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The expression of periostin in the tissue of colorectal cancer patients and its correlation with clinical features were studied. Periostin expression was ~4 fold up-regulated in cancer tissues compared to adjacent non-cancerous tissues. Serum levels of periostin in patients were significantly elevated to 32.6 ± 10.8 ng/mL vs 20.4 ± 11.1 ng/mL in healthy volunteers. Higher preoperative serum periostin levels in patients were closely related to advanced-stage disease (stage III/IV), distant and lymph nodes metastasis. High level of periostin expression was detected in the SW480 human colon carcinoma cells, and could be down-regulated by small interfering RNAs (siRNA). The siRNA-mediated knockdown of periostin arrested the cell cycle at G0/G1 phase and induced apoptotic cell death in the SW480 cells. In conclusion, periostin is a promising prognostic and therapeutic target for colorectal cancer.

Background & Aims: Cancer stemness and immune evasion are closely associated and play critical roles in tumor development and resistance to immunotherapy. However, little is known about the underlying molecular mechanisms that coordinate this association. Methods: The expressions of heterogeneous nuclear ribonucleoprotein M (HNRNPM) in 240 hepatocellular carcinoma (HCC) samples, public databases, and liver development databases were analyzed. Chromatin immunoprecipitation assays were performed to explore the associations between stem-cell transcription factors and HNRNPM. HNRNPM-regulated alternative splicing (AS) and its binding motif were identified by RNA-seq and RIP-seq. HNRNPM-specific antisense oligonucleotides were developed to explore potential therapeutic targets in HCC. CD8+ T cells that were co-cultured with tumor cells were sorted by flow cytometry assays. Results: We identified an elevated oncofetal splicing factor in HCC, HNRNPM, that unifies and regulates the positive association between cancer stemness and immune evasion. HNRNPM knockdown abolished HCC tumorigenesis and diminished cancer stem cell properties in vitro and in vivo. Mechanistically, HNRNPM regulated the AS of MBD2 by binding its flanking introns, whose isoforms played opposing roles. Although MBD2a and MBD2c competitively bound to CpG islands in the FZD3 promoter, MBD2a preferentially increased FZD3 expression and then activated the WNT/β-catenin pathway. Interestingly, FZD3 and β-catenin further provided additional regulation by targeting OCT4 and SOX2. We found that HNRNPM inhibition significantly promoted CD8+ T cell activation and that HNRNPM- antisense oligonucleotides effectively inhibited WNT/β-catenin to enhance anti-programmed cell death protein-1 immunotherapy by promoting CD8+ T cell infiltration. Conclusions: HNRNPM has a tumor-intrinsic function in generating an immunosuppressive HCC environment through an AS-dependent mechanism and demonstrates proof of the concept of targeting HNRNPM in tailoring HCC immunotherapeutic approaches.

Recently, the role of lncRNAs in tumorigenesis and development has received increasing attention, but the mechanism underlying lncRNAs-mediated tumor growth in the hypoxic microenvironment of solid tumors remains obscure. Using RNA sequencing, 25 hypoxia-related lncRNAs were found to be upregulated in HCC, of which lncRNA USP2-AS1 were significantly increased under hypoxia. We further confirmed that USP2-AS1 was significantly upregulated in liver cancer using FISH assay and that USP2-AS1 was associated with advanced liver cancer and increased tumor size. Furthermore, overexpression of USP2-AS1 under hypoxia dramatically increased HCC proliferation and clone formation, whereas the opposite results were observed after USP2-AS1 knockdown. We also found that overexpression of USP2-AS1 increased migration and invasion of HCC cells, while USP2-AS1 knockdown led to the opposite effect. In addition, USP2-AS1 knockdown can increase the efficacy of lenvatinib in our mice tumor xenograft model. Our findings also suggest that USP2-AS1 could increase the protein level of HIF1α by enhancing YBX1 protein binding to HIF1α mRNA under hypoxia and the therapeutic effect of lenvatinib can be enhanced by combination with HIF1α inhibitors in liver cancer.

Abstract Background Distinguishing parotid pleomorphic adenoma (PPA) from parotid adenolymphoma (PA) is important for precision treatment, but there is a lack of readily available diagnostic methods. In this study, we aimed to explore the diagnostic value of radiomic signatures based on magnetic resonance imaging (MRI) for PPA and PA. Methods The clinical characteristic and imaging data were retrospectively collected from 252 cases (126 cases in the training cohort and 76 patients in the validation cohort) in this study. Radiomic features were extracted from MRI scans, including T1-weighted imaging (T1WI) sequences and T2-weighted imaging (T2WI) sequences. The radiomic features from three sequences (T1WI, T2WI and T1WI combined with T2WI) were selected using univariate analysis, LASSO correlation and Spearman correlation. Then, we built six quantitative radiomic models using the selected features through two machine learning methods (multivariable logistic regression, MLR, and support vector machine, SVM). The performances of the six radiomic models were assessed and the diagnostic efficacies of the ideal T1-2WI radiomic model and the clinical model were compared. Results The T1-2WI radiomic model using MLR showed optimal discriminatory ability (accuracy = 0.87 and 0.86, F-1 score = 0.88 and 0.86, sensitivity = 0.90 and 0.88, specificity = 0.82 and 0.80, positive predictive value = 0.86 and 0.84, negative predictive value = 0.86 and 0.84 in the training and validation cohorts, respectively) and its calibration was observed to be good (p > 0.05). The area under the curve (AUC) of the T1-2WI radiomic model was significantly better than that of the clinical model for both the training (0.95 vs. 0.67, p

Summary: The rapid and effective formation and decomposition of Li2O2 during cycling is crucial to solve the problems associated with the practical limitation of lithium-oxygen (Li-O2) batteries. In this work, a highly dispersed electrocatalyst with Ru nanoclusters inside the special organic molecular cage (RuNCs@RCC3) through a reverse double-solvent method for Li-O2 batteries has been proposed for the first time. This RuNCs@RCC3 shows an effective catalyst enabling reversible formation and decomposition of the Li2O2 at the interface between the Li2O2 and the liquid electrolyte, rather than the sluggish solid-solid interface reactions on commonly used solid catalysts. As a result, the Li-O2 cells with RuNCs@RCC3 show enhanced electrochemical performance, including low overpotential (310 mV at a current density of 100 mA g−1), high specific capacity (15,068 mAh g−1), good rate capability (1,800 mAh g−1 at a current density of 2.8 A g−1), and especially superior cycle stability up to 470 cycles. : Electrochemistry; Energy Storage; Energy Materials Subject Areas: Electrochemistry, Energy Storage, Energy Materials

Background: Ferroptosis is a new therapeutic modality that holds promise for pancreatic cancer treatment. Dihydroartemisinin is the first generation of artemisinin derivatives with antimalarial activity, and it exerts anticancer activity through iron-dependent reactive oxygen species generation. This study assessed the potential value of dihydroartemisinin to induce ferroptosis in pancreatic cancer. Methods: The mRNA expression profiles, along with the corresponding clinical information of individuals diagnosed with pancreatic cancer, were acquired from publicly accessible repositories. We analyzed the association of ferroptosis-related gene expression with pancreatic cancer overall survival via The Cancer Genome Atlas. Utilizing molecular docking techniques, we evaluated the potential binding configurations of dihydroartemisinin with genes associated with ferroptosis. Moreover, in-vitro experiments were performed to verify these predicted outcomes. Results: In the The Cancer Genome Atlas cohort, there were significant differences in the expression levels of ten genes associated with ferroptosis when comparing pancreatic cancer tissues with normal tissues. Among them, a strong association between NQO1 expression and unfavorable prognosis was observed. Dihydroartemisinin can regulate target gene expression by interacting with the corresponding binding site, and a ferroptosis inhibitor could reverse the above events. Conclusion: The NQO1 gene, which is associated with ferroptosis, emerges as a robust and autonomous prognostic indicator for individuals with pancreatic cancer. Dihydroartemisinin may contribute to pancreatic cancer progression via the regulation of ferroptosis. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the effects of a strontium-substituted nanohydroxyapatite (Sr-HA) coating, deposited onto porous implant surfaces using an electrochemical process, on implant osseointegration in a rabbit model. Materials and Methods: The surfaces were analyzed by field-emission scanning electron microscopy, x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR), a portable surface roughness tester, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). Thirty implants (half HA-coated and half Sr-HA-coated) were inserted into femurs of 15 rabbits. After 2, 4, and 8 weeks, the femurs were retrieved and prepared for histomorphometric evaluation. Results: Microscopic examination showed a surface topography of rodlike crystals on both surfaces. XRD and FT-IR showed that the phase of the deposits was HA. No differences were found in surface roughness between the two groups. ICP-AES showed that the Sr/(Ca+Sr) molar ratio of Sr-HA coating was 10.1 mol%. Histologic observation showed that new bone appeared on both surfaces after 2 weeks and became mature after 8 weeks. Histomorphometric analysis showed no differences between the two groups in bone-to-implant contact at 2 weeks or in bone area within all threads at 2 and 4 weeks. The Sr-HA coated group had significantly higher bone-to-implant contact at 4 and 8 weeks. Significant differences were also found in bone area at 8 weeks. Conclusion: The present study showed that this Sr-HA coating, deposited using an electrochemical process, has the potential to enhance implant osseointegration. [ABSTRACT FROM AUTHOR]

The effect of a naphthalimide pharmacophore coupled with diverse substituents on the interaction between naphthalimide-polyamine conjugates 1-4 and bovine serum albumin (BSA) was studied by UV absorption, fluorescence and circular dichroism (CD) spectroscopy under physiological conditions (pH = 7.4). The observed spectral quenching of BSA by the compounds indicated that they could bind to BSA. Furthermore, caloric fluorescent tests revealed that the quenching mechanisms of compounds 1-3 were basically static type, but that of compound 4 was closer to a classical type. The Ksv values at room temperature for compound-BSA complexes-1-BSA, 2-BSA, 3-BSA and 4-BSA were 1.438 × 104, 3.190 × 104, 5.700 × 104 and 4.745 × 105, respectively, compared with the value of MINS, 2.863 × 104 at Ex = 280 nm. The obtained quenching constant, binding constant and thermodynamic parameter suggested that the binding between compounds 1-4 with BSA protein, significantly affected by the substituted groups on the naphthalene backbone, was formed by hydrogen bonds, and other principle forces mainly consisting of charged and hydrophobic interactions. Based on results from the analysis of synchronous three-dimensional fluorescence and CD spectra, we can conclude that the interaction between compounds 1-4 and BSA protein has little impact on the BSA conformation. Calculated results obtained from in silico molecular simulation showed that compound 1 did not prefer either enzymatic drug sites I or II over the other. However, DSII in BSA was more beneficial than DSI for the binding between compounds 2-4 and BSA protein. The binding between compounds 1-3 and BSA was hydrophobic in nature, compared with the electrostatic interaction between compound 4 and BSA. [ABSTRACT FROM AUTHOR]

Abstract Background Circular RNAs (circRNAs) play a critical regulatory role in cancer progression. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) metastasis remain mostly unknown. Methods Has_circ_0003998 (circ0003998) was identified by RNAs sequencing in HCC patients with /without portal vein tumor thrombus (PVTT) metastasis. The expression level of circ0003998 was further detected by in situ hybridization on tissues microarray (ISH-TMA) and qRT-PCR in 25 HCC patients with PVTT metastasis. Moreover, the 25 HCC patients with PVTT metastasis and 50 HCC patients without PVTT metastasis were recruited together to analyze the correlation between circ0003998 expression and HCC clinical characteristics. Transwell, migration and CCK8 assays, as well as nude mice model of lung or liver metastasis were used to evaluate the role of circ0003998 in epithelial to mesenchymal transition (EMT) in HCC. The regulatory mechanisms of circ0003998 in miR-143-3p and PCBP1 were determined by dual-luciferase reporter assay, nuclear-cytoplasmic fractionation, fluorescent in situ hybridization, RNA pull- down, microRNA sequence, western blot and RNA immunoprecipitation. Results Compared with adjacent normal liver tissues (ANL), circ0003998 expression was significantly upregulated in PVTT tissues and HCC tissues, and its expression correlates with the aggressive characteristics of HCC patients. Further assays suggested that circ0003998 promoted EMT of HCC both in vitro and in vivo. Mechanistically, our data indicated that circ0003998 may act as a ceRNA (competing endogenous RNA) of microRNA-143-3p to relieve the repressive effect on EMT-related stimulator, FOSL2; meanwhile, circ0003998 could bind with PCBP1-poly(rC) binding protein 1 (PCBP1) to increase the expression level of EMT-related genes, CD44v6. Conclusion Circ0003998 promotes EMT of HCC by circ0003998/miR-143-3p/FOSL2 axis and circ0003998 /PCBP1/CD44v6 axis.

Li–O2 batteries represent one of the promising paths toward high energy density battery systems. Here the authors synthesize single atom Co electrocatalysts to regulate the formation and decomposition of the major discharge product Li2O2, realizing high round-trip efficiency and stability in a Li–O2 cell.