Brown adipose tissue facilitates the fever response following infection with Salmonella enterica serovar Typhimurium in mice.

INTRODUCTION: Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of non-shivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its contribution to immune-induced fever is less clear. METHODS: Male APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism, and wildtype mice were given an intraperitoneal injection of Salmonella enterica serovar Typhimurium (S.tm). Energy expenditure and substrate utilization, plasma lipid levels, fatty acid uptake by adipose tissues, and lipid content and thermogenic markers in adipose tissues were examined. RESULTS: S.tm infection led to a set of characteristic symptoms, including elevated body temperature and decreased body weight. Whole-body energy expenditure was significantly decreased 72 hours post-infection, but fat oxidation was increased and accompanied by a substantial reduction in plasma triglyceride (TG) levels as demonstrated in APOE*3-Leiden.CETP mice. S.tm infection strongly increased uptake of fatty acids from TG-rich lipoproteins (TRLs) by BAT, which showed a positive correlation with body temperature in infected mice. Upon histological examination of BAT from wildtype or APOE*3-Leiden.CETP mice, elevated levels of tyrosine hydroxylase were observed, indicative of stimulated sympathetic activity. In addition, the gene expression profile was consistent with more adrenergic stimulation, while lipid content was reduced. Furthermore, browning of white adipose tissue was observed, evidenced by a modest increase in TG-derived fatty acid uptake, the presence of multilocular cells, and induction of UCP-1 expression. CONCLUSION: We proposed that BAT, or thermogenic adipose tissue in general, is involved in the maintenance of elevated body temperature upon invasive bacterial infection.

Platinum-Ruthenium Bimetallic Nanoparticle Catalysts Synthesized Via Direct Joule Heating for Methanol Fuel Cells.

Platinum-Ruthenium (PtRu) bimetallic nanoparticles are promising catalysts for methanol oxidation reaction (MOR) required by direct methanol fuel cells. However, existing catalyst synthesis methods have difficulty controlling their composition and structures. Here, a direct Joule heating method to yield highly active and stable PtRu catalysts for MOR is shown. The optimized Joule heating condition at 1000 °C over 50 microseconds produces uniform PtRu nanoparticles (6.32 wt.% Pt and 2.97 wt% Ru) with an average size of 2.0 ± 0.5 nanometers supported on carbon black substrates. They have a large electrochemically active surface area (ECSA) of 239 m2 g-1 and a high ECSA normalized specific activity of 0.295 mA cm-2. They demonstrate a peak mass activity of 705.9 mA mgPt -1 for MOR, 2.8 times that of commercial 20 wt.% platinum/carbon catalysts, and much superior to PtRu catalysts obtained by standard hydrothermal synthesis. Theoretical calculation results indicate that the superior catalytic activity can be attributed to modified Pt sites in PtRu nanoparticles, enabling strong methanol adsorption and weak carbon monoxide binding. Further, the PtRu catalyst demonstrates excellent stability in two-electrode methanol fuel cell tests with 85.3% current density retention and minimum Pt surface oxidation after 24 h.

An Effective Deep Learning Framework for Fall Detection: Model Development and Study Design.

BACKGROUND: Fall detection is of great significance in safeguarding human health. By monitoring the motion data, a fall detection system (FDS) can detect a fall accident. Recently, wearable sensors-based FDSs have become the mainstream of research, which can be categorized into threshold-based FDSs using experience, machine learning-based FDSs using manual feature extraction, and deep learning (DL)-based FDSs using automatic feature extraction. However, most FDSs focus on the global information of sensor data, neglecting the fact that different segments of the data contribute variably to fall detection. This shortcoming makes it challenging for FDSs to accurately distinguish between similar human motion patterns of actual falls and fall-like actions, leading to a decrease in detection accuracy. OBJECTIVE: This study aims to develop and validate a DL framework to accurately detect falls using acceleration and gyroscope data from wearable sensors. We aim to explore the essential contributing features extracted from sensor data to distinguish falls from activities of daily life. The significance of this study lies in reforming the FDS by designing a weighted feature representation using DL methods to effectively differentiate between fall events and fall-like activities. METHODS: Based on the 3-axis acceleration and gyroscope data, we proposed a new DL architecture, the dual-stream convolutional neural network self-attention (DSCS) model. Unlike previous studies, the used architecture can extract global feature information from acceleration and gyroscope data. Additionally, we incorporated a self-attention module to assign different weights to the original feature vector, enabling the model to learn the contribution effect of the sensor data and enhance classification accuracy. The proposed model was trained and tested on 2 public data sets: SisFall and MobiFall. In addition, 10 participants were recruited to carry out practical validation of the DSCS model. A total of 1700 trials were performed to test the generalization ability of the model. RESULTS: The fall detection accuracy of the DSCS model was 99.32% (recall=99.15%; precision=98.58%) and 99.65% (recall=100%; precision=98.39%) on the test sets of SisFall and MobiFall, respectively. In the ablation experiment, we compared the DSCS model with state-of-the-art machine learning and DL models. On the SisFall data set, the DSCS model achieved the second-best accuracy; on the MobiFall data set, the DSCS model achieved the best accuracy, recall, and precision. In practical validation, the accuracy of the DSCS model was 96.41% (recall=95.12%; specificity=97.55%). CONCLUSIONS: This study demonstrates that the DSCS model can significantly improve the accuracy of fall detection on 2 publicly available data sets and performs robustly in practical validation.

A review of the biological activities of lactoferrin: mechanisms and potential applications.

Lactoferrin, a multifunctional iron-binding protein found in milk and other body fluids, possesses numerous biological activities. The functional activity of lactoferrin lies not only in its iron-binding capacity but also in the molecular mechanisms by which it can affect important chemical components in the host. However, the molecular mechanisms underlying these activities remain unelucidated. In this paper, we review the structure, properties, and contents of different lactoferrin milk sources. The different biological activities, namely antibacterial, antiviral, immunomodulatory, anti-inflammatory, bone regeneration, and improved metabolic disorder bioactivities, and the associated potential mechanisms of lactoferrin are summarized with the aim of providing a reference for the development of lactoferrin-related products.

circZNF532 promotes endothelial-to-mesenchymal transition in diabetic retinopathy by recruiting TAF15 to stabilize PIK3CD.

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.

Current Research on Probiotics and Fermented Products.

The history of probiotics and fermented products has evolved over millennia [...].

Proteomic and phosphoproteomic reveal immune-related function of milk fat globule membrane in bovine milk of different lactation periods.

Information regarding protein expression and phosphorylation modifications in the bovine milk fat globule membrane is scarce, particularly throughout various lactation periods. This study employed a complete proteome and phosphoproteome between bovine colostrum and mature milk. A total of 11 proteins were seen in both protein expression and phosphorylation levels. There were 400 proteins identified in only protein expression, and 104 phosphoproteins identified in only phosphorylation levels. A total of 232 significant protein characteristics were identified within the proteome and significant phosphorylation sites within 86 phosphoproteins of the phosphoproteome. Biological activities and pathways primarily exhibited associations with the immune system. Simultaneously, a comprehensive analysis of proteins and phosphorylation sites using a multi-omics approach. Hence, the data we have obtained has the potential to expand our understanding of how the bovine milk fat globule membrane might be utilized as a beneficial component in dairy products.

Promotion of 14-3-3ζ/Heme Oxygenase-1 Axis on Endotoxin-Induced Uveitis and Microglia Ferroptosis in Mice.

PURPOSE: Uveitis is a common, sight-threatening inflammatory ocular disease and is the main cause of blindness, which is caused by autoimmune response, infection, and injury. The contribution of 14-3-3ζ in uveitis remains obscure. This study aims to investigate the role of 14-3-3ζ in regulating ferroptosis in retinal inflammation and its contribution to uveitis. METHODS: A lipopolysaccharide (LPS)-induced uveitis mouse model and BV-2 cell line were used to examine the effect of LPS stimulation on the expression of 14-3-3ζ and ferroptosis in microglia. The expression of heme oxygenase-1 (HO-1) was also analyzed to understand its role in promoting microglial ferroptosis. RESULTS: We found that LPS stimulation increased the expression of 14-3-3ζ and promoted ferroptosis in microglia. Additionally, 14-3-3ζ was found to promote microglial ferroptosis by stabilizing the expression of HO-1. These findings suggest that the 14-3-3ζ/HO-1 axis plays a crucial role in promoting microglial ferroptosis in retinal inflammation. CONCLUSION: The study provides valuable insights into the mechanisms underlying uveitis and highlights the potential of the 14-3-3ζ/HO-1 axis as a therapeutic target for the disease. Further research in this area could lead to the development of preventive and therapeutic strategies for uveitis.

Regulation of lipid metabolism by E3 ubiquitin ligases in lipid-associated metabolic diseases.

Previous studies have progressively elucidated the involvement of E3 ubiquitin (Ub) ligases in regulating lipid metabolism. Ubiquitination, facilitated by E3 Ub ligases, modifies critical enzymes in lipid metabolism, enabling them to respond to specific signals. In this review, we aim to present a comprehensive analysis of the role of E3 Ub ligases in lipid metabolism, which includes lipid synthesis and lipolysis, and their influence on cellular lipid homeostasis through the modulation of lipid uptake and efflux. Furthermore, it explores how the ubiquitination process governs the degradation or activation of pivotal enzymes, thereby regulating lipid metabolism at the transcriptional level. Perturbations in lipid metabolism have been implicated in various diseases, including hepatic lipid metabolism disorders, atherosclerosis, diabetes, and cancer. Therefore, this review focuses on the association between E3 Ub ligases and lipid metabolism in lipid-related diseases, highlighting enzymes critically involved in lipid synthesis and catabolism, transcriptional regulators, lipid uptake translocators, and transporters. Overall, this review aims to identify gaps in current knowledge, highlight areas requiring further research, offer potential targeted therapeutic approaches, and provide a comprehensive outlook on clinical conditions associated with lipid metabolic diseases.

A preparation of debranched waxy maize starch derivatives: Effect of drying temperatures on crystallization and digestibility.

The impact of recrystallization conditions and drying temperatures on the crystallization and digestibility of native waxy maize (Zea mays L.) starch (NWMS) was explored. This study involved subjecting NWMS to concurrent debranching and crystallization at 50 °C for up to 7 days. Samples were collected by oven-drying at 40, 60, and 80 °C for 24 h. This simultaneous debranching and crystallization process increased the resistant starch (RS) content by approximately 48 % compared to the native starch. The drying temperatures significantly influenced the RS content, with samples dried at 60 °C exhibiting the lowest digestibility. X-ray diffraction (XRD) analysis revealed that most crystals demonstrated a characteristic A-type arrangement. Debranching and crystallization processes enhanced the crystallinity of the samples. The specific crystal arrangement (A- or B-type) depended on the crystallization conditions. A 15 min heating of NWMS in a boiling water bath increased the digestible fraction to over 90 %, while the samples subjected to debranching and crystallization showed an increase to only about 45 %. A linear correlation between starch fractions and enthalpy was also observed.

Amino acid profile alteration in age-related atrial fibrillation.

BACKGROUND: Amino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear. METHODS: Initially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical indicators were explored. Subsequently, the age-related AF mouse model was constructed and the untargeted myocardial metabolomics was conducted to detect the level of AAs and related metabolites. Additionally, the gut microbiota composition associated with age-related AF was detected by a 16S rDNA amplicon sequencing analysis on mouse fecal samples. RESULTS: Higher circulation levels of lysine (Student's t-test, P = 0.001), tyrosine (P = 0.002), glutamic acid (P = 0.008), methionine (P = 0.008), and isoleucine (P = 0.014), while a lower level of glycine (P = 0.003) were observed in persistent AF patients. The feature AAs identified by machine learning algorithms were glutamic acid and methionine. The association between AAs and age differs between AF and control subjects. Distinct patterns of AA metabolic profiles were observed in the myocardial metabolites of aged AF mice. Aged AF mice had lower levels of Betaine, L-histidine, L-alanine, L-arginine, L-Pyroglutamic acid, and L-Citrulline compared with adult AF mice. Aged AF mice also presented a different gut microbiota pattern, and its functional prediction analysis showed AA metabolism alteration. CONCLUSION: This study provided a comprehensive network of AA disturbances in age-related AF from multiple dimensions, including plasma, myocardium, and gut microbiota. Disturbances of AAs may serve as AF biomarkers, and restoring their homeostasis may have potential benefits for the management of age-related AF.

Revealing the diversity of endogenous peptides and parent proteins in human colostrum and mature milk through peptidomics analysis.

Endogenous peptides and their parent proteins are important nutritional components with diverse biological functions. The objective of this study was to analyze and compare endogenous peptides and parent proteins found in human colostrum (HC) and human mature milk (HM) using a 4D label-free technique. In total, 5162 and 940 endogenous peptides derived from 258 parent proteins were identified in human milk by database (DB) search and de novo, respectively. Among these peptides, 2446 differentially expressed endogenous peptides with various bioactivities were identified. The Gene Ontology analysis unveiled the cellular components, biological processes, and molecular functions associated with these parent proteins. Metabolic pathway analysis suggested that neutrophil extracellular trap formation had the greatest significance with 24 parent proteins. These findings will offer a fresh perspective on the development of infant formula powder, highlighting the potential for incorporating these changes to enhance its nutritional composition and benefits.

Research Progress for Probiotics Regulating Intestinal Flora to Improve Functional Dyspepsia: A Review.

Functional dyspepsia (FD) is a common functional gastrointestinal disorder. The pathophysiology remains poorly understood; however, alterations in the small intestinal microbiome have been observed. Current treatments for FD with drugs are limited, and there are certain safety problems. A class of active probiotic bacteria can control gastrointestinal homeostasis, nutritional digestion and absorption, and the energy balance when taken in certain dosages. Probiotics play many roles in maintaining intestinal microecological balance, improving the intestinal barrier function, and regulating the immune response. The presence and composition of intestinal microorganisms play a vital role in the onset and progression of FD and serve as a critical factor for both regulation and potential intervention regarding the management of this condition. Thus, there are potential advantages to alleviating FD by regulating the intestinal flora using probiotics, targeting intestinal microorganisms. This review summarizes the research progress of probiotics regarding improving FD by regulating intestinal flora and provides a reference basis for probiotics to improve FD.

Bibliometric analysis of photodynamic therapy and immune response from 1989-2023.

Objective: Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune response. This study conducted a bibliometric analysis to identify the research trends and hotspots related to the immune response in PDT. Methods: We analyzed articles and reviews published from 1989 to 2023, retrieved from the Web of Science database. Using Citespace and VOSviewer, we visualized the distribution patterns of these studies in time and space. Results: The analysis revealed a substantial increase in the number of publications on PDT-related immune response since 1989. A total of 1,688 articles from 1,701 institutions were included in this analysis. Among thei nstitutions, the Chinese Academy of Sciences demonstrated exceptional productivity and a willingness to collaborate with others. Additionally, 8,567 authors contributed to the field, with Mladen Korbelik, Michael R. Hamblin, and Wei R. Chen being the most prolific contributors. The current research focus revolves around novel strategies to enhance antitumor immunity in PDT, including PDT-based dendritic cell vaccines, combination therapies with immune checkpoint inhibitors (ICIs), and the use of nanoparticles for photosensitizer delivery. Furthermore, genes such as CD8A, TNF, CD4, IFNG, CD274, IL6, IL10, CALR, HMGB1, and CTLA4 have been evaluated in the context of PDT-related immunity. Conclusion: PDT not only achieves tumor ablation but also stimulates the immune response, bolstering antitumor immunity. This study highlights the emerging hotspots in PDT-related immune response research and provides valuable insights for future investigations aimed at further enhancing antitumor immunity.

Hydrocortisone-associated death and hospital length of stay in patients with sepsis: A retrospective cohort of large-scale clinical care data.

PURPOSE: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset. METHODS: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone. RESULTS: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p < 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p < 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor)epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use. CONCLUSION: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis.

A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects.

Recent advances in wearable ultrasound technologies have demonstrated the potential for hands-free data acquisition, but technical barriers remain as these probes require wire connections, can lose track of moving targets and create data-interpretation challenges. Here we report a fully integrated autonomous wearable ultrasonic-system-on-patch (USoP). A miniaturized flexible control circuit is designed to interface with an ultrasound transducer array for signal pre-conditioning and wireless data communication. Machine learning is used to track moving tissue targets and assist the data interpretation. We demonstrate that the USoP allows continuous tracking of physiological signals from tissues as deep as 164 mm. On mobile subjects, the USoP can continuously monitor physiological signals, including central blood pressure, heart rate and cardiac output, for as long as 12 h. This result enables continuous autonomous surveillance of deep tissue signals toward the internet-of-medical-things.

Enhancement of liposomal properties of thyme essential oil using lysozyme modification: Physicochemical, storage, and antibacterial properties.

Thyme essential oil (TEO) is a natural food antimicrobial agent derived of spice, but suffers from volatility and poor water solubility, which problem can be effectively solved by the encapsulation of liposomes. On this basis, a safe and common natural antibacterial protein, LYZ was used to modify the TEO liposomes (TEO-lips) for gaining better properties. 2.5 mg/mL TEO and 0.05 % LYZ/S100 mass ratio were the best formula for the preparation of LYZ-TEO-lips. After LYZ modification, the particle size and PDI increased, and the zeta potential decreased slightly. The modification of LYZ not only improves the thermal stability of TEO-Lips, weakens the influence of acid and salt ions on liposomes, but also improves the antibacterial properties of TEO-Lips. In brief, LYZ has the potential to improve the overall properties of liposomes and can provide a reference for the development of antimicrobial liposomes.

A Review of Plant-Based Drinks Addressing Nutrients, Flavor, and Processing Technologies.

Plant-based drinks have garnered significant attention as viable substitutes for traditional dairy milk, providing options for individuals who are lactose intolerant or allergic to dairy proteins, and those who adhere to vegan or vegetarian diets. In recent years, demand for plant-based drinks has expanded rapidly. Each variety has unique characteristics in terms of flavor, texture, and nutritional composition, offering consumers a diverse range of choices tailored to meet individual preferences and dietary needs. In this review, we aimed to provide a comprehensive overview of the various types of plant-based drinks and explore potential considerations including their nutritional compositions, health benefits, and processing technologies, as well as the challenges facing the plant-based drink processing industry. We delve into scientific evidence supporting the consumption of plant-based drinks, discuss their potential roles in meeting dietary requirements, and address current limitations and concerns regarding their use. We hope to illuminate the growing significance of plant-based drinks as sustainable and nutritious alternatives to dairy milk, and assist individuals in making informed choices regarding their dietary habits, expanding potential applications for plant-based drinks, and providing necessary theoretical and technical support for the development of a plant-based drink processing industry.

Aggregation studies of alpha-lactalbumin induced by edible azo dyes with different sulfonyl group numbers: A comparative study.

As an opaque and complex colloidal mixture, milk is usually present as a positively charged colloid under acidic conditions. Adding negatively charged colloids can lead to protein aggregation in milk. Alpha-lactalbumin (α-La) is an essential component of whey protein and has good physicochemical properties for functional food development. We combined spectroscopy, computer simulations, and other techniques to comparative analyze the mechanisms and characteristics of isolated α-La aggregation induced by CI Acid Red 27 (C27)/CI Acid Red 14 (FB) containing different sulfonyl groups in vitro. The results showed that C27/FB (5.25 × 10-5 mol·L-1 to 3.15 × 10-4 mol·L-1) induced the formation of fibril-like aggregates under acidic conditions (pH 2.0 and 4.0) mainly benefit from hydrophobic and electrostatic forces. Weakening and redshift of α-La's characteristics negative peak were observed (208 nm to 218 nm) on circular dichroism. ß-Crosslinks self-assembly and reorganization of disulfide bonds occurred during protein fibrillation. Moreover, the different redshift intensity of Congo red binding to amyloid fibrils was observed to be induced by C27 (>551 nm) and FB (>536 nm), and the direct observation by TEM demonstrated the ability to induce protein fibrillation is C27 > FB. Edible azo dyes with more sulfonyl groups would possess a stronger ability to induce protein fibrillation.

Characterization and biological function analysis of endogenous peptides derived from donkey colostrum proteins.

Donkey colostrum, due to its abundance of active ingredients, including lysozyme, proteins, and peptides, is essential for the growth and immune defence of newborns. However, research on endogenous peptides in donkey colostrum is inadequate. This study analysed the profiles of endogenous peptides, their potential bioactivity, and the enzymes that generated these peptides using two different strategies. A total of 6202 endogenous peptides were characterised through a database search, while an additional 2997 peptides were identified de novo. Among the 1142 proteins identified, trypsin and plasmin demonstrated the highest bioactivities. Furthermore, a bioinformatics-based screening identified antioxidant peptides, angiotensin I-converting enzyme inhibitory peptides, and dipeptidyl peptidase IV inhibitory peptides as the three most active peptides. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted. These findings enhance our knowledge of endogenous peptides in donkey colostrum and provide crucial information regarding these peptides as nutritional factors for the future development of functional foods derived from donkey sources.