METTL14-dependent maturation of pri-miR-17 regulates mitochondrial homeostasis and induces chemoresistance in colorectal cancer.

miR-17-5p has been found to be involved in the proliferation and metastasis of colorectal cancer (CRC), and N6-methyladenosine (m6A) modification is the most common RNA modification in eukaryotes. However, whether miR-17-5p contributes to chemotherapy sensitivity in CRC via m6A modification is unclear. In this study, we found that overexpression of miR-17-5p led to less apoptosis and lower drug sensitivity in vitro and in vivo under the 5-fluorouracil (5-FU) treatment, which indicated miR-17-5p led to 5-FU chemotherapy resistance. Bioinformatic analysis suggested that miR-17-5p-mediated chemoresistance was associated with mitochondrial homeostasis. miR-17-5p directly bound to the 3' untranslated region of Mitofusin 2 (MFN2), leading to decreased mitochondrial fusion and enhanced mitochondrial fission and mitophagy. Meanwhile, methyltransferase-like protein 14 (METTL14) was downregulated in CRC, resulting in lower m6A level. Moreover, the low level of METTL14 promoted the expression of pri-miR-17 and miR-17-5p. Further experiments suggested that m6A mRNA methylation initiated by METTL14 inhibits pri-miR-17 mRNA decay via reducing the recognition of YTHDC2 to the "GGACC" binding site. The METTL14/miR-17-5p/MFN2 signaling axis may play a critical role in 5-FU chemoresistance in CRC.

Chelating Polymer-Coated Separators with a BaTiO3 Filler To Improve Reversibility and Round-Trip Efficiency of a 3.3 V Copper-Lithium Battery.

A novel 3.3 V copper-lithium battery using a copper foil as the cathode is a potential candidate for next-generation energy storage system due to its simple manufacturing process. However, the cross-over of copper ions from the cathode to the anode limits the reversibility of the battery. Herein, we suppress self-discharge and migration of copper ions in the cell using a commercial polypropylene separator with a coating of polyacrylic acid (PAA), a chelating polymer. Fourier transform infrared spectroscopy confirms that the PAA layer traps the copper ions and prevents them from passing through. The addition of barium titanate nanoparticles into the PAA layer further enhances ionic transfer through the separator and reduces polarization of the cell at high current rates during charge and discharge. The use of a chelating agent with an inorganic filler as a coating layer on the separator is a cost-effective way to improve reversibility and round-trip efficiency of copper-lithium batteries.

Efficient degradation of naproxen by persulfate activated with zero-valent iron: performance, kinetic and degradation pathways.

Degradation of naproxen (NAP) by persulfate (PS) activated with zero-valent iron (ZVI) was investigated in our study. The NAP in aqueous solution was degraded effectively by the ZVI/PS system and the degradation exhibited a pseudo-first-order kinetics pattern. Both sulfate radical (SO4 •-) and hydroxyl radical (HO•) participate in the NAP degradation. The second-order rate constants for NAP reacting with SO4 •- and HO• were (5.64 ± 0.73) × 109 M- 1 s- 1 and (9.05 ± 0.51) × 109 M- 1 s- 1, respectively. Influence of key parameters (initial pH, PS dosage, ZVI dosage, and NAP dosage) on NAP degradation were evaluated systematically. Based on the detected intermediates, the pathways of NAP degradation in ZVI/PS system was proposed. It was found that the presence of ammonia accelerated the corrosion of ZVI and thus promoted the release of Fe2+, which induced the increased generation of sulfate radicals from PS and promoted the degradation of NAP. Compared to its counterpart without ammonia, the degradation rates of NAP by ZVI/PS were increased to 3.6-17.5 folds and 1.2-2.2 folds under pH 7 and pH 9, respectively.

Gender difference in the effect of progesterone on neonatal hypoxic/ischemic brain injury in mouse.

This study investigated the effects of progesterone (PROG) on neonatal hypoxic/ischemic (NHI) brain injury, the differences in effects between genders, and the underlying mechanisms. NHI brain injury was established in both male and female neonatal mice induced by occlusion of the left common carotid artery followed by hypoxia. The mice were treated with PROG or vehicle. Fluoro-Jade B staining (F-JB), long term behavior testing, and brain magnetic resonance image (MRI) were applied to evaluate neuronal death, neurological function, and brain damage. The underlying molecular mechanisms were also investigated by Western blots. The results showed that, in the male mice, administration of PROG significantly reduced neuronal death, improved the learning and memory function impaired by cerebral HI, decreased infarct size, and maintained the thickness of the cortex after cerebral HI. PROG treatment, however, did not show significant neuroprotective effects on female mice subjected to HI. In addition, the data demonstrated a gender difference in the expression of tumor necrosis factor receptor 1 (TNFR1), TNF receptor associated factor 6 (TRAF6), Fas associated protein with death domain (FADD), and TIR-domain-containing adapter-inducing interferon-ß (TRIF) between males and females. Our results indicated that treatment with PROG had beneficial effects on NHI injured brain in acute stage and improved the long term cognitive function impaired by cerebral HI in male mice. In addition, the activation of TNF and TRIF mediated signaling in response to cerebral HI and the treatment of PROG varied between genders, which highly suggested that gender differences should be emphasized in evaluating neonatal HI brain injury and PROG effects, as well as the underlying mechanisms.