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Cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. A well-monitored diet with a sufficient intake of fruits and vegetables has been confirmed as a primary prevention of CVD. Plant constituents such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory properties. Recent scientific literature has reported the cardiac protective effects of Lut and . Therefore, the aim of this review is to provide an update and detailed overview with cardio-protective molecular mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We further explore how these mechanisms participate in ischemia/reperfusion (I/R) injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of the cardiovascular protective effects and the relative mechanisms of Lut may provide the possibility of new drug design and development for CVD. With the previous studies mainly focused on basic research, we need to advance the prospects of its further clinical utilization against CVD, large prospective clinical trials of Lut are needed to observe its therapeutic effects on patients with I/R injury, HF and AS, especially on the effective therapeutic dosage, and safety of long-term administration.

Diabetic nephropathy (DN) is a critical microvascular complication of diabetes. Increasing evidence suggests that dysregulation of glutamine metabolism contributes to DN pathogenesis. This study aimed to explore alterations in glutamine metabolism-related genes (GMRGs) in DN. Nine differentially expressed GMRGs (DE-GMRGs) were identified by intersecting 103 GMRGs with 2,281 DEGs from the GSE142153 dataset comparing normal and DN groups. Notably, DE-GMRGs located on autosomes were significantly enriched in pathways related to glutamine metabolism and the metabolism of alanine, aspartate, and glutamate. The Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) methods were employed to pinpoint key genes, SLC7A5 and SLC25A12. SLC7A5 was found to be upregulated in DN, whereas SLC25A12 showed decreased expression. The diagnostic potential of these genes was further validated by assessing the area under the receiver operating characteristic (ROC) curve. Correlation analysis revealed strong associations between these key genes and clinical markers such as glomerular filtration rate (GFR), serum creatinine, and immune cells, including mast cells and effector memory CD8 T cells. Drug prediction and molecular docking analyses indicated that valproic acid might serve as an effective therapeutic agent targeting these genes. Glutamine metabolism-related genes SLC7A5 and SLC25A12 were identified as potential diagnostic and therapeutic targets for DN. These findings offer valuable clinical insights for the diagnosis and management of DN.

The intrinsically disordered region (IDR) is a preserved signature of phytobacterial type III effectors (T3Es). The T3E IDR is thought to mediate unfolding during translocation into the host cell and to avoid host defense by sequence diversification. Here, we demonstrate a mechanism of host subversion via the T3E IDR. We report that the Xanthomonas campestris T3E XopR undergoes liquid-liquid phase separation (LLPS) via multivalent IDR-mediated interactions that hijack the Arabidopsis actin cytoskeleton. XopR is gradually translocated into host cells during infection and forms a macromolecular complex with actin-binding proteins at the cell cortex. By tuning the physical-chemical properties of XopR-complex coacervates, XopR progressively manipulates multiple steps of actin assembly, including formin-mediated nucleation, crosslinking of F-actin, and actin depolymerization, which occurs through competition for actin-depolymerizing factor and depends on constituent stoichiometry. Our findings unravel a sophisticated strategy in which bacterial T3E subverts the host actin cytoskeleton via protein complex coacervation. Bacterial pathogens can subvert host cell processes through secreted proteins but the precise mechanisms and repertoire of proteins remains unclear. Here the authors report that a bacterial effector protein of Xanthomonas campestris, XopR, undergoes liquid-liquid phase separation to hijack the host cell actin cytoskeleton.

Background Plant-derived exosomes-like nanovesicles (PDENs) have been found to be advantageous in disease treatment and drug delivery, but research on their biogenesis, compositional analysis, and key marker proteins is still in its infancy, which limits the standardized production of PDENs. Efficient preparation of PDENs continues to be a major challenge. Results Novel PDENs-based chemotherapeutic immune modulators, Catharanthus roseus (L.) Don leaves-derived exosome-like nanovesicles (CLDENs) were isolated from apoplastic fluid. CLDENs were membrane structured vesicles with a particle size of 75.51 ± 10.19 nm and a surface charge of −21.8 mV. CLDENs exhibited excellent stability, tolerating multiple enzymatic digestions, resisting extreme pH environments, and remaining stable in the gastrointestinal simulating fluid. Biodistribution experiments showed that CLDENs could be internalized by immune cells, and targeted at immune organs after intraperitoneal injection. The lipidomic analysis revealed CLDENs’ special lipid composition, which contained 36.5% ether-phospholipids. Differential proteomics supported the origin of CLDENs in multivesicular bodies, and six marker proteins of CLDENs were identified for the first time. 60 ~ 240 μg/ml of CLDENs promoted the polarization and phagocytosis of macrophages as well as lymphocyte proliferation in vitro. Administration of 20 mg/kg and 60 mg/kg of CLDENs alleviated white blood cell reduction and bone marrow cell cycle arrest in immunosuppressive mice induced by cyclophosphamide. CLDENs strongly stimulated the secretion of TNF-α, activated NF-κB signal pathway and increased the expression of the hematopoietic function-related transcription factor PU.1 both in vitro and in vivo. To ensure a steady supply of CLDENs, plant cell culture systems of C. roseus were established to provide CLDENs-like nanovesicles which had similar physical properties and biological activities. Gram-level nanovesicles were successfully obtained from the culture medium, and the yield was three times as high as the original. Conclusions Our research supports the use of CLDENs as a nano-biomaterial with excellent stability and biocompatibility, and for post-chemotherapy immune adjuvant therapy applications. Graphical Abstract

The purpose is to study the performance compensation of the bid purchased during the mergers and acquisitions (M&A) process. An intelligent model of enterprise performance appraisal is built to analyze the performances of the acquired enterprises. First, the evaluation indicators of enterprise performance are selected from both financial and non-financial aspects. An enterprise performance appraisal model is established based on the neural networks and optimized by the factor analysis method and Genetic Algorithm (GA). The principal factors affecting enterprise performance are analyzed. Then the M&A parties’ performances during the M&A commitment period under the earnings compensation mechanism are analyzed quantitatively. Corresponding hypotheses and evaluation indicators are established. Mean test results and regression analyses demonstrate that the hypotheses proposed are valid under particular circumstances. Introducing the earnings compensation mechanism during the M&A process can improve the enterprise performance effectively so that the earnings forecasted in the commitment period are significantly higher than the historical profitability. Hence, the earnings compensation mechanism plays a positive role in guiding enterprise performance. Comparison with models proposed in previous research reveals that the output error ratio of the designed corporate performance evaluation model is 1.16%, which can effectively evaluate corporate performance. The above results provide a reference for studying the impact of the earnings compensation mechanism on enterprise performance during the M&A process.

Given the significant impact of diabetic kidney disease (DKD) on morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) and the potential preventive role of dietary factors, particularly dietary fiber, this study aimed to investigate the relationship between dietary fiber intake and the risk of DKD in adults with T2DM. The medical records and other relevant data from patients with T2DM were retrieved from the United States National Health and Nutrition Examination Surveys (U.S. NHANES) from 2009 to 2018. Multivariate logistic regression and restricted cubic spline (RCS) regression were employed to investigate the relationship between dietary fiber intake and the risk of DKD in adult T2DM patients. The study involved 4,520 T2DM patients with a mean age of 59.16 years, consisting of 2,346 male patients (51.9%) and 2,174 female patients (48.1%). The prevalence of T2DM patients with DKD was 37.92% in the overall population. Regression analyses, after adjusting for confounders, showed that dietary fiber intake was negatively correlated with the prevalence of DKD. RCS analysis demonstrated a nonlinear negative correlation between the level of dietary fiber intake and the prevalence of DKD, with a threshold inflection point of 13.96 g/day. Subgroup analyses revealed that age, gender, race, smoking status, body mass index, hypertension, diabetes duration, glycosylated hemoglobin, and ACEI/ARB medication use did not significantly affect the negative correlations (  > 0.05). Dietary fiber intake was negatively correlated with the prevalence of DKD in T2DM patients.

Background Diabetic peripheral neuropathy (DPN) is a prevalent and serious complication of diabetes mellitus, impacting the nerves in the limbs and leading to symptoms like pain, numbness, and diminished function. While the exact molecular and immune mechanisms underlying DPN remain incompletely understood, recent findings indicate that mitochondrial dysfunction may play a role in the advancement of this diabetic condition. Methods Two RNA transcriptome datasets (codes: GSE185011 and GSE95849), comprising samples from diabetic peripheral neuropathy (DPN) patients and healthy controls (HC), were retrieved from the Gene Expression Omnibus (GEO) database hosted by the National Center for Biotechnology Information (NCBI). Subsequently, differential expression analysis and gene set enrichment analysis were performed. Protein–protein interaction (PPI) networks were constructed to pinpoint key hub genes associated with DPN, with a specific emphasis on genes related to mitochondria and peripheral neuropathy disease (PND) that displayed differential expression. Additionally, the study estimated the levels of immune cell infiltration in both the HC and DPN samples. To validate the findings, quantitative polymerase chain reaction (qPCR) was employed to confirm the differential expression of selected genes in the DPN samples. Results This research identifies four hub genes associated mitochondria or PN. Furthermore, the analysis revealed increased immune cell infiltration in DPN tissues, particularly notable for macrophages and T cells. Additionally, our investigation identified potential drug candidates capable of regulating the expression of the four hub genes. These findings were corroborated by qPCR results, reinforcing the credibility of our bioinformatics analysis. Conclusions This study provides a comprehensive overview of the molecular and immunological characteristics of DPN, based on both bioinformatics and experimental methods.

Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut–brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut–brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut–brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut–brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut–brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.

ChatGPT, a generative pretrained transformer, has garnered global attention and sparked discussions since its introduction on November 30, 2022. However, it has generated controversy within the realms of medical education and scientific research. This paper examines the potential applications, limitations, and strategies for using ChatGPT. ChatGPT offers personalized learning support to medical students through its robust natural language generation capabilities, enabling it to furnish answers. Moreover, it has demonstrated significant use in simulating clinical scenarios, facilitating teaching and learning processes, and revitalizing medical education. Nonetheless, numerous challenges accompany these advancements. In the context of education, it is of paramount importance to prevent excessive reliance on ChatGPT and combat academic plagiarism. Likewise, in the field of medicine, it is vital to guarantee the timeliness, accuracy, and reliability of content generated by ChatGPT. Concurrently, ethical challenges and concerns regarding information security arise. In light of these challenges, this paper proposes targeted strategies for addressing them. First, the risk of overreliance on ChatGPT and academic plagiarism must be mitigated through ideological education, fostering comprehensive competencies, and implementing diverse evaluation criteria. The integration of contemporary pedagogical methodologies in conjunction with the use of ChatGPT serves to enhance the overall quality of medical education. To enhance the professionalism and reliability of the generated content, it is recommended to implement measures to optimize ChatGPT’s training data professionally and enhance the transparency of the generation process. This ensures that the generated content is aligned with the most recent standards of medical practice. Moreover, the enhancement of value alignment and the establishment of pertinent legislation or codes of practice address ethical concerns, including those pertaining to algorithmic discrimination, the allocation of medical responsibility, privacy, and security. In conclusion, while ChatGPT presents significant potential in medical education, it also encounters various challenges. Through comprehensive research and the implementation of suitable strategies, it is anticipated that ChatGPT’s positive impact on medical education will be harnessed, laying the groundwork for advancing the discipline and fostering the development of high-caliber medical professionals.

With the changing times, obesity has become a characteristic epidemic in the context of the current era. Insulin resistance (IR) is most commonly caused by obesity, and IR is a common basis of the pathogenesis of many diseases such as cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes, which seriously threaten human life, as well as health. A major pathogenetic mechanism of obesity-associated IR has been found to be chronic low-grade inflammation in adipose tissue. Specialized pro-resolving mediators (SPMs) are novel lipid mediators that both function as “stop signals” for inflammatory reaction and promote inflammation to subside. In this article, we summarize the pathogenesis of obesity-associated IR and its treatments and outline the classification and biosynthesis of SPMs and their mechanisms and roles in the treatment of obesity-associated IR in order to explore the potential of SPMs for treating metabolic diseases linked with obesity-associated IR.