Type IV galactosemia is a recently discovered inherited metabolic disease. It is caused by mutations in the GALM gene which result in reduced activity of the enzyme galactose mutarotase. This enzyme catalyses the interconversion of the α- and β-anomers of d-galactose and some other monosaccharides. Human galactose mutarotase is monomeric and its structure is largely composed of β-sheets. The catalytic mechanism requires a histidine residue acting as an acid, and a glutamate acting as a base. Together, these residues open the pyranose ring of d-galactose enabling free rotation of the bond between the first two carbon atoms in the monosaccharide. This can cause reversal of the configuration of the hydroxyl group attached to carbon 1. Type IV galactosemia manifests with similar symptoms to type II galactosemia (galactokinase deficiency), i.e. early onset cataracts. However, as a recently discovered disease, the longer-term consequences are unknown. The physiological role, if any, of galactose mutarotase's reactions with other monosaccharides are not yet known. The possible associations with other proteins also require further investigation.Hydroxychavicol (HC), found abundantly in Piper betle leaves is credited with antimicrobial property. Selleckchem Zasocitinib Previously we had shown HC induces reactive oxygen species mediated DNA damage in bacterial cells. HC also resulted in membrane compromise revealing its pleiotropic effects on cellular targets. The kinetics and exact sequence of events leading to inhibition of growth and cell death in E. coli after HC treatment remains poorly understood. We show that sub-lethal concentration (125 μg/mL) of HC causes cellular filamentation within 1 h of treatment, while a higher concentration (750 μg/mL) induces cell breakage. HC-treated cells were found to experience oxidative stress as early as 10 min, while evidence of membrane damage was apparent at 30 min. DNA damage repair genes were found to be activated at 60 min. Interestingly, HC-induced cell permeabilization was inhibited and enhanced by external Mg2+ and EDTA, respectively, suggesting that HC damages the outer membrane. Kinetic experiments revealed that HC-treated cells underwent oxidative stress, membrane damage and DNA damage in that order. Because gram negative bacteria such as E. coli are refractory to several antibiotics due to the presence of the outer membrane, we hypothesized that HC pretreatment would sensitize E. coli to hydrophobic antibiotics. Our study reveals for the first time that HC could sensitize bacteria to clinically used antibiotics due to its outer membrane damaging property.There is increasing evidence that ACE2 gene polymorphism can modulate the interaction between ACE2 and the SARS-CoV-2 spike protein affecting the viral entry into the host cell, and/or contribute to lung and systemic damage in COVID-19. Here we used in silico molecular docking to predict the effects of ACE2 missense variants on the interaction with the spike protein of SARS-CoV-2. HDOCK and FireDock simulations identified 6 ACE2 missense variants (I21T, A25T, K26R, E37K, T55A, E75G) with higher affinity for SARS-CoV-2 Spike protein receptor binding domain (RBD) with respect to wild type ACE2, and 11 variants (I21V, E23K, K26E, T27A, E35K, S43R, Y50F, N51D, N58H, K68E, M82I) with lower affinity. This result supports the hypothesis that ACE2 genetic background may represent the first "genetic gateway" during the disease progression.The pore size distribution of konjac glucomannan (KGM)-based aerogels seriously impacted the air filtration efficiency and filtration resistance. This study aimed to investigate the pore size distribution control of KGM-based aerogels through total solid concentration of the sol and to improve the filtration performance by preparing aerogel stacks, which were made by combining KGM-based aerogels with different pore size distribution (range 0-180 μm). Results indicated that with increased total solid concentration from 50% to 100% of the origin formulae, aerogel pore size became smaller and the porosity was decreased for all the three sample formulae. Meanwhile, the aerogel mechanical property and filtration efficiency were both strengthened with increased total solid concentration, but the air resistance became significantly higher. The changing extent and rule were influenced by the sample components (KGM, starch, gelatin, wheat straw). The aerogel stacks prepared by in series combining the aerogel pieces with different pore size distribution (from large size to small size) was found to improve filtration efficiency (e.g. from 70% to 80% for K1G2S4WS2) and significantly lower the air resistance (e.g. from 270 Pa to 190 Pa for K1G2S4WS2). This study could guide the filtration performance improvement of aerogels.It is urgent the transition from a fossil fuel-based economy to a sustainable bioeconomy based on bioconversion technologies using renewable plant biomass feedstocks to produce high chemicals, bioplastics, and biofuels. β-Glucosidases are key enzymes responsible for degrading the plant cell wall polymers, as they cleave glucan-based oligo- and polysaccharides to generate glucose. Monosaccharide-tolerant or -stimulated β-glucosidases have been reported in the past decade. Here, we describe a novel mechanism of β-glucosidase stimulation by glucose and xylose. The glycoside hydrolase 1 family β-glucosidase from Thermotoga petrophila (TpBgl1) displays a typical glucose stimulation mechanism based on an increased Vmax and decreased Km in response to glucose. Through molecular docking and dynamics analyses, we mapped putative monosaccharide binding regions (BRs) on the surface of TpBgl1. Our results indicate that after interaction with glucose or xylose at BR1 site, an adjacent loop region assumes an extended conformation, which increases the entrance to the TpBgl1 active site, improving product formation. Biochemical assays with TpBgl1 BR1 mutants, TpBgl1D49A/Y410A and TpBgl1D49K/Y410H, resulted in decreasing and abolishing monosaccharide stimulation, respectively. These mutations also impaired the BR1 looping extension responsible for monosaccharide stimulation. This study provides a molecular basis for the rational design of β-glucosidases for biotechnological applications.