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In order to explore the effect of co-fermentation with Monascus and Aspergillus oryzae on the quality of soybean paste, the volatile flavor components in soybean pastes produced using pure and mixed cultures of A. oryzae (Piniang M003) and Monascus (PM001) were determined by headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and comparatively analyzed by principal component analysis (PCA), and Illumina MiSeq sequencing technology was used to analyze the changes in the microbial community structure during the mixed culture fermentation process. Meanwhile, the correlation between the major microorganisms and the major flavor substances was analyzed. The results showed that the composition and content of flavor substances and the composition and relative abundance of microbial communities in the soybean paste produced by co-fermentation were significantly better than those in the soybean paste fermented with A. oryzae monoculture. The major flavor substances in soybean paste were significantly positively correlated with dominant genera such as Aspergillus, Bacillus, Monascus and Leuconostoc. The flavor quality of the soybean paste produced with a mixed culture of A. oryzae and Monascus in a ratio of 3:1 (m/m) was best. The results of the study showed that the mixed culture fermentation with Monascus and A. oryzae could significantly improve the flavor quality of soybean paste, which will be informative for the improvement of the flavor quality of soybean paste.

Abstract Background and aims Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment. Methods Patients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence. Results Data from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p

The sensitivity of the Australian Monsoon to changing climate boundary conditions remains controversial due to limited understanding of forcing processes and past variability. Here, we reconstruct austral summer monsoonal discharge and wind-driven winter productivity across the Middle Pleistocene Transition (MPT) in a sediment sequence drilled off NW Australia. We show that monsoonal precipitation and runoff primarily responded to precessional insolation forcing until ~0.95 Ma, but exhibited heightened sensitivity to ice volume and pCO2 related feedbacks following intensification of glacial-interglacial cycles. Our records further suggest that summer monsoon variability at the precessional band was closely tied to the thermal evolution of the Indo-Pacific Warm Pool and strength of the Walker circulation over the past ~1.6 Myr. By contrast, productivity proxy records consistently tracked glacial-interglacial variability, reflecting changing rhythms in polar ice fluctuations and Hadley circulation strength. We conclude that the Australian Monsoon underwent a major re-organization across the MPT and that extratropical feedbacks were instrumental in driving short- and long-term variability.

The replacement of WC-Co cermet coating partially or entirely has evolved as one of the most promising research hotspots in terms of coating properties as well as economic reasons. In this study, the TiC reinforced AlCoCrFeNi high entropy alloy (HEA) composite coating based on new sintering method was explored. Firstly, the combination of spray drying and plasma spheroidization is proposed to fabricate TiC/HEA composite powder for thermal spraying application. After that, the corresponding composite coating was deposited by high velocity air-fuel (HVAF) process. The results show that the developed TiC/HEA powder has a more compact structure and higher sphericity, which helps to improve powder fluidity, meanwhile, with 50 wt% TiC incorporation, the porosity、hardness、bonding strength and fracture toughness of TiC/HEA composite coating are 0.8 % 765.2 HV0.3, 68.1 Mpa and 2.7 MPa m−1/2, respectively, showing simultaneous hardening, densifying and toughening effects after introducing dual-sized TiC particles. Besides, the good wear performances of TiC/HEA composite coating including low wear rate (4.2 × 10−5 mm3 N−1 m−1) and coefficient of friction (0.34) are obtained，indicating a valuable application prospect. In addition, the wear mechanisms of TiC/HEA composite coating are determined by abrasive and oxidation wears and that of grinding ball is abrasive wear and adhesive wears.

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is a recurring inflammatory demyelinating disease that is commonly observed in Asian countries like China. Prior investigations have shown that mycophenolate mofetil (MMF) with better biocompatibility compared to azathioprine (AZA), and can prevent relapses of NMOSD, but the efficacy was controversially reported in different NMOSD cases. We aimed to explore the factors that weaken efficacy of MMF in NMOSD. Methods A total of 34 NMOSD patients treated with MMF were prospectively enrolled and grouped according to the therapeutic efficacy as effective group (EG, n = 23) versus less-effective group (LEG, n = 11). The purine metabolites were profiled in serum samples and gut microbiota was analyzed using 16S rRNA sequencing with stool samples from the same patients. Results Purine salvage pathway (PSP) metabolites (inosine, hypoxanthine, xanthine, guanine and uric acid) in the serum of NMOSD patients were elevated in the LEG compared to EG (p

In this paper, Cr-coated zirconium fuel claddings were treated with ultrasonic shot-peening process (USPP). The mechanism of improving fatigue performance of Cr-coated zirconium fuel cladding was investigated by low cycle fatigue experiment. It was shown that USPP effectively improved fatigue life of Cr-coated zirconium fuel cladding under different temperatures. The enhancement mechanism is that USPP treatment changes the surface topography, increases in residual compressive stress and decreases surface roughness of the Cr coating. The fracture cross-section of tested specimens show that the Cr coating has little plastic deformation, showing brittle fracture characteristics. In addition, compared to the large amount of cracking inside the original Cr coating, the integrity of the USPP-Cr coating is better. The USPP-Cr coating has fewer cracks penetrating into the substrate, indicating that the Cr coating with USPP treatment has excellent fatigue crack resistance.

Abstract Antimicrobial resistance (AMR) is a major threat to global public health, and antibiotic resistance genes (ARGs) are widely distributed across humans, animals, and environment. Farming environments are emerging as a key research area for ARGs and antibiotic resistant bacteria (ARB). While the skin is an important reservoir of ARGs and ARB, transmission mechanisms between farming environments and human skin remain unclear. Previous studies confirmed that swine farm environmental exposures alter skin microbiome, but the timeline of these changes is ill defined. To improve understanding of these changes and to determine the specific time, we designed a cohort study of swine farm workers and students through collected skin and environmental samples to explore the impact of daily occupational exposure in swine farm on human skin microbiome. Results indicated that exposure to livestock‐associated environments where microorganisms are richer than school environment can reshape the human skin microbiome and antibiotic resistome. Exposure of 5 h was sufficient to modify the microbiome and ARG structure in workers' skin by enriching microorganisms and ARGs. These changes were preserved once formed. Further analysis indicated that ARGs carried by host microorganisms may transfer between the environment with workers' skin and have the potential to expand to the general population using farm workers as an ARG vector. These results raised concerns about potential transmission of ARGs to the broader community. Therefore, it is necessary to take corresponding intervention measures in the production process to reduce the possibility of ARGs and ARB transmission.

BackgroundDirect-acting oral anticoagulants are first-line agents for prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF), but data are limited for the oldest patients, and with reduced dosing.ObjectivesTo determine steady-state apixaban peak and trough concentrations during routine care of older adults with NVAF, compare concentrations to clinical trial concentrations, and explore factors associated with concentrations.MethodsA cross-sectional study of medically stable older adults with NVAF (≥75 years or ≥70 years if Black) receiving apixaban. Peak (2-4.4 hours post-dose) and trough (before next dose) concentrations were determined by anti-Xa activity calibrated chromogenic assay. Patient characteristics associated with concentrations were determined by multivariate modeling.ResultsThe median age of patients (n = 115) was 80 (interquartile range: 77-84) years. The cohort comprised 46 women and 69 men; of which 98 are White, 11 Black, and 6 Asian. With 5 mg twice daily per labelling (n = 88), peak concentrations were higher in women: 248 ± 105 vs 174 ± 67 ng/mL in men (P < 0.001) and exceeded expected 95% range in 6 of 30 vs 0 of 55 men (P = 0.002). With 2.5 mg twice daily per label (n = 11), concentrations were

Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy.