Search

Introduction Itaconate has emerged as a compelling immunomodulatory metabolite produced in the tricarboxylic acid (TCA) cycle (1, 2). The enzyme cis-aconitate decarboxylase 1 (Acod1, also named Irg1) is responsible for [...], Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as immune-responsive gene 1 [IRG1]), are upregulated during atherogenesis in mice. Deletion of Acodl in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4- octyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis.

The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

This study aimed to investigate the risk factors for low postoperative blood pressure and construct a machine learning (ML) model based on these features for real-time prediction in patients with oral cancer following reconstruction surgery. The retrospective cohort analysis included adults who had undergone oral cancer resection and free flap reconstruction surgery between December 2022 and December 2023. Patient clinical characteristics were obtained from the electronic medical records. Seven ML techniques were attempted with postoperative hypotension (POH) (mean arterial pressure ˂ 55 mmHg) as the primary outcome. The best-performing ML model was tuned, and the final performance was evaluated using split-set validation, followed by risk factor identification and model interpretability. Of the 727 patients, 412 were finally included, with 66 (16.2%) experiencing POH, resulting in higher inpatient costs and prolonged hospitalization. With an area under the receiver operating characteristic curve of 0.805 (95% confidence interval [CI]: 0.674–0.935), the random forest model demonstrated excellent performance. Shapley additive explanation and feature importance analysis revealed that systolic pressure, heart rate, tumor size, lactic acid level, diastolic pressure, surgical time, total liquid infusion volume, and body mass index were significant risk factors for POH, indicating the robustness of the random forest model. [ABSTRACT FROM AUTHOR]

The KR desulfurization process in steel plants faces challenges, such as excessive temperature drop and low lime utilization. This study employs numerical simulations to analyze the effects of cross-shaped impeller dimensions on the flow field, velocity distribution, temperature drop, and slag–metal mixing behavior within the molten metal. Optimization parameters were identified to minimize the temperature drop while maintaining the mixing efficiency. Furthermore, a novel perforated cross-shaped impeller design was proposed to enhance slag–metal mixing. The simulation results demonstrate that compared to the conventional cross-shaped impeller, the optimized design increases the molten metal capacity by 2 tons and reduces the temperature drop by 16 °C under identical initial liquid level conditions. [ABSTRACT FROM AUTHOR]

Objective: To explore the changes in carcinoembryonic antigen (CEA) during the immune process of programmed death-1 (PD-1) inhibitor Sintilimab in human epithelial growth factor receptor 2 (HER2) negative advanced gastric cancer patients and its relationship with prognosis. Methods: HER2 negative late stage gastric cancer patients (88 cases) who were treated in North Anhui Coal Power Group General Hospital from May 2020 to April 2022 were selected as study subjects, all of whom received PD-1 inhibitor Sintilimab treatment; according to the prognosis, they were divided into death group (36 cases) and survival group (52 cases). Followed up was conducted every 6 months to collect tumor marker levels before and after treatment. Analyzed relationship between tumor markers (CEA, CA199, CA125) levels and clinical staging, lymph node metastasis and prognosis. Kaplan-Meier survival curve was used to analyze survival time of patients with negative and positive tumor markers. Multivariate Cox regression model and stepwise regression analysis were used to identify risk factors affecting prognosis. Spearman was used for correlation analysis. Results: After two cycles of treatment, 72 cases (81.82%) had disease control and 16 cases (18.18%) had progression. Compared with patients before treatment, positive rate of serum tumor markers in patients after treatment was significantly reduced (P<0.05). Positive rates of CEA and CA199 were significantly correlated with clinical staging (P<0.05). When predicting patient death, sensitivity of CEA level was the highest (48.57%), while CA125 had the highest specificity (95.62%) and the lowest sensitivity (25.71%). Kaplan-Meier survival curve analysis showed that the survival time of patients with positive tumor markers were significantly shorter than that of negative patients (P<0.05). Clinical staging, serum CEA and CA199 levels were independent factors for predicting prognosis (P<0.05). Spearman correlation analysis results showed that the multiple increases in CEA (r=-0.512, P=0.005) and CA199 (r=-0.467, P=0.011) were negatively correlated with patient survival time. Conclusion: After treatment with PD-1 inhibitor Sintilimab, serum tumor markers levels in HER2 negative advanced gastric cancer patients have been significantly reduced on average. High serum levels of CEA, CA199 and CA125 can all predict poor prognosis, and clinical staging, serum CEA and CA199 levels are independent factors in predicting prognosis. The higher the increase in CEA and CA199, the shorter the patient's survival time. [ABSTRACT FROM AUTHOR]

Fairness stands as a pivotal element in maintaining social stability. It is still a highly challenging issue to explain how fairness emerges in society. The ultimatum game (UG) and the dictator game (DG) have become prominent paradigms for exploring the emergence of fairness. A great number of mechanisms have been put forward to promote the emergence of fairness in these two games. In this paper, we sort out the recent relevant evolutionary game models regarding fairness and categorize them according to the mechanisms for the emergence of fairness. The main mechanisms consist of network reciprocity, role assignment, spite, empathy, stake size, and indirect reciprocity. Especially for indirect reciprocity, we make a detailed introduction of a theoretical method and some recent works that use this theoretical approach to explore how fairness evolves. Finally, we suggest several potential avenues for future research. [ABSTRACT FROM AUTHOR]

To clarify the quality characteristics of upper tobacco leaves with high usability and different flavor types from different tobacco growing regions, the upper tobacco leaf samples were collected from industrial enterprise base units. Taking industrial usability as the primary basis, a comparative analysis was conducted on the routine chemical components, appearance quality, and sensory quality of upper tobacco leaves from robust, medium, and fresh flavor type regions. The results showed that: 1) In terms of appearance quality, upper tobacco leaves from robust flavor type regions had relatively higher maturity, looser leaf structure, and more moderate body. Conversely, leaves from medium flavor type regions scored higher in appearance quality indicators, while those from fresh flavor type regions, despite high usability, exhibited relatively lower maturity. 2) Among routine leaf chemical components, the influence of total alkaloid content on the sensory quality indicators of upper tobacco leaves varied significantly across the flavor type regions. A moderate increase in total alkaloid content positively affected aroma quality, enhancing aroma intensity, concentration, and strength, resulting in higher overall sensory evaluation scores for leaves from robust flavor type regions. However, this enhancement notably increased irritation of medium flavor type leaves and had detrimental effects on the aroma quality of fresh flavor type leaves. Furthermore, increasing potassium content and reducing chlorine content emerged as crucial strategies for enhancing the sensory quality of upper tobacco leaves with robust flavor type. 3) For robust and fresh flavor type regions, concentration and strength were key factors influencing the usability of upper tobacco leaves. Upper tobacco leaves with higher usability from robust flavor type regions require higher aroma quantity, concentration and strength, whereas in fresh flavor type regions, these factors may adversely affect usability. [ABSTRACT FROM AUTHOR]

To explore the direction to develop intelligent tobacco flue-curing, the history of tobacco flue-curing equipment and technology was briefly reviewed, and the concept and implementation path of intelligent flue-curing were proposed based on the current status of intelligent agriculture and the characteristics of tobacco flue-curing. The research and practice of intelligent flue-curing for tobacco, including the construction of high-quality data sets, the development of algorithm models and application systems, focusing on the automatic perception of flue-curing data, the autonomous identification of tobacco status during curing, and the adaptive optimization of flue-curing technology, was introduced. It accumulates the research and application experience in intelligent tobacco agriculture from conception, cognition to decision level. [ABSTRACT FROM AUTHOR]