Immune-regulating effect of oxytocin and its association with the hypothalamic-pituitary axes.

Oxytocin can regulate immunological activity directly or indirectly; however, immunological functions and mechanisms of oxytocin actions under chronic stress like cesarean delivery (CD) are poorly understood. Our study found that abnormal oxytocin production and secretion in CD rats caused atrophy of thymic tissues. Neurotoxin kainic acid microinjected into the dorsolateral supraoptic nucleus in male rats selectively reduced hypothalamic oxytocin levels, increased corticotrophin-releasing hormone and plasma interleukin-1ß while reducing plasma oxytocin, thyroxine and testosterone levels and causing atrophy of immune tissues. Thus, plasma oxytocin is essential for immunological homeostasis, which involves oxytocin facilitation of thyroid hormone and sex steroid secretion.

The role of algae in regulating the fate of microplastics: A review for processes, mechanisms, and influencing factors.

As an important emerging pollutant, the fate of microplastics (MPs) in ecosystems is of growing global concern. In addition to hydrodynamics and animals, algae can also affect the transport of MPs in aquatic environments, which could potentially remove MPs from the water column. Although researchers have conducted many studies on the sink of MPs regulated by algae in both marine and freshwater environments, there is still a lack of comprehensive understanding coupled with the increasingly scattered study contents and findings. This review aims to provide a systematic discussion of the processes, mechanisms, and influencing factors, which are coupled with the sink of MPs changes by algae. The main processes identified include retention, flocculation, deposition, and degradation. The retention of MPs is achieved by adhesion of MPs to algae or embedment/encrustation of MPs within the epibiont matrix of algae, thereby preventing MPs from migrating with water currents. The extracellular polymeric substances (EPS) and enzymes produced by algal metabolic activities can lead not only to the formation of aggregates containing MPs but also to the biodegradation of MPs. The processes that algae alter the fate of MPs in aquatic environments are very complex and can be influenced by various factors such as algal attributes, microplastic characteristics and environmental conditions. This review provides insights into recent advances in the fate of aquatic MPs and highlights the need for further research on MPs-algae interactions, potentially shortening the knowledge gap in the sink of MPs in aquatic ecosystems.

New insights into biologic interpretation of bioinformatic pipelines for fish eDNA metabarcoding: A case study in Pearl River estuary.

Environmental DNA (eDNA) metabarcoding is an emerging tool for monitoring biological communities in aquatic ecosystems. The selection of bioinformatic pipelines significantly impacts the results of biodiversity assessments. However, there is currently no consensus on the appropriate bioinformatic pipelines for fish community analysis in eDNA metabarcoding. In this study, we compared three bioinformatic pipelines (Uparse, DADA2, and UNOISE3) using real and mock (constructed with 15/30 known fish) communities to investigate the differences in biological interpretation during the data analysis process in eDNA metabarcoding. Performance evaluation and diversity analyses revealed that the choice of bioinformatic pipeline could impact the biological results of metabarcoding experiments. Among the three pipelines, the operational taxonomic units (OTU)-based pipeline (Uparse) showed the best performance (sensitivity: 0.6250 ± 0.0166; compositional similarity: 0.4000 ± 0.0571), the highest richness (25-102) and minimal inter-group differences in alpha diversity. It suggested the OTU-based pipeline possessed superior capability in fish diversity monitoring compared to ASV/ZOTU-based pipeline. Additionally, the Bray-Curtis distance matrix achieved the highest discriminative effect in the PCoA (43.3%-53.89%) and inter-group analysis (P < 0.01), indicating it was better at distinguishing compositional differences or specific genera of fish community at different sampling sites than other distance matrices. These findings provide new insights into fish community monitoring through eDNA metabarcoding in estuarine environments.

Biocontrol and growth promotion potential of Bacillus velezensis NT35 on Panax ginseng based on the multifunctional effect.

The Bacillus velezensis strain NT35, which has strong biocontrol ability, was isolated from the rhizosphere soil of Panax ginseng. The antifungal effects of the NT35 strain against the mycelium and spore growth of Ilyonectria robusta, which causes ginseng rusty root rot, were determined. The inhibitory rate of I. robusta mycelial growth was 94.12% when the concentration of the NT35 strain was 107 CFU·mL-1, and the inhibitory rates of I. robusta sporulation and spore germination reached 100 and 90.31%, respectively, when the concentration of the NT35 strain was 104 and 108 CFU·mL-1, respectively. Strain NT35 had good prevention effects against ginseng rust rot indoors and in the field with the control effect 51.99%, which was similar to that of commercial chemical and biocontrol agents. The labeled strain NT35-Rif160-Stre400 was obtained and colonized ginseng roots, leaves, stems and rhizosphere soil after 90 days. Bacillus velezensis NT35 can induce a significant increase in the expression of five defensive enzyme-encoding genes and ginsenoside biosynthesis-related genes in ginseng. In the rhizosphere soil, the four soil enzymes and the microbial community improved during different periods of ginseng growth in response to the biocontrol strain NT35. The NT35 strain can recruit several beneficial bacteria, such as Luteimonas, Nocardioides, Sphingomonas, and Gemmatimonas, from the rhizosphere soil and reduce the relative abundance of Ilyonectria, Fusarium, Neonectria and Dactylonectria, which cause root rot and rusty root rot in ginseng plants. The disease indices were significantly negatively correlated with the abundances of Sphingomonas and Trichoderma. Additionally, Sphingomonadales, Sphingomonadaceae and actinomycetes were significantly enriched under the NT35 treatment according to LEfSe analysis. These results lay the foundation for the development of a biological agent based on strain NT35.

Effects of a liquid and dry Saccharomyces cerevisiae fermentation product (SCFP) feeding program on ruminal fermentation, total tract digestibility, and plasma metabolome of Holstein steers receiving a grain-based diet.

The study aimed to determine the effects of a postbiotic feeding program consisting of liquid and dry Saccharomyces cerevisiae fermentation product (SCFP) on ruminal fermentation, digestibility, and plasma metabolome of Holstein steers receiving a grain-based diet. Eight Holstein steers (Body weight; BW 467 ± 13.9 kg) equipped with rumen cannulas were used in a crossover design study, with 21 d per period and a 7 d washout period in between periods. Steers were stratified by initial BW and assigned to one of two treatments. The treatments were (1) Control, basal finishing diet only (CON); (2) SCFP, one-day feeding of liquid SCFP (infused into the rumen via the cannula at 11 mL/100 kg BW) followed by daily feeding of dry SCFP (12 g/d, top-dressed). Feed and spot fecal samples were collected during d 17 to 20 for determination of digestibility and fecal excretion of N, P, Cu, and Zn. Digestibility was measured using acid-insoluble ash as an internal marker. Blood samples were collected on d 21 before the morning feeding. Rumen fluid samples were collected on d 0, 1, 2, 3, 5 and 21 via rumen cannula. Results were analyzed with the GLIMMIX procedure of SAS 9.4 (SAS, 2023). Treatment did not affect DMI (P = 0.15) and digestibility (P ≥ 0.62). The fecal output and absorption of Zn, Cu, P, and N were not affected (P > 0.22) by treatment. On d 1, the liquid SCFP supplementation tended to reduce (P = 0.07) ruminal VFA concentration and increased (P < 0.01) the molar proportion of valerate. Feeding SCFP tended to increase total ruminal VFA on d 5 (P = 0.08) and significantly increased total VFA on d 21 (P = 0.05). Ruminal NH3-N was reduced (P = 0.02) on d 21 by supplementing SCFP. Treatment did not affect the production of proinflammatory cytokines, IL-1ß (P > 0.19) and IL-6 (P > 0.12) in the whole blood in response to various toll-like receptor stimulants in vitro. Feeding SCFP enriched (P ≤ 0.05) plasma metabolic pathways, including citric acid cycle, pyrimidine metabolism, glycolysis/gluconeogenesis, retinol metabolism, and inositol phosphate metabolism pathways. In summary, supplementing liquid SCFP with subsequent dry SCFP enhanced ruminal total VFA production and reduced NH3-N concentration nitrogen in the rumen. Furthermore, feeding SCFP enriched several important pathways in lipid, protein, and glucose metabolism, which may improve feed efficiency of energy and protein in Holstein steers.

Social media use and mental health among older adults with multimorbidity: the role of self-care efficacy.

OBJECTIVES: To describe the prevalence and trends in the use of social media over time and explore whether social media use is related to better self-care efficacy and thus related to better mental health among United States older adults with multimorbidity. MATERIALS AND METHODS: Respondents aged 65 years+ and having 2 or more chronic conditions from the 2017-2020 Health Information National Trends Survey were analyzed (N = 3341) using weighted descriptive and logistic regression analyses. RESULTS: Overall, 48% (n = 1674) of older adults with multimorbidity used social media and there was a linear trend in use over time, increasing from 41.1% in 2017 to 46.5% in 2018, and then further up to 51.7% in 2019, and 54.0% in 2020. Users were often younger, married/partnered, and non-Hispanic White with high education and income. Social media use was associated with better self-care efficacy that was further related to better mental health, indicating a significant mediation effect of self-care efficacy in the relationship between social media use and mental health. DISCUSSION: Although older adults with multimorbidity are a fast-growing population using social media for health, significant demographic disparities exist. While social media use is promising in improving self-care efficacy and thus mental health, relying on social media for the management of multimorbidity might be potentially harmful to those who are not only affected by multimorbidity but also socially disadvantaged (eg, non-White with lower education). CONCLUSION: Great effort is needed to address the demographic disparity and ensure health equity when using social media for patient care.

Fast 3D 31P B1 + mapping with a weighted stack of spiral trajectory at 7 Tesla.

Purpose: Phosphorus Magnetic Resonance Spectroscopy (31P MRS) enables non-invasive assessment of energy metabolism, yet its application is hindered by sensitivity limitations. To overcome this, often high magnetic fields are used, leading to challenges such as spatial B 1 + inhomogeneity and therefore the need for accurate flip angle determination in accelerated acquisitions with short repetition times T R ) . In response to these challenges, we propose a novel short T R and look-up table-based Double-Angle Method for fast 3D 31P B 1 + mapping (fDAM). Methods: Our method incorporates 3D weighted stack of spiral gradient echo acquisitions and a frequency-selective pulse to enable efficient B 1 + mapping based on the phosphocreatine signal at 7T. Protocols were optimised using simulations and validated through phantom experiments. The method was validated in phantom experiments and skeletal muscle applications using a birdcage 1H/31P volume coil. Results: The results of fDAM were compared to the classical DAM (cDAM). A good correlation (r=0.94) was obtained between the two B 1 + maps. A 3D 31P B 1 + mapping in the human calf muscle was achieved in about 10 min using a birdcage volume coil, with a 20% extended coverage relative to that of the cDAM (24 min). fDAM also enabled the first full brain coverage 31P 3D B 1 + mapping in approx. 10 min using a 1 Tx/ 32 Rx coil. Conclusion: fDAM is an efficient method for 31P 3D B 1 + mapping, showing promise for future applications in rapid 31P MRSI.

Patients' Perceptions of Using Technology for Self-Reporting Cancer Medication Safety Events from Home.

Frequent transitions of care among patients with cancer increase their risks for medication safety events (MSEs). Patients and families need to become "vigilant partners" in MSE self-reporting when transitioning back home. However, limited evidence is available to guide patient and family engagement in preventing and managing MSEs. This study explored patients' perceptions of using technology for MSE self-reporting by interviewing 41 patients with breast, prostate, lung, or colorectal cancer. The findings revealed that patients with cancer perceived technology as convenient and easy to use to address urgent MSE concerns. However, the lack of access to technology and being unconfident in using technology can be barriers to using technology for MSE reporting. Personalized support is needed to facilitate patients' engagement in MSE self-reporting. Factors identified in the study will further support the user-centered design and development of technology systems that can support patients' needs and expectations for medication safety.

[Synergistic effect and compatibility structure of active anti-inflammatory ingredients from Lamiophlomis rotata based on network pharmacology and component structure theory].

The synergistic effect and compatibility structure of active anti-inflammatory ingredients(iridoid glycosides: shanzhiside methylester and 8-O-acetylshanzhiside methyl ester, flavonoid glycoside: luteoloside, and phenylethanoid glycoside: forsythoside B) from Lamiophlomis rotata were explored based on network pharmacology and component structure theory. In network pharmacology, CTD, SwisseTargetPrediction, and PharmMapper databases were used to collect and screen the targets of all active ingredients. The inflammation-related targets were obtained from CTD and GeneCards databases. The core targets were obtained by Venny 2.1.0, STRING, and Cytoscape 3.9.1. Core targets were annotated by the GO function and enriched by the KEGG pathway based on the DAVID database. In terms of component structure, based on a uniform design method and xylene-induced ear swelling model in mice, tumor necrosis factor-α and interleukin-6 were taken as the dependent variables, and the compatibility relationship among anti-inflammatory ingredients from L. rotata was explored through the quadratic polynomial stepwise regression. In addition, in vivo pharmacological experiments were conducted to verify the results. A network pharmacology study showed that compared with a single ingredient, the combined action of the three ingredients can synergistically exert anti-inflammatory effects through more biological processes, pathways, and targets. Component structure study showed that the optimal structural ratio of shanzhiside methylester and 8-O-acetylshanzhiside methyl ester in the iridoid glycoside ingredient was 1.21∶1. The optimal structural ratio among the three types of ingredients(iridoid glycosides∶phenylethanol glycoside∶flavonoid glycoside) was 4.8∶1.6∶1. In conclusion, each anti-inflammatory ingredient from L. rotata can work synergistically, and there is an optimal compatibility ratio relationship among these ingredients. This work provides a new experimental basis for the intrinsic quality control of L. rotata.

Customized Music Therapy Combined With the Counseling and Follow-Up System: Stratified Results for Tinnitus Efficacy.

Objective: Chronic subjective tinnitus is a worldwide intractable problem. In our previous studies, customized music therapy combined with a follow-up system can reduce tinnitus perception and improve anxiety/depression. This study aims to explore which characteristics of tinnitus patients are more likely to benefit from our therapy. Study Design: This study included 1031 patients with chronic subjective tinnitus, all of whom completed customized music therapy with the follow-up system. Population demographics, tinnitus characteristics, and tinnitus-related scales at pretherapy and posttherapy were collected. Setting: Huadong Hospital affiliated Fudan University, Department of Otorhinolaryngology-Head & Neck Surgery from 2018 to 2022. Methods: A paired t test and the one-way analysis of variance were utilized to the overall efficacy and stratified difference based on tinnitus duration/age/tinnitus frequency. Results: There were significant statistical differences in the Tinnitus Handicap Inventory (THI), Tinnitus Loudness Visual Analog Scale (VAS), and Hospital Anxiety and Depression Scale (HADS)-A/D scores between pretherapy and 3 months posttherapy. THI and HADS (A/D) scores decreased the most in the 1-year duration tinnitus group. The most significant decrease in THI and VAS scores was observed in the 31- to 50-year-old tinnitus group. Patients with high-frequency tinnitus and extended high-frequency tinnitus had greater decreases generally than those with low-frequency tinnitus though no significance. Conclusion: Group with severe and prolonged tinnitus, shorter duration of tinnitus onset, and 31 to 50 years old benefit more from our therapy. Therefore, standardized personalized music and consulting and follow-up systems while promoting early treatment can reduce tinnitus and its comorbidities.

CircCHSY1 protects hearts against ischemia/reperfusion injury by enhancing heme oxygenase 1 expression via miR-24-3p.

AIMS: Circular RNAs are important players involving in a variety of physiological and pathological processes. However, their functions and mechanisms during myocardial ischemic injury and protection remain largely unknown. We recently found significant alterations of many circRNAs including circCHSY1 following myocardial ischemia/reperfusion (I/R) injury, whereas their exact functions are unclear. Here, we investigated roles of circCHSY1 in the acute myocardial I/R injury and the potential mechanisms involved. METHODS AND RESULTS: The expression of circCHSY1 was detected in cardiomyocytes from mouse, rat and human embryonic stem cells (hESC-CMs). It was further upregulated in mouse I/R (30 min/24 h) hearts, oxygen glucose deprivation/reperfused (OGD/R, 6 h/2 h) primary neonatal rat ventricular cardiomyocytes (NRCMs) and OGD/R (48 h/2 h) hESC-CMs. Adenovirus-mediated circCHSY1-overexpression significantly decreased infarct size and lactate dehydrogenase (LDH) release in mouse I/R hearts. Consistently, circCHSY1 overexpression reduced the LDH release in the OGD/R NRCMs and hESC-CMs, improved cell viability, and preserved mitochondrial function in the OGD/R NRCMs, whereas there were no significant differences in cell viability and LDH release between the OGD/R NRCMs with and without siRNA-mediated circCHSY1 knockdown. Mechanistically, circCHSY1 was detected to bind with miR-24-3p analyzed by dual luciferase assay and RNA pull-down assays. CircCHSY1 overexpression-mediated protective effects on cells and mitochondria in OGD/R NRCMs were reversed by the miR-24-3p mimic. Further, dual luciferase assay showed that miR-24-3p directly bound to heme oxygenase 1 (HO1) via its 3'UTR. The protein level of HO1 was downregulated by miR-24-3p mimic in OGD/R NRCMs but enhanced by the circCHSY1 overexpression in vitro and in vivo. Functionally, the HO1 knockdown by adenovirus in vivo and by siRNA in vitro eliminated cardioprotective effects of circCHSY1 overexpression. CONCLUSION: CircCHSY1 is upregulated following myocardial I/R injury. The higher level of circCHSY1 protects I/R hearts and cardiomyocytes. The protection of circCHSY1 is mediated through enhancement of the HO1 level, resulting in preserving mitochondrial homeostasis via targeting miR-24-3p in cardiomyocytes. These findings suggest circCHSY1 as a protective factor.

Integrative analysis of aging-related genes reveals CEBPA as a novel therapeutic target in non-small cell lung cancer.

BACKGROUND: To explore the impact of ARGs on the prognosis of NSCLC, and its correlation with clinicopathological parameters and immune microenvironment. Preliminary research on the biological functions of CEBPA in NSCLC. METHODS: Using consensus clustering analysis to identify molecular subtypes of ARGs in NSCLC patients; employing LASSO regression and multivariate Cox analysis to select 7 prognostic risk genes and construct a prognostic risk model; validating independent prognostic factors of NSCLC using forest plot analysis; analyzing immune microenvironment correlations using ESTIMATE and ssGSEA; assessing correlations between prognostic risk genes via qPCR and Western blot in NSCLC; measuring mRNA and protein expression levels of knocked down and overexpressed CEBPA in NSCLC using CCK-8 and EdU assays; evaluating the effects of knocked down and overexpressed CEBPA on cell proliferation using Transwell experiments; examining the correlation of CEBPA with T cells and B cells using mIHC analysis. RESULTS: Consensus clustering analysis identified three molecular subtypes, suggesting significant differential expression of these ARGs in NSCLC prognosis and clinical pathological parameters. There was significant differential expression between the two risk groups in the prognostic risk model, with P < 0.001. The risk score of the prognostic risk model was also P < 0.001. CEBPA exhibited higher mRNA and protein expression levels in NSCLC cell lines. Knockdown of CEBPA significantly reduced mRNA and protein expression levels of CEBPB, YWHAZ, ABL1, and CDK1 in H1650 and A549 cells. siRNA-mediated knockdown of CEBPA markedly inhibited proliferation, migration, and invasion of NSCLC cells, whereas overexpression of CEBPA showed the opposite trend. mIHC results indicated a significant increase in CD3 + CD4+, CD3 + CD8+, and CD20 + cell counts in the high CEBPA expression group. CONCLUSIONS: The risk score of the prognostic risk model can serve as an independent prognostic factor, guiding the diagnosis and treatment of NSCLC. CEBPA may serve as a potential tumor biomarker and immune target, facilitating further exploration of the biological functions and immunological relevance in NSCLC.

Deciphering assembly processes, network complexity and stability of potential pathogenic communities in two anthropogenic coastal regions of a highly urbanized estuary.

The existence of potential pathogens may lead to severe water pollution, disease transmission, and the risk of infectious diseases, posing threats to the stability of aquatic ecosystems and human health. In-depth research on the dynamic of potential pathogenic communities is of significant importance, it can provide crucial support for assessing the health status of aquatic ecosystems, maintaining ecological balance, promoting sustainable economic development, and safeguarding human health. Nevertheless, the current understanding of the distribution and geographic patterns of potential pathogens in coastal ecosystems remains rather limited. Here, we investigated the diversity, assembly, and co-occurrence network of potential pathogenic communities in two anthropogenic coastal regions, i.e., the eight mouths (EPR) and nearshore region (NSE), of the Pearl River Estuary (PRE) and a total of 11 potential pathogenic types were detected. The composition and diversity of potential pathogenic communities exhibited noteworthy distinctions between the EPR and NSE, with 6 shared potential pathogenic families. Additionally, in the NSE, a significant pattern of geographic decay was observed, whereas in the EPR, the pattern of geographic decay was not significant. Based on the Stegen null model, it was noted that undominant processes (53.36%/69.24%) and heterogeneous selection (27.35%/25.19%) dominated the assembly of potential pathogenic communities in EPR and NSE. Co-occurrence network analysis showed higher number of nodes, a lower average path length and graph diameter, as well as higher level of negative co-occurrences and modularity in EPR than those in NSE, indicating more complex and stable correlations between potential pathogens in EPR. These findings lay the groundwork for the effective management of potential pathogens, offering essential information for ecosystem conservation and public health considerations in the anthropogenic coastal regions.

IRX5's influence on macrophage polarization and outcome in papillary thyroid cancer.

Background: With a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the molecular level and the immune environment within tumors of various thyroid cancer subtypes in order to identify potential targets for therapy and provide precise treatment for patients with thyroid adenocarcinoma. Methods: First, we analyzed the expression of IRX5 in pan-cancer and papillary thyroid carcinoma by bioinformatics methods and collected paired samples from our center for validation. Subsequently, we analyzed the significance of IRX5 on the prognosis and diagnosis of PTC. Next, we explored the possible mechanisms by which IRX5 affects the prognosis of thyroid cancer patients by GO/KEGG enrichment analysis, and further investigated the effect of IRX5 on immune infiltration of thyroid cancer. Ultimately, by conducting experiments on cells and animals, we were able to show how IRX5 impacts the aggressive characteristics of thyroid cancer cells and its influence on macrophages within the immune system of thyroid cancer. Results: In 11 malignant tumors, including PTC, IRX5 is overexpressed and associated with a poor prognosis. IRX5 may affect the prognosis of PTC through embryonic organ development, ossification, mesenchyme development, etc. Increased IRX5 expression decreases the presence of cytotoxic and Th17 cells in papillary thyroid cancer. IRX5 was highly expressed in different PTC cell lines, such as K-1 and TPC-1. Silencing IRX5 effectively halted the growth and movement of PTC cells while also decreasing M2 polarization and enhancing M1 polarization in tumor-associated macrophages. Conclusion: IRX5 could impact the outlook of individuals with PTC by stimulating the shift of macrophages to M2 in the immune surroundings of thyroid cancer growths, suggesting a potential new focus for treating thyroid cancer, particularly through immunotherapy.

Glycerol-driven adaptive evolution for the production of low-molecular-weight Welan gum: Characterization and activity evaluation.

Through adaptive laboratory evolution (ALE) of Sphingomonas sp. ATCC 31555, fermentation for production of low-molecular-weight welan gum (LMW-WG) was performed using glycerol as sole carbon source. During ALE, GPC-MALS analysis revealed a gradual decrease in WG molecular weight with the increase of adaptation cycles, accompanied by changes in solution conformation. LMW-WG was purified and structurally analyzed using GPC-MALS, monosaccharide composition analysis, infrared spectroscopy, NMR analysis, atomic force microscopy, and scanning electron microscopy. Subsequently, LMW-WG obtains hydration, transparency, antioxidant activity, and rheological properties. Finally, an in vitro simulation colon reactor was used to evaluate potential prebiotic properties of LMW-WG as dietary fiber. Compared with WG produced using sucrose as substrate, LMW-WG exhibited a fourfold reduction in molecular weight while maintaining moderate viscosity. Structurally, L-Rha nearly completely replaced L-Man. Furthermore, LMW-WG demonstrated excellent hydration, antioxidant activity, and high transparency. It also exhibited resistance to saliva and gastrointestinal digestion, showcasing a favorable colonization effect on Bifidobacterium, making it a promising symbiotic agent.

Activation of Nrf2 inhibits atherosclerosis in ApoE-/- mice through suppressing endothelial cell inflammation and lipid peroxidation.

BACKGROUND: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. METHODS: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE-/- mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE-/- mice. RESULTS: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE-/- mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE-/- mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. CONCLUSIONS: Upon HCD feeding in ApoE-/- mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.

Rapid discrimination of Alismatis Rhizoma and quantitative analysis of triterpenoids based on near-infrared spectroscopy.

This study developed a rapid, accurate, objective and economic method to identify and evaluate the quality of Alismatis Rhizoma (AR) commodities. Traditionally, the identification of plant species and geographical origins of AR commodities mainly relied on experienced staff. However, the subjectivity and inaccuracy of human identification negatively impacted the trade of AR. Besides, liquid chromatographic methods such as ultra-high-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC), the major approach for the determination of triterpenoid contents in AR was time-consuming, expensive, and highly demanded in manoeuvre specialists. In this study, the combination of near-infrared (NIR) spectroscopy and chemometrics as the method was developed and utilised to address the two common issues of identifying the quality of AR commodities. Through the discriminant analysis (DA), the raw NIR spectroscopy data on 119 batches samples from two species and four origins in China were processed to the best pre-processed data. Subsequently, orthogonal partial least squares-discriminant analysis (OPLS-DA) and random forest (RF) as the major chemometrics were used to analyse the best pre-processed data. The accuracy rates by OPLS-DA and RF were respectively 100% and 97.2% for the two species of AR, and respectively100% and 94.4% for the four origins of AR. Meanwhile, a quantitative correction model was established to rapidly and economically predict the seven triterpenoid contents of AR through combining the partial least squares (PLS) method and NIR spectroscopy, and taking the triterpenoid contents measured by UPLC as the reference value, and carry out spectral pre-processing methods and band selection. The final quantitative model correlation coefficients of the seven triterpenoid contents of AR ranged from 0.9000 to 0.9999, indicating that prediction ability of this model had good stability and applicability.

The relationship between medication beliefs, patient activation, and self-rated health in patients taking oral anticancer agents.

PURPOSE: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH. METHODS: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, lung, or prostate cancer. Patients completed a self-reported survey including items of SRH, Beliefs about Medicines Questionnaire (BMQ), and Patient Activation Measure (PAM-13). Descriptive statistics, bivariate correlation, hierarchical multiple linear regression, and mediation analysis were conducted. RESULTS: The results indicate that patients taking OAAs have ambivalent attitudes toward medication. Both medication necessity (r = - 0.27) and concerns (r = - 0.21) were negatively associated with SRH, while patient activation was positively associated with SRH (r = 0.38). Patient activation had a negative association with medication concerns (r = - 0.36) and fully mediated the relationship between medication concerns and SRH in patients taking OAAs (indirect effect = - 0.154, 95% confidence interval, - 0.276 to - 0.060). CONCLUSION: The findings highlight the significance of activating patients to better understand and manage their OAAs. It is crucial for oncology professionals to provide multifaceted interventions to promote patient activation with an effort to mitigate the negative impact of medication beliefs on patient-perceived health outcomes.

Thermodynamic Assessment of the P2O5-Na2O and P2O5-MgO Systems.

Knowledge about the thermodynamic equilibria of the P2O5-Na2O and P2O5-MgO systems is very important for controlling the phosphorus content of steel materials in the process of steelmaking dephosphorization. The phase equilibrium and thermodynamic data of the P2O5-Na2O and P2O5-MgO systems were critically evaluated and re-assessed by the CALPHAD (CAlculation of PHAse Diagram) approach. The liquid phase was described by the ionic two-sublattice model for the first time with the formulas (Na+1)P(O-2, PO3-1, PO4-3, PO5/2)Q and (Mg+2)P(O-2, PO3-1, PO4-3, PO5/2)Q, respectively, and the selection of the species constituting the liquid phase was based on the structure of the phosphate melts. A new and improved self-consistent set of thermodynamic parameters for the P2O5-Na2O and P2O5-MgO systems was finally obtained, and the calculated phase diagram and thermodynamic properties exhibited excellent agreement with the experimental data. The difference in the phase composition of invariant reactions from the experimentally determined values reported in the literature is less than 0.9 mol.%. The present thermodynamic modeling contributes to constructing a multicomponent oxide thermodynamic database in the process of steelmaking dephosphorization.

Skip connection information enhancement network for retinal vessel segmentation.

Many major diseases of the retina often show symptoms of lesions in the fundus of the eye. The extraction of blood vessels from retinal fundus images is essential to assist doctors. Some of the existing methods do not fully extract the detailed features of retinal images or lose some information, making it difficult to accurately segment capillaries located at the edges of the images. In this paper, we propose a multi-scale retinal vessel segmentation network (SCIE_Net) based on skip connection information enhancement. Firstly, the network processes retinal images at multiple scales to achieve network capture of features at different scales. Secondly, the feature aggregation module is proposed to aggregate the rich information of the shallow network. Further, the skip connection information enhancement module is proposed to take into account the detailed features of the shallow layer and the advanced features of the deeper network to avoid the problem of incomplete information interaction between the layers of the network. Finally, SCIE_Net achieves better vessel segmentation performance and results on the publicly available retinal image standard datasets DRIVE, CHASE_DB1, and STARE.