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Abstract IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host’s defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

Abstract Background Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. Methods This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. Results 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. Conclusion Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

Background: Studies using machine learning to identify the target characteristics and develop predictive models for coronary artery disease severity in patients with premature myocardial infarction (PMI) are limited. Methods: In this observational study, 1111 PMI patients (≤55 years) at Tianjin Chest Hospital from 2017 to 2022 were selected and divided according to their SYNTAX scores into a low-risk group (≤22) and medium–high-risk group (>22). These groups were further randomly assigned to a training or test set in a ratio of 7:3. Lasso–logistic was initially used to screen out target factors. Subsequently, Lasso–logistic, random forest (RF), k-nearest neighbor (KNN), support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) were used to establish prediction models based on the training set. After comparing prediction performance, the best model was chosen to build a prediction system for coronary artery severity in PMI patients. Results: Glycosylated hemoglobin (HbA1c), angina, apolipoprotein B (ApoB), total bile acid (TBA), B-type natriuretic peptide (BNP), D-dimer, and fibrinogen (Fg) were associated with the severity of lesions. In the test set, the area under the curve (AUC) of Lasso–logistic, RF, KNN, SVM, and XGBoost were 0.792, 0.775, 0.739, 0.656, and 0.800, respectively. XGBoost showed the best prediction performance according to the AUC, accuracy, F1 score, and Brier score. In addition, we used decision curve analysis (DCA) to assess the clinical validity of the XGBoost prediction model. Finally, an online calculator based on the XGBoost was established to measure the severity of coronary artery lesions in PMI patients Conclusions: In summary, we established a novel and convenient prediction system for the severity of lesions in PMI patients. This system can swiftly identify PMI patients who also have severe coronary artery lesions before the coronary intervention, thus offering valuable guidance for clinical decision-making.

AbstractBackground Bile acids play crucial roles in various metabolisms, as well as Lactobacillus in the intestine. But studies on their roles in acute coronary syndrome (ACS) are still insufficient. The aim of this study was to investigate their role and potential association with the severity of coronary lesions and the prognosis of ACS.Methods Three hundred and sixty ACS patients were selected. Detection of gut Lactobacillus levels was done through 16S rDNA sequence analysis. Evaluation of the extent of lesions was done using the SYNTAX (SS) score. Mediation analysis was used to assess the relationship between serum total bile acid (TBA), Lactobacillus, atherosclerotic lesions and prognosis of ACS.Results Logistic regressive analysis disclosed that serum TBA and Lactobacillus were independent predictors of coronary lesions (high vs. low SS: serum TBA adjusted odds ratio (aOR) = 0.8, 95% confidence interval (CI): 0.6–0.9, p

Clear cell renal cell carcinoma (ccRCC) accounts for 80% of renal cell carcinomas (RCCs), and its morbidity and prognosis are unfavorable. Surgical resection is the first-line treatment for ccRCC, but the oncogenesis of ccRCC is very complex. With the development of high-throughput sequencing technology, it is necessary to analyze the transcriptome to determine more effective treatment methods. The tumor microenvironment (TME) is composed of tumor cells, various immune-infiltrating cells, fibroblasts, many cytokines, and catalysts. It is a complex system with a dynamic balance that plays an essential role in tumor growth, invasion, and metastasis. Previous studies have confirmed that potassium channels can affect the immune system, especially T lymphocytes that require potassium channel activation. However, the effect of potassium channels on the TME of ccRCC remains to be studied. Therefore, this study aims to construct a prognostic signature for ccRCC patients based on potassium ion channel-related genes (PCRGs), assess patient risk scores, and divide patients into high- and low-risk groups based on the cutoff value. In addition, we investigated whether there were differences in immune cell infiltration, immune activator expression, somatic mutations, and chemotherapeutic responses between the high- and low-risk groups. Our results demonstrate that the PCRG signature can accurately assess patient prognosis and the tumor microenvironment and predict chemotherapeutic responses. In summary, the PCRG signature could serve as an auxiliary tool for the precision treatment of ccRCC.

Notwithstanding previous studies have proved the anti-apoptotic effect of Bcl-2 associated athanogene3 (BAG3) in myocardium, the structural domains PXXP and BAG responsible for its protection are not reformed. Since BAG3 in cardiomyocytes is a new target for inhibiting apoptosis induced by hypoxia/reoxygenation (H/R) stress, we demonstrated that over-expression of BAG3 reduced the injury induced by H/R in either neonatal or adult rat cardiomyocytes (NRCMs and ARCMs, respectively) and PXXP and BAG domains play an important role in cellular protection in H/R stress. Apoptosis in cardiomyocytes induced by hypoxia-reperfusion was evaluated with propidium iodide (PI) staining, cleaved caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining in cultured NRCMS. Either increasing expression of BAG3 or its mutants was performed to manipulate the level of BAG3. Co-immunoprecipitation (Co-IP) was used to demonstrate the complex that BAG3 is binding to HSC70 and JNK. PXXP and BAG domains of BAG3 played an essential role in BAG3 attenuating cardiomyocytes apoptosis induced by H/R through the JNK signalling pathway. The cellular protection of BAG3 with its structural domain PXXP or BAG is associated with the binding with HSC70 and JNK. These results showed that the protective effect of BAG3 on apoptosis induced by H/R stress is closely related to its structural domains PXXP and BAG. The mechanism may provide a new therapeutic strategy for the patients suffering from ischemic cardiomyopathy and may be a critical role of its PXXP and BAG3 domains.

Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5‐hydroxytryptamine (5‐HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5–S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5–S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1–Piezo2 axis.

Background: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. Methods: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. Conclusions: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. Clinical Trial Registration: This study has been registered on ClinicalTrials.gov (NCT04734418).

On-orbit astronauts and scientists on the ground need to cooperate closely, to complete space science experiments efficiently. However, for the increasingly diverse space science experiments, scientists are unable to train astronauts on the ground about the details of each experiment. The traditional interaction of visual and auditory channels is not enough for scientists to directly guide astronauts to experimentalize. An intuitive and transparent interaction interface between scientists and astronauts has to be built to meet the requirements of space science experiments. Therefore, this paper proposed a vibrotactile guidance system for cooperation between scientists and astronauts. We utilized Kinect V2 sensors to track the movements of the participants of space science experiments, process data in the virtual experimental environment developed by Unity 3D, and provide astronauts with different guidance instructions using the wearable vibrotactile device. Compared with other schemes using only visual and auditory channels, our approach provides more direct and more efficient guidance information that astronauts perceive is what they need to perform different tasks. Three virtual space science experiment tasks verified the feasibility of the vibrotactile operational guidance system. Participants were able to complete the experimental task with a short period of training, and the experimental results show that the method has an application prospect.

The related researches on location privacy in mobile internet were surveyed comprehensively,dissertate sepa-rately from the perspective of LBS(location-based services) and location service.First the privacy protection approaches for LBS were detailed,their features in the view of privacy attacks and LBS applicability were researched.Then the es-sence and research boundary of location privacy in location service were demonstrated,its related research progress and policies were introduced.The future research directions are provided in the end.

Preserving location privacy is an essential requirement in mobile internet.A location privacy protection approach named KAP was proposed which aimed at the privacy issue of location service under the mobile Internet.Through the analysis on locating technology，a weighted adjacent graph-based topology model was given in order to describe the positional relationship between hot spots.Meanwhile，with the help of the model，combining the concept of k-anonymity，three privacy algorithms was shown to make sure the location can not be obtained precisely by attacker.The simulation results verified the correctness and performance of the approach.

The objective of the present study was to investigate the anti-cancer effects of eriodictyol in human hepatocellular carcinoma cells (Hep-G2) and normal liver hepatocyte cell line (AML12) along with evaluating its mode of action. Sulforhodamine B assay was used to evaluate the cytotoxic effect of the compound while as fluorescence microscopy was involved to demonstrate the effect of eriodictyol on cellular apoptosis. Flow cytometry was used to investigate the effect of eriodictyol on cell cycle while Western blot analysis revealed the effect on apoptosis-related protein expressions. Results indicate that eriodictyol-induced selective and concentration-dependent cytotoxic effect on Hep-G2 cancer cells while AML12 normal liver cells were very less susceptible to its effect. Eriodictyol-induced apoptosis related morphological changes including chromatin condensation and nuclear fragmentation. It also induced G2/M cell cycle arrest in these cells. Eriodictyol led to up-regulation of Bax and PARP and down-regulation of Bcl-2 protein. Video Clip of Methodology: Flow cytometry assay: 35 sec Full Screen Alternate