Background: Colorectal cancer (CRC) ranks as the third most common malignancy worldwide but a reliable prognostic biomarker of CRC is still lack. Thus, the purpose of our study was to explore whether ferroptosis - related lncRNAs could predict the prognosis of CRC.Methods: The mRNA expression profiling of colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients in The Cancer Genome Atlas (TCGA) database were downloaded. Univariate Cox and multivariate Cox regression analyses was used to obtain prognostic differently expressed ferroptosis-related lncRNAs (DE-FLs) and a risk signature was developed. Quantitative polymerase chain reaction (q-PCR) was used to validated the different expressions of DE-FLs. The calibration curves, C-index and the receiver operating characteristic (ROC) curves were applied to evaluate the accuracy of nomogram. Gene set enrichment analyses (GSEA) were carried out to explore the biological mechanism between high- and low-risk group and the potential regulated pathway of prognostic DE-FLs in CRC.Results: Forty-nine DE-FLs were identified between CRC and normal tissue. Then, a 4-DE-FLs (AC016027.1, AC099850.3, ELFN1-AS1, and VPS9D1-AS1) prognostic signature model was generated. AC016027.1 was downregulated in CRC tissue; VPS9D1-AS1 and ELFN1-AS1 were upregulated by q-PCR. The model had a better accuracy presenting by 1-, 3-, and 5-years ROC curve (AUC ≥0.6), and identified survival probability (p < 0.05) well. Moreover, the risk signature could play as an independent factor of CRC (p < 0.05). Further, a nomogram including age, pathologic stage, T stage, and risk score with good prognostic capability (C-index = 0.789) was constructed. In addition, we found biological pathways mainly related to metabolism and apoptosis were down-regulated in high-risk group who with poor outcome. Finally, the functional enrichment showed prognostic DE-FLs may significantly impact bile secretion in CRC.Conclusion: A risk model and nomogram based on ferroptosis-related lncRNAs were created to predict 1-, 3-, and 5-years survival probability of CRC patients. Our data suggested that the prognostic lncRNAs could serve as valuable prognostic marker.

Biodegradable Zn alloys have significant application potential for hard-tissue implantation devices owing to their suitable degradation behavior and favorable biocompatibility. Nonetheless, pure Zn and its alloys in the as-cast state are mechanically instable and low in strength, which restricts their clinical applicability. Here, we report the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded Zn-5RE (wt.%, RE = rare earth of Y; or Ho; or Er) alloys intended for use in biodegradable bone substitutes. The microstructural characteristics, mechanical behavior, corrosion resistance, cytocompatibility, osteogenic differentiation, and capacity of osteogenesis in vivo of the Zn-5RE alloys are comparatively investigated. The Zn-5Y alloy demonstrates the best tensile properties, encompassing a 138 MPa tensile yield strength, a 302 MPa ultimate tensile strength, and 63% elongation, while the Zn-5Ho alloy shows the highest compression yield strength of 260 MPa and Vickers hardness of 104 HV. The Zn-5Er alloy shows a 126 MPa tensile yield strength, a 279 MPa ultimate tensile strength, 52% elongation, a 196 MPa compression yield strength, and a 101 HV Vickers microhardness. Further, the Zn-5Er alloy has a 130 µm per year corrosion rate in electrochemical tests and a 26 µm per year degradation rate in immersion tests, which is the lowest among the tested alloys. It also has the best in vitro osteogenic differentiation ability and capacity for osteogenesis and osteointegration in vivo after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications. STATEMENT OF SIGNIFICANCE: This work reports the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded (HE) Zn-5 wt.%-rare earth (Zn-5RE) alloys using single yttrium (Y), holmium (Ho), and erbium (Er) alloying for biodegradable bone-implant applications. Our findings demonstrate that the HE Zn-5Er alloy showed σ_uts of 279 MPa, tensile yield strength of 126 MPa, elongation of 51.6%, compression yield strength of 196 MPa, and microhardness of 101.2 HV. Further, HE Zn-5Er showed the lowest electrochemical corrosion rate of 130 µm/y and lowest degradation rate of 26 µm/y, and the highest in vitro osteogenic differentiation ability, in vivo osteogenesis, and osteointegration ability after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications.

Introduction: Recent studies have found that circular RNA is an abundant RNA species that belongs to part of the competing endogenous RNA network (ceRNA), which was proven to play an important role in the development, diagnosis and progress of diseases. However, the function of circRNAs in imatinib resistance in Gastrointestinal stromal tumor (GIST) are poorly understood so for. The present study aimed to screen and predict the potential circRNAs in imatinib resistance of GIST using microarray analysis. Methods: We determined the expression of circular RNAs in paired normal gastric tissues (N), primary GIST (gastrointestinal stromal tumor) tissues (YC) and imatinib mesylate secondary resistance GIST tissues (C) with microarray and predicted 8677 dysregulated circular RNAs. Results: Compared with the YC group, we identified 15 circRNAs that were up-regulated and 8 circRNAs that were down-regulated in the C group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these host linear transcripts that differentially express circular RNAs are involved in many key biological pathways, predicting the potential tumor-genesis and drug resistance mechanismrelated to HIF-1 pathway, later we draw the cirRNA-miRNA-mRNA network involved in the HIF-1 pathway and found several dysregulated circRNAs and the relationship between circRNA-miRNAs-mRNA, such as circRNA_06551, circRNA_14668, circRNA_04497, circRNA_08683, circRNA_09923(Green, down-regulation) and circRNA_23636, circRNA_15734 (Red, up-regulation). Conclusion: Taken together, we identified a panel of dysregulated circRNAs that may be potential biomarkers even therapy relevant to the GIST, especially imatinib secondary resistance GIST.

Biodegradable zinc (Zn) alloys are promising candidates for bone implants due to their suitable degradation rate and inherent bioactivity. However, current Zn alloys require enhancement of their mechanical properties and biological functions through alloying and thermomechanical processing. Herein, we report the outstanding mechanical properties, corrosion, biocompatibility, and biofunctionalities of hot-rolled (HR) and hot-extruded (HE) Zn-4Ag-0.4Sr (ZAS) alloy in comparison with those of Zn-4Ag (ZA) for biodegradable orthopedic fixation. The HE ZAS sample exhibited the optimal balance of mechanical properties, including ultimate tensile strength of 318.0 MPa, tensile and compressive yield strengths of 257.3 MPa and 343.3 MPa, respectively, elongation at break of 22.3%, and Vickers and Brinell hardness values of 116.7 HV and 105.7 HB, respectively, satisfying the mechanical requirements for bone-implant applications. Nanoindentation identified the SrZn₁₃ phase as a key reinforcement. The HE ZAS alloy exhibited the highest electrochemical corrosion rate of 614 μm/y and the highest degradation rate of 39.7 μm/y after 30 days of immersion, as well as the best biotribological performance in Hanks' solution, among all ZA and ZAS samples. Biologically, extracts of the HE ZAS alloy enhanced osteoblast viability, promoted angiogenesis in HUVECs, and stimulated osteogenic differentiation and mineralization in hBMSCs. Furthermore, the HE ZAS alloy displayed higher antibacterial efficacy against S. aureus in both in vitro and in vivo models while maintaining high biosafety. These results collectively indicate that the HE ZAS alloy is a promising candidate for next-generation biodegradable orthopedic-fixation devices, offering a notable balance of mechanical integrity, controllable degradation, and multifunctional bioactivity. STATEMENT OF SIGNIFICANCE: This work reports the notable mechanical performance, controlled corrosion, enhanced biotribological behavior, and multifunctional bioactivity of the hot-extruded Zn-4Ag-0.4Sr (HE ZAS) alloy for biodegradable orthopedic fixation devices. The HE ZAS alloy exhibits an optimal strength-ductility balance, with an ultimate tensile strength of 318.0 MPa, tensile yield strength of 257.3 MPa, and 22.3% elongation, satisfying the mechanical requirements for bone implants. The alloy also demonstrates the highest electrochemical corrosion rate (614 μm/y), degradation rate (39.7 μm/y), and biotribological performance among the tested alloys. Biologically, the alloy enhances osteoblast viability, stimulates angiogenesis and osteogenic differentiation, and exhibits effective antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while maintaining complete biosafety.

Background: Recent studies have found that circular RNA is an abundant RNA species, belongs to part of the competing endogenous RNA network(ceRNA), which was proved to play an important role in the development, diagnosis and progress of diseases.Methods: We determined the expression of circular RNAs in paired normal gastric tissues(N), primary GIST (gastrointestinal stromal tumor) tissues (Y or YC) and imatinib mesylate secondary resistance GIST tissues(C) with microarray and predicted 8677 dysregulated circular RNAs.Results: We identified 15 circRNAs was up-regulated and 8 circRNAs were down-regulated in C group. Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these host linear transcripts that differentially express circular RNAs are involved in many key biological pathways., predicting the potential tumor-genesis and drug resistance mechanism was related with HIF-1 pathway, later we draw the cirRNA-miRNA-mRNA network involved in the HIF-1 pathway, found that several dysregulated circRNAs and the relationship between circRNA-miRNAs-mRNA, such as circRNA_06551, circRNA_14668, circRNA_04497, circRNA_08683, circRNA_09923(Green, down-regulation) and circRNA_23636, circRNA_15734(Red, up-regulation). Conclusions: Taken together, we identified a panel of dysregulated circRNAs that may be potential biomarkers even therapy relevant to the GIST, especially imatinib secondary resistance GIST.