Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPɛ, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy.
The biomechanics stress and chronic inflammation in obesity are causally linked to osteoarthritis. However, the metabolic factors mediating obesity-related osteoarthritis are still obscure. Here we scanned and identified at least two elevated metabolites (stearic acid and lactate) from the plasma of diet-induced obese mice. We found that stearic acid potentiated LDH-a-dependent production of lactate, which further stabilized HIF1α protein and increased VEGF and proinflammatory cytokine expression in primary mouse chondrocytes. Treatment with LDH-a and HIF1α inhibitors notably attenuated stearic acid-or high fat diet-stimulated proinflammatory cytokine production in vitro and in vivo. Furthermore, positive correlation of plasma lactate, cartilage HIF1α and cytokine levels with the body mass index was observed in subjects with osteoarthritis. In conclusion, saturated free fatty acid induced proinflammatory cytokine production partly through activation of a novel lactate-HIF1α pathway in chondrocytes. Our findings hold promise of developing novel clinical strategies for the management of obesity-related diseases such as osteoarthritis.
Ligands binding to all-inorganic lead halide perovskite nanocrystals (IPNCs) are easy to detach from the surface through proton exchange, causing severe stability issues in practical applications. Here, we have reported an amineand acid-free approach for the synthesis of CsPbBr 3 IPNC with highly improved photochemical stability. The reaction mechanism follows a trioctylphosphinemediated surface passivation route, which provides a proton-free reaction environment to stabilize the ligand capping on the surface of IPNCs. Nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy characterizations reveal that the IPNCs possess a lead-rich surface passivated by carboxylates. The surface capping motif endows IPNCs with comprehensively improved stability against air, water, light, and heat. The IPNCs withstand exposure to ethanol in room light for 30 days and show nearly no fluorescent quenching. More importantly, the IPNCs present high resistance to intense light irradiation. Under continuous irradiation by 10 W/cm 2 blue light in open air, the lifetime of the IPNCs reaches over 2000 h, catching up the photostability of CdSe QDs. The white LEDs based on the IPNCs display a wide color gamut of 122% NTSC and luminous efficacy of 71 lm/W.
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