Although cathepsin C (CTSC) has been reported to maintain malignant biological properties in various cancers, its functions in hepatocellular carcinoma (HCC) remain obscure. We aimed to investigate the potential role of CTSC in HCC. Materials and Methods HCC tissue microarrays (n=122) were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. Quantitative real-time polymerase chain reaction, western blot assay, Cell Counting Kit-8 assay, colony formation, cell migration, and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools. Results By bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients (hazard ratio, 2.402; 95% confidence interval, 1.493 to 3.865; p < 0.001). By gain/loss-of-function assays, we implicated that CTSC functioned as an oncogene to promote the proliferation and metastasis of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis, among which tumor necrosis factor ! (TNF-!)/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-! could activate CTSC expression in a concentration-dependent manner. Ralimetinib, an oral p38 mitogen-activated protein kinase (MAPK) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-!/MAPK (p38) signaling. Conclusion Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.

Colorectal cancer (CRC), as a malignant tumor of lower digestive tract, has been found to have an increasing morbidity and mortality in China. It was particularly important to find some earlier biomarkers to predict the risk and prognosis. In this study, several polymorphisms on 3′UTR of three DNA repair genes including MLH3 rs10862, ERCC1 rs3212986, ERCC1 rs735482, ERCC1 rs2336219, and OGG1 rs1052133 were chosen by bioinformatics exploration, and then, a case–control study of 200 CRC cases and controls was performed. Furthermore, a dual‐luciferase assay was also carried out to certify whether the candidate miRNA can regulate its target gene and the selected SNPs have a valid effect on the target miRNA. Finally, both of ERCC1 rs3212986 and MLH3 rs108621 were shown to be associated with the risk of CRC. Comparing with rs3212986 CC genotype, AA was at a higher risk (OR = 3.079, 95% CI: 1.192–7.952). For MLH3 rs108621, comparing with TT genotype, CC and TC were at a higher risk of CRC in male (OR = 5.171, 95% CI: 1.009–26.494; OR = 1.904, 95% CI: 1.049–3.455). Interestingly, an analysis combining both ERCC1 rs3212986 and MLH3 rs108621 also showed an increased risk of CRC. In addition, a dual‐luciferase assay showed that miR‐193a‐3p could regulate MLH3, and the polymorphism rs108621 could alter the miR‐193a‐3p binding to MLH3. Therefore, MLH3 rs108621 may be associated with the risk of CRC due to the effect of miR‐193a‐3p on MLH3, which reminded the possibility as potential susceptibility biomarkers to predict the risk of CRC.

ObjectiveRevealing the single-cell immune ecosystems in true versus de novo hepatocellular carcinoma (HCC) recurrences could help the optimal development of immunotherapies.DesignWe performed 5’and VDJ single-cell RNA-sequencing on 34 samples from 20 recurrent HCC patients. Bulk RNA-sequencing, flow cytometry, multiplexed immunofluorescence, and in vitro functional analyses were performed on samples from two validation cohorts.ResultsAnalyses of mutational profiles and evolutionary trajectories in paired primary and recurrent HCC samples using whole-exome sequencing identified de novo versus true recurrences, some of which occurred before clinical diagnosis. The tumour immune microenvironment (TIME) of truly recurrent HCCs was characterised by an increased abundance in KLRB1+CD8+T cells with memory phenotype and low cytotoxicity. In contrast, we found an enrichment in cytotoxic and exhausted CD8+T cells in the TIME of de novo recurrent HCCs. Transcriptomic and interaction analyses showed elevated GDF15 expression on HCC cells in proximity to dendritic cells, which may have dampened antigen presentation and inhibited antitumour immunity in truly recurrent lesions. In contrast, myeloid cells’ cross talk with T cells-mediated T cell exhaustion and immunosuppression in the TIME ofde novorecurrent HCCs. Consistent with these findings, a phase 2 trial of neoadjuvant anti-PD-1 immunotherapy showed more responses in de novo recurrent HCC patients.ConclusionTrue and de novo HCC recurrences occur early, have distinct TIME and may require different immunotherapy strategies. Our study provides a source for genomic diagnosis and immune profiling for guiding immunotherapy based on the type of HCC recurrence and the specific TIME.

In the work, sulfur-containing sorbents were employed to remove elemental mercury (Hg0) from coal-fired flue gas. The work used the thermogravimetric analysis, Brunauer–Emmett–Teller method, scanning electron microscopy with energy-dispersive spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy to characterize the physicochemical properties of the sorbents. The Hg0 removal performance of these used sorbents from the simulated coal-fired flue gas was evaluated by a bench-scale fixed-bed reactor. The results indicated that a generous amount of elemental sulfur covered the surface and pore structure of the used sorbent. With the rise of H2S selective oxidation temperature, both the sulfur content and specific surface area decreased rapidly. Used-Fe/SC120 could achieve the mercury removal efficiency of above 90% at 90 °C. The high temperature was not conducive to the mercury capture due to the release of surface elemental sulfur. The presence of O2 and SO2 inhibited Hg0 removal in different degrees because of the decreased active sulfur sites and competitive adsorption. Meanwhile, NO promoted the Hg0 removal efficiency by enhancing the Hg0 oxidation. The further analysis showed that the surface elemental sulfur was vital to capture the Hg0 from coal-fired flue gas, which reacted with Hg0 to form HgS.

Lung cancer is one of the most devastating tumors with a high incidence and mortality worldwide. Polymorphisms and expression of ERCC1 commonly predicted the occurrence and prognosis of lung cancer. However, few studies have focused on long non-coding RNAs related to ERCC1 though some studies reminded the importance of its post-transcriptional regulation. In the present study, an intronic lncRNA AC138128.1 originated from ERCC1 was firstly identified in microarray chip and database, and its possibility as a novel biomarker to predict lung cancer treatment was further discussed. Firstly, the qRT-PCR data showed that AC138128.1 expression was much lower in lung cancer comparing with its para-cancer tissues, which further analyzed by ROC curve. Similarly, the difference was also verified in 16HBE, A549 and LK 2 cells. Then AC138128.1 expression was found to have an increasing trend in a dose or time-dependent manner after cisplatin treatment. Finally, the subcellular distribution of AC138128.1 reminded that AC138128.1 was mainly expressed in the nucleus. Interestingly a positive relationship between AC138128.1 and ERCC1 expression was only found in cancer tissues, which reminded AC138128.1 may be involved in the regulation of ERCC1. Therefore, as a preliminary exploration of the lncRNA originated from ERCC1 , the present study suggested AC138128.1 is of potential value in predicting platinum analogue benefit in lung cancer.