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IntroductionIn pulmonary hypertension (PH), pulmonary arterial remodeling is often accompanied by perivascular inflammation. The inflammation is characterized by the accumulation of activated macrophages and lymphocytes within the adventitial stroma, which is comprised primarily of fibroblasts. The well-known ability of fibroblasts to secrete interleukins and chemokines has previously been implicated as contributing to this tissue-specific inflammation in PH vessels. We were interested if pulmonary fibroblasts from PH arteries contribute to microenvironmental changes that could activate and polarize T-cells in PH.MethodsWe used single-cell RNA sequencing of intact bovine distal pulmonary arteries (dPAs) from PH and control animals and flow cytometry, mRNA expression analysis, and respirometry analysis of blood-derived bovine/human T-cells exposed to conditioned media obtained from pulmonary fibroblasts of PH/control animals and IPAH/control patients (CM-(h)PH Fibs vs CM-(h)CO Fibs).ResultsSingle-cell RNA sequencing of intact bovine dPAs from PH and control animals revealed a pro-inflammatory phenotype of CD4+ T-cells and simultaneous absence of regulatory T-cells (FoxP3+ Tregs). By exposing T-cells to CM-(h)PH Fibs we stimulated their proinflammatory differentiation documented by increased IFNγ and decreased IL4, IL10, and TGFβ mRNA and protein expression. Interestingly, we demonstrated a reduction in the number of suppressive T-cell subsets, i.e., human/bovine Tregs and bovine γδ T-cells treated with CM-(h)PH-Fibs. We also noted inhibition of anti-inflammatory cytokine expression (IL10, TGFβ, IL4). Pro-inflammatory polarization of bovine T-cells exposed to CM-PH Fibs correlated with metabolic shift to glycolysis and lactate production with increased prooxidant intracellular status as well as increased proliferation of T-cells. To determine whether metabolic reprogramming of PH-Fibs was directly contributing to the effects of PH-Fibs conditioned media on T-cell polarization, we treated PH-Fibs with the HDAC inhibitor SAHA, which was previously shown to normalize metabolic status and examined the effects of the conditioned media. We observed significant suppression of inflammatory polarization associated with decreased T-cell proliferation and recovery of mitochondrial energy metabolism.ConclusionThis study demonstrates how the pulmonary fibroblast-derived microenvironment can activate and differentiate T-cells to trigger local inflammation, which is part of the vascular wall remodeling process in PH.

AbstractMarine bioactive peptides (MBPs) are a type of natural compound with a variety of bioactivities, such as anticancer, antimicrobial, antioxidant, and antihypertensive. Due to a wide range of sources, low toxicity, and high specificity, MBPs have now received extensive attention in the fields of food, medicine, and cosmetics. The structure of MBPs determines their biological activities. Therefore, it is essential to analyze the relationship between the structure and bioactivity of MBPs. Because of the advantages of mild conditions, high specificity, safety, and environmental friendliness, enzymatic hydrolysis has become the most commonly used method to produce MBPs. However, the high cost and low yield of enzymatic methods have motivated researchers to search for alternative technologies. Novel pretreatments like ultrasound, microwave, high hydrostatic pressure, and pulsed electric fields have been employed in the production of MBPs. By inducing protein unfolding and increasing enzymatic cleavage sites, these techniques have been demonstrated to accelerate protein hydrolysis and enhance the biological activity of MBPs. This article reviews recent research advances on marine-derived protein hydrolysates and peptides, discusses the relationship between their biological activity and structure, and compares the mechanisms of action of different novel technologies used to promote protein hydrolysis and enhance the biological activity of MBPs. In addition, the current challenges facing the development and application of MBPs are outlined and possible future work in tackling these challenges is also suggested in the current review. It is hoped that this review can promote further development and application of marine active substances. [ABSTRACT FROM AUTHOR]

AbstractFoodborne pathogens are a major threat to both food safety and public health. The current trend toward fresh and less processed foods and the misuse of antibiotics in food production have made controlling these pathogens even more challenging. The outer membrane has been employed as a practical target to combat foodborne Gram-negative pathogens due to its accessibility and importance. In this review, the compositions of the outer membrane are extensively described firstly, to offer a thorough overview of this target. Current strategies for disrupting the outer membrane are also discussed, with emphasized on their mechanism of action. The disruption of the outer membrane structure, whether caused by severe damage of the lipid bilayer or by interference with the biosynthesis pathway, has been demonstrated to represent an effective antimicrobial strategy. Interference with the outer membrane-mediated functions of barrier, efflux and adhesion also contributes to the fight against Gram-negative pathogens. Their potential for control of foodborne pathogens in the production chain are also proposed. However, it is possible that multiple components in the food matrix may act as a protective barrier against microorganisms, and it is often the case that contamination is not caused by a single microorganism. Further investigation is needed to determine the effectiveness and safety of these methods in more complex systems, and it may be advisable to consider a multi-technology combined approach. Additionally, further studies on outer membranes are necessary to discover more promising mechanisms of action. [ABSTRACT FROM AUTHOR]

AbstractFood quality and safety problems caused by inefficient control in the food chain have significant implications for human health, social stability, and economic progress and optical sensor arrays (OSAs) can effectively address these challenges. This review aims to summarize the recent applications of nanomaterials-based OSA for food quality and safety visual monitoring, including colourimetric sensor array (CSA) and fluorescent sensor array (FSA). First, the fundamental properties of various advanced nanomaterials, mainly including metal nanoparticles (MNPs) and nanoclusters (MNCs), quantum dots (QDs), upconversion nanoparticles (UCNPs), and others, were described. Besides, the diverse machine learning (ML) and deep learning (DL) methods of high-dimensional data obtained from the responses between different sensing elements and analytes were presented. Moreover, the recent and representative applications in pesticide residues, heavy metal ions, bacterial contamination, antioxidants, flavor matters, and food freshness detection were comprehensively summarized. Finally, the challenges and future perspectives for nanomaterials-based OSAs are discussed. It is believed that with the advancements in artificial intelligence (AI) techniques and integrated technology, nanomaterials-based OSAs are expected to be an intelligent, effective, and rapid tool for food quality assessment and safety control. [ABSTRACT FROM AUTHOR]

The postharvest softening and corresponding quality deterioration of blueberry fruits are crucial factors that hinder long-distance sales and long-term storage. Cold plasma (CP) is an effective technology to solve this, but the specific mechanism of delaying fruit softening remains to be revealed. Here, this study found that CP significantly improved blueberry hardness. Physiological analysis showed that CP regulated the dynamic balance of reactive oxygen species (ROS) to maintain hardness by increasing antioxidant content and antioxidant enzyme activity, resulting in a 12.1% decrease in the H2O2 content. Transcriptome analysis revealed that CP inhibited the expression of cell wall degradation-related genes such as the pectin hydrolase gene and cellulase gene, but up-regulated the genes of the ROS-scavenging system. In addition, the resistance genes in the MAPK signaling pathway were also activated by CP in response to fruit ripening and softening and exhibited positive response characteristics. These results indicate that CP can effectively regulate the physiological characteristics of blueberries at a genetic level and delay the softening process, which is of great significance to the storage of blueberries. [ABSTRACT FROM AUTHOR]

The recruitment and subsequent polarization of inflammatory monocytes/macrophages in the perivascular regions of pulmonary arteries is a key feature of pulmonary hypertension (PH). However, the mechanisms driving macrophage polarization within the adventitial microenvironment during PH progression remain unclear. We previously established that reciprocal interactions between fibroblasts and macrophages are essential in driving the activated phenotype of both cell types although the signals involved in these interactions remain undefined. We sought to test the hypothesis that adventitial fibroblasts produce a complex array of metabolites and proteins that coordinately direct metabolomic and transcriptomic re-programming of naïve macrophages to recapitulate the pathophysiologic phenotype observed in PH. Media conditioned by pulmonary artery adventitial fibroblasts isolated from pulmonary hypertensive (PH-CM) or age-matched control (CO-CM) calves were used to activate bone marrow derived macrophages. RNA-Seq and mass spectrometry-based metabolomics analyses were performed. Fibroblast conditioned medium from patients with idiopathic pulmonary arterial hypertension or controls were used to validate transcriptional findings. The microenvironment was targeted in vitro using a fibroblast-macrophage co-culture system and in vivo in a mouse model of hypoxia-induced PH. Both CO-CM and PH-CM actively, yet distinctly regulated macrophage transcriptomic and metabolomic profiles. Network integration revealed coordinated rewiring of pro-inflammatory and pro-remodeling gene regulation in concert with altered mitochondrial and intermediary metabolism in response to PH-CM. Pro-inflammation and metabolism are key regulators of macrophage phenotype in vitro, and are closely related to in vivo flow sorted lung interstitial/perivascular macrophages from hypoxic mice. Metabolic changes are accompanied by increased free NADH levels and increased expression of a metabolic sensor and transcriptional co-repressor, C-terminal binding protein 1 (CtBP1), a mechanism shared with adventitial PH-fibroblasts. Targeting the microenvironment created by both cell types with the CtBP1 inhibitor MTOB, inhibited macrophage pro-inflammatory and metabolic re-programming both in vitro and in vivo. In conclusion, coordinated transcriptional and metabolic reprogramming is a critical mechanism regulating macrophage polarization in response to the complex adventitial microenvironment in PH. Targeting the adventitial microenvironment can return activated macrophages toward quiescence and attenuate pathological remodeling that drives PH progression.

AbstractBacterial biofilm has brought a lot of intractable problems in food and biomedicine areas. Conventional biofilm control mainly focuses on inactivation and removal of biofilm. However, with robust construction and enhanced resistance, the established biofilm is extremely difficult to eradicate. According to the mechanism of biofilm development, biofilm formation can be modulated by intervening in the key factors and regulatory systems. Therefore, regulation of biofilm formation has been proposed as an alternative way for effective biofilm control. This review aims to provide insights into the regulation of biofilm formation in food and biomedicine. The underlying mechanisms for early-stage biofilm establishment are summarized based on the key factors and correlated regulatory networks. Recent developments and applications of novel regulatory strategies such as anti/pro-biofilm agents, nanomaterials, functionalized surface materials and physical strategies are also discussed. The current review indicates that these innovative methods have contributed to effective biofilm control in a smart, safe and eco-friendly way. However, standard methodology for regulating biofilm formation in practical use is still missing. As biofilm formation in real-world systems could be far more complicated, further studies and interdisciplinary collaboration are still needed for simulation and experiments in the industry and other open systems. [ABSTRACT FROM AUTHOR]