Analysis of the role of CHPF in colorectal cancer tumorigenesis and immunotherapy based on bioinformatics and experiments.

BACKGROUND: Chondroitin polymerizing factor (CHPF) has been found to be involved in the development of numerous cancers and correlated with poor prognosis. However, its role in the tumorigenesis and development of colorectal cancer (CRC) remains unknown. METHODS: In our research, we explored CHPF expression and clinicopathological characteristics using The Cancer Genome Atlas Program (TCGA), UALCAN, GSE9348, TIMER2.0 and The Human Protein Atlas (HPA) database, in addition, we validated CHPF expression in CRC cell lines by Real-Time Quantitative PCR (qRT-PCR) and Western blot (WB). KM-Plotter, PrognoScan and TCGA were also utilized to verify its prognosis value in CRC. Small-interfer RNA (Si-RNA) was used to perform Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EDU), transwell and wound healing assays to testify its function on the tumor progression. Based on TCGA database, we probed potential biological mechanism by which CHPF play its role via clusterProfiler package and GEPIA database and we validated their correlation by WB assay. Moreover, we explored its potential association with the tumor microenvironment (TME), immune infiltrated cells, immune checkpoints, tumor mutation burden (TMB) as well as microsatellite instability (MSI), and investigated immunotherapy sensitivity via Tumor Immune Dysfunction and Exclusion (TIDE) algorithm as well as potentially effective therapeutic drugs via pRRophetic algorithm. RESULTS: CHPF was identified upregulated in CRC tissues and cells, correlated with poor prognosis, and nodal metastasis status, stage and histological subtype. Down-regulation of CHPF inhibited CRC cell proliferation, migration and its expression correlated with wnt pathway key molecules. In addition, high expression of CHPF was positively correlated with TME scores, Regulatory T cells (Tregs) cell infiltration degree, Programmed death-1 (PD-1), MSI-high (MSI-H), and TIDE scores, however, not with TMB. Targeted drug analysis showed that patients with high CHPF expression were more sensitive to telatinib, recaparib, serdemetan, and trametinib. CONCLUSION: CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.

Ionic titanium is expected to improve the nutritional quality of Tartary buckwheat sprouts through flavonoids and amino acid metabolism.

Tartary buckwheat sprouts are highly valued by consumers for their superior nutritional content. Ionic titanium (Ti) has been shown to enhance crop growth and improve nutritional quality. However, there is limited research on the impact of ionic Ti on the nutritional quality of Tartary buckwheat sprouts. This study cultivated Tartary buckwheat sprouts with ionic Ti and found that the high concentration of ionic Ti significantly increased the contents of chlorophyll a, chlorophyll b, and carotenoids (increased by 25.5%, 27.57%, and 15.11%, respectively). The lower concentration of ionic Ti has a higher accumulation of total flavonoids and total polyphenols. Metabolomics analysis by LC-MS revealed 589 differentially expressed metabolites and 54 significantly different metabolites, enriching 82 metabolic pathways, especially including amino acid biosynthesis and flavonoid biosynthesis. This study shows that ionic Ti can promote the growth of Tartary buckwheat sprouts, improve nutritional quality, and have huge development potential in food production.

[Research progress on active ingredients of Coicis Semen].

As a common medicinal and edible resource in China, Coicis Semen has a long history of cultivation and medicinal use. Traditional Chinese medicine(TCM) clinically believes that Coicis Semen has the effect of strengthening the spleen and tonifying the lungs, clearing heat and dampness, removing pus and paralysis, and stopping diarrhea. Therefore, it is used to treat edema, foot odor, spleen deficiency, diarrhea, and other symptoms. The above effects are closely related to the active ingredients of Coicis Semen, such as esters, fatty acids, polysaccharides, proteins, as well as phenolic acids, sterols, flavonoids, lactams, triterpenes, alkaloids, and adenosine. Modern research has found that Coicis Semen also has anti-cancer, anti-inflammatory, antioxidant, hypoglycemic, and hypotensive effects and other pharmacological activities, and it can improve immunity and regulate lipid metabolism. Coicis Semen is widely distributed in China, mainly produced in Guizhou, Yunnan, Fujian, Sichuan, and other places, and the quality of Coicis Semen from different origins varies. From ancient times to the present, Coicis Semen processing methods have experienced the process from simple to complex, and the types of auxiliary materials are more extensive, such as soil, bran, and river sand. These processing methods have been inherited from generation to generation. Nowadays, the commonly used methods are bran-fried, stir-fried, sand-fried, etc. In this paper, by reviewing the relevant literature in China and abroad in recent years, the main active ingredients and related pharmacological effects of Coicis Semen are sorted out, and the effects of different origins and processing methods on the chemical composition of Coicis Semen are summarized, with a view to providing references for the comprehensive development and utilization of Coicis Semen and the further study of its mechanism of action.

Unveiling immunogenic cell death-related genes in colorectal cancer: an integrated study incorporating transcriptome and Mendelian randomization analyses.

Immunogenic cell death (ICD), a type of cell death that activates the tumor-specific immune response and thus exerts anti-tumor effects, is an emerging target in tumor therapy, but research on ICD-related genes (ICDGs) in colorectal cancer (CRC) remains limited. This study aimed to identify the CRC-specific ICDGs and explore their potential roles. Through RNA sequencing for tissue samples from CRC patients and integration with The Cancer Genome Atlas (TCGA) data, we identified 33 differentially expressed ICDGs in CRC. We defined the ICD score based on these genes in single-cell data, where a high score indicated an immune-active microenvironment. Additionally, molecular subtypes identified in bulk RNA data showed distinct immune landscapes. The ICD-related signature constructed with machine learning effectively distinguished patients' prognosis. The summary data-based Mendelian randomization (SMR) and colocalization analysis prioritized CFLAR for its positive association with CRC risk. Molecular docking revealed its stable binding with chemotherapeutic drugs like irinotecan. Furthermore, experimental validation confirmed CFLAR overexpression in CRC samples, and its knockdown inhibited tumor cell proliferation. Overall, this study expands the understanding of the potential roles and mechanisms of ICDGs in CRC and highlights CFLAR as a promising target for CRC.

Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma.

Background: Lysosomes are essential for the development and recurrence of cancer. The relationship between a single lysosome-related gene and cancer has previously been studied, but the relationship between the lysosome-related genes (LRGs) and colon adenocarcinoma (COAD) remains unknown. This research examined the role of lysosome-related genes in colon adenocarcinoma. Methods: 28 lysosome-related genes associated with prognosis (PLRGs) were found by fusing the gene set that is differently expressed between tumor and non-tumor in colon adenocarcinoma with the gene set that is related to lysosomes. Using consensus unsupervised clustering of PLRGs, the colon adenocarcinoma cohort was divided into two subtypes. Prognostic and tumor microenvironment (TME) comparisons between the two subtypes were then made. The PLRGs_score was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to quantify each patient's prognosis and provide advice for treatment. Lastly, Western Blot and immunohistochemistry (IHC) were used to identify MOGS expression at the protein level in colon adenocarcinoma tissues. Results: PLRGs had more somatic mutations and changes in genetic level, and the outcomes of the two subtypes differed significantly in terms of prognosis, tumor microenvironment, and enrichment pathways. Then, PLRGs_score was established based on two clusters of differential genes in the cancer genome atlas (TCGA) database, and external verification was performed using the gene expression omnibus (GEO) database. Then, we developed a highly accurate nomogram to enhance the clinical applicability of the PLRGs_score. Finally, a higher PLRGs_score was associated with a poorer overall survival (OS), a lower tumor mutation burden (TMB), a lower cancer stem cell (CSC) index, more microsatellite stability (MSS), and a higher clinical stage. MOGS was substantially elevated at the protein level in colon adenocarcinoma as additional confirmation. Conclusion: Overall, based on PLRGs, we identified two subtypes that varied significantly in terms of prognosis and tumor microenvironment. Then, in order to forecast patient prognosis and make treatment suggestions, we developed a diagnostic model with major significance for prognosis, clinical relevance, and immunotherapy. Moreover, we were the first to demonstrate that MOGS is highly expressed in colon adenocarcinoma.

Machine learning-based glycolysis-associated molecular classification reveals differences in prognosis, TME, and immunotherapy for colorectal cancer patients.

Background: Aerobic glycolysis is a process that metabolizes glucose under aerobic conditions, finally producing pyruvate, lactic acid, and ATP for tumor cells. Nevertheless, the overall significance of glycolysis-related genes in colorectal cancer and how they affect the immune microenvironment have not been investigated. Methods: By combining the transcriptome and single-cell analysis, we summarize the various expression patterns of glycolysis-related genes in colorectal cancer. Three glycolysis-associated clusters (GAC) were identified with distinct clinical, genomic, and tumor microenvironment (TME). By mapping GAC to single-cell RNA sequencing analysis (scRNA-seq), we next discovered that the immune infiltration profile of GACs was similar to that of bulk RNA sequencing analysis (bulk RNA-seq). In order to determine the kind of GAC for each sample, we developed the GAC predictor using markers of single cells and GACs that were most pertinent to clinical prognostic indications. Additionally, potential drugs for each GAC were discovered using different algorithms. Results: GAC1 was comparable to the immune-desert type, with a low mutation probability and a relatively general prognosis; GAC2 was more likely to be immune-inflamed/excluded, with more immunosuppressive cells and stromal components, which also carried the risk of the poorest prognosis; Similar to the immune-activated type, GAC3 had a high mutation rate, more active immune cells, and excellent therapeutic potential. Conclusion: In conclusion, we combined transcriptome and single-cell data to identify new molecular subtypes using glycolysis-related genes in colorectal cancer based on machine-learning methods, which provided therapeutic direction for colorectal patients.

Identification of the joint line in revision total knee arthroplasty using a multiple linear regression model: a cadaveric study.

INTRODUCTION: The results of revision total knee arthroplasty (rTKA) may be compromised by excessive joint line (JL) elevation. It is critical but challenging in reestablishing the JL in rTKA. Previous studies have confirmed that, biomechanically and clinically, JL elevation should not exceed 4 mm. Image-based studies described several approaches to locate the JL intraoperatively, however magnification errors could occur. In this cadaveric study, we aim to define an accurate and reliable method to determine the JL. MATERIALS AND METHODS: Thirteen male and eleven female cadavers were used, with an average age of death being 48.3 years. The transepicondylar width (TEW), the distance from the medial (MEJL) and lateral (LEJL) epicondyle, adductor tubercle (ATJL), fibular head (FHJL) and tibial tubercle (TTJL) to the JL were measured in 48 knees. Intra- and interobserver reliability and validity were tested prior to any additional analysis. Pearson correlation and linear regression analysis were used to examine the correlations between landmark-JL distances (LEJL, MEJL, ATJL, FHJL and TTJL) and the TEW, and to further derive models for intraoperative JL determination. The accuracy of different models, quantified by errors between estimated and measured landmark-JL distances, was compared using the Friedman and post hoc Dunn tests. RESULTS: The intra- and inter-observer measurements for TEW, MEJL, LEJL, ATJL, TTJL and FHJL did not differ significantly (p > 0.05). Between genders, significant differences were found on TEW, MEJL, LEJL, ATJL, FHJL and TTJL (p < 0.05). There was no association between TEW and either FHJL or TTJL (p > 0.05), while ATJL, MEJL, and LEJL were found to be correlated with TEW (p < 0.05). Six models were derived: (1) MEJL = 0.37*TEW (r = 0.384), (2) LEJL = 0.28*TEW (r = 0.380), (3) ATJL = 0.47*TEW (r = 0.608), (4) MEJL = 0.413*TEW - 4.197 (R2 = 0.473), (5) LEJL = 0.236*TEW + 3.373 (R2 = 0.326), (6) ATJL = 0.455*TEW + 1.440 (R2 = 0.556). Errors were defined as deviations between estimated and actual landmark-JL distances. The mean absolute value of the errors, created by Model 1-6 was 3.18 ± 2.25, 2.53 ± 2.15, 2.64 ± 2.2, 1.85 ± 1.61, 1.60 ± 1.59 and 1.71 ± 1.5, respectively. The error could be limited to 4 mm in 72.9%, 83.3%, 72.9%, 87.5%, 87.5%, and 93.8% of the cases by referencing Model 1-6, respectively. CONCLUSION: Compared to previous image-based measurements, the current cadaveric study most closely resembles a realistic view of intraoperative settings and could circumvents magnification errors. We recommend using Model 6, the JL can be best estimated by referencing the AT and the ATJL can be calculated as ATJL (mm) = 0.455*TEW (mm) + 1.440 (mm).

Genetic variants in the calcium signaling pathway participate in the pathogenesis of colorectal cancer through the tumor microenvironment.

Background: Cancer risk is influenced by calcium signaling in intracellular and intercellular signaling pathways. However, the relationship between the calcium signaling pathway and colorectal cancer risk remains unknown. We aim to evaluate the role of genetic variants in calcium signaling pathway genes in colorectal cancer risk through the tumor microenvironment. Methods: An analysis of genetic variants in the calcium signaling pathway was conducted using a case-control study that included 1150 colorectal cancer patients and 1342 non-cancer patients. Using the regression model, we assessed whether single-nucleotide polymorphisms (SNPs) increase the risk of colorectal cancer. We also performed a dual luciferase reporter gene assay using HCT116 cell lines and DLD1 cell lines to demonstrate the regulatory relationship between SNP and candidate risk gene. We evaluated the expression of candidate risk gene in different populations. In addition, we also evaluated candidate risk gene and 22 immune cells correlation studies. Results: There was a significant association between the PDE1C rs12538364 T allele and colorectal cancer risk [odds ratio (OR) = 1.57, 95% confidence interval (CI) = 1.30 - 1.90, P = 3.07 × 10-6, P FDR = 0.004]. Mutation of intron region rs1538364 C to T locus reduces promoter activity of PDE1C in DLD1 and HCT116 cell lines (P < 0.05). We identified that PDE1C is significantly down-regulated in colorectal cancer, closely associated with 22 immune cells. Finally, we found that PDE1C could be the biomarker for individual immunotherapy of colorectal cancer. Conclusion: According to our findings, PDE1C may be a key factor contributing to colorectal cancer, thus improving individual immunotherapy for the disease. The potential mechanism by which polymorphisms in the calcium signaling pathway genes may participate in the pathogenesis of colorectal cancer through the tumor microenvironment.

N7-methylguanosine-related lncRNAs: Predicting the prognosis and diagnosis of colorectal cancer in the cold and hot tumors.

Background: 7-Methylguanosine(m7G) contributes greatly to its pathogenesis and progression in colorectal cancer. We proposed building a prognostic model of m7G-related LncRNAs. Our prognostic model was used to identify differences between hot and cold tumors. Methods: The study included 647 colorectal cancer patients (51 cancer-free patients and 647 cancer patients) from The Cancer Genome Atlas (TCGA). We identified m7G-related prognostic lncRNAs by employing the univariate Cox regression method. Assessments were conducted using univariate Cox regression, multivariate Cox regression, receiver operating characteristics (ROC), nomogram, calibration curves, and Kaplan-Meier analysis. All of these procedures were used with the aim of confirming the validity and stability of the model. Besides these two analyses, we also conducted half-maximal inhibitory concentration (IC50), immune analysis, principal component analysis (PCA), and gene set enrichment analysis (GSEA). The entire set of m7G-related (lncRNAs) with respect to cold and hot tumors has been divided into two clusters for further discussion of immunotherapy. Results: The risk model was constructed with 17 m7G-related lncRNAs. A good correlation was found between the calibration plots and the prognosis prediction in the model. By assessing IC50 in a significant way across risk groups, systemic treatment can be guided. By using clusters, it may be possible to distinguish hot and cold tumors effectively and to aid in specific therapeutic interventions. Cluster 1 was identified as having the highest response to immunotherapy drugs and thus was identified as the hot tumor. Conclusion: This study shows that 17 m7G-related lncRNA can be used in clinical settings to predict prognosis and use them to determine whether a tumor is cold or hot in colorectal cancer and improve the individualization of treatment.

Development and validation of a deep learning model to predict survival of patients with esophageal cancer.

Objective: To compare the performance of a deep learning survival network with the tumor, node, and metastasis (TNM) staging system in survival prediction and test the reliability of individual treatment recommendations provided by the network. Methods: In this population-based cohort study, we developed and validated a deep learning survival model using consecutive cases of newly diagnosed stage I to IV esophageal cancer between January 2004 and December 2015 in a Surveillance, Epidemiology, and End Results (SEER) database. The model was externally validated in an independent cohort from Fujian Provincial Hospital. The C statistic was used to compare the performance of the deep learning survival model and TNM staging system. Two other deep learning risk prediction models were trained for treatment recommendations. A Kaplan-Meier survival curve was used to compare survival between the population that followed the recommended therapy and those who did not. Results: A total of 9069 patients were included in this study. The deep learning network showed more promising results in predicting esophageal cancer-specific survival than the TNM stage in the internal test dataset (C-index=0.753 vs. 0.638) and external validation dataset (C-index=0.687 vs. 0.643). The population who received the recommended treatments had superior survival compared to those who did not, based on the internal test dataset (hazard ratio, 0.753; 95% CI, 0.556-0.987; P=0.042) and the external validation dataset (hazard ratio, 0.633; 95% CI, 0.459-0.834; P=0.0003). Conclusion: Deep learning neural networks have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with esophageal cancer.

Analysis of the Prognostic Significance and Immune Infiltration of the Amino Acid Metabolism-Related Genes in Colon Adenocarcinoma.

Amino acid metabolization is verified to be a part in the progression of cancer. However, genes related to the amino acid metabolism have not been identified in colon adenocarcinoma (COAD). A systematic prognostic model of COAD becomes a pressing need. Among genes related to the amino acid metabolism, RIMKLB, ASPG, TH, MTAP, AZIN2, PSMB2, HDC, ACMSD, and PSMA8 were identified to construct a risk model. Kaplan-Meier (K-M) analyses demonstrated that the high-risk group achieved a poor prognosis. Area under the respective ROC (AUC) values indicated the robustness of the model. To highlight its clinical value, multivariate Cox was used to obtain the optimal variables to construct a nomogram. A higher tumor mutation burden was observed in the high-risk group. However, the low-risk group had a stronger immune infiltration. Seven molecular subtypes were found by consensus cluster. Twenty-two hub genes were identified related to the ESTIMATE score using WGCNA. In brief, our research constructed a stable prognostic model related to the amino acid metabolism in COAD, revealing its connection to the immune microenvironment. The model guided the outcome of COAD and the direction of immunotherapy.

PD-1 inhibitor in combination with fruquintinib therapy for initial unresectable colorectal cancer: A case report.

BACKGROUND: PD-1 inhibitors in combination with fruquintinib have not previously been reported as neoadjuvant therapy for patients with colorectal cancer. In this case report, the combination of a PD-1 inhibitor and fruquintinib demonstrated good efficacy in patients with MSI-H colorectal cancer. CASE SUMMARY: The patient was a young man in his 30s who had MSI-H type colon cancer. The patient underwent four cycles of neoadjuvant therapy with a PD-1 inhibitor combined with fruquintinib before surgery, resulting in regression of the mass and a successful surgery. CONCLUSION: Some patients with colorectal cancer have the MSI-H type, and the first-line chemotherapy regimen is not effective. However, PD-1 monoclonal antibody immunotherapy has a good therapeutic effect, which can be improved by combination therapy with fruquintinib. We recommend that patients with a history of colon or rectal cancer receive universal MSI testing; then, neoadjuvant therapy should be used.

Surface Topography-Adaptive Robotic Superstructures for Biofilm Removal and Pathogen Detection on Human Teeth.

The eradication of biofilms remains an unresolved challenge across disciplines. Furthermore, in biomedicine, the sampling of spatially heterogeneous biofilms is crucial for accurate pathogen detection and precise treatment of infection. However, current approaches are incapable of removing highly adhesive biostructures from topographically complex surfaces. To meet these needs, we demonstrate magnetic field-directed assembly of nanoparticles into surface topography-adaptive robotic superstructures (STARS) for precision-guided biofilm removal and diagnostic sampling. These structures extend or retract at multilength scales (micro-to-centimeter) to operate on opposing surfaces and rapidly adjust their shape, length, and stiffness to adapt and apply high-shear stress. STARS conform to complex surface topographies by entering angled grooves or extending into narrow crevices and "scrub" adherent biofilm with multiaxis motion while producing antibacterial reagents on-site. Furthermore, as the superstructure disrupts the biofilm, it captures bacterial, fungal, viral, and matrix components, allowing sample retrieval for multiplexed diagnostic analysis. We apply STARS using automated motion patterns to target complex three-dimensional geometries of ex vivo human teeth to retrieve biofilm samples with microscale precision, while providing "toothbrushing-like" and "flossing-like" action with antibacterial activity in real-time to achieve mechanochemical removal and multikingdom pathogen detection. This approach could lead to autonomous, multifunctional antibiofilm platforms to advance current oral care modalities and other fields contending with harmful biofilms on hard-to-reach surfaces.

Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells.

Macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four M2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research.

Structure-activity relationship and antitumor activity of 1,4-pyrazine-containing inhibitors of histone acetyltransferases P300/CBP.

Acetylation of histone lysine residues by histone acetyltransferase (HAT) p300 and its paralog CBP play important roles in gene regulation in health and diseases. The HAT domain of p300/CBP has been found to be a potential drug target for cancer. Compound screening followed by structure-activity relationship studies yielded a novel series of 1,4-pyrazine-containing inhibitors of p300/CBP HAT with their IC50s as low as 1.4 µM. Enzyme kinetics and other studies support the most potent compound 29 is a competitive inhibitor of p300 HAT against the substrate histone. It exhibited a high selectivity for p300 and CBP, with negligible activity on other classes of HATs in human. Compound 29 inhibited cellular acetylation of several histone lysine residues and showed strong activity against proliferation of a panel of solid and blood cancer cells. These results indicate it is a novel pharmacological lead for drug development targeting these cancers as well as a useful chemical probe for biological studies of p300/CBP.

Effect of the Addition of Thermoplastic Resin and Composite on Mechanical and Thermal Properties of Epoxy Resin.

When the thermoplastic composites reach the service limits during the service, the recovery and utilization are the key concerns. Meanwhile, the improvement of strength, toughness and durability of epoxy resin is the effective method to prolong the service life of materials and structures. In the present paper, three kinds of thermoplastic resins (polypropylene-PP, polyamide 6-PA6 and polyether-ether-ketone-PEEK) and composites (carbon fiber-PEEK, glass fiber-PA6 and glass fiber-PP) were adopted as the fillers to reinforce and toughen the epoxy resin (Ts). The mechanical, thermal and microscopic analysis were conducted to reveal the performance improvement mechanism of Ts. It can be found that adding thermoplastic resin and composite fillers at the low mass ratio of 0.5~1.0% brought about the maximum improvement of tensile strength (7~15%), flexural strength (7~15%) and shear strength (20~30%) of Ts resin. The improvement mechanism was because the addition of thermoplastic fillers can prolong the cracking path and delay the failure process through the load bearing of fiber, energy absorption of thermoplastic resin and superior interface bonding. In addition, the thermoplastic composite had better enhancement effect on the mechanical/thermal properties of Ts resin compared to thermoplastic resin. When the mass ratio was increased to 2.0~3.0%, the agglomeration and stress concentration of thermoplastic filler in Ts resin appeared, leading to the decrease of mechanical and thermal properties. The optimal addition ratios of thermoplastic resin were 0.5~1.0% (PEEK), 1.0~2.0% (PA6) and 0.5~1.0% (PP) to obtain the desirable property improvement. In contrast, the optimal mass ratios of three kinds of composite were determined to be 0.5~1.0%. Application prospect analysis indicated adding the thermoplastic resin and composite fillers to Ts resin can promote the recycling and reutilization of thermoplastic composites and improve the performance of Ts resin, which can be used as the resin matrix, interface adhesive and anti-corrosion coating.

Efficacy and safety of free medial plantar flap in repair of the high-voltage electrical burns in hands.

PURPOSE: The purpose of this work was to validate the efficacy and safety of free medial plantar flap in repair of hand wounds resulted from high-voltage electrical burn. METHODS: 22 patients with high-voltage electrical burn wounds were retrieved between July 2016 and July 2018 in the Affiliated Zhengzhou Central Hospital of Zhengzhou University. All the wounds were the entrance of high-voltage electrical current. After thorough debridement, the blood vessels, nerves, tendons, joints were exposed to defects with different degrees. The soft tissue defects were repaired with the free medial plantar flap repair in 12 patients and medium-thickness skin graft in 10 patients. Postoperative management was similar between the two groups. RESULTS: All the operations were completed within 6 h. In the free medial plantar flap group, the mean follow-up period was (11.3 ± 2.4) months, ranging from 9 to 15 months, and all flaps survived; there were no vessel crises. Flaps of 10 patients healed without any complications, and local necrosis occurred in two cases, with healing after debridement. The two-point discrimination (TPD) was 7.0-11.0 mm, and the mean DASH score was 45.6 ± 7.4. In the medium-thickness skin graft group, the mean follow-up period was (10.9 ± 1.8) months. All flaps survived, and local contracture occurred in 3 cases. The TPD was 8.0-11.0 mm, and the mean DASH score was 60.7 ± 9.3. CONCLUSIONS: The free medial plantar flap is an ideal option for repairing the hand soft defects resulted from the high-voltage electrical burn.

HIST2H2BF Potentiates the Propagation of Cancer Stem Cells via Notch Signaling to Promote Malignancy and Liver Metastasis in Colorectal Carcinoma.

BACKGROUND: Growing evidence demonstrates that the initiation and progression of colorectal carcinoma (CRC) is related to the presence of cancer stem cells (CSCs). However, the mechanism through which the stem cell features of CRC cells are maintained is poorly understood. In this study, we identified the oncogenic histone cluster 2 H2B family member F (HIST2H2BF) and aimed to investigate the function of upregulated HIST2H2BF expression in maintaining the stem cell features of CRC cells, which accelerate the progression of CRC. METHODS: HIST2H2BF expression was quantified using real-time polymerase chain reaction, immunohistochemistry, and western blotting. The correlation between CpG island methylation status and HIST2H2BF re-expression was assessed through bisulfite sequencing polymerase chain reaction, methylation-specific polymerase chain reaction, and 5-Aza-dC treatment. Functional assays were performed on CRC cells and mice to investigate the HIST2H2BF-induced stem cell-like and cancer properties of CRC. Using the Notch pathway inhibitor FLI-06, the regulatory effect of HIST2H2BF on downstream Notch signaling was confirmed. RESULTS: HIST2H2BF was highly expressed in CRC tissues and cell lines. The reactivation of HIST2H2BF in CRC stems at least in part from the hypomethylated CpG islands. CRC patients with high HIST2H2BF expression have poor survival outcomes. Functional studies have shown that HIST2H2BF promotes CSC phenotype, malignancy, and liver metastasis through the activation of Notch signaling in CRC. Blockage of the Notch pathway reduced the stem cell-like and cancer properties. CONCLUSION: Our study suggests that HIST2H2BF upregulation enhances the CSC phenotype, malignancy, and liver metastasis through the activation of Notch signaling in CRC. These results identified a new perspective on the mechanism by which the stem cell features of CRC cells are maintained and highlighted the potential novel therapeutic targets for CRC.

Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages.

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.

SCRIB Promotes Proliferation and Metastasis by Targeting Hippo/YAP Signalling in Colorectal Cancer.

The complex in which scribble planar cell polarity protein (SCRIB) is located is one of the three main polar protein complexes that play an important role in maintaining epithelial polarity and affecting tumour growth. However, the role of SCRIB in colorectal cancer (CRC) remains largely unknown. This study used date from The Cancer Genome Atlas (TCGA) and clinical samples to determine the expression of SCRIB in CRC and explored its mechanism through bioinformatics analysis and in vivo and in vitro experiments. In this study, SCRIB was found to be highly expressed in CRC patients, and it was often associated with malignant characteristics, such as proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Furthermore, we found that SCRIB may interact with the Hippo signalling pathway and affect the phosphorylation of YAP and its distribution inside and outside of the nucleus. We concluded that increased expression of SCRIB is likely to inhibit the Hippo signalling pathway by promoting YAP phosphorylation. This role of SCRIB in the progression of CRC provides an important information for the treatment of CRC.