Quantitative analysis of systemic perfusion and cerebral blood flow in the modeling of aging and orthostatic hypotension.

Introduction: Orthostatic hypotension (OH) is common among the older population. The mechanism hypothesized by OH as a risk factor for cognitive decline and dementia is repeated transient cerebral blood flow deficiency. However, to our knowledge, quantitative evaluation of cardiac output and cerebral blood flow due to acute blood pressure changes resulting from postural changes is rare. Methods: We report a new fluid-structure interaction model to analyze the quantitative relationship of cerebral blood flow during OH episodes. A device was designed to simulate the aging of blood vessels. Results and Discussion: The results showed that OH was associated with decreased transient cerebral blood flow. With the arterial aging, lesions, the reduction in cerebral blood flow is accelerated. These findings suggest that systolic blood pressure regulation is more strongly associated with cerebral blood flow than diastolic blood pressure, and that more severe OH carries a greater risk of dementia. The model containing multiple risk factors could apply to analyze and predict for individual patients. This study could explain the hypothesis that transient cerebral blood flow deficiency in recurrent OH is associated with cognitive decline and dementia.

Cold shock treatment alleviates pitting in sweet cherry fruit by enhancing antioxidant enzymes activity and regulating membrane lipid metabolism.

BACKGROUND: In order to comprehend the regulatory mechanisms that result in the alleviation of sweet cherry pitting disorder through cold shock (0 °C ice-water mixture for 10 min), an investigation was conducted into the impacts of cold shock treatment (CST) on membrane lipid metabolism, antioxidant enzyme activity, as well as pitting of cold-stored sweet cherry fruit. RESULTS: CST significantly inhibited the increase in pitting incidence, pitting index, and decay incidence. The CST treatment provided greater titratable acidity, firmness as well as total content of soluble solids. The use of CST prevented the build-up of superoxide anions, hydrogen peroxide, malondialdehyde, and reduced permeability of cell membranes. When in contrast to control group, the CST also raised the expression levels along with activity of the antioxidant enzymes ascorbate peroxidase (APX), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT). Furthermore, CST reduced the amount of fruit cell membrane peroxidation, suppressed the activity of phospholipase and lipoxygenase, postponed the rise in saturated fatty acids (SFAs) and decrease in unsaturated fatty acids (USFAs), ultimately keeping a high ratio of USFAs to SFAs. CONCLUSION: CST can alleviating pitting disorder in sweet cherry fruit via preventing peroxidation of membrane lipid and elevating the antioxidant enzymes activity. © 2024 Society of Chemical Industry.

Modulatory effects of necroptosis: A potential preventive approach to control diseases in fish.

Necroptosis is a caspase-independent programmed cell death process characterized by morphological similarities to necrosis and the potential to cause significant inflammatory reactions. The initiation, execution, and inhibition of necroptosis involve a complex interplay of various signaling proteins. When death receptors bind to ligands, necroptosis is triggered through the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/Mixed Lineage Kinase Domain-Like (MLKL) axis, leading to inflammatory reactions in the surrounding tissues. This process encompasses numerous physiological regulatory mechanisms and contributes to the development and progression of certain diseases. The mechanisms of necroptosis were not well conserved across terrestrial and aquatic organisms, with differences in some components and functions. Given the significant challenges that aquatic animal diseases pose to aquaculture, research interest in necroptosis has surged recently, particularly in studies focusing on fish. Understanding necroptosis in fish can lead to interventions that offer potential breakthroughs in disease inhibition and fish health improvement.

Faceted crystal growth of cyclodextrin-oil inclusion complexes.

The spontaneous formation of cyclodextrin (CD)-oil inclusion complexes (ICs) and their further growth into patterned crystals present a bottom-up route to the fabrication of periodic macroscopic structure. Although the inclusion processes are well established for the molecules, understanding intermediate structures during the crystal growth and emerging of persistent crystalline order has been lacking. Here we build a hierarchy of oriented micro/nanostructures of CD-oil ICs in solution by choosing different oil guests including several straight-chain alkanes of C12, C14 and C16, oleic acid (OA), glycerol trioleate (TG) and soybean oil (SO), in an attempt to reveal the roles of oil guests in the formation of their crystallites. Remarkably, the ICs tend to grow into clusters and terminate at a certain finite size as long columns or lamella plates with well-defined facets, dependent on the type of oil used. For the first time, we report a non-equilibrium growth of crystallites with surface faceting directed by the guests by means of Arching and Bundling.

Multifunctional biomolecular corona-inspired nanoremediation of antibiotic residues.

Facing complex and variable emerging antibiotic pollutants, the traditional development of functional materials is a "trial-and-error" process based on physicochemical principles, where laborious steps and long timescales make it difficult to accelerate technical breakthroughs. Notably, natural biomolecular coronas derived from highly tolerant organisms under significant contamination scenarios can be used in conjunction with nanotechnology to tackling emerging contaminants of concern. Here, super worms (Tubifex tubifex) with high pollutant tolerance were integrated with nano-zero valent iron (nZVI) to effectively reduce the content of 17 antibiotics in wastewater within 7 d. Inspired by the synergistic remediation, nZVI-augmented worms were constructed as biological nanocomposites. Neither nZVI (0.3 to 3 g/L) nor worms (104 to 105 per liter) alone efficiently degraded florfenicol (FF, as a representative antibiotic), while their composite removed 87% of FF (3 µmol/L). Under antibiotic exposure, biomolecules secreted by worms formed a corona on and modified the nZVI particle surface, enabling the nano-bio interface greater functionality, including responsiveness, enrichment, and reduction. Mechanistically, FF exposure activated glucose-alanine cycle pathways that synthesize organic acids and amines as major metabolites, which were assembled into vesicles and secreted, thereby interacting with nZVI in a biologically response design strategy. Lactic acid and urea formed hydrogen bonds with FF, enriched analyte presence at the heterogeneous interface. Succinic and lactic acids corroded the nZVI passivation layer and promoted electron transfer through surface conjugation. This unique strategy highlights biomolecular coronas as a complex resource to augment nano-enabled technologies and will provide shortcuts for rational manipulation of nanomaterial surfaces with coordinated multifunctionalities.

Novel Botrytis cinerea Zn(II)2Cys6 Transcription Factor BcFtg1 Enhances the Virulence of the Gray Mold Fungus by Promoting Organic Acid Secretion and Carbon Source Utilization.

The Zn(II)2Cys6 zinc cluster protein family comprises a subclass of zinc-finger proteins that serve as transcriptional regulators involved in a diverse array of fugal biological processes. However, the roles and mechanisms of the Zn(II)2Cys6 transcription factors in mediating Botrytis cinerea, a necrotrophic fungus that causes gray mold in over 1000 plant species, development and virulence remain obscure. Here, we demonstrate that a novel B. cinerea pathogenicity-associated factor BcFTG1 (fungal transcription factor containing the GAL4 domain), identified from a virulence-attenuated mutant M20162 from a B. cinerea T-DNA insertion mutant library, plays an important role in oxalic acid (OA) secretion, carbon source absorption and cell wall integrity. Loss of BcFTG1 compromises the ability of the pathogen to secrete OA, absorb carbon sources, maintain cell wall integrity, and promote virulence. Our findings provide novel insights into fungal factors mediating the pathogenesis of the gray mold fungus via regulation of OA secretion, carbon source utilization and cell wall integrity.

Distributed Frank-Wolfe Solver for Stochastic Optimization With Coupled Inequality Constraints.

Distributed stochastic optimization (DSO) with local set constraints and coupled inequality constraints over a multiagent network is considered in this article. Usually, such problems are tackled by projected primal-dual methods, which require expensive projection operations when set constraints are complicated. In this context, this article focuses on the Frank-Wolfe (FW) framework, which provides computational simplicity by avoiding expensive projection operations, for solving DSO with local set and coupled inequality constraints. By combining recursive momentum and weighted averaging, this article proposes a distributed stochastic FW primal-dual algorithm (DSFWPD), which is the first stochastic FW solver for DSO problems with coupled constraints. The proposed algorithm achieves zero constraint violation on average with a sublinear decay of the optimality gap over a directed and time-varying network. The efficacy of DSFWPD is demonstrated by several numerical experiments.

Fractionation of phenolic compounds from hickory by-products using solid phase extraction-sonication: Chemical composition, antioxidant and antimicrobial activity.

Hickory is an abundant source of phenolic compounds that exhibit a diverse range of bioactivities. In this study, phenolic compounds were extracted and purified from hickory green husk (HG), hickory nutshell (HN), and hickory seed coat (HS) using solid-phase extraction and ultrasonication (SPE-US). The effects of the SPE-US treatment on the structure and properties of the phenolic compounds were then investigated, including their composition, antioxidant activity, and antimicrobial activity. The dominant phenolic substances in the different extracts after SPE-US treatment were: ellagic acid and trans ferulic acid (HS); ellagic acid and sinapic acid (HN); and rutin (HG). The HS-SPE-US1 extract exhibited the highest total polyphenol content (416 ± 11 mg GAE/g DW), total flavonoid content (47.51 ± 0.68 mg RE/g DW), Fe3+ reduction ability (74.2 ± 1.0 mmol Fe2+/g DW), radical (DPPH and ABTS) scavenging ability, and antimicrobial activity against Staphylococcus aureus.

Fusarium mycotoxins: The major food contaminants.

Mycotoxins, which are secondary metabolites produced by toxicogenic fungi, are natural food toxins that cause acute and chronic adverse reactions in humans and animals. The genus Fusarium is one of three major genera of mycotoxin-producing fungi. Trichothecenes, fumonisins, and zearalenone are the major Fusarium mycotoxins that occur worldwide. Fusarium mycotoxins have the potential to infiltrate the human food chain via contamination during crop production and food processing, eventually threatening human health. The occurrence and development of Fusarium mycotoxin contamination will change with climate change, especially with variations in temperature, precipitation, and carbon dioxide concentration. To address these challenges, researchers have built a series of effective models to forecast the occurrence of Fusarium mycotoxins and provide guidance for crop production. Fusarium mycotoxins frequently exist in food products at extremely low levels, thus necessitating the development of highly sensitive and reliable detection techniques. Numerous successful detection methods have been developed to meet the requirements of various situations, and an increasing number of methods are moving toward high-throughput features. Although Fusarium mycotoxins cannot be completely eliminated, numerous agronomic, chemical, physical, and biological methods can lower Fusarium mycotoxin contamination to safe levels during the preharvest and postharvest stages. These theoretical innovations and technological advances have the potential to facilitate the development of comprehensive strategies for effectively managing Fusarium mycotoxin contamination in the future.

AnglesRefine: Refinement of 3D Protein Structures Using Transformer Based on Torsion Angles.

The goal of protein structure refinement is to enhance the precision of predicted protein models, particularly at the residue level of the local structure. Existing refinement approaches primarily rely on physics, whereas molecular simulation methods are resource-intensive and time-consuming. In this study, we employ deep learning methods to extract structural constraints from protein structure residues to assist in protein structure refinement. We introduce a novel method, AnglesRefine, which focuses on a protein's secondary structure and employs transformer to refine various protein structure angles (psi, phi, omega, CA_C_N_angle, C_N_CA_angle, N_CA_C_angle), ultimately generating a superior protein model based on the refined angles. We evaluate our approach against other cutting-edge methods using the CASP11-14 and CASP15 datasets. Experimental outcomes indicate that our method generally surpasses other techniques on the CASP11-14 test dataset, while performing comparably or marginally better on the CASP15 test dataset. Our method consistently demonstrates the least likelihood of model quality degradation, e.g., the degradation percentage of our method is less than 10%, while other methods are about 50%. Furthermore, as our approach eliminates the need for conformational search and sampling, it significantly reduces computational time compared to existing refinement methods.

Papillary Muscle Infarction by Cardiac MRI in Patients With Mitral Regurgitation.

BACKGROUND: Papillary muscle (PM) infarction (PMI) detected by cardiac magnetic resonance imaging (CMR) is associated with poor outcomes. Whether PM parameters provide more value for mitral regurgitation (MR) management currently remains unclear. Therefore, we examined the prognostic value of PMI using CMR in patients with MR. METHODS: Between March 2018 and July 2023, we retrospectively enrolled 397 patients with MR undergoing CMR. CMR was used to detect PMI qualitatively and quantitively. We also collected baseline clinical, echocardiography, and follow-up data. RESULTS: Of the 397 patients with MR (52.4 ± 13.9 years), 117 (29.5%) were assigned to the PMI group, with 280 (70.5%) in the non-PMI group. PMI was demonstrated more in the posteromedial PM (PM-PM, 98/117) than in the anterolateral PM (AL-PM, 45/117). Compared with patients without PMI, patients with PMI had a decreased AL-PM (41.5 ± 5.4 vs. 45.6 ± 5.3)/PM-PM diastolic length (35.0 ± 5.2 vs. 37.9 ± 4.0), PM-longitudinal strain (LS, 20.4 ± 6.1 vs. 24.9 ± 4.6), AL-PM-LS (19.7 ± 6.8 vs. 24.7 ± 5.6)/PM-PM-LS (21.2 ± 7.9 vs. 25.2 ± 6.0), and increased inter-PM distance (25.7 ± 8.0 vs. 22.7 ± 6.2, all p < 0.001). Multiple logistic regression analyses identified male sex (odds ratio [OR] = 3.65, 95% confidence interval = 1.881-7.081, p < 0.001) diabetes mellitus (OR/95% CI/p = 2.534/1.13-5.68/0.024), AL-PM diastolic length (OR/95% CI/p = 0.841/0.77-0.92/< 0.001), PM-PM diastolic length (OR/95% CI/p = 0.873/0.79-0.964/0.007), inter-PM distance (OR/95% CI/p = 1.087/1.028-1.15/0.003), AL-PM-LS (OR/95% CI/p = 0.892/0.843-0.94/< 0.001), and PM-PM-LS (OR/95% CI/p = 0.95/0.9-0.992/0.021) as independently associated with PMI. Over a 769 ± 367-day follow-up, 100 (25.2%) patients had arrhythmia. Cox regression analyses indicated that PMI (hazard ratio [HR]/95% CI/p = 1.644/1.062-2.547/0.026), AL-PM-LS (HR/95% CI/p = 0.937/0.903-0.973/0.001), and PM-PM-LS (HR/95% CI/p = 0.933/0.902-0.965/< 0.001) remained independently associated with MR. CONCLUSIONS: The CMR-derived PMI and LS parameters improve the evaluation of PM dysfunction, indicating a high risk for arrhythmia, and provide additive risk stratification for patients with MR.

Outcomes of the EMDataResource cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

Design, Synthesis, and Biological Evaluation of Chroman Derivatives as PD-1/PD-L1 Antagonists.

Programmed death-ligand 1 (PD-L1) has emerged as a promising therapeutic target for various cancers due to its crucial role in promoting tumor immune evasion. Here, we report a novel class of chroman-like small-molecule PD-L1 inhibitors exhibiting significant activity in inhibiting the PD-1/PD-L1 interaction. Employing a "ring-close" strategy for conformational restriction, we have achieved compound C27, which demonstrates superior PD-1/PD-L1 inhibitory activity compared to the positive control. Molecular dynamics simulation and binding free energy calculation predict that (R)-C27 with inhibitory activity surpassed (S)-C27. The experimental results from bioassay and X-ray structural analysis corroborate these findings. All these results collectively indicate that (R)-C27 is a promising lead compound deserving further exploration.

Ferric Oxide Nanomaterials and Plant-Rhizobacteria Symbionts Cogenerate Iron Plaque for Removing Highly Chlorinated Contaminants in Dryland Soils.

Rhizosphere iron plaques derived from Fe-based nanomaterials (NMs) are a promising tool for sustainable agriculture. However, the requirement for flooded conditions to generate iron plaque limits the scope of the NM application. In this study, we achieved in situ Fenton oxidation of a highly chlorinated persistent organic pollutant (2,2',4,5,5'-pentachlorobiphenyl, PCB101) through iron plaque mediated by the interaction between α-Fe2O3 NMs and plant-rhizobacteria symbionts under dryland conditions. Mechanistically, the coexistence of α-Fe2O3 NMs and Pseudomonas chlororaphis JD37 stimulated alfalfa roots to secrete acidic and reductive agents as well as H2O2, which together mediated the rhizosphere Fenton reaction and converted α-Fe2O3 NMs into iron plaque rich in Fe(II)-silicate. Further verifications reproduced the Fenton reaction in vitro using α-Fe2O3 NMs and rhizosphere compounds, confirming the critical role of •OH in the oxidative degradation of PCB101. Significant reductions in PCB101 content by 18.6%, 42.9%, and 23.2% were respectively found in stem, leaf, and soil after a 120-d treatment, proving the effectiveness of this NMs-plant-rhizobacteria technique for simultaneously safe crop production and soil remediation. These findings can help expand the potential applications of nanobio interaction and its mediated iron plaque generation for both agricultural practice and soil remediation.

Distribution pattern analysis of multiple antibiotics in the soil-rice system using a QuEChERS extraction method.

Antibiotics are commonly released into paddy fields as mixtures via human activities. However, the simultaneous extraction and detection of these chemicals from multiple media are technically challenging due to their different physicochemical properties, resulting in unclear patterns of their transport in the soil-rice system. In this study, a "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) method was developed for the simultaneous analysis of 4 tetracyclines (TCs) and 4 fluoroquinolones (FQs) in the soil and rice tissues from a local poultry farm, and thereby the distribution patterns of the target antibiotics in the soil-rice system and their risk levels to the soil were analyzed. After parameter optimization, the calibration range used for the target antibiotics was 0.1-50 µg/L and each calibration curve was linear with a coefficient of determination (R2 > 0.995); The QuEChERS method achieved satisfactory recovery rates (70.3-124.6%) along with sensitive detection limits (0.005-0.21 ng/g) for TCs and FQs in the soil, root, stem, leaf, and grain. Among the 8 antibiotics, enrofloxacin (ENX), ciprofloxacin (CIP), oxytetracycline (OTC), and doxycycline (DOX) were detected around a poultry farm. The four antibiotics in the collected paddy soils around the poultry farm ranged from 7.1 ng/g to 395.5 ng/g. Notably, ENX and DOX had higher ecological risks (risk quotient values >1) than CIP and OTC in soil. ENX, CIP, and DOX were highly enriched in rice roots with concentrations up to 471.9, 857.3, and 547.4 ng/g, respectively, which were also detected in rice aboveground tissues. The findings may provide both technical and practical guidance for the understanding of antibiotic environmental behavior and risks.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Stapokibart in Healthy Volunteers and Adult Subjects with Atopic Dermatitis.

INTRODUCTION: Stapokibart, a novel humanized anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits the signaling of IL-4 and IL-13, which are key drivers of type 2 inflammation in atopic dermatitis (AD). This study aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of stapokibart in a randomized, double-blind, placebo-controlled single ascending dose (SAD) study and a multiple ascending dose (MAD) study. METHODS: The SAD study enrolled 33 healthy male adults aged 18-65 years at a single center. The MAD study enrolled 39 patients with moderate-to-severe AD aged 18-70 years at seven centers. Enrolled subjects were randomized to subcutaneous (SC) doses of stapokibart (75-600 mg) or placebo. Serum thymus and activation-regulated chemokine (TARC) and total immunoglobulin E (IgE) were measured as PD biomarkers for stapokibart. RESULTS: Similar PK characteristics were observed in healthy volunteers and subjects with AD after the initial administration. Stapokibart exhibited non-linear pharmacokinetics in both types of subjects. Following single doses, the mean maximum serum concentration (Cmax) ranged from 5.3 to 63.0 µg/mL, median Tmax ranged from 3.0 to 7.0 days, mean terminal half-life (t1/2z) ranged from 2.39 to 7.43 days, and mean apparent volume (Vz/F) ranged from 3.64 to 6.73 L in healthy subjects. The mean AUC accumulation ratio was 2.29 in subjects with AD after three doses of stapokibart 300 mg administered every 2 weeks. The median serum total IgE and TARC levels on day 43 decreased from baseline by 14.9-25.2% and 48.6-77.0%, respectively, among subjects with AD receiving three doses of stapokibart. No subjects developed grade ≥ 3 adverse events (AEs) or serious AEs or discontinued the study because of AEs. The incidence of AEs was similar between stapokibart and placebo groups. CONCLUSION: Stapokibart showed favorable pharmacokinetics, pharmacodynamics, safety, and tolerability in the SAD and MAD studies. Based on these results, phase II and phase III trials of stapokibart have been performed in subjects with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06161090 (29 November, 2023), NCT04893941 (15 May, 2021).

Phosphine-Catalyzed Stereospecific and Enantioselective Desymmetrizative [3+2] Cycloaddition of MBH Carbonates and N-(2-tert-Butylphenyl)maleimides.

Herein, we report an l-valine-derived amide phosphine-catalyzed [3+2] cyclization of MBH carbonates and N-(2-tert-butylphenyl)maleimides via asymmetric desymmetrization. Bicyclic N-aryl succinimide derivatives bearing three continuous chiral centers with a remote C-N atropisomeric chirality were constructed stereospecifically and enantioselectively. A wide variety of MBH carbonates could be employed in this process to deliver highly optically pure succinimide derivatives in moderate to excellent yields.

Guest-guided anchoring patterns of cyclodextrin supramolecular microcrystals on droplet surfaces.

The growth of cyclodextrin inclusion complexes (ICs) on oil/water interfaces represents a beautiful example of spontaneous pattern formation in nature. How the supramolecules evolve remains a challenge because surface confinement can frustrate microcrystal growth and give rise to unusual phase transitions. Here we investigate the self-assembly of ICs on droplet surfaces using microfluidics, which allows directly visualizing packing, wetting and ordering of the microcrystals anchored on the surface. The oil guests of distinct molecular structures can direct the assembly of the ICs and largely affect anchoring dynamics of the ICs microcrystals, leading to a range of behaviors including orientating, slipping, buckling, jamming, or merging. We discuss the behaviors observed in terms of the flexibility of the building blocks, which offers a new degree of freedom through which to tailor their properties and gives rise to a striking feature of anchoring patterns that have no counterpart in normal colloidal crystals.

Predicting major adverse cardiovascular events within 3 years by optimization of radiomics model derived from pericoronary adipose tissue on coronary computed tomography angiography: a case-control study.

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.

Identification of an Enterococcus faecium strain isolated from raw bovine milk co-harbouring the oxazolidinone resistance genes optrA and poxtA in China.

Oxazolidinones are potent antimicrobial agents used to treat human infections caused by multidrug-resistant Gram-positive bacteria. The growing resistance to oxazolidinones poses a significant threat to public health. In August 2021, a linezolid-resistant Enterococcus faecium BN83 was isolated from a raw milk sample of cow in Inner Mongolia, China. This isolate exhibited a multidrug resistance phenotype and was resistant to most of drugs tested including linezolid and tedizolid. PCR detection showed that two mobile oxazolidinones resistance genes, optrA and poxtA, were present in this isolate. Whole genome sequencing analysis revealed that the genes optrA and poxtA were located on two different plasmids, designated as pBN83-1 and pBN83-2, belonging to RepA_N and Inc18 families respectively. Genetic context analysis suggested that optrA gene on plasmid pBN83-1 was located in transposon Tn6261 initially found in E. faecalis. Comprehensive analysis revealed that Tn6261 act as an important horizontal transmission vector for the spread of optrA in E. faecium. Additionally, poxtA-bearing pBN83-2 displayed high similarity to numerous plasmids from Enterococcus of different origin and pBN83-2-like plasmid represented a key mobile genetic element involved in movement of poxtA in enterococcal species. The presence of optrA- and poxtA-carrying E. faecium in raw bovine milk represents a public health concern and active surveillance is urgently warranted to investigate the prevalence of oxazolidinone resistance genes in animal-derived food products.