The effects of water activity and the glass transition on the rate constants for glycine loss and brown pigment formation due to the Maillard reaction were evaluated in a model food system. Equimolar glucose and glycine were incorporated into amorphous polyvinylpyrrolidones of various molecular weights and moisture contents. Glycine loss and brown pigment formation were quantified during storage at 25°C. At constant water activity, rate constants were higher in systems with lower glass transition temperatures. Glycine rate constants decreased upon matrix collapse, but browning rate constants were not affected by collapse. Changes associated with the glass transition influence bimolecular reactions and should be considered during product formulation and shelf-life testing.

This study's objectives were to investigate the effects of buffer type and concentration on the kinetics of the Maillard reaction in low-moisture solids. Glucose loss and brown pigment formation were evaluated in low-moisture glassy systems obtained by lyophilizing solutions containing various concentrations of phosphate or citrate buffer at pH 7 and 25°C. Rate constants for glucose loss decreased as buffer concentration increased, suggesting that a change in the system pH had occurred. Rate constants for browning increased with increasing phosphate buffer concentration and decreased with increasing citrate concentration. Phosphate buffer appeared to catalyze later pathways of the Maillard reaction.

Research continues to differentiate the impact of water activity (a(W)) and the glass transition temperature (T(g)) on chemical reactions. Invertase with and without sucrose was incorporated into low and high molecular weight poly(vinylpyrrolidone) model systems (PVP-LMW and PVP-K30, respectively). Invertase activity and sucrose hydrolysis were monitored during storage at a(W) = 0.32-0.75 and 30 degrees C. Pseudo-first-order rate constants for activity loss in PVP-K30 were not different, regardless of the system being glassy or rubbery. In PVP-LMW, invertase stability decreased with increasing a(W). An a(W) > 0.62 was required for sucrose hydrolysis to occur in PVP-LMW. PVP molecular weight appeared to affect invertase stability and reactivity. No dramatic change around T(g) was found in either invertase stability or sucrose hydrolysis, suggesting that T(g)-dictated mobility has a minimal effect on these reactions in amorphous solids.

N6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myeloid leukemia (AML). Identification of the key regulators of m6A modifications in AML could provide further insights into AML biology and uncover more effective therapeutic strategies for AML patients. Here we report overexpression of YTHDF1, an m6A reader protein, in human AML samples at the protein level with enrichment in leukemia stem cells (LSCs). Whereas YTHDF1 was dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuated self-renewal, proliferation, and leukemic capacity of primary human and mouse AML cells in vitro and in vivo. Mechanistically, YTHDF1 promoted the translation of cyclin E2 in an m6A-dependent manner. Structure-based virtual screening of FDA-approved drugs identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocked the direct binding of YTHDF1 with m6A-modified mRNAs and inhibited YTHDF1-regulated cyclin E2 translation. Moreover, tegaserod reduced the viability of patient-derived AML cells in vitro and prolonged survival in patient-derived xenograft models. Together, our study defines YTHDF1 as an integral regulator of AML progression by regulating the expression of m6A-modified mRNAs, which might serve as a potential therapeutic target for AML.

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