantly associated with a variety of tumor-infiltrating immune cells (TIICs), particularly memory B cells, CD8+T cells and neutrophils. Subsequently, we evaluated the most notable KEGG pathways, including glycolysis gluconeogenesis, the P53 signaling pathway, RNA degradation, and the B cell receptor signaling pathway, among others. Our findings provide evidence that the decreased expression of RGL4 is significantly associated with poor prognosis and immune cell infiltration in patients with LUAD and highlight the use of RGL4 as a novel predictive biomarker for the prognosis of LUAD and other cancers. RGL4 may also be used in combination with immune checkpoints to identify the benefits of immunotherapy. Subjects: Bioinformatics, Genomics, Oncology, Thoracic surgery.

Prognostic biomarker MITD1 and its correlation with immune infiltrates in hepatocellular carcinoma (HCC).

BACKGROUND: Hepatocellular carcinoma (HCC) is globally recognized as one of the most frequently occurring primary malignant liver tumors, making the identification of HCC biomarkers critically important. The protein MITD1 (Microtubule Interacting and Trafficking Domain containing 1) has been shown to interact with ESCRT-III and participates in cytokinesis, the last step in cell division. This is the first investigation into the expression of MITD1 and its prognostic value, potential biological functions and effects on the immune system in HCC patients. METHODS: The gene expression and clinicopathology analysis, enrichment analysis and immune infiltration analysis are based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. The statistical analysis was conducted in R and immune responses of MITD1 expression in HCC were analyzed using TIMER and CIBERSORT. In addition, GEPIA, K-M survival analysis and data from the HPA were used to validate the outcomes. RESULTS: Our results highlighted that MITD1 plays a key role as an independent prognostic factor in patients with HCC. MITD1 expression was associated with age, grade, stage and tumor status. GSEA revealed that MITD1 is closely correlated with cell cycle control via the NOTCH signaling pathway. CIBERSORT analysis revealed that the amount of NK cells decreased when MITD1 expression was high. CONCLUSIONS: The identification of MITD1 as a new biomarker for HCC could help elucidate how changes in cytokinesis and the immune environment promote liver cancer development. With further analysis, MITD1 may be able to serve as a predictor for human HCC prognosis.

Increased expression of TTC21A in lung adenocarcinoma infers favorable prognosis and high immune infiltrating level.

BACKGROUND: Lung adenocarcinoma (LUAD) is a crucial pathological type of lung cancer. Immune-infiltration of the tumor microenvironment positively associated with overall survival in LUAD. TTC21A is a gene has not reported in cancer, and the mechanism behind it is still unclear. Our study assesses TTC21A role in LUAD, via TCGA data. METHODS: GEPIA was utilized to analyze the expression of TTC21A in LUAD. We evaluated the influence of TTC21A on survival of LUAD patients by survival module. Then, data sets of LUAD were downloaded from TCGA. The correlations between clinical information and TTC21A expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression. In addition, we explored the correlation between TTC21A and cancer immune infiltrates using CIBERSORT and "Correlation" module of GEPIA. RESULTS: The univariate analysis using logistic regression, wherein TTC21A expression served as a categorical dependent variable (with a median expression value of 2.5), indicated that increased TTC21A expression is significantly correlated with pathological stage, tumor status and lymph nodes. Moreover, multivariate analysis revealed that the up-regulated TTC21A expression, negative results of pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, a positive correlation between increased TTC21A expression and immune infiltrating level of B cells, Neutrophils, Mast cells and T cells was established using CIBERSORT analysis. Furthermore, we confirmed it in "correlation" module of GEPIA. CONCLUSION: Together with all these findings, increased TTC21A expression correlates with favorable prognosis and increased proportion of immune cells, such as B cells, Neutrophils, Mast cells and T cells in LUAD. These conclusions indicate that TTC21A could serve as a potential biomarker to assess prognosis and immune infiltration level in LUAD.

Reduced GRAMD1C expression correlates to poor prognosis and immune infiltrates in kidney renal clear cell carcinoma.

There has been an increase in the mortality rate and morbidity of kidney cancer (KC) with kidney renal clear cell carcinoma (KIRC) being the most common subtype of KC. GRAMD1C (GRAM Domain Containing 1C) has not been reported to relate to prognosis and immunotherapy in any cancers. Using bioinformatics methods, we judged the prognostic value of GRAMD1C expression in KIRC and investigated the underlying mechanisms of GRAMD1C affecting the overall survival of KIRC based on data downloaded from The Cancer Genome Atlas (TCGA). The outcome revealed that reduced GRAMD1C expression could be a promising predicting factor of poor prognosis in kidney renal clear cell carcinoma. Meanwhile, GRAMDIC expression was significantly correlated to several tumor-infiltrating immune cells (TIICs), particularly the regulatory T cells (Tregs). Furthermore, GRAMD1C was most significantly associated with the mTOR signaling pathway, RNA degradation, WNT signaling pathway, toll pathway and AKT pathway in KIRC. Thus, GRAMD1C has the potential to become a novel predictor to evaluate prognosis and immune infiltration for KIRC patients.