α-Glucosidase, α-amylase inhibition kinetics,in vitro gastro-intestinal digestion,and apoptosis inducing abilities of Ficus microcarpa L. f. and Ficus racemosa L. fruit polysaccharides

Food Science and Biotechnology - A rich source of nutrients, figs have a number of clinically validated benefits. This study aimed to evaluate the in vitro simulated gastrointestinal digestion, and...     

Description of the thermodynamic properties and fluid-phase behavior of aqueous solutions of linear,branched, and cyclic amines

The SAFT-γ Mie group-contribution equation of state is used to represent the fluid-phase behavior of aqueous solutions of a variety of linear, branched, and cyclic amines. New group interactions are developed in order to model the mixtures of interest, including the like and unlike interactions between alkyl primary, secondary, and tertiary amine groups (NH₂, NH, N), cyclic secondary and tertiary amine groups (cNH, cN), and cyclic methine-amine groups (cCHNH, cCHN) with water (H₂O). The group-interaction parameters are estimated from appropriate experimental thermodynamic data for pure amines and selected mixtures. By taking advantage of the group-contribution nature of the method, one can describe the fluid-phase behavior of mixtures of molecules comprising those groups over broad ranges of temperature, pressure, and composition. A number of aqueous solutions of amines are studied including linear, branched aliphatic, and cyclic amines. Liquid–liquid equilibria (LLE) bounded by lower critical solution temperatures (LCSTs) have been reported experimentally and are reproduced here with the SAFT-γ Mie approach. The main feature of the approach is the ability not only to represent accurately the experimental data employed in the parameter estimation, but also to predict the vapor–liquid, liquid–liquid, and vapor–liquid–liquid equilibria, and LCSTs with the same set of parameters. Pure compound and binary phase diagrams of diverse types of amines and their aqueous solutions are assessed in order to demonstrate the main features of the thermodynamic and fluid-phase behavior.     

Regulatory RNAs: A Universal Language for Inter-Domain Communication

In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not produce miRNAs themselves, and therefore it is unclear how these eukaryotic RNA molecules could function in the bacterial recipient. In this review, we compare and contrast the biogenesis and functions of regulatory RNAs in eukaryotes and bacteria. As a result, we discovered several conserved features and homologous components in these distinct pathways. These findings enabled us to propose novel mechanisms to explain how eukaryotic miRNAs could function in bacteria. Further understanding in this area is necessary to validate the findings of existing studies and could facilitate the use of miRNAs as novel tools for the directed remodelling of the human microbiota.     

Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Indoor heterogeneous photochemistry of furfural drives emissions of nitrous acid

People spend approximately 80% of their time indoor, making the understanding of the indoor chemistry an important task for safety. The high surface-area-to-volume ratio characteristic of indoor environments leads the semi-volatile organic compounds (sVOCs) to deposit on the surfaces. Using a long path absorption photometer (LOPAP), this work investigates the formation of nitrous acid (HONO) through the photochemistry of adsorbed nitrate anions and its enhancement by the presence of furfural. Using a high-resolution proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS), this work also investigates the surface emissions of VOCs from irradiated films of furfural and a mix of furfural and nitrate anions. Among the emitted VOCs, 2(5H)-furanone/2-Butenedial was observed at high concentrations, leading to maleic anhydride formation after UV irradiation. Moreover, the addition of potassium nitrate to the film formed NO_x and HONO concentrations up to 10 ppb, which scales to ca. 4 ppb for realistic indoor conditions. This work helps to understand the high levels of HONO and NO_x measured indoors.     

COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

Food recognition using neural network classifier and multiple hypotheses image segmentation

ABSTRACT

This paper proposes the multiple-hypotheses image segmentation and feed-forward neural network classifier for food recognition to improve the performance. Initially, the food or meal image is given as input. Then, the segmentation is applied to identify the regions, where a particular food item is located using salient region detection, multi-scale segmentation, and fast rejection. Then, the features of every food item are extracted by the global feature and local feature extraction. After the features are obtained, the classification is performed for each segmented region using a feed-forward neural network model. Finally, the calorie value is computed with the aid of (i) food volume and (ii) calorie and nutrition measure based on mass value. The experimental results and performance evaluation are validated. The outcome of the proposed method attains 0.947 for Macro Average Accuracy (MAA) and 0.959 for Standard Accuracy (SA), which provides better classification performance.