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Activating mutations in PIK3CA are frequently found in estrogen-receptor-positive (ER+) breast cancer, and the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib with anti-ER inhibitors is approved for therapy. We have previously demonstrated that the PI3K pathway regulates ER activity through phosphorylation of the chromatin modifier KMT2D. Here, we discovered a methylation site on KMT2D, at K1330 directly adjacent to S1331, catalyzed by the lysine methyltransferase SMYD2. SMYD2 loss attenuates alpelisib-induced KMT2D chromatin binding and alpelisib-mediated changes in gene expression, including ER-dependent transcription. Knockdown or pharmacological inhibition of SMYD2 sensitizes breast cancer cells, patient-derived organoids, and tumors to PI3K/AKT inhibition and endocrine therapy in part through KMT2D K1330 methylation. Together, our findings uncover a regulatory crosstalk between post-translational modifications that fine-tunes KMT2D function at the chromatin. This provides a rationale for the use of SMYD2 inhibitors in combination with PI3Kα/AKT inhibitors in the treatment of ER+/ PIK3CA mutant breast cancer. [Display omitted] • KMT2D is methylated at K1330 by SMYD2 • There is crosstalk between phosphorylation of KMT2D at S1331 and methylation at K1330 • Loss of SMYD2 abrogates PI3Ki-induced KMT2D chromatin binding and ER-dependent transcription • Inhibition of KMT2D methylation sensitizes cells and tumors to PI3K/AKT inhibition Blawski et al. show that KMT2D is methylated by the lysine methyltransferase SMYD2 at K1330. SMYD2 loss attenuates PI3K inhibitor-induced KMT2D chromatin binding at estrogen-receptor (ER) loci and ER-dependent transcription. SMYD2 inhibition sensitizes cells, patient-derived organoids, and tumors to PI3K/AKT inhibition and endocrine therapy through KMT2D K1330 methylation. [ABSTRACT FROM AUTHOR]

Abstract Metal carbonate hydroxide is a promising electrode material for advanced supercapacitors but suffers from the poor electronic conductivity. Herein, we address this issue through the in-situ formation of Ni 1/3 Co 2/3 (CO 3) 0.5 OH·0.11H 2 O anchoring onto the surface of polypyrrole nanotubes via a hydrothermal method. The Ni 1/3 Co 2/3 (CO 3) 0.5 OH·0.11H 2 O/polypyrrole nanotubes composites possess high specific surface area and electronic conductivity, resulting in large charge storage and fast charge/discharge rate. The synthesized composite electrodes exhibit a high specific capacitance of 964.8 F g−1 at 1 A g−1 and low the equivalent series resistance of 0.24 Ω. Moreover, the assembled asymmetric supercapacitors exhibit high energy density of 41.86 Wh kg−1 with a power density of 562 W kg−1, and high power density of 11.25 kW kg−1 with an energy density of 16.97 Wh kg−1. The capacitance retention remains 80.2% after 5000 cycles at 5 A g−1, indicating the excellent cycling stability. The results indicate that Ni 1/3 Co 2/3 (CO 3) 0.5 OH·0.11H 2 O/polypyrrole nanotubes composites are a potential electrode material for high-performance supercapacitors. [ABSTRACT FROM AUTHOR]

N-doped porous carbon nanosheets (N-CNS) were prepared from coal tar pitch with the addition of urea and KOH activation. In the synthesis route, urea plays an important role in constructing the 2D sheet-like structure, which serves as a nitrogen source, chemical blowing agent and the in-situ formation of g-C 3 N 4 self-degraded template. At a low activation temperature (600 °C), the as-prepared N-doped porous carbon nanosheets possess high nitrogen content (7.06 at. %) and high specific surface area (1181 m 2  g −1 ), which offers remarkable capacitive performances due to the unique architecture and pseudocapacitance contribution of the N doping. The N-CNS exhibits high capacitive performance (210 F g −1 at 0.1 A g −1 ), and an excellent cycling stability. Additionally, the assembled symmetric supercapacitor displays an energy density of 7.15 Wh kg −1 , and the capacitance retention remains 91.2% after 5000 cycles at 1 A g −1 . The facile and low-cost route to massively prepare N-doped porous carbon nanosheets from coal tar pitch would be favorable to the applications of carbon materials for high performance supercapacitors. [ABSTRACT FROM AUTHOR]

A novel formaldehyde-free phosphorus–nitrogen flame retardant with multiple reactive groups, dioxo (3-triethylphosphite-5-chlorine−1−triazine) neopentyl glycol (DTCTNG), has been synthesized and was applied to cotton fabrics. The molecular structure of DTCTNG was characterized by FTIR, 1 H NMR, and 31 P NMR. The thermal degradation property of DTCTNG was assessed by thermogravimetric analysis (TGA), which revealed that it has good thermal stability on the high temperature condition. To achieve a covalent bond between DTCTNG and fiber matrix, the finishing conditions of cotton fabrics with different add-on's DTCTNG were investigated by using TGA, vertical flammability test, limiting oxygen index (LOI) and scanning electron microscope test (SEM). The water resistance of the treated cotton fabrics under optimal finishing condition was studied by LOI test. Furthermore, the mechanism of cross-linking reaction between DTCTNG and cotton fiber was discussed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). All the results showed that cotton fabrics treated with DTCTNG has good flame retardancy and steady water resistance. [ABSTRACT FROM AUTHOR]

Low molybdenum (Mo) bioavailability in acidic soil obstructs vegetable nitrogen assimilation and thus increases the health risk of vegetable ingestion due to nitrate accumulation. Constantly providing available Mo in acidic soil is a challenge for decreasing nitrate accumulation in vegetables. In this study, three Mo application methods, including biochar-based Mo slow-release fertilizer (Mo-biochar), seed dressing, and basal application, were investigated to enhance Mo bioavailability in acidic soil and nitrogen assimilation in Chinese flowering cabbage (Brassica parachinensis). The results showed that Mo-biochar constantly and sufficiently supplied Mo nutrients throughout the growing period of Brassica parachinensis , as evidenced by the soil available Mo, plant Mo uptake, and Mo values. The improved Mo supply was attributed to the alleviation of acidic soil (pH from 5.10 to 6.99) and the slow release of Mo adsorbed on biochar. Mo-biochar increased the nitrate reductase (NR) activity by 238.6% and glutamate dehydrogenase activity by 27.5%, indicating an enhancement of the rate-limiting steps of nitrogen assimilation, especially for nitrate reduction and amino acid synthesis. The increase in Mo-containing NR could be directly ascribed to the high level of Mo in Brassica parachinensis. Compared with the control, the nitrate content of Brassica parachinensis decreased by 42.9% due to the nitrate reduction induced by increased NR. Additionally, Mo-biochar was beneficial to vegetable growth and quality. In contrast, the transformation from NO 3 − to NH 4 + was blocked with Mo seed dressing and basal application because of low Mo bioavailability in the soil, resulting in a high nitrate content in Brassica parachinensis. Conclusively, Mo-biochar can slowly release Mo and improve the neutral environment for Mo bioavailability, which is an effective strategy to mitigate the high nitrate accumulation of vegetables planted in acidic soil. [Display omitted] • Mo-biochar enhancing nitrogen assimilation relies on increasing the plant Mo content. • The plant NO 3 − content of Mo-biochar was reduced by 42.9% compared to no Mo-biochar. • N and Mo use efficiency increased by Mo-biochar compared to Mo basal application. • Mo-biochar was beneficial to vegetable growth and quality. [ABSTRACT FROM AUTHOR]