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MgtE is a Mg 2+-selective channel regulated by the intracellular Mg 2+ concentration. MgtE family proteins are highly conserved in all domains of life and contribute to cellular Mg 2+ homeostasis. In humans, mutations in the SLC41 proteins, the eukaryotic counterparts of the bacterial MgtE, are known to be associated with various diseases. The first MgtE structure from a thermophilic bacterium, Thermus thermophilus, revealed that MgtE forms a homodimer consisting of transmembrane and cytoplasmic domains with a plug helix connecting the two and that the cytoplasmic domain possesses multiple Mg 2+ binding sites. Structural and electrophysiological analyses revealed that the dissociation of Mg 2+ ions from the cytoplasmic domain induces structural changes in the cytoplasmic domain, leading to channel opening. Thus, previous works showed the importance of MgtE cytoplasmic Mg 2+ binding sites. Nevertheless, due to the limited structural information on MgtE from different species, the conservation and diversity of the cytoplasmic Mg 2+ binding site in MgtE family proteins remain unclear. Here, we report crystal structures of the Mg 2+-bound MgtE cytoplasmic domains from two different bacterial species, Chryseobacterium hispalense and Clostridiales bacterium, and identify multiple Mg 2+ binding sites, including ones that were not observed in the previous MgtE structure. These structures reveal the conservation and diversity of the cytoplasmic Mg 2+ binding site in the MgtE family proteins.

Summary: High‐fat‐and‐fructose diet (HFFD) is one of the causes of hyperlipidaemia (HLP), which could directly cause serious diseases that are harmful to human health. The phenolic composition of stevia extract (WeiKe) and its effect of different concentrations on glucose–lipid metabolism, oxidative stress, and intestinal microecology in hyperlipidaemia mice were investigated. The results showed that WeiKe could effectively inhibit the increase in body weight and blood glucose levels and regulate lipid metabolism. WeiKe repaired the gut morphology, promoted short‐chain fatty acid (SCFA) production, and improved food digestion and absorption. Furthermore, WeiKe reduced the Firmicutes/Bacteroidetes ratio and increased the relative abundance of Lactobacillus. These results suggested that stevia extract had a potential modulatory effect on HFFD‐induced HLP. [ABSTRACT FROM AUTHOR]

This study aims to establish a mechanistic model of using inherent safety and health concepts to conduct industrial workplace risk reduction strategies during the project planning stage. Accordingly, a dedicated implementation tool termed inherently safer and healthier design model for industrial workplaces (ISHDM‐IW) is developed. First, the safety and health by design checklist is adapted to derive industrial workplace safety and health risk indicators. Then, the risk indicators are rated and weighted using the methods of risk matrix and precedence chart. Subsequently, the risk indicators are aggregated via fuzzy risk representation with the indicators' risk values and weights. Last, the inherent safety and health principles are used to do risk‐based baseline design optimization. The case study demonstrates the capabilities of the proposed ISHDM‐IW to upgrade the workplace design scheme from risk level II to risk level I, thus generating a more satisfactory workplace design alternative. The proposed ISHDM‐IW offers a novel design mechanism of inherent safety and health for industrial workplaces, which can be expected to ensure employees' safety, health, and well‐being with fundamentally better ergonomics of industrial work environments. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase transition (LLPT) is the transformation of a liquid from one distinctive structure to another with the same composition. However, the origin of the structural variation at LLPT is still controversial. Here, we used ab initio molecular dynamics simulation to verify and investigate a high-temperature LLPT in a Pd40Ni40P20 melt; this melt showed a reduction in the nuclei interference of the conventional low-temperature LLPT. An abnormal endothermic LLPT was confirmed with flash differential scanning calorimetry, indicating a change in the atomic short-range-order structure around the P–P bond and a decrease in the number of specific icosahedral-like clusters, such as ⟨0 2 8 0⟩ and ⟨0 2 8 1⟩. The structural change of the P-centered clusters changed the solidification path through potential energy adjustments. Our results showed the structural mechanism of the unusual endothermic phenomenon and provided a different insight into regulating the properties of metallic glasses. [ABSTRACT FROM AUTHOR]

Aim: Tyrosine decarboxylase (TDC) presented in the gut‐associated strain Enterococcus faecalis can convert levodopa (L‐dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L‐dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria‐mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L‐dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L‐dopa on Parkinson's disease (PD). Methods: Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis. Then, the inhibitory effects of PIP on L‐dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L‐dopa and PIP on 6‐hydroxydopamine (6‐OHDA)‐lesioned rats and tested the regulations of L‐dopa bioavailability and brain DA level by pharmacokinetics study and MALDI‐MS imaging. Finally, we evaluated the microbiota‐dependent improvement effect of PIP on L‐dopa availability using pseudo‐germ‐free and E. faecalis‐transplanted rats. Results: We found that PIP combined with L‐dopa could better ameliorate the move disorders of 6‐OHDA‐lesioned rats by remarkably improving L‐dopa availability and brain DA level than L‐dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L‐dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6‐OHDA‐lesioned rats. Conclusion: Oral administration of L‐dopa combined with PIP can improve L‐dopa availability and brain DA level in 6‐OHDA‐lesioned rats by suppressing intestinal bacterial TDC. [ABSTRACT FROM AUTHOR]

Abnormally expressed miRNAs have been employed as crucial indicators for the diagnosis and prognosis of disease. It is essential to develop quick, affordable, accurate, and multiplexed methods for miRNA detection. In this study, polyethylene glycol (PEG) hydrogel microparticles were used as solid-phase carriers for the hybridization chain reaction (HCR) in combination with cation-exchange fluorescence amplification, thus enabling the development of a new method for miRNA determination. The assay was sensitive with the detection limit for miRNA let7a equal to 46 pM. The assay was specific, the base-mismatched sequences of miRNA let7a were distinguished, and the serum matrix did not cause any interference. Moreover, by integration with a microfluidic chip, the throughput was significantly enhanced and the process was noticeably simplified. With further development, the developed method may be suitable for practical clinical analysis. [ABSTRACT FROM AUTHOR]