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YH12852 increased the average weekly frequency of spontaneous bowel movements and loosened the stool. In addition, YH12852 increased quality of life satisfaction, and decreased severity of constipation symptom and GI symptoms. YH12852 was safe and well-tolerated up to 3 mg and showed nearly dose proportional PKs. In conclusion, YH12852 was safe and enhanced GI motility. YH12852 can be developed as an effective treatment option for GI motility disorders, including functional constipation. Further studies are warranted to confirm this possibility.

Xanthomonas axonopodis pv. glycines (Xag) is a hazardous pathogen able to cause bacterial pustule disease in soybean, reducing crop yield and quality. Although flavonoids rutin and genistein are known to play an important role in soybean defence, soybean is only able to produce Biochanin A in low concentration.

In this work, Biochanin A was found to produce higher antibacterial activity against Xag in comparison with genistein (minimum inhibitory concentration < 100 μg/mL). Biochanin A was able to inhibit DNA synthesis and flagella formation in Xag, and altered the composition of the bacterial membrane. These effects reduced swimming motility, extracellular protease activity and biofilm formation. Further, Biochanin A was tested for the control of Xag in soybean leaves, showing similar, or even higher, inhibitory ability in comparison with some products commonly used for the control of this pathogen.

The antibacterial properties of Biochanin A against Xag have been studied for the first time, revealing new insights on the potential applications of this isoflavonoid for the management of bacterial pustule disease. © 2020 Society of Chemical Industry.

The antibacterial properties of Biochanin A against Xag have been studied for the first time, revealing new insights on the potential applications of this isoflavonoid for the management of bacterial pustule disease. © 2020 Society of Chemical Industry.Sjögren's syndrome (SS) is an autoimmune disease with no effective treatment options. Resolvin D1 (RvD1) belongs to a class of lipid-based specialized pro-resolving mediators that showed efficacy in preclinical models of SS. We developed a physiologically-based pharmacokinetic (PBPK) model of RvD1 in mice and optimized the model using plasma and salivary gland pharmacokinetic (PK) studies performed in NOD/ShiLtJ mice with SS-like features. The predictive performance of the PBPK model was also evaluated with two external datasets from the literature reporting RvD1 PKs. The PBPK model adequately captured the observed concentrations of RvD1 administered at different doses and in different species. The PKs of RvD1 in virtual humans were predicted using the verified PBPK model at various doses (0.01-10 mg/kg). The first-in-human predictions of RvD1 will be useful for the clinical trial design and translation of RvD1 as an effective treatment strategy for SS.The current diagnosis of Parkinson's disease (PD) mostly relies on clinical rating scales related to motor dysfunction. Given that clinical symptoms of PD appear after significant neuronal cell death in the brain, it is required to identify accessible, objective, and quantifiable biomarkers for early diagnosis of PD. In this study, a total of 20 patients with idiopathic PD and 20 age-matched patients with essential tremor according to the UK Brain Bank Criteria were consecutively enrolled to identify peripheral blood biomarkers for PD. Clinical data were obtained by clinical survey and assessment. Using albumin-depleted and immunoglobulin G-depleted plasma samples, we performed immunoblot analysis of seven autophagy-related proteins and compared the levels of proteins to those of the control group. We also analyzed the correlation between the levels of candidate proteins and clinical characteristics. Finally, we validated our biomarker models using receiver operating characteristic curve analysis. We found that the levels of BCL2-associated athanogene 2 (BAG2) and cathepsin D were significantly decreased in plasma of patients with PD (P = 0.009 and P = 0.0077, respectively). The level of BAG2 in patients with PD was significantly correlated with Cross-Culture Smell Identification Test score, which indicates olfactory dysfunction. We found that our biomarker model distinguishes PD with 87.5% diagnostic accuracy (area under the curve (AUC) = 0.875, P less then 0.0001). Our result suggests BAG2 and cathepsin D as candidates for early-diagnosis plasma biomarkers for PD. selleck products We provide the possibility of plasma biomarkers related to the autophagy pathway, by which decreased levels of BAG2 and cathepsin D might lead to dysfunction of autophagy.Neonicotinoids are selective modulators of insect nicotinic acetylcholine receptors (nAChRs). These widely deployed insecticides interact with the orthosteric sites of nAChRs, not only to activate nAChRs on their own, but also to block the desensitizing component of nAChR responses. To date recombinant vertebrate or insect/vertebrate hybrid nAChRs have been deployed to understand the mechanism of selectivity and diversity of neonicotinoid actions as well as to show that both α/α and α/non-α interfaces are involved in the interactions with neonicotinoids. However, many of the fine details of insecticide interactions with sites on nAChRs remain to be resolved. The breakthrough of functional expression of insect nAChRs allows such questions to be addressed, not only for neonicotinoids but for other insecticides targeting insect nAChRs. © 2020 Society of Chemical Industry.Uncoupling protein 1 (UCP1) is found in the inner mitochondrial membrane of brown adipocytes. In the presence of long-chain fatty acids (LCFAs), UCP1 increases the proton conductance, which, in turn, increases fatty acid oxidation and energy release as heat. Atomic models of UCP1 and UCP2 have been generated based on the NMR backbone structure of UCP2 in dodecylphosphocholine (DPC), a detergent known to inactivate UCP1. Based on NMR titration experiments on UCP1 with LCFA, it has been proposed that K56 and K269 are crucial for LCFA binding and UCP1 activation. Given the numerous controversies on the use of DPC for structure-function analyses of membrane proteins, we revisited those UCP1 mutants in a more physiological context by expressing them in the mitochondria of Saccharomyces cerevisiae. Mitochondrial respiration, assayed on permeabilized spheroplasts, enables the determination of UCP1 activation and inhibition. The K56S, K269S, and K56S/K269S mutants did not display any default in activation, which shows that the NMR titration experiments in DPC detergent are not relevant to UCP1 function.