Screening and Analysis of Core Genes for Osteoporosis Based on Bioinformatics Analysis and Machine Learning Algorithms.

Objective: This study aimed to identify osteoporosis-related core genes using bioinformatics analysis and machine learning algorithms. Methods: mRNA expression profiles of osteoporosis patients were obtained from the Gene Expression Profiles (GEO) database, with GEO35958 and GEO84500 used as training sets, and GEO35957 and GSE56116 as validation sets. Differential gene expression analysis was performed using the R software "limma" package. A weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and modular genes of osteoporosis. Kyoto Gene and Genome Encyclopedia (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were performed on the differentially expressed genes. LASSO, SVM-RFE, and RF machine learning algorithms were used to screen for core genes, which were subsequently validated in the validation set. Predicted microRNAs (miRNAs) from the core genes were also analyzed, and differential miRNAs were validated using quantitative real-time PCR (qPCR) experiments. Results: A total of 1280 differentially expressed genes were identified. A disease key module and 215 module key genes were identified by WGCNA. Three core genes (ADAMTS5, COL10A1, KIAA0040) were screened by machine learning algorithms, and COL10A1 had high diagnostic value for osteoporosis. Four core miRNAs (has-miR-148a-3p, has-miR-195-3p, has-miR-148b-3p, has-miR-4531) were found by intersecting predicted miRNAs with differential miRNAs from the dataset (GSE64433, GSE74209). The qPCR experiments validated that the expression of has-miR-195-3p, has-miR-148b-3p, and has-miR-4531 was significantly increased in osteoporosis patients. Conclusion: This study demonstrated the utility of bioinformatics analysis and machine learning algorithms in identifying core genes associated with osteoporosis.

NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation.

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

Correction to: Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI.

[This corrects the article DOI: 10.1093/nsr/nwae057.].

Enzyme-linked immunoassay for simultaneous detection of methyl parathion and sibutramine in apple cider vinegar.

Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system depressant, helps lose weight by disrupting hormone regulation, stimulating sympathetic nerves, and suppressing appetite. However, some unethical businesses fail to properly handle raw materials in foods like apple cider vinegar, leading to residual methyl parathion in apples or illegal excessive addition of sibutramine. Therefore, it is imperative to develop an immunoassay for the rapid detection of methyl parathion and sibutramine. The corresponding two haptens were prepared and coupled with the carrier proteins according to methyl parathion-sulfur-bovine serum protein (BSA)/chicken ovalbumin (OVA)-sibutramine (20 : 1 : excess, 15 : 1 : excess, 10 : 1 : excess, and 5 : 1 : excess), and sibutramine-BSA/OVA-methyl parathion (20 : 1 : excess, 10 : 1 : excess: 5 : 1 : excess, and 0 : 1 : excess). The result shows that the inhibition rate of the antibody obtained by methyl parathion-BSA/OVA-sibutramine (20 : 1 : excess) was higher than that of sibutramine-BSA/OVA-methyl parathion, which was 67.93%, and the concentration of methyl parathion was 8.65 ng mL-1 at this inhibition rate. Thus, methyl parathion-BSA/OVA-sibutramine (8.65 : 1 : excess) and the corresponding antibodies were selected for subsequent method establishment. By changing the concentration of the coating and antibody, the inhibition rate was found when the coating was 0.125 ng mL-1 and the antibody was diluted 4000 times. The antibody was used to develop a standard curve for the detection of sibutramine at the half-maximum inhibitory concentration (IC50) is 4.59 ng mL-1, the limit of detection (IC10) is 2.21 ng mL-1, the detection range is 2.89 to 7.28 ng mL-1, methyl p-phosphorus at the half-maximum inhibitory concentration (IC50) is 15.34 ng mL-1, the limit of detection (IC10) is 0.42 ng mL-1, the detection range is ng mL-1. Under these conditions, the recovery rate was between 88% and 102%, within reasonable limits, indicating the successful establishment of a rapid enzyme-linked ELISA assay.

Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.

Low glucose is a common microenvironment for rapidly growing solid tumors, which has developed multiple approaches to survive under glucose deprivation. However, the specific regulatory mechanism remains largely elusive. In this study, we demonstrate that glucose deprivation, while not amino acid or serum starvation, transactivates the expression of DCAF1. This enhances the K48-linked polyubiquitination and proteasome-dependent degradation of Rheb, inhibits mTORC1 activity, induces autophagy, and facilitates cancer cell survival under glucose deprivation conditions. This study identified DCAF1 as a new cellular glucose sensor and uncovered new insights into mechanism of DCAF1-mediated inactivation of Rheb-mTORC1 pathway for promoting cancer cell survival in response to glucose deprivation.

Efficacy and acceptability of anti-inflammatory agents in major depressive disorder: a systematic review and meta-analysis.

Background: Anti-inflammatory agents have emerged as a potential new therapy for major depressive disorder (MDD). In this meta-analysis, our aim was to evaluate the antidepressant effect of anti-inflammatory agents and compare their efficacy. Methods: We conducted a comprehensive search across multiple databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. The primary outcome measures of our meta-analysis were efficacy and acceptability, while the secondary outcome measures focused on remission rate and dropout rate due to adverse events. We used odds ratio (OR) and 95% confidence interval (95% CI) to present our results. Results: A total of 48 studies were included in our analysis. In terms of efficacy, anti-inflammatory agents demonstrated a significant antidepressant effect compared to placebo (OR = 2.04, 95% CI: 1.41-2.97, p = 0.0002). Subgroup analyses revealed that anti-inflammatory agents also exhibited significant antidepressant effects in the adjunctive therapy subgroup (OR = 2.17, 95% CI: 1.39-3.37, p = 0.0006) and in MDD patients without treatment-resistant depression subgroup (OR = 2.33, 95% CI: 1.53-3.54, p < 0.0001). Based on the surface under the cumulative ranking curve (SUCRA) value of network meta-analysis, nonsteroidal anti-inflammatory drugs (NSAIDs) (SUCRA value = 81.6) demonstrated the highest acceptability among the included anti-inflammatory agents. Conclusion: In summary, our meta-analysis demonstrates that anti-inflammatory agents have significant antidepressant effects and are well-accepted. Furthermore, adjunctive therapy with anti-inflammatory agents proved effective in treating MDD. Among the evaluated anti-inflammatory agents, NSAIDs exhibited the highest acceptability, although its efficacy is comparable to placebo. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=422004), identifier CRD42023422004.

Estimation of urinary cadmium benchmark dose thresholds for preschool children in a cadmium-polluted area based on Bayesian model averaging.

Urinary cadmium (U-Cd) values are indicators for determining chronic cadmium toxicity, and previous studies have calculated U-Cd indicators using renal injury biomarkers. However, most of these studies have been conducted in adult populations, and there is a lack of research on U-Cd thresholds in preschool children. We aimed to apply benchmark dose (BMD) analysis to estimate the U-Cd threshold level associated with renal impairment in preschool children in the cadmium-polluted area. 518 preschool children aged 3-5 years were selected by systematic sampling (275 boys, 243 girls). Urinary cadmium and three biomarkers of early renal injury (urinary N-acetyl-ß-D-glucosaminidase, UNAG; urinary ß2-microglobulin, Uß2-MG; urinary retinol-binding protein, URBP) were determined. Bayesian model averaging estimated the BMD and lower confidence interval limit (BMDL) of U-Cd. The medians U-Cd levels in both boys and girls exceeded the recommended national standard threshold (5 µg/g cr) and U-Cd levels were higher in girls than in boys. Urinary N-acetyl-ß-D-glucosaminidase (UNAG) was the most sensitive biomarker of renal effects in preschool children. The overall BMDL5 (BMDL at a benchmark response value of 5) was 2.76 µg/g cr. In the gender analysis, the BMDL5 values were 1.92 µg/g cr for boys and 4.12 µg/g cr for girls. This study shows that the U-Cd threshold (BMDL5) is lower than the national standard (5 µg/g cr) and boys' BMDL5 was lower than the limit set by the European Parliament and Council in 2019 (2 µg/g cr), which provides a reference point for making U-Cd thresholds for preschool children.

A novel computed tomography scoring system for evaluating the risk of dural defects in anterior surgery for cervical ossification of the posterior longitudinal ligament.

OBJECTIVE: To develop and validate a computed tomography (CT)-based scoring system for evaluating the risk of dural defects (DDs) in anterior surgery for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: We retrospectively analyzed CT imaging features of 114 OPLL patients in our institute who received anterior decompression surgery. Intraoperative DDs were found in 16 patients. A multivariable logistic regression was used to evaluate the predictors. According to the odd ratio of the included risk factors, we developed a CT scoring system for evaluating the risk of DDs in anterior OPLL surgery. The system was further validated in an independent group of 39 OPLL patients. RESULTS: We developed a CT scoring system as follows: hook sign (2 points), K-line (-) (1 point) and broad base (1 point). Thus, the system comprised 4 total points, and patients were at high risks of dural defects when the score ≥3 points. The operating characteristics of a score ≥3 for predicting DDs in the validation group were: sensitivity of 0.83, specificity of 0.94, LR positive of 13.75, LR negative of 0.18 and AUC of 0.886. The discriminatory ability of the proposed score could be demonstrated in the validation cohort. CONCLUSIONS: The relatively simple and easy-to-use scoring system we propose integrates the 3 most reliable spinal CT findings observed in patients with OPLL and a DD. The likelihood to identify the underlying risks of spinal CSF leaks may be useful to triage patients who may benefit from indirect decompression techniques.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

Healthcare preferences of chronic disease patients under China's hierarchical medical system: an empirical study of Tianjin's reform practice.

To alleviate the contradiction in healthcare resources, the Chinese government formally established the framework of a hierarchical medical system in 2015, which contains the following brief generalities: " separate treatment of emergencies and slows, first-contact care at the primary, two-way referral, and upper and lower linkage, ". This study systematically summarizes and models the connotations of China's hierarchical medical system and a sample of 11,200 chronic disease patients in Tianjin, the largest port city in northern China, was selected for the empirical study to investigate the relationship between chronic disease patients' policy perceptions of the hierarchical medical system and their preference for healthcare. We found that under the strategy of separate treatment, improving the healthcare accessibility, drug supply, and lowering the cost of medical care would have a positive impact on increasing the preference of patients with chronic diseases to go to the primary hospitals. Under the two-way triage strategy, improving the level of physician services, referral convenience and treatment Standards have a positive impact on chronic disease patients' preference for primary care; The impact of the hierarchical medical system on the preference for healthcare differed between groups, focusing on differences in health literacy level, age and household type; The role of " upper and lower linkage " is crucial in the hierarchical medical system and it plays a part in mediating the influence of the " separate treatment of emergencies and slows" design and the "two-way referral " order on the treatment preferences of chronic disease patients. The results of the study provide a reference for the further development of a scientific and rational hierarchical medical system in the future.

Glutathione-depleting Liposome Adjuvant for Augmenting the Efficacy of a Glutathione Covalent Inhibitor Oridonin for Acute Myeloid Leukemia Therapy.

BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

Establishment of enzyme-linked immunosorbent assay for aristolochic acid.

In recent years, the nephrotoxicity and carcinogenicity of aristolochic acid have attracted worldwide attention, and the traditional Chinese medicine containing this ingredient has been banned in many places, affecting the TCM industry. To meet this challenge, researchers have developed various detection methods, such as high-performance liquid chromatography, gas chromatography-mass spectrometry and thin-layer chromatography. A rapid detection method must therefore be developed to ensure safety. A polyclonal antibody capable of recognizing aristolochic acid was prepared, and an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established to detect the amount of aristolochic acid in the sample to be measured. Methods Using 1-(4-chlorophenyl) cyclobutylamine as a hapten, immunogens and coating antigens were obtained by coupling with bovine serum albumin (BSA) and chicken ovalbumin (OVA) using the active ester method. UV scanning confirmed the successful coupling of the conjugate, and New Zealand white rabbits were immunized. The obtained antibody serum was screened for the best antibody by ic-ELISA detection. Use the chessboard method to determine three optimal combinations of original coating concentration and antibody dilution ratio, establish a standard curve for each combination to obtain the best combination, and establish a rapid detection method. Finally, the standard aristolochic acid A was added to the purchased apple vinegar and canned coffee for recycling experiments to verify the detection method.By changing the antigen antibody concentration, the antibody showed the highest sensitivity to aristolochic acid standard at the original coating, 1000-fold dilution, IC50 of 24.88 ng/mL, limit of detection IC10 of 3.19 ng/mL, and detection range IC20-IC80 of 6.81-90.91 ng/mL. The recovery experiments under this conditions yielded a recovery rate of 92%-105%, within reasonable limits, indicating the success of the ELISA rapid detection method. Conclusion The enzyme-linked immunoassay method established in this paper can quickly detect the content of aristolochic acid in the sample to be tested, and the antibody prepared by this method has good broad-spectrum and can detect other aristolochic acid, such as aristolochic acid A, aristolochic acid B, aristolochic acid C, and aristolochic acid D.

Adverse events reporting of XPO1 inhibitor - selinexor: a real-word analysis from FAERS database.

As the world's first oral nuclear export inhibitor, selinexor is increasingly being used in clinical applications for malignant tumors. However, there is no extensive exploration on selinexor's adverse events (ADEs), necessitating a real-word assessment of its clinical medication safety. FAERS data (July 2019-June 2023) were searched for selinexor ADE reports across all indications. Use the system organ class (SOC) and preferred terms (PT) from the medical dictionary for regulatory activities (MedDRA) to describe, categorize, and statistic ADEs. Disproportionality analysis was employed through calculation of reporting odds ratio (ROR) and proportional reporting ratio (PRR). Based on total of 4392 selinexor related ADE reports as the primary suspect (PS), of which 2595 instances were severe outcomes. The predominant ADEs included gastrointestinal disorders, myelosuppression symptoms, and various nonspecific manifestations. 124 signals associated with selinexor ADE were detected, and 10 of these top 15 signals were not included into the instructions. Our study provides real-world evidence regarding the drug safety of selinexor, which is crucial for clinicians to safeguard patients' health.

Insecticidal Activities and Phenological Variations of Characteristic Component from Michelia yunnanensis.

Volatile secondary metabolites of plants interact with environments heavily. In this work, characteristic components of Michelia yunnanensis essential oils (EOs) were isolated, purified and identified by column chromatography, GC-MS and NMR. Leaves of M. yunnanensis were collected monthly and extracted for EOs to investigate chemical and insecticidal activity variations as well as potential influencing environments. Different organs were employed to reveal distribution strategies of characteristic components. Results of insecticidal activities showed that all EOs samples exerted stronger contact activity to Lasioderma serricorne, but repellent effect was more efficient on Tribolium castaneum. One oxygenated sesquiterpene was isolated from EOs, basically it could be confirmed as (+)-cyclocolorenone (1). It exerted contact toxicity to L. serricorne (LD 50 = 28.8 µg/adult). Chemical analysis showed that M. yunnanensis leaves in reproductive period would produce and accumulate more 1 than in vegetative period. Moreover, reproductive organs (flowers and fruits) contained more 1 than vegetative organs (leaves and twigs). Partial correlation analysis indicated that temperature-related elements positively correlated with the relative content of 1.

Side effects and cognitive benefits of buspirone: A systematic review and meta-analysis.

Buspirone, a 5-hydroxytryptamine 1A (5-HT1A) receptor agonist, has been investigated for its use in various diseases. However, knowledge about its side effects and potential cognitive benefits in different conditions is limited. Cognitive impairment is also a prevalent symptom in many diseases, yet effective treatments are still lacking. Therefore, to explore the potential side effects of buspirone and the possible cognitive benefits of buspirone, we conducted a comprehensive search of several databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. Our primary outcome measures included both side effects (adverse events) and cognitive benefits. For continuous variables, we utilized effect size with a 95% confidence interval (CI), whereas for dichotomous variables, we used odds ratios (OR) with a 95% CI. In total, 16 studies were included in this analysis, with 13 studies reporting on buspirone's side effects and 4 studies focusing on cognitive tasks. In terms of side effects, buspirone exhibited a higher rate of dizziness (OR = 4.66, 95% CI: 2.07-10.47), constipation (OR = 4.11, 95% CI: 1.34-12.55), and gastric distress (OR = 1.97, 95% CI: 1.03-3.78) than the placebo group. Regarding cognitive functions, buspirone showed significant benefits (g = 0.20, 95% CI: 0.06-0.34) while the placebo did not. Subgroup analysis indicated superior performance in visual learning and memory (g = 0.49, 95% CI: 0.21-0.78), logical reasoning (g = 0.42, 95% CI: 0.14-0.71), and attention (g = 0.37, 95% CI: 0.13-0.61) when compared to placebo. Our findings indicated that participants in the buspirone group experienced side effects of dizziness, constipation, and gastric distress in different diseases. Despite these adverse events, however, buspirone demonstrated significant cognitive benefits, particularly in the domains of visual learning and memory, logical reasoning, and attention.

Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study.

INTRODUCTION: Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found. METHODS/DESIGN: The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35-45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases. ETHICS AND DISSEMINATION: The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300072472).

Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a pivotal tool for global disease diagnosis and management. Since its clinical availability in 2009, the off-label use of ferumoxytol for ferumoxytol-enhanced MRI (FE-MRI) has significantly reshaped CE-MRI practices. Unlike MRI that is enhanced by gadolinium-based contrast agents, FE-MRI offers advantages such as reduced contrast agent dosage, extended imaging windows, no nephrotoxicity, higher MRI time efficiency and the capability for molecular imaging. As a leading superparamagnetic iron oxide contrast agent, ferumoxytol is heralded as the next generation of contrast agents. This review delineates the pivotal clinical applications and inherent technical superiority of FE-MRI, providing an avant-garde medical-engineering interdisciplinary lens, thus bridging the gap between clinical demands and engineering innovations. Concurrently, we spotlight the emerging imaging themes and new technical breakthroughs. Lastly, we share our own insights on the potential trajectory of FE-MRI, shedding light on its future within the medical imaging realm.

Epigenetic mechanism of SET7/9-mediated histone methylation modification in high glucose-induced ferroptosis in retinal pigment epithelial cells.

Ferroptosis of the retinal pigment epithelial (RPE) cells leads to retinal neuron injury and even visual loss. Our study aims to investigate the role of the SET domain with lysine methyltransferase 7/9 (SET7/9) in regulating high glucose (HG)-induced ferroptosis in RPE cells. The cell model was established by HG treatment. The levels of SET7/9 and Sirtuin 6 (SIRT6) were inhibited and Runt-related transcription factor 1 (RUNX1) was overexpressed through cell transfection, and then their levels in ARPE-19 cells were detected. Cell viability and apoptosis was detected. The levels of reactive oxygen species, malondialdehyde, glutathione, ferrous ion, glutathione peroxidase 4, and acyl-CoA synthetase long-chain family member 4 were detected. SET7/9 and trimethylation of histone H3 at lysine 4 (H3K4me3) levels in the RUNX1 promoter region and RUNX1 level in the SIRT6 promoter region were measured. The relationship between RUNX1 and SIRT6 was verified. SET7/9 and RUNX1 were highly expressed while SIRT6 was poorly expressed in HG-induced ARPE-19 cells. SET7/9 inhibition increased cell viability and inhibited cell apoptosis and ferroptosis. Mechanistically, SET7/9 increased H3K4me3 on the RUNX1 promoter to promote RUNX1, and RUNX1 repressed SIRT6 expression. Overexpression of RUNX1 or silencing SIRT6 partially reversed the inhibitory effect of SET7/9 silencing on HG-induced ferroptosis. In conclusion, SET7/9 promoted ferroptosis of RPE cells through the SIRT6/RUNX1 pathway.