Identification of a novel lactylation-related gene signature predicts the prognosis of multiple myeloma and experiment verification.

Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan-Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis.

Infant age inversely correlates with gut carriage of resistance genes, reflecting modifications in microbial carbohydrate metabolism during early life.

The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants (N = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0-7) and a tetracycline-mupirocin-ß-lactam-dominant phase (Months 8-14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with Escherichia (25.5%) harboring the most resistance genes. In a further analysis with all available infants (N = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years (p < 0.001). Using a random-forest approach, a set of 34 resistance genes could be used to predict age (R 2 = 68.0%). Leveraging microbial host inference analyses, we inferred the age-dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., Escherichia coli more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate-active enzymes from Bacteroidota and a decreasing need for Pseudomonadota during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life.

Prediction of Epidermal Growth Factor Receptor Mutation Subtypes in Non-Small Cell Lung Cancer From Hematoxylin and Eosin-Stained Slides Using Deep Learning.

Accurate assessment of epidermal growth factor receptor (EGFR) mutation status and subtype is critical for the treatment of non-small cell lung cancer patients. Conventional molecular testing methods for detecting EGFR mutations have limitations. In this study, an artificial intelligence-powered deep learning framework was developed for the weakly supervised prediction of EGFR mutations in non-small cell lung cancer from hematoxylin and eosin-stained histopathology whole-slide images. The study cohort was partitioned into training and validation subsets. Foreground regions containing tumor tissue were extracted from whole-slide images. A convolutional neural network employing a contrastive learning paradigm was implemented to extract patch-level morphologic features. These features were aggregated using a vision transformer-based model to predict EGFR mutation status and classify patient cases. The established prediction model was validated on unseen data sets. In internal validation with a cohort from the University of Science and Technology of China (n = 172), the model achieved patient-level areas under the receiver-operating characteristic curve (AUCs) of 0.927 and 0.907, sensitivities of 81.6% and 83.3%, and specificities of 93.0% and 92.3%, for surgical resection and biopsy specimens, respectively, in EGFR mutation subtype prediction. External validation with cohorts from the Second Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of Wannan Medical College (n = 193) yielded patient-level AUCs of 0.849 and 0.867, sensitivities of 79.2% and 80.7%, and specificities of 91.7% and 90.7% for surgical and biopsy specimens, respectively. Further validation with the Cancer Genome Atlas data set (n = 81) showed an AUC of 0.861, a sensitivity of 84.6%, and a specificity of 90.5%. Deep learning solutions demonstrate potential advantages for automated, noninvasive, fast, cost-effective, and accurate inference of EGFR alterations from histomorphology. Integration of such artificial intelligence frameworks into routine digital pathology workflows could augment existing molecular testing pipelines.

Sex Differences in Prognosis of Childhood Arterial Ischemic Stroke: Results From Chinese Pediatric Ischemic Stroke Registry Multicenter Registry.

BACKGROUND: Current studies on the impact of sex in the prognosis of childhood arterial ischemic stroke (AIS) are limited. We aimed to explore the sex differences in outcomes in patients with childhood AIS. METHODS: A retrospective analysis was conducted using the prospective data from the Chinese Pediatric Ischemic Stroke Registry. Baseline characteristics between sexes were compared in the total population cohort, propensity score (PS)-matched cohort, and inverse probability of treatment weighting cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was applied to further analyze the improvement in pediatric modified Rankin Scale (mRS) scores between sexes from 90 days to one year. Survival analysis was used to estimate the recurrence rates during the follow-up period. RESULTS: A total of 468 patients were finally included. Multivariate logistic regression showed that there were no significant differences between females and males in achieving favorable outcome (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.63 to 1.72), functional independence (OR 0.98, 95% CI 0.59 to 1.63), or shift to worse pediatric mRS scores (OR 0.83, 95% CI 0.59 to 1.17) at 90-day. Mixed-effects regression and survival analysis indicated that females and males exhibited comparable functional recovery from 90 days to one year and had similar recurrent risk during the follow-up period. CONCLUSIONS: This nationally-representative observational study indicated that both male and female pediatric patients with AIS exhibited comparable similar clinical outcomes at 90 days, as well as similar improvements and risks of recurrence during the follow-up period.

Multimodal MALDI imaging mass spectrometry for improved diagnosis of melanoma.

Imaging mass spectrometry (IMS) provides promising avenues to augment histopathological investigation with rich spatio-molecular information. We have previously developed a classification model to differentiate melanoma from nevi lesions based on IMS protein data, a task that is challenging solely by histopathologic evaluation. Most IMS-focused studies collect microscopy in tandem with IMS data, but this microscopy data is generally omitted in downstream data analysis. Microscopy, nevertheless, forms the basis for traditional histopathology and thus contains invaluable morphological information. In this work, we developed a multimodal classification pipeline that uses deep learning, in the form of a pre-trained artificial neural network, to extract the meaningful morphological features from histopathological images, and combine it with the IMS data. To test whether this deep learning-based classification strategy can improve on our previous results in classification of melanocytic neoplasia, we utilized MALDI IMS data with collected serial H&E stained sections for 331 patients, and compared this multimodal classification pipeline to classifiers using either exclusively microscopy or IMS data. The multimodal pipeline achieved the best performance, with ROC-AUCs of 0.968 vs. 0.938 vs. 0.931 for the multimodal, unimodal microscopy and unimodal IMS pipelines respectively. Due to the use of a pre-trained network to perform the morphological feature extraction, this pipeline does not require any training on large amounts of microscopy data. As such, this framework can be readily applied to improve classification performance in other experimental settings where microscopy data is acquired in tandem with IMS experiments.

Fructo-oligosaccharides supplementation enhances the growth of nursing dairy calves while stimulating the persistence of Bifidobacterium and hindgut microbiome's maturation.

The colonization and development of the gut microbiome in dairy calves play a crucial role in their overall health and future productivity. Despite the widely proposed benefits of inulin-related products on the host, there is insufficient information about how supplementing fructo-oligosaccharides (FOS) impacts the colonization and development of the gut microbiome in calves. In a randomized intervention trial involving newborn male Holstein dairy calves, we investigated the impact of FOS on the calf hindgut microbiome, short-chain fatty acids, growth performance, and the incidence of diarrhea. The daily administration of FOS exhibited a time-dependent increase in the average daily gain and the concentration of short-chain fatty acids. Concurrently, FOS delayed the natural decline of Bifidobacterium, promoting the maturation and stabilization of the hindgut microbiome. These findings not only contribute to a theoretical understanding of the judicious application of prebiotics but also hold significant practical implications for the design of early life dietary interventions in the rearing of dairy calves.

Enhancement of aerodynamic performance of a bristled wing by elliptic cylinders.

Enhancing the aerodynamic performance of bristled wings is an important topic for small flying robotics. This paper numerically investigates this situation at very low Reynolds numbers by using elliptic cylinders as the bristles instead of circular cylinders. Optimal configuration of the bristled wing with five elliptic cylinders is obtained, which corresponds to the maximum lift. The results show that, compared with the case of circular cylindrical bristles, the aerodynamic performance of the elliptical bristles can be enhanced effectively. The enhancement can be more significant as the aspect ratio of the ellipses increases and the gap width decreases. The bristled wing generates more lift compared to a flat-plate wing with a length five times that of the major axis of an ellipse. For the cases that the attack angleαfor the whole wing is equal to those for the elliptical bristlesθ, the optimal attack angle for ellipses maximizing the total lift force of the five-bristle model is between 40° and 45°. Forα ≠θwith the Reynold numberRe≪ 0.1, the optimal ellipse attack angle is between 40° and 45°. Forα ≠θwithRe∼ 1, the optimal ellipse attack angle deviates heavier from the range between 40° and 45° at someαvalues and reaches approximately 32° atα= 20°. This paper can lay a foundation for optimal design of small flying robotics and enhancement of flow through porous structures in future.

SRRM2 may be a potential biomarker and immunotherapy target for multiple myeloma: a real-world study based on flow cytometry detection.

Serine/arginine repetitive matrix 2 (SRRM2) has been implicated in tumorigenesis, cancer development, and drug resistance through aberrant splicing; however, its correlation with multiple myeloma (MM) has not been reported. We investigated the potential of SRRM2 as a biomarker and immunotherapeutic target in MM by examining its expression in MM cells using flow cytometry. Our study included 95 patients with plasma cell disease, including 80 MM cases, and we detected SRRM2 expression on plasma cells and normal blood cells to analyze its relationship with clinical profiles. We found widespread positive expression of SRRM2 on plasma cells with little expression on normal blood cells, and its expression on abnormal plasma cells was higher than that on normal plasma cells. Comparative analysis with clinical data suggests that SRRM2 expression on plasma cells correlates with MM treatment response. MM patients with high SRRM2 expression had higher levels of serum ß2-mg and LDH, ISS staging, and plasma cell infiltration, as well as high-risk mSMART 3.0 stratification and cytogenetic abnormalities, particularly 1q21 amplification. In patients with previous MM, high SRRM2 expression on plasma cells was associated with higher plasma cell infiltration, high-risk mSMART 3.0 risk stratification, cytogenetic abnormalities, more relapses, and fewer autologous stem cell transplant treatments. In summary, SRRM2 may serve as a novel biomarker and immunotherapeutic target for MM. Its expression level on plasma cells can help in risk stratification of MM and monitoring of treatment response.

The roles and mechanisms of TGFB1 in acute myeloid leukemia chemoresistance.

Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) patients usually have very poor prognoses, and drug-resistance is one of the major limiting factors. In this study, we aimed to explore the functions of Transforming Growth Factor-ß1 (TGFB1) in AML drug-resistance. First, TGFB1 levels in serum and bone marrow are higher in R/R patients compared with newly diagnosed patients, this phenomenon could be due to different sources of secreted TGFB1 according to immunohistochemistry of marrow biopsies. Similarly, TGFB1 expression in AML drug-resistant cell lines is higher than that in their parental cell lines, and blocking the TGFB signaling pathway by specific inhibitors decreased resistance to chemotherapeutic agents. On the other hand, exogenous TGFB1 can also promote AML parental cells senescence and chemotherapy resistance. Next, we found SOX4 level is upregulated in drug-resistant cells, and parental cells treated with exogenous TGFB1 induced upregulation of SOX4 levels. Interference of SOX4 expression by siRNA diminished the TGFB1-induced sensitivity to chemotherapeutic agents. Finally, we conduct metabolomic analysis and find Alanine, aspartate and glutamate metabolism pathway, and Glycerophospholipid metabolism pathway are decreased after inhibiting TGFB signaling pathway or interfering SOX4 expression. This study concludes that TGFB1 level in R/R AML patients and drug-resistant strains is significantly increased. Blocking the TGFB signaling pathway can enhance the chemosensitivity of drug-resistant cells by suppressing SOX4 expression and metabolic reprogramming.

Association of NLRPs with pathogenesis of dry age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and Dry AMD is the most common clinical subtype. However, effective measures for the early diagnosis and treatment of dry AMD have not been proposed. In recent years, NOD-like receptors (NLRs) have received attention in the study of AMD as an important class of pattern recognition receptors. We attempted to elucidate the pathogenesis of NLRs in dry AMD from the perspective of chronic inflammation. METHODS: This study involved 13 patients with dry AMD, 10 age- and sex-matched normal population without any history of disease and 8 patients with wet AMD as controls. Using RT-qPCR, the mRNA expression levels of NLRs in peripheral blood peripheral blood mononuclear cells (PBMCs) were compared to analyze the statistical differences in the expression contents among the three populations. RESULTS: The relative RNA expression of nucleotide-binding oligomerization-like receptor protein 12 (NLRP12) with negative regulation of inflammation was significantly lower in dry AMD patients than in normal people and wet AMD patients. And NLRX1, which also has an anti-inflammatory effect, was lower in dry AMD patients than in wet AMD patients. However, NLRP3 with proinflammatory effect was significantly expressed in wet AMD. CONCLUSION: The significant decrease in NLRP12 in dry AMD may become a breakthrough in the study of dry AMD and systemic chronic inflammatory response. However, NLRP3 may have a more important role in wet AMD.

[Effect of Gualou Xiebai Decoction on pulmonary fibrosis in rats based on pyroptosis pathway].

This study investigated the effect of Gualou Xiebai Decoction on rats with bleomycin-induced pulmonary fibrosis. The rats were randomly divided into a control group, a model group, a low-dose Gualou Xiebai Decoction group(2.4 g·kg~(-1)), a high-dose Gualou Xiebai Decoction group(4.8 g·kg~(-1)), and pirfenidone group(150 mg·kg~(-1)). The model of pulmonary fibrosis was established by intratracheal instillation of bleomycin in all groups, except the control group. Since the second day of modeling, the corresponding drugs were given to rats by intragastric administration, once a day for 14 d and 28 d. The hematoxylin-eosin(HE) staining was used to evaluate the degree of inflammatory injury in lung tissues. The immunofluorescence staining was used to detect the expression of CD68 and CD163 in lung tissues of rats. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in serum and brochoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The expression of pyroptosis-related genes in lung tissues of rats was detected by qRT-PCR. The results of HE staining and immunofluorescence staining showed that the lung tissue structure was normal in the control group. In addition, there were alveolar collapse or even closure in lung tissues of rats in the model group, with obvious inflammatory cell infiltration, and the expression of CD68 and CD163 was significantly up-regulated. As compared with the model group, the lung tissue structure of rats in the Gualou Xiebai Decoction groups was significantly improved, with alleviated inflammation, and the expression of CD68 and CD163 was decreased. As compared with the control group, the level of TNF-α in serum and BALF of rats in the model group was significantly increased(P<0.01), the mRNA expression levels of alpha smooth muscle actin(α-SMA), collagen type Ⅰ alpha 1 chain(Col1a1), caspase-1, IL-1ß, IL-18, gasdermin D(Gsdmd), and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in lung tissues were significantly increased(P<0.05, P<0.01), and the mRNA expression level of E-cadherin was significantly decreased(P<0.01). As compared with the model group, the level of TNF-α in serum and BALF was significantly down-regulated in the high-dose Gualou Xiebai Decoction group(P<0.05, P<0.01), and that of IL-10 was up-regulated(P<0.05, P<0.01). The mRNA expression levels of α-SMA, Col1a1, caspase-1, IL-18, Gsdmd, NLRP3 and IL-1ß in lung tissues were significantly decreased(P<0.05, P<0.01) in the high-dose Gualou Xiebai Decoction group, and the mRNA expression level of E-cadherin was significantly increased(P<0.05, P<0.01). In conclusion, Gualou Xiebai Decoction can down-regulate the levels of inflammatory factors and related genes and effectively mitigate pulmonary fibrosis by regulating the pyroptosis pathways.

Effect of INR on Outcomes of Endovascular Treatment for Acute Vertebrobasilar Artery Occlusion.

Endovascular treatment (EVT) has been proven to be the standard treatment for acute vertebrobasilar artery occlusion (VBAO). This study aimed to analyze the effects of international normalized ratio (INR) indicators on outcomes in patients with acute VBAO treated with EVT. Dynamic data on INR in patients with VBAO who received endovascular treatment (EVT) at 65 stroke centers in China were retrospectively enrolled. Outcome measures included the modified Rankin Scale (mRS) score at 90 days and 1 year and symptomatic intracranial hemorrhage (sICH). The associations between elevated INR (INR > 1.1), INR variability (time-weighted variance of INR changes), and various clinical outcomes were analyzed in all patients and subgroups stratified by oral anticoagulation (OAC) by mixed logistic regression analysis. A total of 1825 patients met the study criteria, of which 1384 had normal INR and 441 had elevated INR. Multivariate analysis showed that elevated INR was significantly associated with poor functional outcomes (mRS 4-6) at 90 days (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.08-1.72) and 1 year (OR 1.32, 95% CI 1.05-1.66), but was not associated with an increased risk of sICH (OR 1.00, 95% CI 0.83-1.20). Similar associations exist between INR variability and poor functional outcomes at 90 days (OR 2.17, 95% CI 1.09-4.30), 1 year (OR 2.28, 95% CI 1.16-4.46), and sICH (OR 1.11, 95% CI 0.93-1.33). Subgroup analyses further revealed that elevated INR and INR variability remained associated with poor functional outcomes in patients not receiving oral anticoagulation (OAC) therapy, while no significant associations were observed in OAC-treated patients, regardless of whether they were on warfarin or direct oral anticoagulants. Elevated INR and INR variability in VBAO patients treated with EVT were associated with poor functional outcomes. The mechanism underlying the association between elevated INR and poor functional outcomes might be attributed to the fact that elevated INR indirectly reflects the burden of comorbidities, which could independently worsen outcomes. These findings underscore the importance of a comprehensive and dynamic evaluation of INR levels in the management of VBAO patients receiving EVT, providing valuable insights for optimizing patient outcomes.

Conjugative transfer of streptococcal prophages harboring antibiotic resistance and virulence genes.

Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting antimicrobial resistance genes (ARGs). Herein we characterize a prevalent family of prophages in Streptococcus, designated SMphages, which harbor twenty-five ARGs that collectively confer resistance to ten antimicrobial classes, including vanG-type vancomycin resistance locus and oxazolidinone resistance gene optrA. SMphages integrate into four chromosome attachment sites by utilizing three types of integration modules and undergo excision in response to phage induction. Moreover, we characterize four subtypes of Alp-related surface proteins within SMphages, the lethal effects of which are extensively validated in cell and animal models. SMphages transfer via high-frequency conjugation that is facilitated by integrative and conjugative elements from either donors or recipients. Our findings explain the widespread of SMphages and the rapid dissemination of ARGs observed in members of the Streptococcus genus.

Immune-related lncRNAs pairs prognostic score model for prediction of survival in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is one of the most common malignant and aggressive hematologic tumors, and risk stratification is indispensable to ensure proper treatment. But immune-related long noncoding RNAs (ir-lncRNAs) pairs prognostic risk models used to stratify AML have yet to be reported. In this study, we established a prognostic risk model based on eight ir-lncRNAs pairs using LASSO-penalized Cox regression analysis and successfully validated the model in an independent cohort. According to risk scores, patients were divided into a high-risk group and a low-risk group. High-risk patients presented more tumor mutation frequency and higher expression of human leukocyte antigen (HLA)-related genes and immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) indicated that the transforming growth factors ß (TGFß) pathway was activated in the high-risk group; meanwhile, we found that TGFß1 mRNA levels were significantly elevated in AML patients and correlated with poor prognosis, which is closely related to drug resistance. Consistently, in vitro studies found that exogenous TGFß1 can protect AML cells from chemotherapy-induced apoptosis. Collectively, we developed an ir-lncRNA prognostic model that helps predict the prognosis of AML patients and provides valuable information about their response to immune checkpoint inhibitors, and we found that increased TGFß1 levels resulting in chemoresistance may be one of the leading causes of treatment failure in high-risk AML patients.

Emulsion-Templated Liquid Oil Structuring with Egg White Protein Microgel- Xanthan Gum.

In this study, oleogels were prepared by the emulsion-template method using egg-white protein microgel as a gelator and xanthan gum (XG) as thickener. The physicochemical properties of the emulsion and oleogels were investigated. The adsorption of protein on the surface of the oil droplet reached saturation when the protein microgel concentration reached 2%. The excess protein combined with XG and accumulated on the outer layer of the oleogel, which prevented the emulsion from flocculation, enhanced the oil-holding capacity of the oleogel, and had a positive effect on preventing the oxidation of oil. When the concentration of XG was less than 0.4%, the EWP microgel, combined with the XG, stabilized the emulsion. As the concentration of XG was greater than 0.4%, excessive XG in the emulsion improved the viscosity and mechanical properties of the emulsion to prevent the aggregation of oil droplets. However, the change in XG concentration had no significant effect on the oxidation of the oil.

SQSTM1/p62 Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma.

Migration and invasion play crucial roles in the progression of hepatocellular carcinoma (HCC), but the underlying mechanisms are not clear. Analysis of clinical samples indicates that SQSTM1/p62 is highly expressed in HCC and seriously affects the prognosis of patients. Subsequently, we showed that SQSTM1/p62 knockout using the CRISPR/Cas9 system led to impaired migration and invasion of HCC, upregulated Keap1, and promoted the inhibitory effect of Keap1 on Nrf2. Then, the inactivation of Nrf2 inhibited the expression of matrix metalloproteinases (MMPs), thus attenuating the migration and invasion of HCC. We also found that SQSTM1/p62 knockout significantly inhibited migration and invasion in a lung metastasis model of nude mice with HCC. Furthermore, we found that cisplatin not only significantly inhibited the expression of SQSTM1/p62 but also slowed down the migration and invasion of HCC, while the inflammatory microenvironment accelerated the migration and invasion of HCC. These results suggest for the first time that SQSTM1/p62 knockout inhibits the migration and invasion of HCC through the Keap1/Nrf2/MMP2 signaling pathway. SQSTM1/p62 may be developed into a key drug target to regulate the migration and invasion of HCC cells.

Canagliflozin Attenuates Lipotoxicity in Cardiomyocytes by Inhibiting Inflammation and Ferroptosis through Activating AMPK Pathway.

Diabetic cardiomyopathy (DCM) is a myocardial disease independent of other cardiovascular diseases, such as coronary heart disease, hypertension, etc. Lipotoxicity is closely related to DCM. In this study, we investigated the mechanism of lipid metabolism disturbance in DCM in HL-1 cells. Through bioinformatics and Western blotting analysis, we found that canagliflozin (CAN) significantly inhibited the expression of inflammatory factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Ferroptosis is mediated by lipid peroxidation. We demonstrated the presence of ferroptosis in cardiomyocytes by detecting intracellular Fe2+ content and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), and mitochondrial membrane potential (MMP). CAN could significantly regulate the indicators of ferroptosis. By using specific inhibitors celecoxib (coxib), S-methylisothiourea sulfate (SMT), Ferrostatin-1 (Fer-1), and Compound C, we further found that CAN regulated inflammation and ferroptosis through AMP-activated protein (AMPK), and inflammation interacted with ferroptosis. Our study indicated that CAN attenuated lipotoxicity in cardiomyocytes by regulating inflammation and ferroptosis through activating the AMPK pathway. This study provides a new direction of myocardial lipotoxicity and some new information for the treatment of DCM.

Novel extraction technologies and potential applications of egg yolk proteins.

The high nutritional value and diverse functional properties of egg yolk proteins have led to its widespread use in the fields of food, medicine, and cosmetics. Various extraction methods have been reported to obtain the proteins from egg yolk, however, their utilization is limited due to the relatively low extraction efficiency and/or toxic solvents involved. Several simpler and greener technologies, especially physical fields (ultrasound), have been successfully developed to improve the extraction efficiency. The egg yolk proteins may exert multiple biological activities, enabling them to be a promising tool in improve human health and wellbeing, such as anti-obesity, anti-atherosclerosis, anti-osteoporosis, diagnosis and therapy for SARS-CoV-2 infections. This article summarizes the novel extraction technologies and latest applications of the egg yolk proteins in the recent 5 years, which should stimulate their utilization as health-promoting functional ingredients in foods and other commercial products.

Changes in partial properties of glycosylated egg white powder during storage.

BACKGROUND: Glycosylation is an effective method to modify protein. However, there is a lack of research on the property changes of glycosylated protein during storage. In the present study, the changes in the physicochemical, functional, and structural properties of xylo-oligosaccharide (XOS) glycosylated egg white powder (EWP) (XOS-EWP conjugates) prepared with different glycosylation conditions (XOS/EWP ratio and reaction time) were investigated when stored at 25 °C and 60% relative humidity. RESULTS: In the 12 weeks of storage, the degree of grafting, browning, and the formation of Maillard reaction products of XOS-EWP conjugates increased. The increase in XOS/EWP ratio and reaction time led to an increase in protein aggregation, though a decrease in solubility, due to increased degree of glycosylation and structural changes. Furthermore, improved gel hardness of XOS-EWP conjugates deteriorated, while improved emulsification ability was kept stable during storage. For the sample with a lower XOS/EWP ratio and reaction time, the gel hardness and emulsifying properties underwent little or no deterioration even improving during storage. The results could be attributed to the limited degree of glycosylation, further unfolding of the protein structure, increased surface hydrophobicity of protein, and improved thermal characteristics. CONCLUSION: During storage, the Maillard reaction would continue to occur in the glycosylated EWP, further affecting the performance of modified EWP. Modified EWP prepared under different glycosylation conditions performed differently during storage. Modified EWP with a larger XOS/EWP ratio and reaction time meant it was harder to maintain good performance. Modified EWP with a smaller XOS/EWP ratio and reaction time changed significantly to better performances. © 2022 Society of Chemical Industry.