MiR-20a-5p represses the multi-drug resistance of osteosarcoma by targeting the SDC2 gene

Abstract Background As one of the hallmarks of cancer, chemoresistance hinders curative cancer chemotherapy in osteosarcoma (OS). MicroRNAs (miRNAs) act as key regulators of gene expression in diverse biological processes including the multi-chemoresistance of cancers. Methods Based on the CCK8 experiments, we performed an RNA-seq-based miR-omic analysis of osteosarcoma (OS) cells (a multi-chemosensitive OS cell line G-292 and a multi-chemoresistant OS cell line SJSA-1) to detect the levels of miR-20a-5p. We predicted Homo sapiens syndecan 2 (SDC2) as one of the target genes of miR-20a-5p via several websites, which was further validated by detecting their expression of both mRNA and protein level in both the miR-20a-5p-mimic transfected G-292 and miR-20a-5p-antagomiR transfected SJSA-1 cells. The involvement of SDC2 with OS chemoresistance was checked by siRNA-mediated repression or overexpression of SDC2 gene. Cell viability was assessed by CCK8 assay. Results We found that the miR-20a-5p level was higher in G-292 cells than in SJSA-1 cells. Forced expression of miR-20a-5p counteracted OS chemoresistance in both cell culture and tumor xenografts in nude mice. As one of miR-20a-5p’s targets, SDC2 was found to mediate the miR-20a-5p-induced repression of OS chemoresistance. Conclusions Our results suggest that miR-20a-5p and SDC2 contribute to OS chemoresistance. The key players in the miR-20a-5p/SDC2 axis may be a potential diagnostic biomarker and therapeutic target for OS patients

Research on variable universe fuzzy PID control for semi-active suspension with CDC dampers based on dynamic adjustment functions

Abstract The vehicle suspension system is a complex system with multiple variables, nonlinearity and time-varying characteristics, and the traditional variable universe fuzzy PID control algorithm has the problems of over-reliance on expert experience and non-adaptive adjustment of the contracting-expanding factor parameters, which make it difficult to achieve a better control effect. In this paper, the system error e(t) and its change rate ec(t) are introduced into the contracting-expanding factor as dynamic parameters to realize the adaptive adjustment of the contracting-expanding factor parameters, and propose a variable universe fuzzy PID control based on dynamic adjustment functions (VUFP-DAF), which uses the real-time contracting-expanding factor to realize the adaptive adjustment of the fuzzy universe, so as to improve the ride comfort of vehicles. The research results show that the proposed VUFP-DAF has strong adaptability and can effectively improve the ride comfort and handling stability of vehicles under different speeds and road excitations, providing a certain technical basis for the development of the semi-active suspension system

Additional file 1: Figure S1. of The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

The interested miRNA and mRNA genes based on the websites and RNA-seq analysis. A dozen of miRNAs were differentially expressed in the multi-chemoresistant OS cells SJSA-1 and the multi-chemosensitive OS cells G-292 and MG63.2 based on the websites, and the ratio over 2 of SJSA-1/G-292 based on RNA-seq-based miR-omic analysis were showed in descending order, has-miR-34a-5p was one of them (A). Reference to similar methods, the downstream genes of has-miR-34a-5p were also showed, the ratio of G-292/SJSA-1 based on RNA-seq analysis were showed in descending order, AGTR1 is located (B). (TIF 88.5 mb

2015 ヘイセイ 27ネンド カダイ ケンキュウ ダイモク イチラン

The 17030 differentially expressed mRNAs were showed through the RNA-seq analysis between SJSA-1 and G-292 cells, the ratio of G-292/SJSA-1 was also presented, and the target gene AGTR1 also located in. (PDF 11.3 mb

T proliferating cells derived autophagy signature associated with prognosis and immunotherapy resistance in a pan-cancer analysis

Summary: Despite autophagy modulating tumor immunity in the tumor microenvironment (TME), the immunotherapeutic efficacy and potential mechanism of autophagy signature was not explicit. We manually curated an autophagy gene set and defined a pan-cancer autophagy signature by comparing malignant tissues and normal tissues in The Cancer Genome Atlas (TCGA) cohort. The pan-cancer autophagy signature was derived from T proliferating cells as demonstrated in multiple single-cell RNA sequencing (scRNA-seq) datasets. The pan-cancer autophagy signature could influence the cell-cell interactions in the TME and predict the responsiveness of immune checkpoint inhibitors (ICIs) in the metastatic renal cell carcinoma, non-small cell lung cancer, bladder cancer, and melanoma cohorts. Metabolism inactivation accompanied with dysregulation of autophagy was investigated with transcriptomic and proteomic data. The immunotherapeutic predictive role and mechanism regulation of the autophagy signature was validated in an in-house cohort. Our study provides valuable insights into the mechanisms of ICI resistance

Surface-Mediated Chemical Dissolution of Two-Dimensional Nanomaterials toward Hole Creation

Chemically engineered holes on two-dimensional (2D) nanomaterials may significantly increase the number of edge sites to tune their intrinsic properties to achieve promising performance. Here, we report a general and mild approach to the convenient creation of holes on atomically thin nanosheets for engineering bandgaps and enhancing properties of 2D materials. Through surface blocking, controlled dissolution, and chemical stabilization, WO₃ nanosheets are readily treated to create holes in the presence of bovine serum albumin (BSA) via the reaction of WO₃ with OH^– ions at pH 8. Arising from the increased bandgaps and more edge sites as demonstrated experimentally and theoretically, the resulting holey WO₃ nanosheets exhibit enhanced photocurrents and much better performance during selective adsorption and photocatalytic degradation compared with those of bulky WO₃ and nonporous nanosheets. Also, this approach is further extended to the convenient creation of holes on more 2D nanomaterials such as MoS₂ and C₃N₄ nanosheets, which are facilely made in aqueous solutions of diluted H₂O₂ and HCl, respectively. Overall, this work not only demonstrates a surface-mediated chemical dissolution strategy for generating holes on various ultrathin nanosheets but also provides new opportunities to exploit exotic properties and novel applications of geometrically constructed 2D nanomaterials

Signature of Many-Body Localization of Phonons in Strongly Disordered Superlattices

Many-body localization (MBL) has attracted significant attention because of its immunity to thermalization, role in logarithmic entanglement entropy growth, and opportunities to reach exotic quantum orders. However, experimental realization of MBL in solid-state systems has remained challenging. Here, we report evidence of a possible phonon MBL phase in disordered GaAs/AlAs superlattices. Through grazing-incidence inelastic X-ray scattering, we observe a strong deviation of the phonon population from equilibrium in samples doped with ErAs nanodots at low temperature, signaling a departure from thermalization. This behavior occurs within finite phonon energy and wavevector windows, suggesting a localization-thermalization crossover. We support our observation by proposing a theoretical model for the effective phonon Hamiltonian in disordered superlattices, and showing that it can be mapped exactly to a disordered 1D Bose-Hubbard model with a known MBL phase. Our work provides momentum-resolved experimental evidence of phonon localization, extending the scope of MBL to disordered solid-state systems