Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.

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.

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.

The value of CT shape quantification in predicting pathological classification of lung adenocarcinoma.

OBJECTIVE: To evaluate whether quantification of lung GGN shape is useful in predicting pathological categorization of lung adenocarcinoma and guiding the clinic. METHODS: 98 patients with primary lung adenocarcinoma were pathologically confirmed and CT was performed preoperatively, and all lesions were pathologically ≤ 30 mm in size. On CT images, we measured the maximum area of the lesion's cross-section (MA). The longest diameter of the tumor (LD) was marked with points A and B, and the perpendicular diameter (PD) was marked with points C and D, which was the longest diameter perpendicular to AB. and D, which was the longest diameter perpendicular to AB. We took angles A and B as big angle A (BiA) and small angle A (SmA). We measured the MA, LD, and PD, and for analysis we derived the LD/PD ratio and the BiA/SmA ratio. The data were analysed using the chi-square test, t-test, ROC analysis, and binary logistic regression analysis. RESULTS: Precursor glandular lesions (PGL) and microinvasive adenocarcinoma (MIA) were distinguished from invasive adenocarcinoma (IAC) by the BiA/SmA ratio and LD, two independent factors (p = 0.007, p = 0.018). Lung adenocarcinoma pathological categorization was indicated by the BiA/SmA ratio of 1.35 and the LD of 11.56 mm with sensitivity of 81.36% and 71.79%, respectively; specificity of 71.79% and 74.36%, respectively; and AUC of 0.8357 (95% CI: 0.7558-0.9157, p < 0.001), 0.8666 (95% CI: 0.7866-0.9465, p < 0.001), respectively. In predicting the pathological categorization of lung adenocarcinoma, the area under the ROC curve of the BiA/SmA ratio combined with LD was 0.9231 (95% CI: 0.8700-0.9762, p < 0.001), with a sensitivity of 81.36% and a specificity of 89.74%. CONCLUSIONS: Quantification of lung GGN morphology by the BiA/SmA ratio combined with LD could be helpful in predicting pathological classification of lung adenocarcinoma.

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.

Progress in TLE treatment from 2003 to 2023: scientific measurement and visual analysis based on CiteSpace.

Objective: Temporal lobe epilepsy (TLE) is the most common cause of drug-resistant epilepsy and can be treated surgically to control seizures. In this study, we analyzed the relevant research literature in the field of temporal lobe epilepsy (TLE) treatment to understand the background, hotspots, and trends in TLE treatment research. Methods: We discussed the trend, frontier, and hotspot of scientific output in TLE treatment research in the world in the last 20 years by searching the core collection of the Web of Science database. Excel and CiteSpace software were used to analyze the basic data of the literature. Result: We identified a total of 2,051 publications on TLE treatment from 75 countries between 2003 and 2023. We found that the publication rate was generally increasing. The United States was the most publishing country; among the research institutions on TLE treatment, the University of California system published the most relevant literature and collaborated the most with other institutions. The co-citation of literature, keyword co-occurrence, and its clustering analysis showed that the early studies focused on open surgical treatment, mainly by lobectomy. In recent years, the attention given to stereotactic, microsurgery, and other surgical techniques has gradually increased, and the burst analysis indicated that new research hotspots may appear in the future in the areas of improved surgical procedures and mechanism research.

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.

Mapping trends and hotspot regarding testicular torsion: A bibliometric analysis of global research (2000-2022).

Background: Testicular torsion is an acute scrotal disorder requiring immediate emergency treatment. Ischemic injury and reperfusion injury are important causes of oxidative stress and irreversible oxidative damage after testicular torsion. Although a large number of literatures have discussed the causes and treatment of testicular torsion, there is currently a lack of systematic exploration of the historical evolution of testicular torsion and the construction of a knowledge framework. Method: The Web of Science Core Collection was searched for studies on testicular torsion published between 2000 and 2022. The basic data of the literature were analyzed by using Excel and CiteSpace software. Result: A total of 1,007 publications on testicular torsion published were found in 64 countries between 2000 and 2022, with an increasing annual publication level. Early detection, early diagnosis and early treatment of testicular torsion had always been at the core of clinical practice, and the pathological cascade reaction of ischemic injury and ischemia-reperfusion injury after testicular torsion were also at the core of basic research. Emphasis had been placed on the development of protective drugs for ischemia and reperfusion after testicular torsion in various countries, regions and institutions. Conclusion: Over the past 20 years, the research on testicular torsion had been widely concerned. Hot topics in testicular torsion in recent years were ischemia-reperfusion injury, oxidative stress, rat, doppler ultrasonography, diagnosis and orchiectomy. This article may provide a useful resource for clinicians and basic researchers regarding testicular torsion.

Systematic analysis of circRNA biomarkers for diagnosis, prognosis and therapy in colorectal cancer.

As the third most common cancer and the second leading cause of cancer death worldwide, colorectal cancer (CRC) poses a serious threat to people's health. In recent years, circRNA has been widely reported as a new biomarker in CRC, but a comprehensive summary and analysis is lacking. This study aims to evaluate the diagnostic, therapeutic and prognostic significance of circRNAs in CRC by systematically analysing their expression patterns, biological functions and clinical significance in CRC. The literature on circRNA in CRC was searched in the PubMed database and included for analysis after screening according to strict inclusion and exclusion criteria. The UALCAN online tool was used to obtain host gene expression data. The miRTargetLink 2.0 was used to predict target genes for miRNAs action in CRC patients. Cytoscape was used to construct circRNA-miRNA-mRNA interaction networks. From the 236 included papers, we identified 217 circRNAs and their associated 108 host genes and 145 miRNAs. Among the 145 miRNAs, 27 miRNAs had no corresponding target genes. After prediction of target genes and differential analysis, a total of 25 target genes were obtained and a circRNA-miRNA-mRNA interaction network was constructed. Among the 217 circRNAs, 74 were associated with diagnosis, 160 with treatment and 51 with prognosis. And 154 of them function as oncogenes while 58 as tumour suppressor genes. In addition, these circRNAs include 32 exosomal circRNAs, which have unique advantages as biomarkers. In total, we summarize and analyze the expression patterns, biological functions and clinical significance of circRNAs in CRC. In addition, we constructed some new circRNA-miRNA-mRNA regulatory axes based on the miRNAs sponged by circRNAs.

Strong and Flexible High-Performance Anion Exchange Membranes with Long-Distance Interconnected Ion Transport Channels for Alkaline Fuel Cells.

Anion exchange membrane fuel cells (AEMFCs), which operate on a variety of green fuels, can achieve high power without emitting greenhouse gases. However, the lack of high ionic conductivity and long-term durability of anion-exchange membranes (AEMs) as their key components is a major obstacle hindering the commercial application of AEMFCs. Here, a series of homogeneous semi-interpenetrating network (semi-IPN) AEMs formed by cross-linking a copolymer of styrene (St) and 4-vinylbenzyl chloride (VBC) with branched polyethylenimine (BPEI) were designed. The pure carbon copolymer skeleton without sulfone/ether bonds accompanied by the semi-IPN endows the AEMs with excellent chemical stability. Moreover, the cross-linking effect of flexible BPEI chains is supposed to promote the "strong-flexible" mechanical properties, while the presence of multiquaternary ammonium groups can boost the formation of microphase separation, thereby enhancing the ionic conductivity of these AEMs. Consequently, the optimized (S1V1)3Q AEM exhibits an excellent hydroxide conductivity of 106 mS cm-1 at 80 °C, as well as more than 81% residual conductivity after soaking in 1 M NaOH at 60 °C for 720 h. Furthermore, the H2/O2 fuel cell assembled with (S1V1)3Q AEM delivers a peak power density of 150.2 mW cm-2 at 60 °C and 40% relative humidity. All results indicate that the approach of combining a pure carbon backbone polymer with a semi-IPN structure may be a viable strategy for fabricating AEMs that can be used in AEMFCs for long-term applications.

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.

Identification of ABCA5 among ATP-Binding Cassette Transporter Family as a New Biomarker for Colorectal Cancer.

Background: The increasing incidence and mortality of colorectal cancer (CRC) urgently requires updated biomarkers. The ABC transporter family is a widespread family of membrane-bound proteins involved in the transportation of substrates associated with ATP hydrolysis, including metabolites, amino acids, peptides and proteins, sterols and lipids, organic and inorganic ions, sugars, metals, and drugs. They play an important role in the maintenance of homeostasis in the body. Purpose: This study aims to search for new markers in the ABC transporter gene family for diagnostic and prognostic purposes through data mining of The Cancer Genome Atlas (TCGA) and GEO (Gene Expression Omnibus) datasets. Methods: A total of 980 samples, including 684 CRC patients and 296 controls from five different datasets, were included for analysis. The construction of the PPI (protein-protein interaction) network and pathway analysis were performed in STRING database and DAVID (database for annotation, visualization, and integrated discovery), respectively. In addition, GSEA (gene set enrichment analysis) and WGCNA (weighted gene co-expression network analysis) were also used for functional analysis. Results: After several rounds of screening and validation, only the ABCB5 gene was retained among the 49 genes. Conclusions: The results demonstrated that ABCA5 expression is reduced in CRC and patients with high ABCA5 expression have better OS, which can provide guidance for better management and treatment of CRC in the future.

Functions and Mechanisms of Lysine Glutarylation in Eukaryotes.

Lysine glutarylation (Kglu) is a newly discovered post-translational modification (PTM), which is considered to be reversible, dynamic, and conserved in prokaryotes and eukaryotes. Recent developments in the identification of Kglu by mass spectrometry have shown that Kglu is mainly involved in the regulation of metabolism, oxidative damage, chromatin dynamics and is associated with various diseases. In this review, we firstly summarize the development history of glutarylation, the biochemical processes of glutarylation and deglutarylation. Then we focus on the pathophysiological functions such as glutaric acidemia 1, asthenospermia, etc. Finally, the current computational tools for predicting glutarylation sites are discussed. These emerging findings point to new functions for lysine glutarylation and related enzymes, and also highlight the mechanisms by which glutarylation regulates diverse cellular processes.

Diagnostic and prognostic value of ABC transporter family member ABCG1 gene in clear cell renal cell carcinoma.

As the most common histologic subtype of renal cancer, clear cell renal cell carcinoma (ccRCC) poses a serious threat to public health. However, there are no specific molecular-targeted drugs for ccRCC at present. Human ATP-binding cassette (ABC) transporter family plays an important role in homeostasis maintenance. This study aimed to evaluate the potential diagnostic value of ABC genes in ccRCC. A total of 952 samples of ccRCC patients (707) and controls (245) from three different datasets were included for analysis. Receiver operating characteristic analysis and t-test were used to analyze the differential expression of ABC genes in ccRCC patients and control samples at mRNA level during screening and validations. The Cancer Genome Atlas (TCGA-ccRCC) dataset was utilized to investigate the correlation between ABC genes expression and prognostic value in ccRCC. We then investigated the interactions between ABCG1 and proteins in the Comparative Toxicogenomics Database (CTD). Finally, we found that ATP-binding cassette transporter G member 1 (ABCG1) was over-expressed in ccRCC patients compared with healthy samples at mRNA level. Cox regression analysis and Kaplan-Meier analysis showed that ccRCC patients with high ABCG1 expression had better overall survival (OS) than those patients with low expression (hazard ratio (HR) = 0.662, p = 0.007). This study demonstrated that ABCG1 is a potential diagnostic and prognostic biomarker in ccRCC and discussed the molecular mechanisms underlying the relationship between ccRCC and ABCG1, which might provide guidance for better management and treatment of ccRCC in the future.

Alterations in Rumen Bacterial Community and Metabolome Characteristics of Cashmere Goats in Response to Dietary Nutrient Density.

This study was conducted to investigate the impacts of dietary energy and protein on rumen bacterial composition and ruminal metabolites. A total of 12 ruminal samples were collected from Shaanbei white cashmere goats which were divided into two groups, including high-energy and high-protein (Group H; crude protein, CP: 9.37% in dry matter; metabolic energy, ME: 9.24 MJ/kg) and control (Group C; CP: 8.73%; ME: 8.60 MJ/kg) groups. Thereby, 16S rRNA gene sequencing and a quantitative polymerase chain reaction were performed to identify the rumen bacterial community. Metabolomics analysis was done to investigate the rumen metabolites and the related metabolic pathways in Groups C and H. The high-energy and high-protein diets increased the relative abundance of phylum Bacteroidetes and genera Prevotella_1 and Succiniclasticum, while decreasing the number of Proteobacteria (p < 0.05). The dominant differential metabolites were amino acids, peptides, and analogs. Tyrosine metabolism played an important role among the nine main metabolic pathways. Correlation analysis revealed that both Prevotella_1 (r = 0.608, p < 0.05) and Ruminococcus_2 (r = 0.613, p < 0.05) showed a positive correlation with catechol. Our findings revealed that the diets with high energy and protein levels in Group H significantly altered the composition of ruminal bacteria and metabolites, which can help to improve the dietary energy and protein use efficiency in goats.

An insight into the influence of hydrogen bond acceptors on cellulose/1-allyl-3-methyl imidazolium chloride solution.

Although ionic liquids have been well established as effective solvents for the dissolution and processing of natural cellulose fibers, the detailed dissolution mechanism at the molecular level still remains unclear. Herein, the turbidimetric measurement showed that the solubility of cellulose in 1-allyl-3-methyl imidazolium chloride (AmimCl) decreased with increasing temperature. The temperature dependence of the OH stretching vibration band of cellulose in AmimCl was investigated by infrared spectroscopy. The interaction between AmimCl and different hydrogen bond acceptors were investigated by turbidimetry and NMR spectroscopy, which indicated that the excellent compatibility of the hydrogen bond acceptors with AmimCl provides more interaction sites for the hydroxyl groups of the cellulose. In addition, ionic liquids with a similar anionic structure of hydrogen bond acceptors have been synthesized. This study provides a green and safe guide for the preparation of ionic liquids with excellent solubility of cellulose.

Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners.

The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC-Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC-ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC-ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC-ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC-ARM binding partners.