Complexity of avian evolution revealed by family-level genomes.

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1-3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.

Anion-π interactions suppress phase impurities in FAPbI3 solar cells.

Achieving both high efficiency and long-term stability is the key to the commercialization of perovskite solar cells (PSCs)1,2. However, the diversity of perovskite (ABX3) compositions and phases makes it challenging to fabricate high-quality films3-5. Perovskite formation relies on the reaction between AX and BX2, whereas most conventional methods for film-growth regulation are based solely on the interaction with the BX2 component. Herein, we demonstrate an alternative approach to modulate reaction kinetics by anion-π interaction between AX and hexafluorobenzene (HFB). Notably, these two approaches are independent but work together to establish 'dual-site regulation', which achieves a delicate control over the reaction between AX and BX2 without unwanted intermediates. The resultant formamidinium lead halides (FAPbI3) films exhibit fewer defects, redshifted absorption and high phase purity without detectable nanoscale δ phase. Consequently, we achieved PSCs with power conversion efficiency (PCE) up to 26.07% for a 0.08-cm2 device (25.8% certified) and 24.63% for a 1-cm2 device. The device also kept 94% of its initial PCE after maximum power point (MPP) tracking for 1,258 h under full-spectrum AM 1.5 G sunlight at 50 ± 5 °C. This method expands the range of chemical interactions that occur in perovskite precursors by exploring anion-π interactions and highlights the importance of the AX component as a new and effective working site to improved photovoltaic devices with high quality and phase purity.

GRASLND regulates melanoma cell progression by targeting the miR-218-5p/STAM2 axis.

BACKGROUND: Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. METHODS: SiRNA transfection, wound - healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. RESULTS: The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. CONCLUSION: In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA-mRNA functional network and a new potential therapeutic target for SKCM.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Ferroptosis: potential targets and emerging roles in pancreatic diseases.

Ferroptosis is a newly discovered form of regulatory cell death characterized by excessive iron-dependent lipid peroxidation. In the past decade, significant breakthroughs have been made in comprehending the features and regulatory mechanisms of ferroptosis, and it has been confirmed that ferroptosis plays a pivotal role in the pathophysiological processes of various diseases, including tumors, inflammation, neurodegenerative diseases, and infectious diseases. The pancreas, which is the second largest digestive gland in the human body and has both endocrine and exocrine functions, is a vital organ for controlling digestion and metabolism. In recent years, numerous studies have confirmed that ferroptosis is closely related to pancreatic diseases, which is attributed to abnormal iron accumulation, as an essential biochemical feature of ferroptosis, is often present in the pathological processes of various pancreatic exocrine and endocrine diseases and the vulnerability of the pancreas to oxidative stress stimulation and damage. Therefore, comprehending the regulatory mechanism of ferroptosis in pancreatic diseases may provide valuable new insights into treatment strategies. In this review, we first summarize the hallmark features of ferroptosis and then analyze the exact mechanisms by which ferroptosis is precisely regulated at multiple levels and links, including iron metabolism, lipid metabolism, the GPX4-mediated ferroptosis defense system, the GPX4-independent ferroptosis defense system, and the regulation of autophagy on ferroptosis. Finally, we discuss the role of ferroptosis in the occurrence and development of pancreatic diseases and summarize the feasibility and limitations of ferroptosis as a therapeutic target for pancreatic diseases.

Preliminary field validity of ActiGraph-based energy expenditure estimation in wheelchair users with spinal cord injury.

STUDY DESIGN: Cross-sectional validation study. OBJECTIVES: To develop a raw acceleration signal-based random forest (RF) model for predicting total energy expenditure (TEE) in manual wheelchair users (MWUs) and evaluate the preliminary field validity of this new model, along with four existing models published in prior literature, using the Doubly Labeled Water (DLW) method. SETTING: General community and research institution in Pittsburgh, USA. METHODS: A total of 78 participants' data from two previous studies were used to develop the new RF model. A seven-day cross-sectional study was conducted to collect participants' free-living physical activity and TEE data, resting metabolic rate, demographics, and anthropometrics. Ten MWUs with spinal cord injury (SCI) completed the study, with seven participants having valid data for evaluating the preliminary field validity of the five models. RESULTS: The RF model achieved a mean absolute error (MAE) of 0.59 ± 0.60 kcal/min and a mean absolute percentage error (MAPE) of 23.6% ± 24.3% on the validation set. For preliminary field validation, the five assessed models yielded MAE from 136 kcal/day to 1141 kcal/day and MAPE from 6.1% to 50.2%. The model developed by Nightingale et al. in 2015 achieved the best performance (MAE: 136 ± 96 kcal/day, MAPE: 6.1% ± 4.7%), while the RF model achieved comparable performance (MAE: 167 ± 99 kcal/day, MAPE: 7.4% ± 5.1%). CONCLUSIONS: Two existing models and our newly developed RF model showed good preliminary field validity for assessing TEE in MWUs with SCI and the potential to detect lifestyle change in this population. Future large-scale field validation studies and model iteration are recommended.

Effect of salting and dehydration treatments on the physicochemical and gel properties of hen and duck egg yolks, plasma and granules.

BACKGROUND: Salted hen egg yolks are less oily and less flavorful than salted duck egg yolks. However, hen eggs have a more adequate market supply and have a broader application prospect than duck eggs. In the present study, egg yolks, plasma, and granules were dehydrated by adding 1% NaCl to simulate traditional curing process of salted egg yolk. The changes in the pickling process of hen egg yolks (HEY) and duck egg yolks (DEY) plasma and granules were compared to reveal the gelation mechanism and the underlying causes of quality differences in salted HEY and DEY. Salted HEY can be compared with the changes in DEY during the pickling process to provide a theoretical basis for the quality improvement of salted HEY to salted DEY. RESULTS: The results showed that both plasma and granules were involved in gel formation, but exhibited different aggregation behaviors. Based on the intermolecular forces, the HEY proteins achieved aggregation mainly through hydrophobic interactions and DEY proteins mainly through covalent binding. According to spin-spin relaxation time, HEY gels immobilized a large amount of lipid and interacted strongly with lipids. DEY gels showed much free lipid and had weak interaction with lipid. The microstructure showed that HEY proteins were easily unfolded to form a homogeneous three-dimensional gel network structure after salting, whereas heterogeneous aggregates were formed to hinder the gel development in DEY. Changes in protein secondary structure content showed that pickling can promote the transformation of the α-helices to ß-sheets structure in HEY gels, whereas more α-helices structure was formed in DEY gels. CONCLUSION: The present study has demonstrated that different gelation behaviors of hen and duck egg yolk proteins (especially in plasma) through salting treatment led to the difference in the quality of salted HEY and DEY. © 2024 Society of Chemical Industry.

CRISPR/Cas9-mediated simultaneous mutation of three salicylic acid 5-hydroxylase (OsS5H) genes confers broad-spectrum disease resistance in rice.

Salicylic acid (SA) is an essential plant hormone that plays critical roles in basal defence and amplification of local immune responses and establishes resistance against various pathogens. However, the comprehensive knowledge of the salicylic acid 5-hydroxylase (S5H) in rice-pathogen interaction is still elusive. Here, we reported that three OsS5H homologues displayed salicylic acid 5-hydroxylase activity, converting SA into 2,5-dihydroxybenzoic acid (2,5-DHBA). OsS5H1, OsS5H2, and OsS5H3 were preferentially expressed in rice leaves at heading stage and responded quickly to exogenous SA treatment. We found that bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) strongly induced the expression of OsS5H1, OsS5H2, and OsS5H3. Rice plants overexpressing OsS5H1, OsS5H2, and OsS5H3 showed significantly decreased SA contents and increased 2,5-DHBA levels, and were more susceptible to bacterial blight and rice blast. A simple single guide RNA (sgRNA) was designed to create oss5h1oss5h2oss5h3 triple mutants through CRISPR/Cas9-mediated gene mutagenesis. The oss5h1oss5h2oss5h3 exhibited stronger resistance to Xoo than single oss5h mutants. And oss5h1oss5h2oss5h3 plants displayed enhanced rice blast resistance. The conferred pathogen resistance in oss5h1oss5h2oss5h3 was attributed to the significantly upregulation of OsWRKY45 and pathogenesis-related (PR) genes. Besides, flg22-induced reactive oxygen species (ROS) burst was enhanced in oss5h1oss5h2oss5h3. Collectively, our study provides a fast and effective approach to generate rice varieties with broad-spectrum disease resistance through OsS5H gene editing.

Tungstate-mediated In-situ Passivation of Grain Boundary Grooves in Perovskite Solar Cells.

Possessed with advantageous optoelectronic properties, perovskites have boosted the rapid development of solution-processed solar cells. The performance of perovskite solar cells (PSCs) is significantly weakened by the carrier loss at grain boundary grooves (GBGs); however, it receives limited attention and there lacks effective approach to solve this issue. Herein, for the first time, we constructed the tungstate/perovskite heterointerface via a "two step" in situ reaction approach that provides effective defect passivation and ensures efficient carrier dynamics at the GBGs. The exposed perovskite at grain boundaries is converted to wide-band-gap PbWO4 via an in-situ reaction between Pb2+ and tungstate ions, which passivate defects due to the strong ionic bonding. Moreover, recombination loss is further suppressed via the heterointerface energetics modification based on an additional transformation from PbWO4 to CaWO4 . PSCs based on this groove modification strategy showed good universality in both normal and inverted structure, with an improved efficiency of 23.25 % in the n-i-p device and 23.33 % in the p-i-n device. Stable power output of the modified device could maintain 91.7 % after around 1100 h, and the device efficiency could retain 92.5 % after aging in air for around 2110 h, and 93.1 % after aging at 85 °C in N2 for 972 h.

Genome sequencing and transcriptome analyses provide insights into the origin and domestication of water caltrop (Trapa spp., Lythraceae).

Humans have domesticated diverse species from across the plant kingdom; however, our current understanding of plant domestication is largely founded on major cereal crops. Here, we examine the evolutionary processes and genetic basis underlying the domestication of water caltrop (Trapa spp., Lythraceae), a traditional, yet presently underutilized non-cereal crop that sustained early Chinese agriculturalists. We generated a chromosome-level genome assembly of tetraploid T. natans, and then divided the allotetraploid genome into two subgenomes. Based on resequencing data from 57 accessions, representing cultivated diploid T. natans, wild T. natans (2x and 4x) and diploid T. incisa, we showed that water caltrop was likely first domesticated in the Yangtze River Valley as early as 6300 yr BP, and experienced a second improvement c. 800 years ago. We also provided strong support for an allotetraploid origin of T. natans within the past 230 000-310 000 years. By integrating selective sweep and transcriptome profiling analyses, we identified a number of genes potentially selected and/or differentially expressed during domestication, some of which likely contributed not only to larger fruit sizes but also to a more vigorous root system, facilitating nutrient uptake, environmental stress response and underwater photosynthesis. Our results shed light on the evolutionary and domestication history of water caltrop, one of the earliest domesticated crops in China. This study has implications for genomic-assisted breeding of this presently underutilized aquatic plant, and improves our general understanding of plant domestication.

Predicting physical activity intensity using raw accelerometer signals in manual wheelchair users with spinal cord injury.

STUDY DESIGN: Cross-sectional validation study. OBJECTIVES: The performance of previously published physical activity (PA) intensity cutoff thresholds based on proprietary ActiGraph counts for manual wheelchair users (MWUs) with spinal cord injury (SCI) was initially evaluated using an out-of-sample dataset of 60 individuals with SCI. Two types of PA intensity classification models based on raw accelerometer signals were developed and evaluated. SETTING: Research institutions in Pittsburgh PA, Birmingham AL, and Bronx NY. METHODS: Data were collected from 60 MWUs with SCI who followed a structured activity protocol while wearing an ActiGraph activity monitor on their dominant wrist and portable metabolic cart which measured criterion PA intensity. Data was used to assess published models as well as develop and assess custom models using recall, specificity, precision, as well as normalized Mathew's correlation coefficient (nMCC). RESULTS: All the models performed well for predicting sedentary vs non-sedentary activity, yielding an nMCC of 0.87-0.90. However, all models demonstrated inadequate performance for predicting moderate to vigorous PA (MVPA) with an nMCC of 0.76-0.82. CONCLUSIONS: The mean absolute deviation (MAD) cutoff threshold yielded the best performance for predicting sedentary vs non-sedentary PA and may be used for tracking daily sedentary activity. None of the models displayed strong performance for MVPA vs non-MVPA. Future studies should investigate combining physiological measures with accelerometry to yield better prediction accuracies for MVPA.

Correction: Comparative validity of energy expenditure prediction algorithms using wearable devices for people with spinal cord injury.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Comparative validity of energy expenditure prediction algorithms using wearable devices for people with spinal cord injury.

STUDY DESIGN: Cross-sectional validation study. OBJECTIVES: To conduct a literature search for existing energy expenditure (EE) predictive algorithms using ActiGraph activity monitors for manual wheelchairs users (MWUs) with spinal cord injury (SCI), and evaluate their validity using an out-of-sample dataset. SETTING: Research institution in Pittsburgh, USA. METHODS: A literature search resulted in five articles containing five sets of predictive equations using an ActiGraph activity monitor for MWUs with SCI. Out-of-sample data were collected from 29 MWUs with chronic SCI who were asked to follow an activity protocol while wearing an ActiGraph GT9X Link on the dominant wrist. They also wore a portable metabolic cart which provided the criterion measure for EE. The out-of-sample dataset was used to evaluate the validity of the five sets of EE predictive equations. RESULTS: None of the five sets of predictive equations demonstrated equivalence within 20% of the criterion measure based on an equivalence test. The mean absolute error for the five sets of predictive equations ranged from 0.87 to 6.41 kilocalories per minute (kcal min-1) when compared with the criterion measure, and the intraclass correlation estimates ranged from 0.06 to 0.59. The range between the Bland-Altman upper and lower limits of agreement was from 4.70 kcal min-1 to 25.09 kcal min-1. CONCLUSIONS: The existing EE predictive equations based on ActiGraph monitors for MWUs with SCI showed varied performance when compared with the criterion measure. Their accuracies may not be sufficient to support future clinical and research use. More work is needed to develop more accurate EE predictive equations for this population.

Rare heterochronous liver and pancreatic multiple primary cancers: a case report and literature review.

In recent years, with the continuous improvement of medical diagnostic techniques, the incidence of multiple primary carcinoma (MPC) has increased gradually. Elderly patients are at high risk of MPC. However, the risk of developing a second primary malignancy is 1 % for primary liver malignancy 1. The risk of pancreatic cancers as secondary malignancies with primary liver malignancy is very rare. Here, we report a rare case of heterochronous liver and pancreatic MPCs and review the related literature. We report this case to raise the clinician's attention to the disease because the long-term survival rate can be effectively improved by timely diagnosis and appropriate treatment. For patients with HCV-positive primary cancers, active antiviral therapy should be simultaneously provided with antitumor therapy, thereby effectively reducing the incidence of MPC.

Clinical significance of LOXL4 expression and features of LOXL4-associated protein-protein interaction network in esophageal squamous cell carcinoma.

Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). Similar Kaplan-Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. The analyses based on the protein-protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.

Elucidating transport dynamics and regional division of PM2.5 and O3 in China using an advanced network model.

Air pollution exhibits significant spatial spillover effects, complicating and challenging regional governance models. This study innovatively applied and optimized a statistics-based complex network method in atmospheric environmental field. The methodology was enhanced through improvements in edge weighting and threshold calculations, leading to the development of an advanced pollutant transport network model. This model integrates pollution, meteorological, and geographical data, thereby comprehensively revealing the dynamic characteristics of PM2.5 and O3 transport among various cities in China. Research findings indicated that, throughout the year, the O3 transport network surpassed the PM2.5 network in edge count, average degree, and average weighted degree, showcasing a higher network density, broader city connections, and greater transmission strength. Particularly during the warm period, these characteristics of the O3 network were more pronounced, showcasing significant transport potential. Furthermore, the model successfully identified key influential cities in different periods; it also provided detailed descriptions of the interprovincial spillover flux and pathways of PM2.5 and O3 across various time scales. It pinpointed major pollution spillover and receiving provinces, with primary spillover pathways concentrated in crucial areas such as the Beijing-Tianjin-Hebei (BTH) region and its surrounding areas, the Yangtze River Delta, and the Fen-Wei Plain. Building on this, the model divided the O3, PM2.5, and synergistic pollution transmission regions in China into 6, 7, and 8 zones, respectively, based on network weights and the Girvan Newman (GN) algorithm. Such division offers novel perspectives and strategies for regional joint prevention and control. The validity of the model was further corroborated by source analysis results from the WRF-CAMx model in the BTH area. Overall, this research provides valuable insights for local and regional atmospheric pollution control strategies. Additionally, it offers a robust analytical tool for research in the field of atmospheric pollution.

Research on regional ozone prevention and control strategies in eastern China based on pollutant transport network and FNR.

O3 pollution in China has worsened sharply in recent years, and O3 formation sensitivity (OFS) in many regions have gradually changed, with eastern China as the most typical region. This study constructed the transport networks of O3 and NO2 in different seasons from 2017 to 2020. The transport trends and the clustering formation patterns were summarized by analyzing the topological characteristics of the transport networks, and the patterns of OFS changes were diagnosed by analyzing the satellite remote sensing data. Based on that, the main clusters that each province or city belongs to in different pollutant transport networks were summarized and proposals for the inter-regional joint prevention and control were put forward. As the results showed, O3 transport activity was most active in spring and summer and least active in winter, while NO2 transport activity was most active in autumn and winter and least active in summer. OFS in summer mainly consisted of transitional regimes and NOx-limited regimes, while that in other seasons was mainly VOC-limited regimes. Notably, there was a significant upward trend in the proportion of transitional regimes and NOx-limited regimes in spring, autumn, and winter. For regions showing NOx-limited regime, areas with higher out-weighted degrees in the NO2 transport network should focus on controlling local NOx emissions, such as central regions in summer. For regions showing VOC-limited regime, areas with higher out-weighted degrees in the O3 transport network should focus on controlling local VOCs emissions, such as central and south-central regions in summer. For regions that belong to the same cluster and present the same OFS in each specific season, regional cooperative emission reduction strategies should be established to block important transmission paths and weaken regional pollution consistency.

Novel Insights into the Effects of Different Cooking Methods on Salted Egg Yolks: Physicochemical and Sensory Analysis.

In this study, the flavor characteristics and physicochemical properties of salted egg yolk (SEY) under different cooking methods (steaming/baking/microwaving) were investigated. The microwave-treated SEY exhibited the highest levels of salt content, cooking loss, lightness, and b* value, as well as the highest content of flavor amino acids. A total of 31, 27, and 29 volatile compounds were detected after steaming, baking, and microwave treatments, respectively, covering 10 chemical families. The partial least squares discriminant analysis confirmed that 21 compounds, including octanol, pyrazine, 2-pentyl-furan, and 1-octen-3-ol, were the key volatile compounds affecting the classification of SEY aroma. The electronic nose revealed a sharp distinction in the overall flavor profile of SEY with varying heat treatments. However, no dramatic differences were observed in terms of fatty acid composition. Microwave treatment was identified as presenting a promising approach for enhancing the aroma profile of SEY. These findings contribute novel insights into flavor evaluation and the development of egg products as ingredients for thermal processing.

Ticagrelor regulates the differentiation of MDSCs after acute myocardial infarction to reduce cardiac injury.

Myeloid-derived suppressor cells (MDSCs) are important participants after acute myocardial infarction (AMI), but the role of their different subtypes in AMI remains controversial. The anti-inflammatory effect of ticagrelor in AMI has been discovered. However, the detailed anti-inflammatory mechanism has not been fully demonstrated. In this study, we aimed to determine whether ticagrelor can regulate the differentiation of MDSCs into anti-inflammatory subgroups to exert anti-inflammatory effects after AMI. In vitro experiments revealed no difference in the mRNA and protein expression of P2Y12 receptors on MDSCs and macrophages. Ticagrelor promotes the differentiation of in vitro cultured MDSCs to monocytic-MDSCs (M-MDSCs). A mouse AMI model was established to investigate the anti-inflammatory effects of ticagrelor in vivo after AMI by interfering with the differentiation of MDSCs. On the first day after AMI, spleen-derived polymorphonuclear-MDSCs (PMN-MDSCs) were predominant in the circulation and infarcted heart. Ticagrelor increased the percentage of M-MDSCs in the circulation and infarcted heart of AMI mice in a dose-dependent manner, attenuated cardiac inflammation and increased cardiac contractile function. M-MDSC injection significantly decreased cardiac inflammation levels and improved cardiac function in splenectomized AMI mice compared with PMN-MDSC injection. These data point to a novel anti-inflammatory role for ticagrelor after AMI by interfering with the differentiation of MDSCs.

Studies on the Properties and Stability Mechanism of Double Emulsion Gels Prepared by Heat-Induced Aggregates of Egg White Protein-Oligosaccharides Glycosylation Products.

Multiple emulsions can dissolve some substances with different properties, such as hydrophilicity and lipophilicity, into different phases. They play an important role in protection, controlled release and targeted release of the encapsulated substances. However, it's poor stability has always been one of the main problems restricting its application in the food industry. For this reason, a heat-induced aggregate (HIA) of Maillard graft product of isomalto-oligosaccharides (IMO), as well as egg white protein (EWP), was used as hydrophilic emulsifier to improve the stability of W1/O/W2 emulsions. Moreover, gelatin was added into the internal aqueous phase (W1) to construct W1/O/W2 emulsion-gels system. The encapsulation efficiency of HIA-stabilized W1/O/W2 emulsions remained nearly unaltered, dropping by only 0.86%, significantly outperforming the conjugates and physical mixture of IMO and EWP in terms of encapsulation stability. The emulsion-gels system was constructed by adding 5% gelatin in the W1, and had the highest EE% and good salt and heat stability after 30 days of storage. This experiment provides guidance for improving the stability of W1/O/W2 emulsions system and its application in the package delivery of functional substances in the food field.