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Abstract Refractory multi-principal-element alloys (RMPEAs) exhibit high specific strength at elevated temperatures (T). However, current RMPEAs lack a balance of room-temperature (RT) ductility, high-T strength, and high-T creep resistance. Using density-functional theory methods, we scanned composition space using four criteria: (1) formation energies for operational stability: $$-150\le {E}_{{\rm {f}}}$$ − 150 ≤ E f ≤ +70 meV per atom; (2) higher strength found via interstitial electron density with Young’s moduli E > 250 GPa; (3) inverse Pugh ratio for ductility: G/B 2500 °C. Using rapid bulk alloy synthesis and characterization, we validated theory and down-selected promising alloy compositions and discovered Mo72.3W12.8Ta10.0Ti2.5Zr2.5 having well-balanced RT and high-T mechanical properties. This alloy has comparable high-T compressive strength to well-known MoNbTaW but is more ductile and more creep resistant. It is also superior to a commercial Mo-based refractory alloy and a nickel-based superalloy (Haynes-282) with improved high-T tensile strength and creep resistance.

Abstract Emerging evidence suggests that plant-based fiber-rich diets improve ageing-associated health by fostering a healthier gut microbiome and microbial metabolites. However, such effects and mechanisms of resistant starches from dietary pulses remain underexplored. Herein, we examine the prebiotic effects of dietary pulses-derived resistant starch (RS) on gut metabolome in older (60-week old) mice carrying a human microbiome. Gut metabolome and its association with microbiome are examined after 20-weeks feeding of a western-style diet (control; CTL) fortified (5% w/w) with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin (INU; reference control). NMR spectroscopy-based untargeted metabolomic analysis yield differential abundance linking phenotypic differences in specific metabolites among different RS groups. LEN and CKP increase butyrate, while INU promotes propionate. Conversely, bile acids and cholesterol are reduced in prebiotic groups along with suppressed choline-to-trimethylamine conversion by LEN and CKP, whereas amino acid metabolism is positively altered. Multi-omics microbiome-metabolome interactions reveal an association of beneficial metabolites with the Lactobacilli group, Bacteroides, Dubosiella, Parasutterella, and Parabacteroides, while harmful metabolites correlate with Butyricimonas, Faecalibaculum, Colidextribacter, Enterococcus, Akkermansia, Odoribacter, and Bilophila. These findings demonstrate the functional effects of pulses-derived RS on gut microbial metabolism and their beneficial physiologic responses in an aged host.

In this study, a two-dimensional computational domain featuring gas and solid phases is computationally studied for Geldart-B-type particles. In addition to the baseline case of a uniform gas-phase injection velocity, three different inlet velocity profiles were simulated, and their effects on the fluidized bed hydrodynamics and bubble dynamics have been studied. An in-house computer program was developed to track the bubbles and determine the temporal evolution of their size and position prior to their breakup. This program also provides information on the location of bubble coalescence and breakup. The gas-solid interactions were simulated using a Two-Fluid Model (TFM) with Gidaspow’s drag model. The results reveal that the bed hydrodynamics feature a counter-rotating vortex pair for the solid phase, and bubble dynamics, such as coalescence and breakup, can be correlated with the vortices’ outer periphery and the local gradients in the vorticity.

To improve the packaging properties of pea protein isolate (PPI) films, 2 wt% of essential oil (EO) from garlic, ginger, or cinnamon was individually incorporated into the films. The film properties were evaluated after the addition of EOs. The resulting PPI active films were applied to salmon to explore their efficacy in a real food system. The results indicated that the moisture content (MC), total soluble matter (TSM), water vapor permeability (WVP), water contact angle (WCA), tensile strength (TS), and elongation at break (EAB) of PPI film decreased after adding EOs, with the extent of the decrease varying based on the type of oil. SEM images revealed that the distribution of EOs within the film matrix differed: garlic EO was mainly distributed within the internal structure, while ginger and cinnamon EOs were primarily on the surface. FTIR analysis confirmed the interactions between PPI and EOs. When applied to salmon, garlic EO and ginger EO promoted lipid oxidation, whereas cinnamon EO significantly delayed it. Although PPI-based active films containing garlic or cinnamon EOs showed remarkable antibacterial activity in vitro, they did not inhibit bacterial growth in salmon. Additionally, EOs in active films may notably alter the color and sensory properties of salmon, potentially influencing consumer acceptance. Our findings demonstrated that the EO type is a key factor in influencing the properties of edible films. More importantly, the effectiveness of active films is closely related to the specific food system in which they are applied.

BackgroundStimulator of Interferon Genes (STING) is a dsDNA sensor that triggers type I inflammatory responses. Recent data from our group and others support the therapeutic efficacy of STING agonists applied intratumorally or systemically in a range of murine tumor models, with treatment benefits associated with tumor vascular normalization and improved immune cell recruitment and function within the tumor microenvironment (TME). However, such interventions are rarely curative and STING agonism coordinately upregulates expression of immunoregulatory interferon-stimulated genes (ISGs) including Arg2, Cox2, Isg15, Nos2, and Pdl1 that may limit treatment benefits. We hypothesized that combined treatment of melanoma-bearing mice with STING agonist ADU-S100 together with antagonists of regulatory ISGs would result in improved control of tumor growth vs. treatment with ADU-S100 alone.MethodsMice bearing either B16 (BRAFWTPTENWT) or BPR20 (BRAFV600EPTEN-/-) melanomas were treated with STING agonist ADU-S100 plus various inhibitors of ARG2, COX2, NOS2, PD-L1, or ISG15. Tumor growth control and changes in the TME were evaluated for combination treatment vs ADU-S100 monotherapy by tumor area measurements and flow cytometry/transcriptional profiling, respectively.ResultsIn the B16 melanoma model, we noted improved antitumor efficacy only when ADU-S100 was combined with neutralizing/blocking antibodies against PD-L1 or ISG15, but not inhibitors of ARG2, COX2, or NOS2. Conversely, in the BPR20 melanoma model, improved tumor growth control vs. ADU-S100 monotherapy was only observed when combining ADU-S100 with ARG2i, COX2i, and NOS2i, but not anti-PD-L1 or anti-ISG15. Immune changes in the TME associated with improved treatment outcomes were subtle but included increases in proinflammatory innate immune cells and activated CD8+CD69+ T cells and varied between the two tumor models.ConclusionsThese data suggest contextual differences in the relative contributions of individual regulatory ISGs that serve to operationally limit the anti-tumor efficacy of STING agonists which should be considered in future design of novel combination protocols for optimal treatment benefit.

Halari donkey breed is one of the indigenous breeds of India and its population is rapidly decreasing. The Jenny milk is more similar to human milk, exhibits a wide range of probiotic diversity and hypo-allergenicity, especially among infants suffering from cow and buffalo milk protein allergy. Some studies indicated low levels of κ-casein fraction of casein protein in donkey milk. The k-casein gene was not amplified from the DNA derived from the milk somatic cells of Halari donkeys. The Halari donkey milk has low somatic cells count. We report the first isolation of DNA from milk somatic cells of Halari donkeys with subsequent characterization of k-casein gene. Through our work, we showed that the milk somatic cells can be used as a non-invasive source for DNA isolation towards molecular studies. It also proved the presence of k-casein gene in Halari donkey milk by its amplification from isolated DNA.

Pea protein isolate (PPI)-based active films were prepared by incorporating 0.5 %, 1.0 %, or 2.0 % of oregano essential oil (OEO), either in the form of micro-emulsion (MOEO) or nano-emulsion (NOEO). The particle size and polydispersity index of OEO droplets were 2755.00 nm and 0.63 for MOEO, and 256.30 nm and 0.20 for NOEO. The surface and cross-sectional SEM results revealed the presence of holes and internal pores within the film upon the addition of OEO. The molecular interaction between PPI and OEO was confirmed by FTIR. The addition of OEO significantly increased film thickness, decreased water contact angle, and imparted a more yellow color. At a low concentration (0.5 %), the addition of OEO significantly improved the water vapor barrier and mechanical properties of the film. However, at higher concentrations, these film properties were significantly weakened. Additionally, the film antimicrobial properties were assessed after OEO addition. In vitro inhibition zone results indicated that a 2.0 % addition of OEO significantly suppressed the growth of three Salmonella strains [Salmonella Typhimurium (ATCC14028), Salmonella Infantis 94-1, and Salmonella Enteritidis PT-30]. Application of pea protein-based film with 2.0 % OEO on chicken breast demonstrated significant reduction in microbial count. Our results further showed that reducing the particle size of OEO from micrometer-scale to nanometer-scale in the PPI film matrix did not significantly alter film properties or antimicrobial activities. The study demonstrated that the antibacterial film based on pea protein and OEO is an innovative food packing material for prohibiting bacteria growth on poultry products.

Strains of Salmonella are a frequent cause of foodborne illness and are known to contaminate poultry products. Most Salmonella testing methods can qualitatively detect Salmonella and cannot quantify or estimate the Salmonella load in samples. Therefore, the aim of this study was to standardize and validate a partitioned-based digital PCR (dPCR) assay for the detection and estimation of Salmonella contamination levels in poultry rinses. Pure culture Salmonella strains were cultured, enumerated, cold-stressed for 48 h, and used to inoculate whole carcass chicken rinse (WCCR) at 1–4 log CFU/30 mL and enriched at 37 °C for 5 h. Undiluted DNA samples with primer and probes targeting the Salmonella-specific invA gene were used for the dPCR assay. The dPCR assay was highly specific, with a limit of detection of 0.001 ng/μL and a limit of quantification of 0.01 ng/μL. The dPCR assay further showed no PCR reaction inhibition up to 5 μg of crude DNA extract. The assays accurately detected all cold-stressed Salmonella in inoculated WCCR samples following a 5-h enrichment. Most importantly, when converted to log, the dPCR copies/μL values accurately estimated the inoculated Salmonella levels. The dPCR assay standardized in this study is a robust method for the detection and estimation of Salmonella concentration in contaminated food samples. This approach can allow same-day decision-making for poultry processors attempting to maintain limits and controls on Salmonella contamination.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease, entails chronic inflammation of the gastrointestinal tract. The pathogenesis of IBD implicates genetic factors, gut microbiome alterations, and immune dysregulation, contributing to its increasing global prevalence. The sturgeon-derived peptide, which exhibits promising anti-inflammatory effects, provides potential therapeutic insights for managing IBD symptoms. This study aims to elucidate the therapeutic mechanisms of novel sturgeon-derived peptide (LLLE, Leu-Leu-Leu-Glu) by investigating their effects on intestinal inflammation, gut microbiota composition, and fecal metabolites in a mouse model of IBD. LLLE administration alleviated weight loss and disease activity index (DAI) scores in dextran sulfate sodium salt (DSS)-induced colitis in mice. Histopathological examination showed LLLE pretreatment improved colon morphology and histopathological condition and decreased serum interleukin-6 (IL-6) levels. 16S rRNA sequencing indicated LLLE-modulation of gut microbiota, especially alleviated DSS-elevated Bacteroidetes. Fecal metabolomic analysis unveiled that LLLE restores critical metabolites such as indole-3-propionic acid, which is pivotal in anti-inflammatory responses. Altogether, sturgeon peptide exhibits considerable promise as a therapeutic agent for colitis, owing to its anti-inflammatory effects, modulation of gut microbiota, and restoration of essential fecal metabolites.

Abstract The design of alloys for use in gas turbine engine blades is a complex task that involves balancing multiple objectives and constraints. Candidate alloys must be ductile at room temperature and retain their yield strength at high temperatures, as well as possess low density, high thermal conductivity, narrow solidification range, high solidus temperature, and a small linear thermal expansion coefficient. Traditional Integrated Computational Materials Engineering (ICME) methods are not sufficient for exploring combinatorially-vast alloy design spaces, optimizing for multiple objectives, nor ensuring that multiple constraints are met. In this work, we propose an approach for solving a constrained multi-objective materials design problem over a large composition space, specifically focusing on the Mo-Nb-Ti-V-W system as a representative Multi-Principal Element Alloy (MPEA) for potential use in next-generation gas turbine blades. Our approach is able to learn and adapt to unknown constraints in the design space, making decisions about the best course of action at each stage of the process. As a result, we identify 21 Pareto-optimal alloys that satisfy all constraints. Our proposed framework is significantly more efficient and faster than a brute force approach.

Background and Aims: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in bowel habits. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are poorly absorbed short-chain carbohydrates that may drive commensal microbial gas production, promoting abdominal pain in IBS. Low-FODMAP diet can result in symptomatic improvement in 50%–80% of IBS patients. However, this diet is not meant to be sustained long term, with concern for downstream nutrition and microbial issues. In this study, we evaluate the function of a targeted FODMAP enzymatic digestion food supplement FODMAP enzymatic digestion (FODZYME) containing a fructan-hydrolase enzyme (with significant inulinase activity) in a simulated gastrointestinal environment. Methods: Using SHIME (Simulator of the Human Intestinal Microbial Ecosystem), a multi-compartment simulator of the human gut, FODZYME dose finding assay in modeled gastrointestinal conditions assessed enzymatic ability to hydrolyze 3 g of inulin. Full intestinal modeling assessing digestion of inulin, absorption of fructose, gas production, and other measures of commensal microbial behavior was completed using 1.125 g of FODZYME. Results: After 30 minutes, 90% of the inulin was converted to fructose by 1.125 g of FODZYME. Doubling dosage showed no significant improvement in conversion, whereas a half dose decreased performance to 77.2%. Seventy percent of released fructose was absorbed during simulated small intestinal transit, with a corresponding decrease in microbial gas production, and a small decrease in butyrate and short-chain fatty acid production. Conclusion: FODZYME specifically breaks down inulin in representative gastrointestinal conditions, resulting in decreased gas production while substantially preserving short-chain fatty acid and butyrate production in the model colon. Our results suggest dietary supplementation with FODZYME would decrease intestinal FODMAP burden and gas production.

Abstract Background Multiple non-arthroplasty surgical techniques are described for the management of large and massive irreparable rotator cuff tears. There is currently no consensus on the best management strategy. Our aim was to compare clinical outcomes following arthroscopic debridement, arthroscopic partial cuff repair, superior capsule reconstruction, balloon spacers or graft interposition for the management of large and massive irreparable rotator cuff tears. Methods A comprehensive search was performed of the following databases: Medline, Embase, CINAHL and Cochrane Database of Systematic Reviews. Data were extracted from relevant studies published since January 2000 according to the pre-specified inclusion criteria. The primary outcome was the post-operative improvement in shoulder scores. Meta-analysis of the primary outcome was performed. Secondary outcomes included retear rates and complications. Results Eighty-two studies were included reporting the outcomes of 2790 shoulders. Fifty-one studies were included in the meta-analysis of the primary outcome. The definition of an irreparable tear varied. All procedures resulted in improved shoulder scores at early follow-up. Shoulder scores declined after 2 years following balloon spacers, arthroscopic debridement and partial cuff repair. High retear rates were seen with partial cuff repairs (45%), graft interposition (21%) and superior capsule reconstruction (21%). Conclusions Large initial improvements in shoulder scores were demonstrated for all techniques despite high retear rates for reconstructive procedures. Shoulder scores may decline at mid- to long-term follow-up.

The oyster industry is a significant component of United States aquaculture and is vulnerable to various food frauds. In addition to species substitution, mislabeling of oyster geographical origin is performed for economic gains. The geographical origin misrepresentations are performed to claim a famed region of origin known for its unique flavor profile. DNA barcoding is the gold standard method for identifying seafood species but has limited resolution to the species level. This pilot study was conducted to characterize and compare the oyster gill microbiome as an alternative approach for tracking oysters’ origin. Commercially available raw east coast oysters (Crassostrea virginica) from two distinct geographical locations were purchased. Genomic DNA isolated from the gills was processed for microbiome analysis. The data revealed distinct microbiome signatures among the two sample sets. Oysters from Louisiana showed the presence of eighteen unique bacterial genera, whereas Maryland oysters showed a higher abundance of twelve genera. Findings from this study demonstrate the applicability of microbiome analysis as an emerging alternative approach for identifying geographical origin misrepresentations.

In recent years, the increased population has led to an increase in the demand for various industrially processed edibles and other consumable products. These industries regularly alter the proteins found in raw materials to generate more commercially viable end-products in order to keep up with consumer demand. These modifications result in a substance that may cause allergic reactions in consumers, thereby creating a protein allergen. The detection of such proteins in various substances is essential for the prevention, diagnosis and treatment of allergic conditions. Bioinformatics and computational methods can be used to analyze the information contained in amino-acid sequences to detect possible allergens. The article presents a deep learning based ensemble approach to identify protein allergens using Extra Tree, Deep Belief Network (DBN), and CatBoost models. The proposed ensemble model achieves higher detection accuracy by combining the prediction results of the three models using majority voting. The evaluation of the proposed model was carried out on the benchmark protein allergen dataset, and the performance analysis revealed that the proposed model outperforms the other state-of-the-art literature techniques with a protein allergen detection accuracy of 89.16%.