AMTB, a TRPM8 antagonist, suppresses growth and metastasis of osteosarcoma through repressing the TGFß signaling pathway.

Since its first identification in prostate cancers and prostate tissues, transient receptor potential melastatin-subfamily member 8 (TRPM8) is subsequently found to be overexpressed in a wide range of cancers and is shown to be implicated in tumorigenesis and tumor progression. Here, we used N-(3-aminopropyl)-2-[(3-methylphenyl) methoxy] -N-(2-thienylmethyl) benzamide hydrochloride (AMTB), a specific TRPM8 antagonist, to explore its antitumoral effect on osteosarcoma. We find that AMTB suppresses osteosarcoma cell proliferation, metastasis and induces cellular apoptosis. Xenograft model in nude mice experiments also define that AMTB can increase the sensitivity of tumor cells to cisplatin, the cytotoxic chemotherapeutic regimens in treating osteosarcoma. Molecularly, AMTB specifically antagonizes TRPM8 which is upregulated in osteosarcoma and its expression level in osteosarcoma tissues is negatively related to patients' prognosis. Finally, RNA sequencing analysis was performed to explore the mechanism underlying the antitumoral effect of AMTB on osteosarcoma cells and the results prove that AMTB suppresses the Transforming Growth Factor ß (TGFß) signaling pathway. Our study provides evidence that TRPM8 could be a potential therapeutic target and AMTB can suppress growth and metastasis of osteosarcoma cells through repressing the TGFß signaling pathway and increase the sensitivity of tumor cells to cisplatin.

RDM1 plays an oncogenic role in human ovarian carcinoma cells.

Ovarian cancer is one of the deadliest gynecological cancer, with a low overall 5-year survival rate. RDM1, RAD52 motif-containing protein 1, is sensitive to cisplatin, a common chemotherapy drug and it has an important role inDNA damage repair pathway. Until now, the effect of RDM1 in ovarian cancer is undiscovered. Here, clinical data shows that the tumour tissues of ovarian carcinoma patients with higher mRNA and protein expression of RDM1. Knockdown of RDM1 in ovarian carcinoma cells reduces cell proliferation and promotes apoptosis, consistent with the role RDM1 in the overexpression experiments. The research of xenograft mouse model shows stable knockdown of RDM1 significantly inhibits ovarian cancer tumour growth. These in vitro and in vivo results conclude that RDM1 plays an oncogenic role in human ovarian carcinoma. Interestingly, p53/RAD51/RAD52 signalling pathway can be regulated by RDM1, and the negative regulation of p53 by RDM1 may be one of major mechanisms for RDM1 to accomplish its oncogenic functions in ovarian carcinoma. Therefore, RDM1 may be a new target for the treatment of ovarian carcinoma.

Treatment of landfill leachate using magnetically attracted zero-valent iron powder electrode in an electric field.

This study combined electro-oxidation (EO) and electrocoagulation (EC) process (EO/EC) to treat landfill leachate by using RuO2-IrO2/Ti plate and microscale zero-valent iron powder composite anode. EO was achieved by direct oxidation and indirect oxidation on RuO2-IrO2/Ti plate, whereas EC was achieved using iron powder to lose electrons and produce coagulants in situ. The influences of variables including type of anode material, applied voltage, zero-valent iron dosage, interelectrode gap, and reaction temperature on EO/EC were evaluated. Results showed that at an applied voltage of 10 V, zero-valent iron dosage of 0.2 g, interelectrode gap of 1 cm, and non-temperature-controlled mode, the removal efficiencies were 72.5 % for total organic carbon (TOC), 98.5 % for ammonia, and 98.6 % for total phosphorus (TP). Some heavy metals and hardness were also removed. Further analysis indicated that the removal of TOC, ammonia, and TP followed pseudo-first order, pseudo-zero order, and pseudo-second order kinetic models, respectively. Other characteristics were examined by scanning electron microscopy-energy dispersive spectrometry, X-ray diffraction, and X-ray photoelectron spectroscopy. Overall, our results showed that EO/EC can be used to efficiently remove organic matter, ammonia, TP, and heavy metals from landfill leachate.

Alginate Adsorbent Immobilization Technique Promotes Biobutanol Production by Clostridium acetobutylicum Under Extreme Condition of High Concentration of Organic Solvent.

In Acetone-Butanol-Ethanol fermentation, bacteria should tolerate high concentrations of solvent products, which inhibit bacteria growth and limit further increase of solvents to more than 20 g/L. Moreover, this limited solvent concentration significantly increases the cost of solvent separation through traditional approaches. In this study, alginate adsorbent immobilization technique was successfully developed to assist in situ extraction using octanol which is effective in extracting butanol but presents strong toxic effect to bacteria. The adsorbent improved solvent tolerance of Clostridium acetobutylicum under extreme condition of high concentration of organic solvent. Using the developed technique, more than 42% of added bacteria can be adsorbed to the adsorbent. Surface area of the adsorbent was more than 10 times greater than sodium alginate. Scanning electron microscope image shows that an abundant amount of pore structure was successfully developed on adsorbents, promoting bacteria adsorption. In adsorbent assisted ABE fermentation, there was 21.64 g/L butanol in extracting layer compared to negligible butanol produced with only the extractant but without the adsorbent, for the reason that adsorbent can reduce damaging exposure of C. acetobutylicum to octanol. The strategy can improve total butanol production with respect to traditional culture approach by more than 2.5 fold and save energy for subsequent butanol recovery, which effects can potentially make the biobutanol production more economically practical.