Immunity plays an important role in tumor development. In this study, we aimed to investigate molecular classification and its prognostic value in hepatocellular carcinoma (HCC) based on immune signature. Gene set enrichment analysis (GSEA) was used to calculate scores of immune pathways for HCC and hierarchical clustering in two databases (The Cancer Genome Atlas [TCGA], Liver Cancer-RIKEN, JP [LIRI_JP]). The scores of the immune microenvironment and the proportions of 22 immune cells were also calculated. Single-sample GSEA (ssGSEA) was used to screen survival prognosis-related immune pathways and calculate the hazard radio of differentially expressed immune-related genes (IRGs), which were validated in clinical samples and multiple datasets. Based on the immune characteristics, we identified three HCC subtypes, namely immunity high (Immunity_H), immunity medium (Immunity_M), and immunity low (Immunity_L), and confirmed that the classification was reliable and predictable. Immunity_H with a higher immune and stromal score indicated better survival rate. Cox regression analysis showed that IL18RAP and IL7R were the protective genes. Immune risk score was the independent risk factor of overall survival in HCC patients. These results indicated that immunogenomic classification could distinguish HCC patients with different immune status, which could impact the prognosis of the patients with HCC.

Increasing evidence indicates that the dysregulation of miRNAs plays a vital role in tumorigenesis and progression of nasopharyngeal carcinoma (NPC). Thus, it is necessary to further investigate the function and mechanism of miRNAs in NPC.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death due to early metastasis or recurrence. Tumor angiogenesis plays an essential role in the tumorigenesis of HCC. Accumulated studies have validated the crucial role of lncRNAs in tumor angiogenesis. Here, we established an angiogenesis-related multi-lncRNAs risk model based on the machine learning for HCC prognosis prediction. Firstly, a total of 348 differential expression angiogenesis-related lncRNAs were identified by correlation analysis. Then, 20 of these lncRNAs were selected through univariate cox analysis and used for in-depth study of machine learning. After 1,000 random sampling cycles calculating by random forest algorithm, four lncRNAs were found to be highly associated with HCC prognosis, namely LUCAT1, AC010761.1, AC006504.7 and MIR210HG. Subsequently, the results from both the training and validation sets revealed that the four lncRNAs-based risk model was suitable for predicting HCC recurrence. Moreover, the infiltration of macrophages and CD8 T cells were shown to be closely associated with risk score and promotion of immune escape. The reliability of this model was validated by exploring the biological functions of lncRNA MIR210HG in HCC cells. The results showed that MIR210HG silence inhibited HCC growth and migration through upregulating PFKFB4 and SPAG4. Taken together, this angiogenesis-related risk model could serve as a reliable and promising tool to predict the prognosis of HCC.

Annexin A1 is a member of a large superfamily of glucocorticoid-regulated, calcium- and phospholipid-binding proteins. Our previous studies have shown that the abnormal expression of Annexin A1 is related to the occurrence and development of nasopharyngeal carcinoma (NPC). To understand the roles of Annexin A1 in the tumorigenesis of NPC, targeted proteomic analysis was performed on Annexin A1-associated proteins from NPC cells. We identified 436 proteins associated with Annexin A1, as well as two Annexin A1-interacted key proteins, S100A9 and Vimentin, which were confirmed by co-immunoprecipitation. Gene function classification revealed that the Annexin A1-associated proteins can be grouped into 21 clusters based on their molecular functions. Protein-protein interaction analysis indicated that Annexin A1 /S100A9/Vimentin interactions may be involved in the invasion and metastasis of NPC because they can form complexes in NPC cells. The down-regulation of Annexin A1 in NPC may lead to the overexpression of S100A9/Vimentin, which may increase the possibility of the invasion ability of NPC cells by adjusting the function of cytoskeleton proteins. Results suggested that the biological functions of Annexin A1 in NPC were diverse, and that Annexin A1 can inhibit the in vitro invasive ability of NPC cells through Annexin A1 /S100A9/Vimentin interaction.

It has been suggested that microRNA-9 (miR-9) is associated with the development of knee osteoarthritis (OA). This study was aimed to investigate the association between the mechanism of miR-9 targeting nuclear factor kappa-B1 (NF-κB1) and the proliferation and apoptosis of knee OA chondrocytes.Cartilage samples were collected from 25 patients with knee OA and 10 traumatic amputees, and another 15 OA rat models, together with 15 rats without knee OA lesions were also established. MiR-9 expressions in both knee OA cartilage and normal cartilage samples were detected using quantitative real-time PCR. The expressions of related genes (NF-κB1, IL-6, and MMP-13) in the two groups were also detected. Dual luciferase reporter gene assay was employed to examine the effect of miR-9 on the luciferase activity of NF-κB1 3'UTR. Knee OA chondrocytes were transfected with miR-9 mimics, miR-9 inhibitor, and NF-κB1 siRNA, respectively, and changes in cellular proliferation and apoptosis were detected via MTT assay and flow cytometric analysis, respectively. Western blotting assay was used to detect the expressions of NF-κB1, interleukin-6 (IL-6), and matrix metalloproteinase-13 (MMP-13).According to results from human OA samples and rat OA models, miR-9 was significantly downregulated in knee OA cartilage tissues compared with normal cartilage tissues (P < 0.01). The expressions of NF-κB1, IL-6, and MMP-13 in knee OA cartilage tissues were significantly higher than those in normal cartilage tissues (P < 0.01). Dual luciferase reporter gene assay showed that miR-9 could bind to the 3'UTR of NF-κB1 and significantly inhibit the luciferase activity by 37% (P < 0.01). Upregulation of miR-9 or downregulation of NF-κB1 could promote cell proliferation and suppress cell apoptosis.Conclusively, downregulated miR-9 can facilitate proliferation and antiapoptosis of knee OA chondrocytes by directly binding to NF-kB1, implying that stimulating miR-9 expressions might assist in treatment of knee OA.

Utilizing genomic data to predict cancer prognosis was insufficient. Proteomics can improve our understanding of the etiology and progression of cancer and improve the assessment of cancer prognosis. And the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has generated extensive proteomics data of the vast majority of tumors. Based on CPTAC, we can perform a proteomic pan-carcinoma analysis. We collected the proteomics data and clinical features of cancer patients from CPTAC. Then, we screened 69 differentially expressed proteins (DEPs) with R software in five cancers: hepatocellular carcinoma (HCC), children's brain tumor tissue consortium (CBTTC), clear cell renal cell carcinoma (CCRC), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). GO and KEGG analysis were performed to clarify the function of these proteins. We also identified their interactions. The DEPs-based prognostic model for predicting over survival was identified by least absolute shrinkage and selection operator (LASSO)-Cox regression model in training cohort. Then, we used the time-dependent receiver operating characteristics analysis to evaluate the ability of the prognostic model to predict overall survival and validated it in validation cohort. The results showed that the DEPs-based prognostic model could accurately and effectively predict the survival rate of most cancers.

Acute pancreatitis (AP) is a clinically common acute inflammatory disease in digestive system, leading to systemic inflammatory response syndrome (SIRS) and severe acute pancreatitis (SAP). It was reported that PINK1/PARK2 dependent mitophagy played an important role in various inflammatory diseases. However, its role in AP has not been elucidated. Herein, we explore the effect of mitophagy in the pathogenesis of AP.

Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy of tumors. Understanding the molecular basis to chemoresistance is likely to provide better treatment. Cell lines resistant to cis-diamminedichloroplatinum (CNE2/cDDP) were established from human nasopharyngeal carcinoma (NPC) cell lines CNE2. Comparative proteomics involving 2-dimensional gel electrophoresis (2-DE) and ESI-Q-TOF-MS were performed on protein extracted from CNE2 and CNE2/cDDP cell lines to screen drug resistance-related proteins. Keratin 1 (KRT1), cathepsin D (CTSD) and annexin a5 (ANXA5) were identified as three proteins showing higher expression in CNE2/cDDP compared to CNE2. Furthermore, suppression of KRT1 expression by siRNA resulted in decreased MDR in siRNA-CNE2/cDDP cells. And upregulation of KRT1 could result in increased of drug resistance in NPC cell lines. Taken together, KRT1 protein and its activity levels were higher in cDDP-resistant NPC cell lines compared to their parental cell lines. These data clearly linked KRT1 and cDDP resistance mechanisms. KRT1 could serve as a biomarker for chemotherapy sensitivity of NPC.

Emerging evidence suggests that long non-coding RNA (lncRNA) plays a crucial part in the development and progress of hepatocellular carcinoma (HCC). The objective was to develop novel molecular-clinicopathological prediction methods for overall survival (OS) and recurrence of HCC.

Using smart photochromic and luminescent tissues in camouflage/cloaking of natural creatures has inspired efforts to develop synthetic stimuli-responsive materials for data encryption and anticounterfeiting. Although many optical data-encryption materials have been reported, they generally require only one or a simple combination of few stimuli for decryptions and rarely offer output corruptibility that prevents trial-and-error attacks. Here, we report a series of multiresponsive donor-acceptor Stenhouse adducts (DASAs) with unprecedented switching behavior and controlled reversibility via diamine conformational locking and substrate free-volume engineering and their capability of sequential logic encryption (SLE). Being analogous to the digital circuits, the output of DASA gel-based data-encryption system depends not only on the present input stimulus but also on the sequence of past inputs. Incorrect inputs/sequences generate substantial fake information and lead attackers to the point of no return. This work offers new design concepts for advanced data-encryption materials that operate via SLE, paving the path toward advanced encryptions beyond digital circuit approaches.

Emerging evidence suggests that competing endogenous RNAs plays a crucial role in the development and progress of pancreatic adenocarcinoma (PAAD). The objective was to identify a new lncRNA-miRNA-mRNA network as prognostic markers, and develop and validate a multi-mRNAs-based classifier for predicting overall survival (OS) in PAAD.

Compelling lines of evidence indicate that DNA methylation of non-coding RNAs (ncRNAs) plays critical roles in various tumour progression. In addition, the differential methylation of ncRNAs can predict prognosis of patients. However, little is known about the clear relationship between DNA methylation profile of ncRNAs and the prognosis of pancreatic adenocarcinoma (PAC) patients.

The present study was designed to investigate the protective effect of moracin on primary culture of nucleus pulposus cells in intervertebral disc and explore the underlying mechanism. Moracin treatment significantly inhibited the LPS-induced inflammatory cytokine accumulation (IL-1β, IL-6 and TNF-α) in nucleus pulposus cells. And moracin also dramatically decreased MDA activity, and increased the levels of SOD and CAT induced by LPS challenge. Moreover, the expressions of Nrf-2 and HO-1 were decreased and the protein levels of p-NF-κBp65, p-IκBα, p-smad-3 and TGF-β were increased by LPS challenge, which were significantly reversed after moracin treatments. Moracin treatments also decreased the levels of matrix degradation enzymes (MMP-3, MMP-13) as indicated by RT-PCR analysis. However, Nrf-2 knockdown abolished these protective effects of moracin. Together, our results demonstrated the ability of moracin to antagonize LPS-mediated inflammation in primary culture of nucleus pulposus in intervertebral disc by partly regulating the Nrf2/HO-1 and NF-κB/TGF-β pathway in nucleus pulposus cells.