Bis(acetyl­acetonato)oxido(triphenyl­phosphine oxide)vanadium(IV)

In the structure of the title compound, [V(C5H7O2)2O(C18H15OP)], the V atom adopts a slightly distorted octa­hedral geometry with its coordination completed by four O atoms of two acetyl­acetonate (acac) ligands, one oxo group and one O atom of the triphenyl­phosphine oxide (OPPh3) ligand

Upregulation of miR-214 Induced Radioresistance of Osteosarcoma by Targeting PHLDA2 via PI3K/Akt Signaling

Osteosarcoma is an aggressive bone tumor with high resistance to radiotherapy. Pleckstrin homology-like domain family A member 2 (PHLDA2) displays low expression in human osteosarcoma as a proapoptosis factor. miRNAs have been shown to be important in modulating translation and therapeutic responsiveness in solid tumors. Herein, we used luciferase assay to show that miR-214 downregulates the PHLDA2 expression by targeting its 3′-untranslated region (UTR). A high level of miR-214 was identified in tumor tissues from 30 osteosarcoma patients via qPCR analysis, associated positively with lung metastasis. Ectopic expression miR-214 enhanced radioresistance in osteosarcoma cells, with decreased IR-induced apoptosis. Moreover, the depletion of miR-214 enhanced radiosensitivity in both osteosarcoma cells and mouse xenograft models. Importantly, we showed that miR-214 regulated the activation of phosphatidylinositol-3-kinase/Akt signaling pathway by inhibiting PHLDA2. Finally, the introduction of PHLDA2 cDNA lacking the 3′-UTR or treatment with Akt inhibitor LY294002 partially abrogated miR-214-induced radioresistance. In summary, our results reveal that the upregulation of miR-214 as a frequent event in osteosarcoma contributes to radioresistance by regulating the PHLDA2/Akt pathway. The miR-214/PHLDA2/Akt axis provides a new avenue toward understanding the mechanism of radiosensitivity and may be a potential target for osteosarcoma intervention

Label-Free SERS Analysis of Serum Using Ag NPs/Cellulose Nanocrystal/Graphene Oxide Nanocomposite Film Substrate in Screening Colon Cancer

Label-free surface-enhanced Raman scattering (SERS) analysis shows tremendous potential for the early diagnosis and screening of colon cancer, owing to the advantage of being noninvasive and sensitive. As a clinical diagnostic tool, however, the reproducibility of analytical methods is a priority. Herein, we successfully fabricated Ag NPs/cellulose nanocrystals/graphene oxide (Ag NPs/CNC/GO) nanocomposite film as a uniform SERS active substrate for label-free SERS analysis of clinical serum. The Ag NPs/CNC/GO suspensions by self-assembling GO into CNC solution through in-situ reduction method. Furthermore, we spin-coated the prepared suspensions on the bacterial cellulose membrane (BCM) to form Ag NPs/CNC/GO nanocomposite film. The nanofilm showed excellent sensitivity (LOD = 30 nM) and uniformity (RSD = 14.2%) for Nile Blue A detection. With a proof-of-concept demonstration for the label-free analysis of serum, the nanofilm combined with the principal component analysis-linear discriminant analysis (PCA-LDA) model can be effectively employed for colon cancer screening. The results showed that our model had an overall prediction accuracy of 84.1% for colon cancer (n = 28) and the normal (n = 28), and the specificity and sensitivity were 89.3% and 71.4%, respectively. This study indicated that label-free serum SERS analysis based on Ag NPs/CNC/GO nanocomposite film combined with machine learning holds promise for the early diagnosis of colon cancer

A novel SLC26A4

Abstract Background Variants in the SLC26A4 gene are correlated with nonsyndromic hearing loss with an enlarged vestibular aqueduct (EVA). This study aimed to identify the genetic causes in a Chinese family with EVA, and the pathogenicity of the detected variants. Methods We collected blood samples and clinical data from a pair of deaf twin sisters with EVA and their family members. As controls, a group of 500 normal‐hearing people were enrolled in our study. Twenty‐one exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations by polymerase chain reaction and bidirectional Sanger sequencing. Minigene assays were used to verify whether the novel SLC26A4 intronic mutation influenced the normal splicing of mRNA. Results Hearing loss in the twins with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.919‐2A>G and c.1614+5G>A were detected in SLC26A4, the latter of which has not been reported in the literature. The minigene expression in vitro confirmed that c.1614+5G>A could cause aberrant splicing, resulting in skipping over exon 14. Conclusions On the SLC26A4 gene, c.1614+5G>A is a pathogenic mutation. This finding enriches the mutational spectrum of the SLC26A4 gene and provides a basis for the genetic diagnosis of EVA