Search

Lithium-rich manganese-based transition metal oxide Li 1.2 Ni 0.2 Mn 0.6 O 2 (LNMO) can achieve high energy density due to the interaction of anionic redox kinetics in Li 2 MnO 3. However, the irreversible release of oxygen and migration of Mn ions during deep de-lithiation disrupts the layer structure of LNMO, leading to a decrease in voltage and capacity. Herein, we confine oxygen anion through Zr and Al co-doping. Combined analysis of structure refinement, XPS and XAS, the co-doped strategy effectively prohibits cation disordering of Li/Ni, inhibits the Jahn-Teller effect and reduces the transition metal (TM) and oxygen hybridization. As a result, the Zr and Al co-doping LNMO sample (ZA-LNMO) possesses a capacity retention of 92% after 100 cycles and 86% after 200 long-term cycles, much higher than the value of the undoped sample (79% for 100 cycles and 58% for 200 cycles). Even at the harsh conditions such as ultra-high current rate (10 C) or high temperature (60 °C), ZA-LNMO also maintains 70% retention after 200 cycles. Our findings provide an insight into the synergistic effect of cation co-doping and help to design layered oxides for future applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] Coptisine markedly inhibits osteosarcoma cell proliferation and tumor growth. [•] Coptisine impedes osteosarcoma cell migration, invasion, and tube formation. [•] Coptisine has very low toxicity with moderate increase in RBC and Hb levels. [ABSTRACT FROM AUTHOR]

Catalytic steam gasification of biomass can produce clean and renewable hydrogen. In this study, Ce/Fe bimetallic catalysts were used to promote hydrogen production from cellulose steam catalytic reforming at 500–900 °C. The effect of different Ce/Fe ratios on the catalytic performance of hydrogen production was studied. The distribution of products, gas composition, carbon deposition and the stability of the catalyst were analyzed with variant approaches. The results show that the catalytic performance of the CeO 2 /Fe 2 O 3 catalyst in relation to hydrogen production was much better than pure CeO 2 or Fe 2 O 3 . When the ratio of Ce:Fe was 3:7, the maximum yield of the H 2 was 28.58 mmol at 800 °C. CeFeO 3 could be generated at 800 °C or higher temperature after redox reactions without forming CeO 2 /Fe 2 O 3 clathrate. And the existence of CeFeO 3 enhanced the thermal stability of Ce/Fe catalyst. The presence of CeO 2 not only improved the oxidative ability of the iron catalysts, but also was in favour of the oxidation of possible deposited carbon on the surface of the used catalysts. [ABSTRACT FROM AUTHOR]

Gastric cancer is ranked as the third leading cause of cancer-related death in the world. Although extensive efforts have been made in recent decades to treat gastric cancer with various anticancer drugs, effective anti-gastric cancer therapeutics to cure the disease are still lacking in the clinics. Therefore, potent novel anti-gastric cancer drugs are greatly needed. In this study, we explored a novel anti-gastric cancer agent from a medicinal herb named Juncus effusus and found that the active component dehydroeffusol (DHE), a small molecular phenanthrene, effectively inhibited gastric cancer cell proliferation and tumorigenesis by inducing tumor suppressive endoplasmic reticulum (ER) stress and by triggering moderate apoptosis. Mechanistic studies revealed that DHE selectively activated the intracellular tumor suppressive stress response by promoting the overexpression of the key ER stress marker DNA damage-inducible transcript 3 (DDIT3), through upregulation of activating transcription factor 4 (ATF4). Concurrently, DHE suppressed the expression of the cell survival and ER stress marker glucose regulated protein of molecular mass 78 (GRP78) via downregulation of the transcription factor ATF6. In addition, DHE markedly activated the stress response signaling pathway MEKK4-MKK3/6-p38-DDIT3, but significantly inhibited ERK signaling. Our data suggest that DHE inhibits gastric cancer cell growth and tumorigenicity through selectively inducing a robust tumor suppressive ER stress response and a moderate apoptosis response. Therefore, DHE may provide a novel drug candidate for further development of potential anti-gastric cancer therapeutics. [ABSTRACT FROM AUTHOR]

Abstract: Uncontrolled tumor cell proliferation and robust neovascularization are prominent features of aggressive ovarian cancers. Although great efforts in anti-ovarian cancer therapy have been made in the past 4 decades, the 5-year survival rates for ovarian cancer patients are still poor, and effective drugs to cure ovarian cancer patients are absent. In this study, we evaluated the anti-cancer effects of lycorine hydrochloride (LH), a novel anti-ovarian cancer agent, using the highly-invasive ovarian cancer cell line, Hey1B, as a model. Our data showed that LH effectively inhibited mitotic proliferation of Hey1B cells (half maximal inhibitory concentration=1.2μM) with very low toxicity, resulting in cell cycle arrest at the G2/M transition through enhanced expression of the cell cycle inhibitor p21 and marked down-regulation of cyclin D3 expression. Moreover, LH suppressed both the formation of capillary-like tubes by Hey1B cells cultured in vitro and the ovarian cancer cell-dominant neovascularization in vivo when administered to Hey1B-xenotransplanted mice. LH also suppressed the expression of several key angiogenic genes, including VE-cadherin, vascular endothelial growth factor, and Sema4D, and reduced Akt phosphorylation in Hey1B cells. These results suggest that LH selectively inhibits ovarian cancer cell proliferation and neovascularization and is a potential drug candidate for anti-ovarian cancer therapy. [Copyright &y& Elsevier]

Cervical cancer (CC) patients with lymph node (LN) metastasis often have an extremely poor prognosis. However, the precise molecular mechanisms involved in LN metastasis of CC remain largely unknown. Herein, through RNA screening, we identified a novel long noncoding RNA (lncRNA), LncCCLM, that was downregulated in cervical cancer tissues and closely associated with lymphatic metastasis in cervical cancer patients. Gain-of-function and loss-of-function studies in CC cells demonstrated that LncCCLM inhibited cervical cancer-associated lymphangiogenesis, and CC cell migration and invasion in vitro and suppressed LN metastasis in vivo, but did not affect the growth of CC cells. Mechanistically, LncCCLM localized in the cytoplasm and interacted with staufen double-stranded RNA binding protein 1 (STAU1), promoting the binding of the STAU1 protein to the 3' untranslated region (3'UTR) of insulin-like growth factor 1 (IGF-1) mRNA, which accelerated the degradation of IGF-1 mRNA and decreased the IGF-1 protein level, ultimately reducing lymphangiogenesis and lymphatic metastasis in cervical cancer. Collectively, our findings suggest that LncCCLM acts as a tumor suppressor and may be used as a prognostic biomarker and therapeutic target for clinical intervention in LN-metastatic cervical cancer. [ABSTRACT FROM AUTHOR]

Background Programmed cell death ligand-1 (PD-L1) with its receptor PD-1 pathway is overactivated in many tumors. Inhibiting the interaction of PD-L1 and PD-1 is an attractive strategy to restore tumor-specific T cell immunity for tumor therapy. Methods A fully human anti-PD-L1 monoclonal antibody (mAb) B60-55 was identified by yeast surface display. The affinity, specificity, activity, and efficacy of mAb B60-55 were investigated in vitro or in vivo. Results mAb B60-55 (purity > 99%) could bind to PD-L1 that is expressed on HEK293 cells with a dissociation constant of 0.2 nM, and specifically bind to human or cynomolgus macaque PD-L1 without a cross-reaction with murine PD-L1. Moreover, mAb B60-55 is an antagonistic antibody, which can block PD-L1 binding to its receptors, including PD-1 (PDCD1) and B7.1 (CD80). In vitro assays demonstrated the ability of mAb B60-55 to enhance T cell responses and cytokine production in the mixed lymphocyte reaction. In vivo studies showed that administration of mAb B60-55 exhibited a potent antitumor activity toward tumor cell carcinoma xenograft, with a mean half-life of 177.9 h in cynomolgus monkeys. Conclusion mAb B60-55 is a potential candidate for clinical development in cancer treatment. [ABSTRACT FROM AUTHOR]

• 9 pairs of cervical cancer and paracancerous tissues were used. • We identified a new circZNF208 related ceRNA network through bioinformatic analysis. • circZNF208 can promote fibroblast proliferation. • circZNF208 interfering with hsa-miR-324-3p regulate downstream gene LPHN3. • Our results might be valuable for diagnosis and treatment of cervical cancer. Cervical cancer is one of the major cancers that threaten the health of women. CircRNA is an important factor in the regulation of cancer development and progression. The role of circRNA in cervical cancer is less well studied. The aim of this study was to explore the mechanism of circRNA effects on cervical cancer using circRNA-seq technology to study the expression profile data of 9 pairs of primary cervical cancer and paracancerous tissues. DESeq2 was used to analyse differentially expressed circRNA and mRNA in cervical cancer and paracancerous tissues. MiRanda and TargetScan are used to predict miRNAs that interact with circRNAs and mRNAs and to construct circRNA-miRNA-mRNA regulatory networks. KEGG and GO are used for functional annotation of differentially expressed genes. TIDE, TIMER2.0 was used to assess the status of the tumour immune microenvironment in cervical cancer. GEPIA2 was used to validate the results of differential expression analysis. We eventually obtained 22 differentially expressed circRNAs (7 up-regulated and 15 down-regulated) and 1834 differentially expressed genes (613 up-regulated and 1221 down-regulated). The results of the KEGG analysis showed that the differentially expressed genes were mainly enriched in cell cycle and cancer-related signalling pathways. The new circRNA: circZNF208 was identified to promote fibroblast proliferation by interfering with its downstream hsa-miR-324-3p regulating four downstream genes LPHN3. The level of fibroblast infiltration is implicated in the poor prognosis of cervical cancer. We have identified a novel circRNA: circZNF208 that can interfere with fibroblast proliferation in cervical cancer through a ceRNA regulatory network, thereby promoting fibroblast proliferation in cervical cancer and affecting the prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Osteosarcoma is one of the most common malignant bone tumors in children and adolescents. Although extensive efforts have been made in anti-osteosarcoma therapy in recent decades, there are no effective low-toxicity drugs for treating patients with metastatic osteosarcoma. Hence, potent anti-metastatic osteosarcoma drugs are highly desired. In this study, we explored novel small molecular anti-metastatic osteosarcoma agents and found that columbamine (COL), an active component of the herb Coptis chinensis, inhibited the proliferation and neovascularization of metastatic osteosarcoma U2OS cells. COL effectively suppressed U2OS cell proliferation in vitro with an IC50 of 21.31±0.38μM, with low cytotoxicity. Mechanistic studies revealed that COL induces cell cycle arrest at the G2/M transition, which is associated with attenuating CDK6 gene expression and diminishing STAT3 phosphorylation. COL did not significantly promote U2OS cell apoptosis at any of the dosages tested. Additionally, COL inhibited U2OS cell-mediated neovascularization, which was accompanied by the down-regulation of matrix metalloproteinase (MMP) 2 expression and reduction of cell migration, adhesion, and invasion. Taken together, our data show that COL exerts anti-proliferative and anti-vasculogenic effects on metastatic human osteosarcoma U2OS cells with low toxicity. These results warrant further investigation of COL as a potential anti-osteosarcoma and anti-cancer drug. [Copyright &y& Elsevier]