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Hirshfeld surface analysis and density of states analysis found that cocrystal 3 had the highest strong interaction contribution and the closest electronic density, respectively, followed by cocrystal 2 and cocrystal 1, suggesting CAF could competitively form a cocrystal with MYR much more easily than QUE and BAI. Cocrystallization is a promising approach for green and effective separation of natural products with similar chemical structures.As cryo-EM approaches the physical resolution limits imposed by electron optics and radiation damage, it becomes increasingly urgent to address the issues that impede high-resolution structure determination of biological specimens. One of the persistent problems has been beam-induced movement, which occurs when the specimen is irradiated with high-energy electrons. Beam-induced movement results in image blurring and loss of high-resolution information. It is particularly severe for biological samples in unsupported thin films of vitreous water. By controlled devitrification of conventionally plunge-frozen samples, the suspended film of vitrified water was converted into cubic ice, a polycrystalline, mechanically stable solid. It is shown that compared with vitrified samples, devitrification reduces beam-induced movement in the first 5 e Å-2 of an exposure by a factor of ∼4, substantially enhancing the contribution of the initial, minimally damaged frames to a structure. A 3D apoferritin map reconstructed from the first frames of 20 000 particle images of devitrified samples resolved undamaged side chains. DC661 mw Devitrification of frozen-hydrated specimens helps to overcome beam-induced specimen motion in single-particle cryo-EM, as a further step towards realizing the full potential of cryo-EM for high-resolution structure determination.A synthetic strategy for the formation of stoichiometric quaternary and non-stoichiometric quinary solids is outlined. A series of 2-nitro-resorcinol-based quaternary cocrystals were developed from binary precursors in two conceptual stages. In the first stage, ternary solids are synthesized based on the structural inequivalence at two recognition sites in the binary. In the second stage, the ternary is homologated into a stoichiometric quaternary based on the same concept. Any cocrystal without an inequivalence becomes a synthetic dead end. The combinatorial approach involves lower cocrystal systems with different structural environments and preferred synthon selection from a synthon library in solution. Such are the stepping stones for the isolation of higher cocrystals. In addition, a quaternary cocrystal of 4,6-di-chloro-resorcinol is described wherein an unusual synthon is observed with two resorcinol molecules in a closed loop with two different ditopic bases. The concept of the virtual synthon in binaries with respect to isolated ternaries is validated for the 4,6-di-chloro-resorcinol system. It is possible that only some binary systems are amenable to homologation into higher cocrystals. The reasons for this could have to do with the existence of preferred synthon modules, in other words, the critical components of the putative higher assembly that cannot be altered. Addition of the third and fourth component might be more flexible, and the choices of these com-ponents, possible from a larger pool of chemically related molecules.The members of the avidin protein family are well known for their high affinity towards d-biotin and their structural stability. These properties make avidins a valuable tool for various biotechnological applications. In the present study, two avidin-like biotin-binding proteins (named streptavidin C1 and C2) from Streptomyces cinnamonensis were newly identified while exploring antifungal proteins against Fusarium oxysporum f. sp. cucumerinum. Streptavidin C1 reveals a low correlation (a sequence identity of approximately 64%) with all known streptavidins, whereas streptavidin C2 shares a sequence identity of approximately 94% with other streptavidins. Here, the crystal structures of streptavidin C1 in the mature form and in complex with biotin at 2.1 and 2.5 Å resolution, respectively, were assessed. The overall structures present similar tetrameric features with D2 symmetry to other (strept)avidin structures. Interestingly, the long C-terminal region comprises a short α-helix (C-Lid; residues 169-179) and an extension C-terminal peptide (ECP; residues 180-191) which stretches into the biotin-binding sites of the same monomer. This ECP sequence (-180VTSANPPAS188-) is a newly defined biotin-binding site, which reduces the ability to bind to (strept)avidin family proteins. The novel streptavidin C1 could help in the development of an engineered tetrameric streptavidin with reduced biotin-binding capacity as well as other biomaterial tools.Understanding the nucleation pathway and achieving regulation to produce the desired crystals are mutually beneficial. The authors previously proposed a nucleation pathway of conformational polymorphs in which solvation and solute self-assembly could affect the result of the conformational rearrangement and further nucleation outcomes. Based on this, herein α,ω-alkanedi-carb-oxy-lic acids (DAn, where n represents the number of carbon atoms in the molecule, n = 2-6, 8-11) were designed as homologous additives to interfere with the self-assembly of pimelic acid (DA7) to further induce the form II compound, which differs from form I only in conformation. Interestingly, longer-chain additives (DA6-11) have a stronger form II-inducing ability than short-chain ones (DA2-4). In addition, an apparent gradient of the degree of interference with solute self-assembly, consistent with form II-inducing ability, was detected by infrared and nuclear magnetic resonance spectroscopy. The calculated molecular electrostatic potential charges also clearly indicate that additive-solute electrostatic interactions gradually increase with increasing carbon chain length of the additives, reaching a maximum value with DA6-11. This novel use of additives demonstrates a direct link between solute aggregation and conformational polymorph nucleation.The production of diffraction-quality protein crystals is challenging and often requires bespoke, time-consuming and expensive strategies. A system has been developed in which the BCL6 BTB domain acts as a crystallization chaperone and promiscuous assembly block that may form the basis for affinity-capture crystallography. The protein of interest is expressed with a C-terminal tag that interacts with the BTB domain, and co-crystallization leads to its incorporation within a BTB-domain lattice. This strategy was used to solve the structure of the SH3 domain of human nebulin, a structure previously solved by NMR, at 1.56 Å resolution. This approach is simple and effective, requiring only routine protein complexation and crystallization screening, and should be applicable to a range of proteins.An algorithmic strategy to design stoichiometric quaternary and solid-solution quinary solids is described. The strategy involves recognition of structural inequivalences to generate ternary and quaternary cocrystals which can then be extended to five-component solid solutions through matching of suitable interactions.The new approach of Dittrich [IUCrJ (2021). 8, 305-318] towards describing, understanding and modelling disorders is discussed.What is 'structure' in the context of a molecular solid?
The global impact of the COVID-19 pandemic has disproportionately affected some communities and populations more than others. We propose that an interdisciplinary framework of 'One Health Disparities' advances understanding of the social and systemic issues that drive COVID-19 in vulnerable populations. One Health Disparities integrates the social environment with One Health perspectives on the interconnectedness of human, animal, and environmental health. To apply this framework, we consider One Health Disparities that emerge in three key components of disease transmission exposure, susceptibility, and disease expression. Exposure disparities arise through variation in contact with COVID-19's causative agent, SARS-CoV-2. Disparities in susceptibility and disease expression also exist; these are driven by biological and social factors, such as diabetes and obesity, and through variation in access to healthcare. We close by considering how One Health Disparities informs understanding of spillback into new animal reservoirs, and what this might mean for further human health disparities.

One Health focuses on interconnections between human, animal, and environmental health. We propose that social environments are also important to One Health and help illuminate disparities in the coronavirus pandemic, including its origins, transmission and susceptibility among humans, and spillback to other species. We call this framework One Health Disparities.
One Health focuses on interconnections between human, animal, and environmental health. We propose that social environments are also important to One Health and help illuminate disparities in the coronavirus pandemic, including its origins, transmission and susceptibility among humans, and spillback to other species. We call this framework One Health Disparities.
Despite having numerous physiological benefits, toxicological assessment of green coffee beans is sparce. Here, we document the oral acute and sub-chronic toxicity of a standardized decaffeinated green coffee bean extract containing 50% chlorogenic acids (CGA-7™) in rats.

We have performed a limit test at single oral dose of 2000 mg/kg to evaluate the acute toxicity in female Wistar rats. Furthermore, repeated dose 90-day toxicity study was conducted to assess the risk of long-term use of CGA-7.

A 14-day observation revealed no clinical signs of toxicity or mortality in animals at 2000 mg/kg acute oral dose of CGA-7. The administration of 250, 500, and 1000 mg/kg CGA-7 showed significant alterations in some parameters such as food consumption, relative organ weights of brain and spleen, haematological and biochemical parameters compared to control. These changes were not consistent and dose-dependent throughout the study. Furthermore, the changes were within the physiological range and toxicologically insignificant. CGA-7 did not affect the normal metabolism and physiology of the animals up to 1000 mg/kg dose. Macroscopic and histological examination of organs did not reveal any organ toxicity.

Finally, the findings from this study suggest the safety of green coffee bean extract.
Finally, the findings from this study suggest the safety of green coffee bean extract.
Genetic and epigenetic mechanisms regulate antimicrobial immunity against
(Mtb) infection.

The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages.

The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in fluorescence
hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR-874-3p, as shown by bioinformatics, dual-luciferase reporter gene analysis and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3'-untranslated region (UTR) in Mtb-infected macrophages and thus promoting intracellular Mtb growth.
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