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Background: Multiple Myeloma (MM) is a hematologic malignant disease whose underlying molecular mechanism has not yet fully understood. Generally, cell adhesion plays an important role in MM progression. In our work, we intended to identify key genes involved in cell adhesion in MM. Methods: First, we identified differentially expressed genes (DEGs) from the mRNA expression profiles of GSE6477 dataset using GEO2R with cutoff criterion of p < 0.05 and [logFC] ≥ 1. Then, GO and KEGG analysis were performed to explore the main function of DEGs. Moreover, we screened hub genes from the protein-protein interaction (PPI) network analysis and evaluated their prognostic and diagnostic values by the PrognoScan database and ROC curves. Additionally, a comprehensive analysis including clinical correlation analysis, GSEA and transcription factor (TF) prediction, pan-cancer analysis of candidate genes was performed using both clinical data and mRNA expression data. Results: First of all, 1383 DEGs were identified. Functional and pathway enrichment analysis suggested that many DEGs were enriched in cell adhesion. 180 overlapped genes were screened out between the DEGs and genes in GO terms of cell adhesion. Furthermore, 12 genes were identified as hub genes based on a PPI network analysis. ROC curve analysis demonstrated that ITGAM, ITGB2, ITGA5, ITGB5, CDH1, IL4, ITGA9, and LAMB1 were valuable biomarkers for the diagnosis of MM. Further study demonstrated that ITGA9 and LAMB1 revealed prognostic values and clinical correlation in MM patients. GSEA and transcription factor (TF) prediction suggested that MYC may bind to ITGA9 and repress its expression and HIF-1 may bind to LAMB1 to promote its expression in MM. Additionally, pan-cancer analysis showed abnormal expression and clinical outcome associations of LAMB1 and ITGA9 in multiple cancers. Conclusion: In conclusion, ITGA9 and LAMB1 were identified as potent biomarkers associated with cell adhesion in MM.

Proteasome inhibitor bortezomib is one of the most effective drugs currently available for the treatment of multiple myeloma (MM). However, the intrinsic and acquired resistance to bortezomib can limit its effectiveness. The activation of heat shock response has been characterized as a potential resistance mechanism protecting MM cells from bortezomib-induced cell death. In this study, in response to bortezomib therapy, we discovered that HSP70 is one of the most substantially upregulated heat shock proteins. In order to further explore approaches to sensitizing bortezomib-based treatment for MM, we investigated whether targeting HSP70 using a specific inhibitor VER-155008 combined with bortezomib could overcome the acquired resistance in MM. We found that HSP70 inhibitor VER-155008 alone significantly decreased MM cell viability. Moreover, the combination of VER-155008 and bortezomib synergistically induced MM cell apoptosis markedly in vitro. Notably, the combined treatment was found to increase the cleavage of PARP, an early marker of chemotherapy-induced apoptosis. Importantly, the reduction of anti-apoptotic Bcl-2 family member Bcl-2, Bcl-xL, and Mcl-1 and the induction of pro-apoptotic Bcl-2 family member BH3-only protein NOXA and Bim were confirmed to be tightly associated with the synergism. Finally, the ER stress marker CHOP (CCAAT-enhancer binding protein homologous protein), which can cause transcriptional activation of genes involved in cell apoptosis, was markedly induced by both VER-155008 and bortezomib. Taken together, our finding of a strong synergistic interaction between VER-155008 and bortezomib may support for combination therapy in MM patients in the future.

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Flexible multidirectional strain sensors capable of simultaneously detecting strain amplitudes and directions have attracted tremendous interest. Herein, we propose a flexible multidirectional strain sensor based on a newly designed single-layer hierarchical aligned micro-/nanowire (HAMN) network. The HAMN network is efficiently fabricated using a one-step femtosecond laser patterning technology based on a modulated line-shaped beam. The anisotropic performance is attributed to the significantly different morphological changes caused by an inhomogeneous strain redistribution among the HAMN network. The fabricated strain sensor exhibits high sensitivity (gauge factor of 65 under 2.5% strain and 462 under larger strains), low response/recovery time (140 and 322 ms), and good stability (over 1000 cycles). Moreover, this single-layer strain sensor with high selectivity (gauge factor differences of ∼73 between orthogonal strains) is capable of distinguishing multidimensional strains and exhibits decoupled responses under low strains (<1%). Therefore, the strain sensors enable the precise monitoring of subtle movements, including radial pulses and wrist bending, and the rectification of pen-holding posture. Benefitting from these remarkable performances, the HAMN-based strain sensors show potential applications, including healthcare and complex human motion monitoring.