Targeting DKK1 enhances the antitumor activity of paclitaxel and alleviates chemotherapy-induced peripheral neuropathy in breast cancer.

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

Microscopic mechanism study of the rheological behavior of non-Newtonian fluids based on dissipative particle dynamics.

Non-Newtonian fluid rheological properties are a hot research topic for realizing intelligent applications. In order to investigate the microscopic mechanism and structural evolution process of the nonlinear rheological behavior of non-Newtonian fluids, this paper systematically investigates two continuous nonlinear rheological behaviors of non-Newtonian fluids, namely shear-thickening and shear-thinning rheological properties, using a non-Newtonian fluid system composed of polyethylene glycol (PEG) mixed with nano-silica (Nano-SiO2) by a dissipative particle dynamics (DPD) method. It is shown that at low shear rates, the molecular chains of PEG in the fluid are stretched due to shear flow and the molecular structure is transformed into an ordered state; and the effective hydrodynamic radius of Nano-SiO2 beads decreases, which makes the translational friction coefficient of the beads decrease and the system mobility increases, exhibiting shear-thinning behavior. When the shear rate exceeds the critical value, the contact and collision probability between Nano-SiO2 beads in the non-Newtonian fluid increases; a large number of silicon hydroxyl groups exist on the surface of Nano-SiO2, which form a large number of hydrogen bonds when they are close to each other and constrain the particle separation, resulting in a large aggregation of Nano-SiO2 beads, leading to an increase in the effective kinetic radius of Nano-SiO2 beads and an increase in the coefficient of translational friction, forming a blockage of the fluid system and exhibiting a shear-thickening behavior. Our study provides insights for understanding the rheological behavior of non-Newtonian fluids from a microscopic perspective, and contributes to the intelligent application of non-Newtonian fluids.

Adaptive VMD-K-SVD-Based Rolling Bearing Fault Signal Enhancement Study.

To address the challenges associated with nonlinearity, non-stationarity, susceptibility to redundant noise interference, and the difficulty in extracting fault feature signals from rolling bearing signals, this study introduces a novel combined approach. The proposed method utilizes the variational mode decomposition (VMD) and K-singular value decomposition (K-SVD) algorithms to effectively denoise and enhance the collected rolling bearing signals. Initially, the VMD method is employed to separate the overall noise into intrinsic mode functions (IMFs), reducing the noise content within each IMF. To optimize the mode component, K, and the penalty factor, α, in VMD, an improved arithmetic optimization algorithm (IAOA) is employed. This ensures the selection of optimal parameters and the decomposition of the signal into a set of IMFs, forming the original dictionary. Subsequently, the signals are decomposed into multiple IMFs using VMD, and an original dictionary is constructed based on these IMFs. K-SVD is then applied to the original dictionary to further reduce the noise in each IMF, resulting in a denoised and enhanced signal. To validate the efficacy of the proposed method, rolling bearing signals collected from Case Western Reserve University (CWRU) and thrust bearing test rigs were utilized. The experimental results demonstrate the feasibility and effectiveness of the proposed approach in denoising and enhancing the rolling bearing signals.

Single-cell RNA-seq dissecting heterogeneity of tumor cells and comprehensive dynamics in tumor microenvironment during lymph nodes metastasis in gastric cancer.

Lymph node metastasis is the common metastasis route of gastric cancer. However, until now, heterogeneities of tumor cells and tumor microenvironment in primary tumors (PT) and metastatic lymph nodes (MLN) of gastric cancer (GC) remains uncharacterized. In our study, single cell RNA sequencing was performed on tissues from PT and MLN of gastric cancer. Trajectory analysis and function enrichment analyses were conducted to decode the underlying mechanisms contributing to LN metastasis of gastric cancer. Heterogeneous composition of immune cells and distinct intercellular interactions in PT and MLN were analyzed. Based on the generated single cell transcriptome profiles, dynamics of gene expressions in cancer cells between PT and MLN were characterized. Moreover, we reconstructed the developmental trajectory of GC cells' metastasis to LN and identified two subtypes of GC cells with distinct potentials of having malignant biological behaviors. We characterized the repression of neutrophil polarization associated genes, like LCN2, which would contribute to LN metastasis, and histochemistry experiments validated our findings. Additionally, heterogeneity in neutrophils, rather than macrophages, was characterized. Immune checkpoint associated interaction of SPP1 was found active in MLN. In conclusion, we decode the dynamics of tumor cells during LN metastasis in GC and to identify a subtype of GC cells with potentials of LN metastasis. Our data indicated that the disordering the neutrophils polarization and maturation and the activation of immune checkpoint SPP1 might contribute to LN metastasis in GC, providing a novel insight on the mechanism and potential therapeutic targets of LN metastasis in GC.

Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

Silencing of FOXO6 inhibits the proliferation, invasion, and glycolysis in colorectal cancer cells.

Forkhead box class O6 (FOXO6) is an important member of FOXO family, which has been demonstrated to be implicated in tumor development. However, the role of FOXO6 in colorectal cancer (CRC) is still unclear. The study aimed to investigate the potential roles of FOXO6 in the development of CRC. Our results showed that FOXO6 was overexpressed in CRC tissues and cell lines. FOXO6 knockdown inhibited cell proliferation, as well as repressed the migration and invasion of CRC cells. Additionally, we found that FOXO6 knockdown altered cellular metabolism by inhibiting glycolysis and promoting mitochondrial respiration. Furthermore, FOXO6 knockdown inhibited the activation of PI3K/Akt/mTOR pathway in CRC cells. The results herein indicated that FOXO6 knockdown inhibited cell proliferation, migration, invasion, and glycolysis in CRC cells. PI3K/Akt/mTOR pathway was involved in the effects of FOXO6 on CRC cells. These findings suggested that FOXO6 might be a potential target for the CRC therapy.

ZNF281 Regulates Cell Proliferation, Migration and Invasion in Colorectal Cancer through Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: Zinc Finger Protein 281 (ZNF281) was recently identified as a novel oncogene in several human carcinomas. However, the clinical significance of ZNF281 in colorectal cancer (CRC) and the molecular mechanisms by which ZNF281 promotes the growth and metastasis of CRC remain unknown. METHODS: ZNF281 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of ZNF281 expression. Cell Transwell assays and a wound healing assay were performed to assess the effects of ZNF281 on CRC cell migration and invasion in vitro. Western blotting was applied to analyze the potential mechanisms. RESULTS: ZNF281 mRNA and protein levels were significantly increased in CRC tissues compared with normal colon tissues, and high ZNF281 expression was associated with advanced T stage, N stage, TNM stage and differentiation. Therefore, ZNF281 expression might be an independent prognostic indicator in CRC patients. Moreover, knockdown of ZNF281 expression suppressed cell proliferation, migration and invasion by inhibiting the Wnt/ß-catenin pathway. CONCLUSION: Our study indicates that ZNF281 plays a critical role in the progression and metastasis of CRC and could represent a potential therapeutic target for CRC.

Knockdown of A-kinase anchor protein 4 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/ß-catenin pathway in human gastric cancer cells.

Hypoxia induces epithelial-mesenchymal transition (EMT) in tumorigenesis. A-kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia-inducible factor-1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia-induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/ß-catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia-induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/ß-catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.

Prevalence of and Risk Factors for Abdominal Bleeding in Patients with External Duodenal Fistula.

BACKGROUND Abdominal bleeding is a severe complication of duodenal fistula, but few studies have focused on this problem. The purpose of the present study was to investigate the prevalence of and risk factors for intra-abdominal bleeding in patients with external duodenal fistula. MATERIAL AND METHODS From January 2014 to December 2016, medical records of 97 patients with external duodenal fistula were retrospectively reviewed and analyzed. The prevalence and risk factors for intra-abdominal bleeding were evaluated. RESULTS The prevalence of abdominal bleeding in patients with external duodenal fistula was 31.9% (95%CI: 22.5-41.4%). A total of 31 patients had intra-abdominal bleeding. Results revealed that acute kidney failure (OR: 8.462, 95% CI: 1.921-37.28, p=0.005) and retroperitoneal infection (OR: 5.373, 95% CI: 1.504-19.197, p=0.010) were associated with abdominal bleeding. CONCLUSIONS The prevalence of abdominal bleeding in patients with external duodenal fistula was 31.9%, and acute kidney failure and retroperitoneal infection were found to be risk factors for intra-abdominal bleeding.

XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer.

BACKGROUND/AIMS: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. METHODS: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells. RESULTS: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke's staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells. CONCLUSION: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy.

XRCC1 R399Q polymorphism and colorectal cancer risk in the Chinese Han population: a meta-analysis.

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in DNA repair, genetic instability, and tumorigenesis. The XRCC1 R399Q polymorphism has been reported in some studies to influence the risk of colorectal cancer (CRC), though this remains controversial. We performed a meta-analysis to determine the association of XRCC1 R399Q polymorphisms with CRC risk in the Chinese Han population. A literature search was conducted using PubMed, EMBASE, and the China National Knowledge Infrastructure to identify eligible studies published before June 2014. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate the effect of XRCC1 R399Q polymorphisms on CRC risk. Eleven case-control studies with a total of 3194 CRC cases and 4472 controls were identified. No significant association between the XRCC1 R399Q polymorphism and CRC risk was observed in the Chinese Han population (Gln/Gln vs. Arg/Arg, OR = 1.26, 95% CI = 0.85-1.87, P OR = 0.242; Arg/Gln vs. Arg/Arg, OR = 0.95, 95% CI = 0.70-1.18, P OR = 0.651; dominant model, OR = 1.09, 95% CI = 0.86-1.38, P OR = 0.480; and recessive model, OR = 1.24, 95% CI = 0.91-1.70, P OR = 0.177). After excluding two studies that deviated from the Hardy-Weinberg equilibrium, there remained no significant association between XRCC1 R399Q and CRC risk. No publication bias was found using the funnel plot and Egger's test. Our meta-analysis results suggest that the XRCC1 R399Q polymorphism is not associated with increased risk of CRC in the Chinese Han population.

Identification and validation of the role of ZNF281 in 5-fluorouracil chemotherapy of gastric cancer.

BACKGROUND: The early diagnosis of gastric cancer (GC) and overcoming chemotherapy resistance is challenging. The aberrant expression of zinc finger protein 281 (ZNF281) and the over-activation of the Wnt/ß-catenin pathway are oncogenic factors and confer tumor chemoresistance. ZNF281 modulates the Wnt/ß-catenin pathway to influence malignant tumor behavior. However, the role of ZNF281 in GC chemotherapy and the relationship with the Wnt/ß-catenin pathway have not been elucidated by researchers. METHODS: We explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281's role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/ß-catenin pathway proteins. RESULTS: ZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/ß-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells. CONCLUSION: We identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/ß-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.

Immunogenicity and safety of ebolavirus vaccines in healthy adults: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV). METHODS: We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls. RESULTS: Twenty-nine RCTs (n = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28-15.41; I2 = 33%; P < 0.01) between the two groups. There was a significant difference in RR of adverse events (AEs) of EVV (RR 1.49; 95% CI 1.27-1.74; I2 = 88%; P < 0.01), although no difference in RR of serious AE (SAE) between the two groups. Subgroup analysis showed that there was no significant difference in RR of AEs for DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines, compared with controls. CONCLUSIONS: The DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines are likely to be safe and immunogenic, tending to support the vaccination against Ebola disease. These findings should provide much-needed evidence for public health policy makers to develop preventive measures based on disease prevalence features and socio-economic conditions.

Global research trends on the relationship between IBD and CRC: a bibliometric analysis from 2000 to 2023.

OBJECTIVE: This study aimed to conduct a bibliometric analysis of research articles on the relationship between inflammatory bowel disease (IBD) and colorectal cancer (CRC) using CiteSpace to summarize the current research status, hotspots, and trends in this field and present the results visually. METHOD: Research articles on the relationship between IBD and CRC published from 2000 to 2023 and in English were selected from the Web of Science Core Collection (Woscc) database. The articles were downloaded as "full record and references". CiteSpace was used to conduct cooperative, cluster, co-citation, and burst analyses. RESULTS: The literature search revealed 4244 articles; of which, 5 duplicates were removed, resulting in the inclusion of 4239 articles in this study. The United States of America had the highest number of publications, with Mayo Clinic and Harvard University being the most active institutions, and Bas Oldenburg being the most active author. Collaboration among core authors was inadequate. JA Eaden was the most cited author, and CRC was the most common keyword. Burst analysis indicated that Sun Yat-sen University might be one of the institutions with a large contribution to this research field in the future. Cluster analysis showed that earlier research focused more on microsatellite instability, whereas "gut microbiota" and "oxidative stress" are considered current research hotspots and trends. CONCLUSION: At present, the primary focus areas of research are "gut microbiota" and "oxidative stress". With the improvement of healthcare policies and standards, regular endoscopic monitoring of patients with IBD has become an indispensable diagnostic and therapeutic practice. More drugs will be developed to reduce the risk of progression from IBD to CRC. The findings of this study provide valuable insights into the relationship between IBD and CRC for researchers in the same field.

Tumor suppressor ING4 overexpression contributes to proliferation and invasion inhibition in gastric carcinoma by suppressing the NF-κB signaling pathway.

There is growing evidence that inhibitor of growth 4 (ING4) plays a pivotal role in development and progression of multiple different tumors; however, its precise function in gastric carcinoma remains to be elucidated. In the present study, we investigated ING4 level in gastric carcinoma tissues and cells, and preliminarily elucidated the role of ING4 in the proliferation and invasion of gastric carcinoma. The results demonstrated that expressions of ING4 mRNA and protein in gastric carcinoma tissues and cells were significantly lower than those in normal tissues and cells (P < 0.05). ING4 level in gastric carcinoma cells stably expressing ING4 was markedly higher than those in untreated group and empty vector pcDNA3.1 group (P < 0.05). Elevated ING4 level resulted in the inhibition of proliferation and invasion in three of gastric carcinoma cell lines MKN-28, SGC-7901 and MKN-45. Most notably, increased ING4 level evidently evoked the down-regulation of p65, p-IκBα, MMP-9 and uPA proteins and the up-regulation of IκBα protein. Our results presented herein suggest that ING4 level elevation mediated proliferation and invasion inhibition may be tightly associated with the suppression of NF-κB signaling pathway.

Combined bulk RNA and single-cell RNA analyses reveal TXNL4A as a new biomarker for hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) has a high mortality rate worldwide. The dysregulation of RNA splicing is a major event leading to the occurrence, progression, and drug resistance of cancer. Therefore, it is important to identify new biomarkers of HCC from the RNA splicing pathway. Methods: We performed the differential expression and prognostic analyses of RNA splicing-related genes (RRGs) using The Cancer Genome Atlas-liver hepatocellular carcinoma (LIHC). The International Cancer Genome Consortium (ICGC)-LIHC dataset was used to construct and validate prognostic models, and the PubMed database was used to explore genes in the models to identify new markers. The screened genes were subjected to genomic analyses, including differential, prognostic, enrichment, and immunocorrelation analyses. Single-cell RNA (scRNA) data were used to further validate the immunogenetic relationship. Results: Of 215 RRGs, we identified 75 differentially expressed prognosis-related genes, and a prognostic model incorporating thioredoxin like 4A (TXNL4A) was identified using least absolute shrinkage and selection operator regression analysis. ICGC-LIHC was used as a validation dataset to confirm the validity of the model. PubMed failed to retrieve HCC-related studies on TXNL4A. TXNL4A was highly expressed in most tumors and was associated with HCC survival. Chi-squared analyses indicated that TXNL4A expression positively correlated positively with the clinical features of HCC. Multivariate analyses revealed that high TXNL4A expression was an independent risk factor for HCC. Immunocorrelation and scRNA data analyses indicated that TXNL4A was correlated with CD8 T cell infiltration in HCC. Conclusion: Therefore, we identified a prognostic and immune-related marker for HCC from the RNA splicing pathway.

Expression of ZNF281 in colorectal cancer correlates with response to radiotherapy and survival.

BACKGROUND: The treatment of Colorectal cancer (CRC) is extremely complex and survival rates vary depending on the stage of the disease at the time of diagnosis. Neoadjuvant chemoradiotherapy (NACRT), is the conventional treatment for locally advanced rectal cancer (LARC); however, the resistance to chemoradiotherapy in LARC is difficult to predict. MATERIALS AND METHODS: In this study, clinical data of 126 LARC patients were collected and analyzed, and relevant validation was performed using GEO database and in vitro and in vivo experiments, including Western blotting and Real-time quantitative PCR, immunohistochemistry, immunofluorescence, clonogenic cell survival assays, and nude-mouse xenograft models. RESULTS: In patients with LARC who were treated with neoadjuvant radiotherapy (NART), higher ZNF281 expression in malignant tissue was associated with a poorer prognosis and lesser degree of tumor regression. Cell and mouse experiments have shown that ZNF281 reduces the damage caused by X-rays to CRC cells and tumors grown in mice. CONCLUSION: We found that the expression of ZNF281 predicted the radiation response of CRC cells and suggested the prognosis of patients with LARC who received neoadjuvant radiation therapy.

I kappa B kinase interacting protein as a promising biomarker in pan-cancer: A multi-omics analysis.

Background: Human chromosome 12 contains I kappa B kinase interacting protein (IKBIP) is also commonly known as IKIP. The involvement of IKBIP in the growth of tumors has only been discussed in a small number of publications. Purpose: To explore the role that IKBIP plays in the development of a wide variety of neoplasms, as well as the tumor immunological microenvironment. Methods: UALCAN, HPA, Genotype Tissue Expression, Cancer Genome Maps, and other datasets were used to analyze IKBIP expression. We thoroughly investigated the predictive importance of IKBIP in pan-cancer, clinical traits, and genetic anomalies. We studied whether there is a link between IKBIP and immune-related genes, microsatellite instability (MSI), and the incidence of tumor mutational burden (TMB). The link between immune cell infiltration and IKBIP expression was examined using data on immune cell infiltration from ImmuCellAI, TIMER2, and earlier studies. Finally, gene set enrichment analysis (GSEA) was performed to determine the signaling pathways associated with IKBIP. Results: IKBIP is highly expressed in most cancers and is negatively associated with the prognosis of several major cancer types. Furthermore, IKBIP expression was linked to TMB in 13 cancers and MSI in seven cancers. Additionally, IKBIP is associated with numerous immunological and cancer-promoting pathways. Simultaneously, various cancer types have unique tumor-infiltrating immune cell profiles. Conclusion: IKBIP has the potential to act as a pan-cancer oncogene and is crucial for both carcinogenesis and cancer immunity. Elevated IKBIP expression implies an immunosuppressive environment and may be used as a prognostic biomarker and therapeutic target.

Experimental Study on Chemical-Mechanical Synergistic Preparation for Cemented Carbide Insert Cutting Edge.

Typical edge defects in the edge region of a new cemented carbide insert without edge preparation include burrs, poor surface quality, micro-breakages, and irregularities along the edge. To address the problems in new cemented carbide inserts without edge preparations, a chemical-mechanical synergistic preparation (CMSP) method for the cemented carbide insert cutting edge was proposed. Firstly, the CMSP device for the insert cutting edge was constructed. Then, the polishing slurry of the CMSP for the insert cutting edge was optimized using the Taguchi method combined with a grey relation analysis and fuzzy inference. Finally, orthogonal experiments, the Taguchi method, and analysis of variance (ANOVA) were used to investigate the effect of the polishing plate's rotational speed, swing angle, and input frequency of the controller on the edge preparation process, and the parameters were optimized. The results showed that the best parameter combination for the polishing slurry for the cemented carbide inserts was the mass concentration of the abrasive particle of 10 wt%, the mass concentration of the oxidant of 10 wt%, the mass concentration of the dispersant of 2 wt%, and the pH of 8. The CMSP process parameter combination for the linear edge had the polishing plate's rotational speed of 90 rpm, the swing angle of 6°, and the input frequency of the controller of 5000 Hz. The optimum CMSP process parameter combination for the circular edge had the polishing plate's rotational speed of 90 rpm, the swing angle of 6°, and the input frequency of the controller of 7000 Hz. The polishing plate's rotational speed had the most significant impact on the edge preparation process, followed by the swing angle, and the effect of the input frequency of the controller was the smallest. This study demonstrated that CMSP is a potential way to treat the cemented carbide insert cutting edge in a tool enterprise.

Global status of research on radiotherapy for rectal cancer: A bibliometric and visual analysis.

Radiotherapy for rectal cancer has received increasing research attention in recent years; however, no bibliometric assessment has been conducted on the progress of research in this field. This study aimed to visualize the research evolution and emerging research hotspots in the field of rectal cancer radiotherapy using bibliometric methods. Data were collected from the Web of Science Core Collection database, including countries, institutions, authors, keywords, and co-citations of references, and the CiteSpace software was used for bibliometric analysis. A total of 5,372 publications on radiotherapy for rectal cancer, published between January 2000 and January 2022, were included. An increasing trend in the number of published articles was observed. There is an overall upward trend in the number of publications published, with the US publishing the most in this field, followed by China and the Netherlands. Italian writer Vincenzo Valentini and German writer R. Sauer ranked first in terms of published articles and co-cited authors, respectively. Literature co-citation and keyword co-occurrence analyses showed that early studies focused on topics such as preoperative radiotherapy, combined radiotherapy and chemotherapy, and total mesorectal excision. In recent years, gradually increasing attention has been paid to short-course radiotherapy, x-ray brachytherapy, and stereotactic systemic radiotherapy. Burst analysis suggested that magnetic resonance (MR)-guided neoadjuvant radiotherapy studies, mechanistic studies, and clinical trials may emerge as new research hotspots. Rectal cancer radiotherapy has been widely studied and the research hotspots have considerably changed in recent years. Future research hotspots may include MR-guided neoadjuvant radiotherapy studies, mechanistic studies, and clinical trials.