Relationship between preoperative FT3 levels and new-onset atrial fibrillation after off-pump coronary artery bypass grafting.

Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. While thyroid dysfunction can predict POAF, the association between preoperative serum free triiodothyronine (FT3) levels and POAF in patients undergoing off-pump coronary artery bypass (OPCAB) grafting remains unclear. This study aimed to investigate the relationship between preoperative FT3 levels and POAF in OPCAB patients. Methods: This prospective observational study included patients with sinus rhythm and no history of atrial fibrillation or thyroid disease who underwent OPCAB and FT3 testing at the Tianjin Chest Hospital from June 2021 to March 2023. The relationship between FT3 level and POAF was evaluated using restricted cubic spline. Cox proportional hazards regression models were used to analyze the associations between FT3 concentration categories [low T3 syndrome (LT3S) (FT3 below the normal range), low normal FT3 (3.10-4.59 pmol/L), high normal FT3 (4.60-6.80 pmol/L)] and POAF, adjusting for potential confounders. Stratified analyses were performed to assess effect modification by gender and age (<60 vs. ≥60 years old). Results: Among 875 patients, 259 (29.6%) developed POAF within 2 days after surgery. Restricted cubic spline analysis showed an S-shaped association between FT3 concentration and POAF risk. Compared to the low normal FT3 group, LT3S was associated with an increased risk of POAF [hazard ratio (HR), 1.41; 95% confidence interval (CI): 1.90-2.19], while high normal FT3 was associated with a decreased risk (HR, 0.72; 95% CI: 0.51-0.99). The association between FT3 and increased POAF risk was more pronounced in patients aged ≥60 years (HR, 1.41; 95% CI: 1.89-2.22). Conclusions: Preoperative FT3 levels most likely could predict POAF risk after OPCAB, especially in patients aged 60 years and older. Measuring FT3 preoperatively may identify high-risk patients benefiting from close monitoring and prophylactic treatment. Further investigation of thyroid hormone replacement therapy for LT3S is warranted.

Machine learning-based prediction of off-pump coronary artery bypass grafting-associated acute kidney injury.

Background: The cardiac surgery-associated acute kidney injury (CSA-AKI) occurs in up to 1 out of 3 patients. Off-pump coronary artery bypass grafting (OPCABG) is one of the major cardiac surgeries leading to CSA-AKI. Early identification and timely intervention are of clinical significance for CSA-AKI. In this study, we aimed to establish a prediction model of off-pump coronary artery bypass grafting-associated acute kidney injury (OPCABG-AKI) after surgery based on machine learning methods. Methods: The preoperative and intraoperative data of 1,041 patients who underwent OPCABG in Chest Hospital, Tianjin University from June 1, 2021 to April 30, 2023 were retrospectively collected. The definition of OPCABG-AKI was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The baseline data and intraoperative time series data were included in the dataset, which were preprocessed separately. A total of eight machine learning models were constructed based on the baseline data: logistic regression (LR), gradient-boosting decision tree (GBDT), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), random forest (RF), support vector machine (SVM), k-nearest neighbor (KNN), and decision tree (DT). The intraoperative time series data were extracted using a long short-term memory (LSTM) deep learning model. The baseline data and intraoperative features were then integrated through transfer learning and fused into each of the eight machine learning models for training. Based on the calculation of accuracy and area under the curve (AUC) of the prediction model, the best model was selected to establish the final OPCABG-AKI risk prediction model. The importance of features was calculated and ranked by DT model, to identify the main risk factors. Results: Among 701 patients included in the study, 73 patients (10.4%) developed OPCABG-AKI. The GBDT model was shown to have the best predictions, both based on baseline data only (AUC =0.739, accuracy: 0.943) as well as based on baseline and intraoperative datasets (AUC =0.861, accuracy: 0.936). The ranking of importance of features of the GBDT model showed that use of insulin aspart was the most important predictor of OPCABG-AKI, followed by use of acarbose, spironolactone, alfentanil, dezocine, levosimendan, clindamycin, history of myocardial infarction, and gender. Conclusions: A GBDT-based model showed excellent performance for the prediction of OPCABG-AKI. The fusion of preoperative and intraoperative data can improve the accuracy of predicting OPCABG-AKI.

Identification of the CDH18 gene associated with age-related macular degeneration using weighted gene co-expression network analysis.

Purpose: Age-related macular degeneration (AMD) is a chronic and progressive macular degenerative disease that culminates in a gradual deterioration of central vision. Despite its prevalence, the key biomarkers for AMD have not yet been fully elucidated. In this study, we aimed to efficiently identify biomarkers crucial for diagnosing AMD. Methods: Three datasets pertaining to retinal pigment epithelium (RPE)/choroid tissues associated with AMD were selected from the GEO database. The GSE50195 dataset was utilized to conduct weighted gene co-expression network analysis (WGCNA) for identifying module genes linked to AMD. KEGG and GO enrichment analyses were subsequently conducted on these module genes. GSE29801 and GSE135092 datasets were subjected to differential expression analysis to pinpoint the DEGs intersecting with the module genes. Subsequently, wet AMD (wAMD) and dry AMD (dAMD) mouse models were developed, from which RPE/choroid tissues were harvested to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA, we selected the "antiquewhite4" module (r = 0.91 and p = 7e-07), which contains a total of 325 genes. Through the intersection of module genes with DEGs, nine hub genes were identified. Pathways involved in complement and coagulation cascades, ECM-receptor interactions, unsaturated fatty acid biosynthesis, and fatty acid elongation play important roles in AMD. Notably, CDH18 demonstrated notable variance across all three datasets. Post validation using RT-qPCR experiments revealed a significant downregulation of CDH18 in both dAMD and wAMD. EGLN3 was expressed at low levels in wAMD. In dAMD, EYA2, LTB, and PODXL were significantly downregulated, whereas APOC1 was notably upregulated. Western blot confirmed that CDH18 was lowly expressed in dAMD and wAMD mouse models. Conclusion: CDH18 was identified as the key gene involved in the pathogenesis of AMD. An imbalance of the complement and coagulation cascades is a potential mechanism of AMD. This study provides a novel idea for diagnosing and treating AMD in the future.

Differential Expression of mRNA in Peripheral Blood Mononuclear Cells May Predict Postoperative Atrial Fibrillation in Coronary Artery Bypass Surgery Patients.

Postoperative Atrial Fibrillation (POAF) frequently follows Coronary Artery Bypass Grafting (CABG) surgery. This prospective study investigates genes linked to POAF in CABG patients, aiming to create a predictive model. Employing differential gene and methylation analyses, the study identified four genes (WARS2, CKAP2, CHI3L1, HSD17B6) associated with POAF. Preoperative plasma samples and clinical data were collected from 139 CABG patients, categorized into POAF (+) (43) and POAF (-) (96). Real-time quantitative PCR assessed gene expression, and a predictive model using the LASSO method demonstrated robust performance, with AUC values of 0.8895 in the training set and 0.7840 in the test set. This pioneering study integrates genomics and clinical data, suggesting WARS2, CKAP2, and CHI3L1 as potential indicators for POAF prediction.

Construction and validation of a risk prediction model for postoperative delirium in patients with off­pump coronary artery bypass grafting.

Background: Compared with cardiopulmonary bypass surgery, off-pump coronary artery bypass grafting (OPCABG) reduces trauma to the body. However, there is still a risk of neurological complications, including postoperative delirium (POD). To date, few studies have been conducted on the risk of POD in OPCABG patients, and no standardized prediction model has been established. Thus, this study sought to analyze the factors influencing POD in OPCABG patients and to construct a risk prediction model. Methods: A total of 1,258 patients with OPCABG were enrolled and divided into the training set for model construction (944 cases) and the test set for model validation (314 cases). A risk prediction model for POD in OPCABG patients was established by least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression, and a nomogram was drawn. The discrimination and calibration degree of the model was evaluated by the receiver operator characteristic (ROC) curve and calibration curve. Results: Eight variables [i.e., age, tissue oxygen saturation, mean arterial pressure (MAP), carotid stenosis, the anterior-posterior diameter of the aortic sinus, ventricular septum thickness, left ventricular ejection fraction (LVEF), and Mini-Mental State Examination (MMSE) scores] were screen out by the LASSO regression and multivariate logistic regression, and the model was constructed. The area under the ROC curve of the training set was 0.702 [95% confidence interval (CI): 0.662-0.743], and that of the test set was 0.658 (95% CI: 0.585-0.730). The results of the Hosmer-Lemeshow goodness-of-fit test showed that the predicted POD risk of OPCABG patients in the training and test sets was consistent with the actual POD risk (χ2=5.154, P=0.74). Conclusions: The occurrence of POD in OPCABG patients is related to age, tissue oxygen saturation, MAP, carotid artery stenosis, the anterior-posterior diameter of aortic sinus, ventricular septal thickness, LVEF, and MMSE scores. The prediction model constructed with the above variables had high predictive performance, and thus may be helpful in the early identification of such patients.

Anthropocene 129I Record in the Yellow Sea Sediments and Its Indication for River-Delivered Radioactive Pollution to Marginal Seas.

As the number of coastal nuclear facilities rapidly increases and the wastewater from the Fukushima Nuclear Plant has been discharged into the Pacific Ocean, the nuclear environmental safety of China's marginal seas is gaining increased attention along with the heightened potential risk of nuclear accidents. However, insufficient work limits our understanding of the impact of human nuclear activities on the Yellow Sea (YS) and the assessment of their environmental process. This study first reports the 129I and 127I records of posthuman nuclear activities in the two YS sediments. Source identification of anthropogenic 129I reveals that, in addition to the gaseous 129I release and re-emission of oceanic 129I discharged from the European Nuclear Fuel Reprocessing Plants (NFRPs), the Chinese nuclear weapons testing fallout along with the global fallout is an additional 129I input for the continental shelf of the YS. The 129I/127I atomic ratios in the North YS (NYS) sediment are significantly higher than those in the other adjacent coastal areas, attributed to the significant riverine input of particulate 129I by the Yellow River. Furthermore, we found a remarkable 129I latitudinal disparity in the sediments than those in the seawaters in the various China seas, revealing that sediments in China's marginal seas already received a huge anthropogenic 129I from terrigenous sources via rivers and thus became a significant sink of anthropogenic 129I. This study broadens an insight into the potential impacts of terrigenous anthropogenic pollution on the Chinese coastal marine radioactive ecosystem.

Benzotriazole ultraviolet absorbents in surface waters and sediments of the Bohai Sea and North Yellow Sea: Spatial trends and influencing factors.

Benzotriazole ultraviolet absorbents (BUAs) of emerging concern were recently monitored in seawater and sediments from the Bohai Sea (BS) and North Yellow Sea (NYS), which are impacted by human activities, to elucidate their regional occurrence patterns, phase distributions, and contamination profiles. Although environmental variables such as sedimentary organic carbon, particle size, and salinity, as well as hydrological conditions, affected the environmental occurrence of BUAs in the BS and NYS, the source dependence of BUA distributions associated with urban impacts and riverine inputs was highlighted. Substantial spatial variability in the composition patterns and contamination profiles of BUAs identified through correlation and principal component analyses were likely caused by region-specific sources and characteristics. The distribution of target BUAs between the sediment and seawater phases showed no dependence on the octanol-water partition coefficient (KOW) but exhibited marked spatial variations. The diversity of BUA sorption behaviors was further explained by the total organic carbon (TOC)-normalized distribution coefficient (KTOC). Classic logKTOC-logKOW linear relationships accurately predicted the phase distributions of UV-326, UV-328, and UV-234, but deviations were found for lighter and heavier BUAs, possibly due to the influences of physical disturbance and microparticle binding.

Trends and patterns of antibiotic using from 2014 to 2018 in stomatology hospitals of China.

OBJECTIVE: To analyze trends of antibiotic consumption and expenditure in Chinese stomatology hospitals between 2014 and 2018 with a longitudinal study design, and show the impacts of the comprehensive policy on dental antibiotic use in China. SUBJECT AND METHODS: Consumption was quantified as the number of daily defined doses (DDDs) and expenditure as the procurement costs, using medical institutions' drug procurement data from the Chinese Monitoring Network for Rational Use of Drugs. Descriptive statistics was employed and the compound annual growth rate (CAGR) was calculated to show the average annual growth rate. RESULTS: Between 2014 and 2018, overall antibiotic consumption increased from 842.6 thousand DDDs to 1376.7 thousand DDDs (p < 0.001) and expenditure increased from 11.6 million RMB to 20.9 million RMB (p < 0.001), where other ß-lactam antibacterials accounted for the largest proportion of total consumption (37.1%-50.1%) and expenditure (52.9%-66.6%), and also increase the largest (CAGR = 18.4%, p < 0.001). The proportion of oral antibiotics was nearly 9 times of parenteral antibiotics in consumption (CAGR = 0.3%, p = 0.023) and only 2 times in expenditure (CAGR = -1.7%, p = 0.112). The non-restricted group accounted for more than 90% of consumption (CAGR = 0.6%, p < 0.001). In 2018, oral first-generation cephalosporins (22.8%), oral imidazole derivatives (22.3%), and oral second-generation cephalosporins (19.2%) were the most frequently used antibiotic classification, while parenteral second-generation cephalosporins were top one (19.8%) for expenditure. At chemical substance levels, the consumption of oral cefradine ranked top one (21.4%) and parenteral cefuroxime accounted for the largest proportion of expenditure (14.5%) in 2018. Oral cefradine, oral metronidazole, and oral cefaclor were the top three frequently consumed antibiotics throughout the five years. CONCLUSIONS: Despite the potential antibiotic overuse, the comprehensive antibiotic stewardship regulations of China got a satisfactory and better performance in dental practices. More effort is needed to establish more explicit guidelines to improve antibiotic stewardship, such as priority recommending amoxicillin and its derivatives for endodontic infections.

The predictive role of neutrophil gelatinase-associated lipocalin in coronary artery disease.

The prognosis holds significant implications for the long-term quality of life among patients suffering from coronary artery disease. However, a pressing challenge lies in the absence of reliable biomarkers that can establish a definitive correlation between these biomarkers and the prognosis of coronary artery heart disease. This review paper delves into the critical role of neutrophil gelatinase-associated lipocalin (NGAL) in predicting outcomes in coronary artery disease. It examines the influence of NGAL on various clinical manifestations, including stable angina, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and isolated coronary artery dilation. Furthermore, this review provides recommendations aimed at enhancing the rigor and impact of future research, thereby serving as a valuable reference for subsequent studies in this domain.

YTHDF1's grip on CRC vasculature: insights into LINC01106 and miR-449b-5p-VEGFA axis.

BACKGROUND: Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. METHODS: Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. RESULTS: YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1's inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. CONCLUSIONS: This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.

Air-plant interaction and air-soil exchange of polycyclic aromatic hydrocarbons in a large human-influenced reservoir in southwest China.

The Three Gorges Reservoir (TGR) is totally manmade, strongly influenced by anthropogenic activity, and lies on the upper reaches of Yangtze River. The periodic storage and discharge of water from the Three Gorges Dam could have altered the original air-plant/soil interactions of contaminants in TGR. Herein, paired atmospheric gas-particle, air-plant, and air-soil samples were collected to investigate the air-plant interaction and air-soil exchange of 16 USEPA priority polycyclic aromatic hydrocarbons (PAHs). The air-plant interaction based on McLachlan's framework to our datasets suggests that PAHs were absorbed via gaseous deposition that was restricted by the plant-gas dynamic equilibrium. The equilibrium indicates a dynamic balance between the gaseous phase and plant surface in PAH absorption. The main limiting factor influencing the PAH uptake was the plant species rather than the atmospheric PAH concentration. The air-soil exchange of PAHs exhibited a net volatilization flux of 16.71 ng/m2/d from the soil to the air based on annual average. There was more volatilization and less deposition in summer and more deposition and less volatilization in autumn and winter. The soil serves as a secondary source of atmospheric PAHs. As the first attempt on probing the multi-interface geochemical process of PAHs, this study highlights the influence of manual water level manipulation from the TGD and environmental factors (such as temperature, humidity, and soil properties) on the regional fate of PAHs in the TGR.

MdbZIP44-MdCPRF2-like-Mdα-GP2 regulate starch and sugar metabolism in apple under nitrogen supply.

Nitrogen (N) is regarded as an essential macronutrient and is tightly associated with carbon (C) metabolism in plants. The transcriptome data obtained from this study showed that the expression level of the apple basic leucine zipper (bZIP) transcription factor (TF) MdbZIP44 was up-regulated in 'Oregon Spur Delicious' (Malus domestica Borkh.) apple fruits under nitrogen supply. MdbZIP44 bound to the promoter of Mdα-GP2 gene and inhibited its expression, thereby promoting starch accumulation and decreasing glucose content in apple and tomato fruits. Besides, overexpression of MdbZIP44 promoted sucrose accumulation by regulating the activities of sucrose metabolism-related enzymes and the expression of sugar metabolism-related genes in apple callus and tomato fruits. Furthermore, biochemical assays indicated that MdbZIP44 directly interacted with MdCPRF2-like, another bZIP gene in apple. Meanwhile, this study found that MdCPRF2-like, along with the MdbZIP44 and MdCPRF2-like complex, could activate the expression of Mdα-GP2, respectively. In conclusion, this study provides a new reference for potential mechanisms underlying that MdbZIP44-MdCPRF2-like-Mdα-GP2 regulates starch and sugar metabolism under nitrogen supply.

Overexpression of Rhodiola crenulata glutathione peroxidase 5 increases cold tolerance and enhances the pharmaceutical value of the hairy roots.

Rhodiola crenulata, a plant of great medicinal value found in cold high-altitude regions, has been excessively exploited due to the difficulty in cultivation. Understanding Rhodiola crenulata's adaptation mechanisms to cold environment can provide a theoretical basis for artificial breeding. Glutathione peroxidases (GPXs), critical enzymes found in plants, play essential roles in antioxidant defense through the ascorbate-glutathione cycle. However, it is unknown whether GPX5 contributes to Rhodiola crenulata's cold tolerance. In this study, we investigated the role of GPX5 in Rhodiola crenulata's cold tolerance mechanisms. By overexpressing Rhodiola crenulata GPX5 (RcGPX5) in yeast and Arabidopsis thaliana, we observed down-regulation of Arabidopsis thaliana GPX5 (AtGPX5) and increased cold tolerance in both organisms. Furthermore, the levels of antioxidants and enzyme activities in the ascorbate-glutathione cycle were elevated, and cold-responsive genes such as AtCBFs and AtCORs were induced. Additionally, RcGPX5 overexpressing lines showed insensitivity to exogenous abscisic acid (ABA), suggesting a negative regulation of the ABA pathway by RcGPX5. RcGPX5 also promoted the expression of several thioredoxin genes in Arabidopsis and interacted with two endogenous genes of Rhodiola crenulata, RcTrx2-3 and RcTrxo1, located in mitochondria and chloroplasts. These findings suggest a significantly different model in Rhodiola crenulata compared to Arabidopsis thaliana, highlighting a complex network involving the function of RcGPX5. Moreover, overexpressing RcGPX5 in Rhodiola crenulata hairy roots positively influenced the salidroside synthesis pathway, enhancing its pharmaceutical value for doxorubicin-induced cardiotoxicity. These results suggested that RcGPX5 might be a key component for Rhodiola crenulata to adapt to cold stress and overexpressing RcGPX5 could enhance the pharmaceutical value of the hairy roots.

The LEPIS-HuR-TMOD4 axis regulates hepatic cholesterol homeostasis and accelerates atherosclerosis.

BACKGROUND AND AIMS: Long noncoding RNAs (lncRNAs) play important roles in the progression of atherosclerosis. In this study, we identified an uncharacterized lncRNA, Liver Expressions by PSRC1 Induced Specifically (LEPIS). This study aimed to clarify the mechanism though which LEPIS affects atherosclerosis (AS). METHODS: The expression of LEPIS and its potential target, tropomodulin 4 (TMOD4), was increased in the livers of ApoE-/- mice fed a high-fat diet (HFD). An ApoE-/- mouse model in which LEPIS or TMOD4 was overexpressed in the liver was established. The plaque load in the aorta was assessed, plasma was collected to measure blood lipid levels, and the liver was collected to study cholesterol metabolism. RESULTS: We found that both LEPIS and TMOD4 increased the AS burden and reduced hepatic cholesterol levels. A further study revealed that LEPIS and TMOD4 affected the expression of genes related to hepatic cholesterol homeostasis, including proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR), which are closely related to hypercholesterolemia. Mechanistically, human antigen R (HuR), an RNA-binding protein (RBP), was shown to be critical for the regulation of TMOD4 by LEPIS. Furthermore, we found that verexpression of LEPIS promoted the shuttling of HuR from the nucleus to the cytoplasm, enhanced the stability of TMOD4 mRNA, and in turn promoted the expression of TMOD4. In addition, TMOD4 was found to affect intracellular cholesterol levels through PCSK9. CONCLUSIONS: These results suggest that the LEPIS-HuR-TMOD4 axis is a potential intervention target for dysregulated hepatic cholesterol homeostasis and AS and may provide the basis for further reductions in the circulating LDL-C concentration and arterial plaque burden.

APE1 inhibition enhances ferroptotic cell death and contributes to hepatocellular carcinoma therapy.

Ferroptosis, a regulated form of cell death triggered by iron-dependent lipid peroxidation, has emerged as a promising therapeutic strategy for cancer treatment, particularly in hepatocellular carcinoma (HCC). However, the mechanisms underlying the regulation of ferroptosis in HCC remain to be unclear. In this study, we have identified a novel regulatory pathway of ferroptosis involving the inhibition of Apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme with dual functions in DNA repair and redox regulation. Our findings demonstrate that inhibition of APE1 leads to the accumulation of lipid peroxidation and enhances ferroptosis in HCC. At the molecular level, the inhibition of APE1 enhances ferroptosis which relies on the redox activity of APE1 through the regulation of the NRF2/SLC7A11/GPX4 axis. We have identified that both genetic and chemical inhibition of APE1 increases AKT oxidation, resulting in an impairment of AKT phosphorylation and activation, which leads to the dephosphorylation and activation of GSK3ß, facilitating the subsequent ubiquitin-proteasome-dependent degradation of NRF2. Consequently, the downregulation of NRF2 suppresses SLC7A11 and GPX4 expression, triggering ferroptosis in HCC cells and providing a potential therapeutic approach for ferroptosis-based therapy in HCC. Overall, our study uncovers a novel role and mechanism of APE1 in the regulation of ferroptosis and highlights the potential of targeting APE1 as a promising therapeutic strategy for HCC and other cancers.

TIPE2: A Candidate for Targeting Antitumor Immunotherapy.

TNF-α-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a recently discovered negative regulator of innate and adaptive immunity. TIPE2 is expressed in a wide range of tissues, both immune and nonimmune, and is implicated in the maintenance of immune homeostasis within the immune system. Furthermore, TIPE2 has been shown to play a pivotal role in the regulation of inflammation and the development of tumor. This review focuses on the structural characteristics, expression patterns, and functional roles of TIPE proteins, with a particular emphasis on the role and underlying mechanisms of TIPE2 in immune regulation and its involvement in different diseases. However, the current body of evidence is still limited in providing a comprehensive understanding of the complex role of TIPE2 in the human body, warranting further investigation to elucidate the possible mechanisms and functions of TIPE2 in diverse disease contexts.

Exosomal lncRNA DUXAP8 affecting CHPF2 in the pathogenesis of intracranial aneurysms.

OBJECTIVE: This study endeavored to explore the relationship between exosome-derived lncRNA Double Homeobox A Pseudogene 8 (DUXAP8) and Chondroitin Polymerizing Factor 2 (CHPF2), and their roles in the pathogenesis of intracranial aneurysm (IA). METHODS: The shared targeted molecules (DUXAP8 and CHPF2) were detected via GSE122897 and GSE75436 datasets. A total of 312 patients with IAs were incorporated into this study. Exosomes were isolated from serum samples, and their identity was confirmed using Western blotting for exosomal markers (CD9, CD63 and ALIX). Inflammatory responses in IA tissues were evaluated using Hematoxylin-Eosin staining. CHPF2 protein concentration and the expression levels of DUXAP8 and CHPF2 mRNA in exosomal samples were assessed using Immunochemistry (IHC), Western Blotting, and qRT-PCR, respectively. Cell-based assays involving Human Umbilical Vein Endothelial Cells (HuvECs), including transfection with exosomal DUXAP8, Western Blotting, qRT-PCR, and Cell Counting Kit-8, were conducted. Receiver Operating Characteristic (ROC) curves were derived using SPSS. RESULTS: DUXAP8 level affects the level of CHPF2. DUXAP8 expression within exosomes was associated with increased CD9, CD63, ALIX and CHPF2 levels during IA development and inflammatory stress. In HuvECs, transfection with exosomes carrying DUXAP8 siRNA resulted in reduced CHPF2 expression, whereas DUXAP8 mimic increased CHPF2 concentrations. The Area Under the ROC Curve (AUC) for exosomal DUXAP8 expression and CHPF2 levels, and aneurysm size was 0.768 (95% CI, 0.613 to 0.924), 0.937 (95% CI, 0.853 to 1.000), and 0.943 (95% CI, 0.860, 1.000), respectively. CONCLUSION: Exosome-derived DUXAP8 promotes IA progression by affecting CHPF2 expression.

Reducing SULT2B1 promotes the interaction of LncRNAgga3-204 with SMAD4 to inhibit the macrophage inflammatory response and delay atherosclerosis progression.

Inflammation is a crucial pathophysiological mechanism in atherosclerosis (AS). This study aims to investigate the impact of sulfotransferase family 2b member 1 (SULT2B1) on the inflammatory response of macrophages and the progression of AS. Here, we reported that SULT2B1 expression increased with the progression of AS. In AS model mice, knockdown of Sult2b1 led to remission of AS and reduced inflammation levels. Further exploration of the downstream molecular mechanisms of SULT2B1 revealed that suppressing Sult2b1 in macrophages resulted in decreased levels of 25HC3S in the nucleus, elevated expression of Lxr, and increased the transcription of Lncgga3-204. In vivo, knockdown of Lncgga3-204 aggravated the inflammatory response and AS progression, while the simultaneous knockdown of both Sult2b1 and Lncgga3-204 exacerbated AS and the inflammatory response compared with knockdown of Sult2b1 alone. Increased binding of Lncgga3-204 to SMAD4 in response to oxidized-low density lipoprotein (ox-LDL) stimulation facilitated SMAD4 entry into the nucleus and regulated Smad7 transcription, which elevated SMAD7 expression, suppressed NF-κB entry into the nucleus, and ultimately attenuated the macrophage inflammatory response. Finally, we identified the presence of a single nucleotide polymorphism (SNP), rs2665580, in the SULT2B1 promoter region in monocytes from coronary artery disease (CAD) patients. The predominant GG/AG/AA genotypes were observed in the Asian population. Elevated SULT2B1 expression in monocytes with GG corresponded to elevated inflammatory factor levels and more unstable coronary plaques. To summarize, our study demonstrated that the critical role of SULT2B1/Lncgga3-204/SMAD4/NF-κB in AS progression. SULT2B1 serves as a novel biomarker indicating inflammatory status, thereby offering insights into potential therapeutic strategies for AS.