Introduction: Hepatocellular carcinoma (HCC) ranks fourth in global cancer mortality, accounting for 8.2% of all cancer deaths. Early detection of HCC has a significant impact on clinical outcomes. The aim of this study was to identify blood-based biomarkers which are HCC-specific. Methods: Comprehensive gene expression raw data of purified RNA of peripheral blood mononuclear cells (PBMC) was downloaded from GEO and was then analyzed. Differentially expressed genes (DEGs) in HCC were screened and the method of weighted gene co-expression network analysis was applied to identify candidate blood-based biomarkers associated with HCC. Results: Three modules closely related to HCC were screened using WGCNA. Nuclear localization signal (NLS)-bearing protein import into nucleus biological process was the most significant enriched physiological process identified by MCODE, and 3 genes (DICER1, GMPS and NCOR1) were selected as biomarkers. Conclusion: In our study, three novel blood-based HCC-specific diagnostic biomarkers for human hepatocellular carcinoma were identified. These findings may contribute to the non-invasive detection of early HCC patients.

Background and Aim:Methylated SEPT9 is a novel circulating tumor DNA marker for colorectal cancer, while the effects of various colorectal cancer clinicopathological factors on its detection performance have not been fully evaluated. This study aims to investigate the significance of the clinicopathological factors on methylated SEPT9 performance in a symptomatic endoscopy cohort, with a specific focus on colorectal cancer.Methods:A total of 1160 participants were recruited in this study, including 300 patients with colorectal cancer, 122 patients with adenoma, 103 patients with hyperplastic polyps, 568 normal participants (no evidence of disease), and 67 patients with other gastrointestinal diseases. Peripheral blood samples of these participants were collected from 3 Chinese hospitals, and the methylated SEPT9 level was measured using the Epi proColon 2.0 assay.Results:Cancer stage, size, and invasion depth were positively correlated with the detection sensitivity, while no difference in sensitivity was identified among cancers at various locations. Infiltrative colorectal cancer exhibited higher sensitivity than ulcerative and protrude colorectal cancer, while no difference in sensitivity was observed among assessed histological types. The colorectal cancer differentiation showed a clear correlation with the cancer stage, and moderate and poorly differentiated colorectal cancer exhibited higher sensitivity than well-differentiated colorectal cancer. Furthermore, colorectal cancer with distal metastasis (M1) showed higher sensitivity than those without any metastasis, while colorectal cancer with lymph node metastasis (N1 and N2) did not show statistical significance compared to those without it. Finally, local vessel or nerve invasion did not affect the sensitivity.Conclusion:Factors that reflect the colorectal cancer intrinsic properties, including cancer stage, size, invasion depth, classification, differentiation, and metastasis, exhibited significant effect on the mSEPT9 detection performance.

Sulfur is a promising cathode material with a high theoretical capacity of 1672 mAh g−1, however, the practical energy density of Li-S battery is far away from such promising due to its low active material utilization and low sulfur loading. Moreover, the challenges of the low electrical conductivity of sulfur and the high solubility of polysulfide intermediates still hinder its practical application. Here, we report a kind of free-standing and foldable cathodes consisting of 3D activated carbon fiber matrix and sulfur cathode. The 3D activated carbon fiber matrix (ACFC) has continuous conductive framework and sufficient internal space to provide a long-distance and continuous high-speed electron pathway. It also gives a very larger internal space and tortuous cathode region to ACFC accommodate a highly sulfur loading and keeps polysulfide within the cathode. The unique structured 3D foldable sulfur cathode using a foldable ACFC as matrix delivers a reversible capacity of about 979 mAh g−1 at 0.2C, a capacity retention of 98% after 100 cycles, and 0.02% capacity attenuation per cycle. Even at an areal capacity of 6 mAh cm−2, which is 2 times higher than the values of Li-ion battery, it still maintains an excellent rate capability and cycling performance.

Background Cytokine-induced killer cells induced with tumor antigen-pulsed dendritic cells (DC-CIK) immunotherapy is a promising strategy for the treatment of malignant tumors. However, itsefficacy isrestricted by the immunosuppression, which is mediated by the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathway. In order to overcome the negative co-stimulation from these T cells,we screened a nanobody targeted for CTLA-4 (Nb36) and blocked the CTLA-4 signaling with Nb36. Methods Peripheral blood mononuclear cells (PBMCs) were collected from healthy donors to beused to induce CIK cells in vitro, after which they were co-cultured with DC cells that had received tumor antigens. In addition, wetested whether blocking CTLA-4 signaling with Nb36 could promote in vitro DC-CIK cells proliferation, pro-inflammatory cytokine production and cytotoxicity,or not. For the in vivo experiments, we constructed a subcutaneously transplanted tumor model and placed it in NOD/SCID mice to verify the anti-tumor effect of this therapy. Results After stimulation with Nb36, the DC-CIK cells presented enhanced proliferation and production of IFN-γ in vitro, which strengthened the killing effect on the tumor cells. For the in vivo experiments, it was found that Nb36-treated DC-CIK cells significantly inhibited the growth of subcutaneously transplanted livercancer tumors, as well as reduced the tumor weight and prolonged the survival of tumor-bearing NOD/SCID mice. Conclusions Ourfindings demonstrated that in response to CTLA-4 specific nanobody stimulation, DC-CIK cells exhibited a better anti-tumor effect. In fact, this Nb-based CTLA-4 blocking strategy achieved an anti-tumor efficacy close to that of monoclonal antibodies. Our findings suggest that DC-CIK cells + Nb36 have the potential totreatmalignant tumors through in vivo adoptive therapy.

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Long noncoding RNAs (lncRNAs) refers to a class of RNAs that have at least 200 nucleotides and do not encode proteins, and the relationship between lncRNA and cancer has recently attracted considerable research attention. The lncRNA FGD5-AS1 is a newly discovered lncRNA with a length of 3772 nucleotides. Studies have found that FGD5-AS1 is abnormally highly expressed in many cancer tissues and was closely related to the lymph node metastasis, tumor invasion, survival time, and recurrence rate of various cancers. Mechanistic analyses show that FGD5-AS1 can stabilize mRNA expression by sponging miRNA, which not only induces cancer cell proliferation, metastasis, invasion, and chemoresistance in vitro, but also promotes tumor growth and metastasis in vivo. In addition, FGD5-AS1 can serve as a diagnostic or prognostic marker for a variety of cancers. This review demonstrates the clinical significance of FGD5-AS1 in human cancer and its role in tumorigenesis and tumor progression.

Background: Novel tuppherapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15-IN-1 and KIF11 inhibitor ispinesib in GC. Methods: We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo. Results: KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo. Conclusion: This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.

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