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Compound fermented seasonings were increasingly favored by consumers. This study using Aspergillus oryzae and soybeans as raw materials to make koji. Lactobacillus plantarum and Pediococcus pentosaceus were used as starters for common fermentation with mature koji and beef to obtain a fermented beef-soybean paste. The physicochemical parameters, volatile flavor compounds, and microbial community of beef-soybean paste during fermentation were determined, and the relationship between flavor changes and microbial community changes was analyzed. Compared to the soybean paste, the addition of beef for fermentation can significantly enhanced the content of protein, amino acid nitrogen, and free amino acids in the compound fermented soybean paste, improved the nutritional and health value of the product. The addition of beef also caused a decrease in pH and total acid content in the compound soybean paste. The flavor changed during the fermentation process of beef-soybean paste were related to the changed in its microbial community. [ABSTRACT FROM AUTHOR]

Aiming to address the multi-objective cooperative optimization problem of ship structure lightweight and crashed-resistance, this study proposed a concave reentrant honeycomb-based negative Poisson's ratio (NPR) sandwich structure to replace the stiffened plate. The feasibility of using the sandwich structure to improve ship crashworthiness is demonstrated through finite element analysis. An intelligent optimization method is established to address the issues of multiple parameters and complex effects associated with composite structures and optimize the crashworthiness of the sandwich structure. The effectiveness of the optimization method and the feasibility of the NPR sandwich structure in ship crashworthiness have been validated, providing a reference for the design of new multi-functional ship structures. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using MR: BiRatio and BiLIML, which are extensions of the standard ratio, and limited information maximum likelihood (LIML) methods, respectively. We compared the performance of the two proposed methods with the naive application of UMR methods through extensive simulations of several scenarios involving varying numbers of strong and weak IVs. Our simulation results showed that when multiple strong IVs are used, the proposed methods provided accurate bidirectional causal effect estimation in terms of median absolute bias and relative median absolute bias. Furthermore, compared to the BiRatio method, the BiLIML method provided a more accurate estimation of causal effects when weak IVs were used. Therefore, based on our simulations, we concluded that the BiLIML should be used for bidirectional causal effect estimation. We applied the proposed methods to investigate the potential bidirectional relationship between obesity and diabetes using the data from the Multi-Ethnic Study of Atherosclerosis cohort. We used body mass index (BMI) and fasting glucose (FG) as measures of obesity and type 2 diabetes, respectively. Our results from the BiLIML method revealed the bidirectional causal relationship between BMI and FG in across all racial populations. Specifically, in the White/Caucasian population, a 1 kg/m2 increase in BMI increased FG by 0.70 mg/dL (95% confidence interval [CI]: 0.3517–1.0489; p = 8.43×10−5), and 1 mg/dL increase in FG increased BMI by 0.10 kg/m2 (95% CI: 0.0441–0.1640; p = 6.79×10−4). Our study provides novel findings and quantifies the effect sizes of the bidirectional causal relationship between BMI and FG. However, further studies are needed to understand the biological and functional mechanisms underlying the bidirectional pathway. [ABSTRACT FROM AUTHOR]

Background: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients. Aim: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients. Methods: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared. Results: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2–5) and 793 were without PD (baseline mRS 0–1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS. Conclusion: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm. [ABSTRACT FROM AUTHOR]

Chlorogenic acid (CA), gallic acid (GA), and resveratrol (RES) were added to a gelatin (GEL)-chitosan (CHI)-glycerol (GLY) edible coating, and their effects on the coating of fresh beef preservation were investigated. The results revealed that CA had the most significant improvement effect on fresh beef preservation. The combination of GEL-CHI-GLY-CA preserved the color of the beef better and delayed the increase of the total volatile base nitrogen, even though its total phenolic content decreased at a faster rate during beef preservation. GA also improved the preservation effect as on the 12th day of storage, the beef samples treated with GEL-CHI-GLY-GA had the lowest thiobarbituric acid reactive substances (0.76 mg Malondialdehyde (MDA)/kg) and total viable count (6.0 log cfu/g). On the whole, though RES showed an improvement on beef preservation, the improvement was not as good as the other two polyphenols. After 12 days of storage, the beef samples treated with GEL-CHI-GLY-RES had a higher pH value (6.25) than the other two polyphenol treatmed groups. Overall, the three polyphenol-added combinations increased the shelf life of beef by approximately 3–6 days compared to the control group (treated GEL-CHI-GLY with distilled water). [ABSTRACT FROM AUTHOR]

In order to explore the processing and application potential of Chinese yam starch, nine kinds of Chinese yam starch (GY11, GY5, GY2, GXPY, LCY, SFY, MPY, SYPY, ASY) from South China were collected and characterized. The chemical composition, rheological properties, thermal properties, and in vitro starch digestion were compared, and the correlation between the structure and processing properties of these yam starches was analyzed using Pearson correlation. The results show that GY2 had the highest amylose content of 28.70%. All the yam starches were similarly elliptical, and all the yam starch gels showed pseudoplastic behavior. Yam starches showed similar pasting temperatures and resistant starch content, but SYPY showed the largest particle size (28.4 μm), SFY showed the highest setback (2712.33 cp), and LCY showed the highest peak viscosity (6145.67 cp) and breakdown (2672.33 cp). In addition, these yam starches also showed different crystal types (A-type, B-type, C-type), relative crystallinity (26.54–31.48%), the ratios of 1045/1022 cm−1 (0.836–1.213), pasting properties, and rheological properties, so the yam starches have different application potentials. The rheological and pasting properties were related to the structural properties of starch, such as DI, Mw, and particle size, and were also closely related to the thermodynamic properties. The appropriate processing methods and purposes of the processed products of these yam starches can be selected according to their characteristics. [ABSTRACT FROM AUTHOR]

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Motivation Quaternary structure determination for transmembrane/soluble proteins requires a reliable computational protocol that leverages observed distance restraints and/or cyclic symmetry (C n symmetry) found in most homo-oligomeric transmembrane proteins. Results We survey 118 X-ray crystallographically solved structures of homo-oligomeric transmembrane proteins (HoTPs) and find that ∼97% are C n symmetric. Given the prevalence of C n symmetric HoTPs and the benefits of incorporating geometry restraints in aiding quaternary structure determination, we introduce two new filters, the distance-restraints (DR) and the Symmetry-Imposed Packing (SIP) filters. SIP relies on a new method that can rebuild the closest ideal C n symmetric complex from docking poses containing a homo-dimer without prior knowledge of the number (n) of monomers. Using only the geometrical filter, SIP, near-native poses of 7 HoTPs in their monomeric states can be correctly identified in the top-10 for 71% of all cases, or 29% among 31 HoTP structures obtained through homology modeling, while ZDOCK alone returns 14 and 3%, respectively. When the n is given, the optional n -mer filter is applied with SIP and returns the near-native poses for 76% of the test set within the top-10, outperforming M-ZDOCK's 55% and Sam's 47%. While applying only SIP to three HoTPs that comes with distance restraints, we found the near-native poses were ranked 1st, 1st and 10th among 54 000 possible decoys. The results are further improved to 1st, 1st and 3rd when both DR and SIP filters are used. By applying only DR, a soluble system with distance restraints is recovered at the 1st-ranked pose. Availability and implementation https://github.com/capslockwizard/drsip. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Superagonist diabetogenic peptides: Type 1 diabetes is an autoimmune disease triggered, in part, by activation of CD4+ T cells specific for insulin-derived autoantigens. Wang et al. prepared ternary complexes of diabetogenic T cell receptors attached to ligands formed by binding of insulin B-chain peptides to mouse or human MHC class II proteins known to be associated with genetic susceptibility to diabetes. Structural and functional analyses revealed that fusion peptides featuring covalent linkage of the C terminus of an insulin B-chain peptide to specific fragments of insulin C-peptide were highly potent ligands, enabling avid binding of both mouse and human TCRs. These findings point to transpeptidation reactions in lysosomes as a potential source of superagonist chimeric insulin peptides with an important driver role in autoimmune diabetes. In type 1 diabetes (T1D), proinsulin is a major autoantigen and the insulin B:9-23 peptide contains epitopes for CD4+ T cells in both mice and humans. This peptide requires carboxyl-terminal mutations for uniform binding in the proper position within the mouse IAg7 or human DQ8 major histocompatibility complex (MHC) class II (MHCII) peptide grooves and for strong CD4+ T cell stimulation. Here, we present crystal structures showing how these mutations control CD4+ T cell receptor (TCR) binding to these MHCII-peptide complexes. Our data reveal stricking similarities between mouse and human CD4+ TCRs in their interactions with these ligands. We also show how fusions between fragments of B:9-23 and of proinsulin C-peptide create chimeric peptides with activities as strong or stronger than the mutated insulin peptides. We propose transpeptidation in the lysosome as a mechanism that could accomplish these fusions in vivo, similar to the creation of fused peptide epitopes for MHCI presentation shown to occur by transpeptidation in the proteasome. Were this mechanism limited to the pancreas and absent in the thymus, it could provide an explanation for how diabetogenic T cells escape negative selection during development but find their modified target antigens in the pancreas to cause T1D. [ABSTRACT FROM AUTHOR]

Ca2+-binding human S100A1 protein is a type of S100 protein. S100A1 is a significant mediator during inflammation when Ca2+ binds to its EF-hand motifs. Receptors for advanced glycation end products (RAGE) correspond to 5 domains: the cytoplasmic, transmembrane, C2, C1, and V domains. The V domain of RAGE is one of the most important target proteins for S100A1. It binds to the hydrophobic surface and triggers signaling transduction cascades that induce cell growth, cell proliferation, and tumorigenesis. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the interaction between S100A1 and the RAGE V domain. We found that S100B could interact with S100A1 via NMR 1H-15N HSQC titrations. We used the HADDOCK program to generate the following two binary complexes based on the NMR titration results: S100A1-RAGE V domain and S100A1-S100B. After overlapping these two complex structures, we found that S100B plays a crucial role in blocking the interaction site between RAGE V domain and S100A1. A cell proliferation assay WST-1 also supported our results. This report could potentially be useful for new protein development for cancer treatment. [ABSTRACT FROM AUTHOR]