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Thoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1 C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1 +/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1 smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1 +/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1. Thoracic aortic aneurysm (TAA) causes many sudden deaths each year, however, no effective drug treatment is available. Here, the authors show that AGGF1 protein therapy attenuates TAA in three different mouse models through integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signalling.

This study investigates the electric field distribution and breakdown characteristics of oil-paper insulation in a 500 kV converter transformer under AC/DC superimposed voltages. The electric field distribution within the winding end insulation structure at the valve side was analyzed under various voltage conditions using finite element simulations. Experiments were conducted on insulating oil and oil-paper samples to measure their breakdown strengths under different AC/DC components. The results reveal that under DC voltage, the electric field concentrates inside the insulation paper, whereas under AC voltage, it is mainly distributed across the oil gap. Under AC/DC superimposed voltages, a decreasing AC ratio shifts the electric field from the oil gap to the insulation paper and increases the maximum electric field strength. As the DC component rises, the breakdown strength of both oil and oil-paper samples first decreases and then increases, with oil-paper insulation consistently exhibiting higher strength. These findings indicate that although oil-paper insulation can withstand higher electric fields and thus ensure transformer safety, low DC components may increase the risk of oil discharge or failure. Therefore, the design of next-generation high-voltage converter transformers must account for oil-paper insulation degradation under low DC ratios, and effective mitigation strategies—such as controlling the internal electric field or enhancing dielectric strength—are essential for ensuring reliability under AC/DC superimposed voltages.

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR] = 11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥ 3 years post-diabetes diagnosis (n = 1019), we compared youth with steady versus reclassified diabetes type. In the entire cohort, after adjustment for confounders, diabetes type was unknown in 62 youth (3%), associated with older age, negative IA–2 autoantibody, lower C-peptide, and no diabetic ketoacidosis (all, p < 0.05). In the longitudinal subcohort, diabetes type was reclassified in 35 youth (3.4%); this was not statistically associated with any single characteristic. In sum, among racially/ethnically diverse youth with diabetes, 6.4% had inaccurate diabetes classification at diagnosis. Further research is warranted to improve accurate diagnosis of pediatric diabetes type.

Sepsis is a life-threatening organ malfunction induced by the host's abnormal reaction to infection. Sepsis can induce cellular senescence, thereby exacerbating tissue damage and organ dysfunction. However, the key biomarkers of cellular senescence and the corresponding targeted therapeutics in sepsis remain unknown. This study identified eight differentially expressed senescence-related genes, including TXN, CDKN1C, UTP6, BCL11B, SMAD3, ITPKB, PRPF19, and BCL2, through bioinformatics analysis and machine learning. These hub genes had good diagnostic performance for sepsis. Six hub genes showed consistent trends in the validation set and experimental samples with those in the training set. Immunoinfiltration analysis showed that eosinophils, macrophages M1, macrophages M2, NK cells activated, NK cells resting, T cells CD8, and Tregs were substantially linked with all hub genes. A large number of targeted compounds or drugs were obtained from the DSigDB database based on hub genes. These drugs primarily interacted with CDKN1C, BCL2, and SMAD3. The binding energies of fenofibrate with these target proteins were less than -5.0 kcal/mol. In both and models of sepsis-induced acute kidney injury (AKI), fenofibrate has been observed to alleviate senescence and inflammation. In conclusion, the present study identified eight DE-SRGs associated with sepsis and validated their diagnostic efficacy. And, fenofibrate might exert anti-inflammatory and anti-senescence effects in sepsis-induced AKI by regulating senescence genes, shedding fresh light on sepsis treatment.

The movement and rotation of the human head can significantly degrade the control performance of active headrests with virtual microphones. This paper investigates the performance robustness of an active headrest with virtual microphones against the head rotation in a pure tone diffracted diffuse sound field. A physical model of a headrest system with a diffractive sphere is firstly developed, based on which the influence of acoustic transfer responses on the performance robustness against head rotation is analyzed. Then, the multi-objective optimization with constraints is developed to improve the performance robustness of the system, by designing optimized plant responses. Simulation results show that the method is effective in improving the robustness of single and dual channel systems. For a dual-channel headrest system with the proposed arrangements of secondary sources and microphones, the promotion of the minimum noise reduction is more than 7 dB after optimization when the head rotates from −90 degrees to 90 degrees at 125 Hz, 250 Hz and 500 Hz. In addition, the influence of different parameters on the optimization method is discussed for this dual-channel system. Finally, experiments carried out in an ordinary room validate the effectiveness of the proposed method.

Purpose To investigate the characteristics of balance and gait functions in Generalized Joint Hypermobility (GJH) subjects residing in high-altitude areas. Methods This study included 61 university students (28 with GJH and 33 healthy controls) all from the high-altitude region of Linzhi, Tibet Autonomous Region. The Riablo™ wearable intelligent rehabilitation assessment and training system was used to assess static balance (with eyes open and closed) and gait function (during flat walking) in both groups. Results Compared to healthy subjects, GJH subjects exhibited significantly impaired balance, indicated by an increased distance of the center of pressure position from the ideal center of gravity(EO: P  = 0.007, EC: P  = 0.031) and greater amplitude of center of pressure displacements (EO: P  = 0.043, EC: P  = 0.032). Gait velocity( P  = 0.007), stride length( P  = 0.012), and swing stance phase of the gait cycle( P  = 0.046) were significantly reduced in GJH subjects compared to healthy subjects. A significant increase in the flat-foot phase of the gait cycle( P  = 0.022) was observed in GJH subjects compared to healthy subjects. Conclusion The current study demonstrated that GJH subjects residing in high-altitude areas exhibit impairments in balance and gait, providing a basis for training and prevention strategies tailored for this population. And this study used the wearable intelligent rehabilitation evaluation and training system in high-altitude areas, providing methodological references for scientific research on balance and gait function under non laboratory conditions. Trial registration Controlled Trials No.102772023RT133, Registered 13 October 2023.

Postoperative pneumonia (POP) is prevalent in patients undergoing cardiovascular surgery, associated with poor clinical outcomes, prolonged hospital stay and increased medical costs. This article aims to clarify the incidence, risk factors, and interventions for POP after cardiovascular surgery. A comprehensive literature search was performed to identify previous reports involving POP after cardiovascular surgery. Current situation, predictors and preventive measures on the development of POP were collected and summarized. Many studies showed that POP was prevalent in various cardiovascular surgical types, and predictors varied in different studies, including advanced age, smoking, chronic lung disease, chronic kidney disease, cardiac surgery history, cardiac function, anemia, body mass index, diabetes mellitus, surgical types, cardiopulmonary bypass time, blood transfusion, duration of mechanical ventilation, repeated endotracheal intubation, and some other risk factors. At the same time, several targeted interventions have been widely reported to be effective to reduce the risk of POP and improve prognosis, including preoperative respiratory physiotherapy, oral care and subglottic secretion drainage. Through the review of the current status, risk factors and intervention measures, this article may play an important role in clinical prevention and treatment of POP after cardiovascular surgery.

Background Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. Methods In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut‐off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan–Meier method, and significant differences were evaluated by the log‐rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early‐stage disease (stage 0‐II) for sensitivity analysis. Results Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19‐9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p < 0.05). These prognostic factors were used to establish and verify the OS nomogram. Poorer OS was linked to higher RDW (HR = 1.52; 95% CI, 1.11–2.08; p < 0.01) and ΔRDW (HR = 1.65; 95% CI, 1.19–2.28; p < 0.01) in all‐stage patients, and was only linked to higher RDW in early‐stage patients. In competing risk model, H‐RDW and H‐ΔRDW were confirmed to be independent risk factors for CSS in CRC patients. Conclusions High preoperative RDW and ΔRDW are both risk factors for OS and CSS in CRC.

Background Despite surgical advances, acute type A aortic dissection remains a life-threatening disease with high mortality and morbidity. Tracheostomy is usually used for patients who need prolonged mechanical ventilation in the intensive care unit (ICU). However, data on the risk factors for requiring tracheostomy and the impact of tracheostomy on outcomes in patients after Stanford type A acute aortic dissection surgery (AADS) are limited. Methods A retrospective single-institutional study including consecutive patients who underwent AADS between January 2016 and December 2019 was conducted. Patients who died intraoperatively were excluded. Univariate analysis and multivariate logistic regression analysis were used to identify independent risk factors for postoperative tracheostomy (POT). A nomogram to predict the probability of POT was constructed based on independent predictors and their beta-coefficients. The area under the receiver operating characteristic curve (AUC) was performed to assess the discrimination of the model. Calibration plots and the Hosmer–Lemeshow test were used to evaluate calibration. Clinical usefulness of the nomogram was assessed by decision curve analysis. Propensity score matching analysis was used to analyze the correlation between requiring tracheostomy and clinical prognosis. Results There were 492 patients included in this study for analysis, including 55 patients (11.2%) requiring tracheostomy after AADS. Compared with patients without POT, patients with POT experienced longer ICU and hospital stay and higher mortality. Age, cerebrovascular disease history, preoperative white blood cell (WBC) count and renal insufficiency, intraoperative amount of red blood cell (RBC) transfusion and platelet transfusion were identified as independent risk factors for POT. Our constructed nomogram had good discrimination with an AUC = 0.793 (0.729–0.856). Good calibration and clinical utility were observed through the calibration and decision curves, respectively. For better clinical application, we defined four intervals that stratified patients from very low to high risk for occurrence of POT. Conclusions Our study identified preoperative and intraoperative risk factors for POT and found that requiring tracheostomy was related to the poor outcomes in patients undergoing AADS. The established prediction model was validated with well predictive performance and clinical utility, and it may be useful for individual risk assessment and early clinical decision-making to reduce the incidence of tracheostomy.

Polycystic ovary syndrome (PCOS) is associated with a high prevalence of obstructive sleep apnea (OSA); however, its impact on the clinical manifestations of PCOS remains unclear. This study aimed to investigate the clinical characteristics, reproductive endocrine profiles, and glucose-lipid metabolic features in women with PCOS complicated by OSA and to evaluate their potential implications for pregnancy outcomes. A total of 294 infertile women with PCOS treated at Heze Municipal Hospital between February 2023 and December 2024 were enrolled after excluding ineligible participants. Clinical characteristics and reproductive endocrine and metabolic parameters were collected, and factors associated with OSA in women with PCOS were analyzed using the univariate analysis and the logistic regression analysis. Additionally, 101 women with PCOS and OSA were randomly assigned to either a lifestyle intervention control group or a lifestyle intervention and continuous positive airway pressure (CPAP) group, and changes in hormonal and metabolic parameters as well as pregnancy outcomes were evaluated. The prevalence of OSA in women with PCOS was 34.4%, of whom 10.9% had moderate to severe OSA. Higher body mass index, hyperinsulinemia, elevated triglycerides (TGs), and reduced anti-Müllerian hormone (AMH) levels were independently associated with an increased risk of OSA in women with PCOS. Compared with the control group, the CPAP treatment group exhibited significant reductions in serum testosterone (T), insulin (INS), and triglyceride (TG) levels, along with a significantly higher clinical pregnancy rate (  < 0.05). Infertile women with PCOS and OSA exhibit significant disturbances in reproductive endocrine and glucose-lipid metabolism. CPAP therapy may improve these metabolic abnormalities, and when combined with ovulation induction and assisted reproduction, it may lead to better pregnancy outcomes, highlighting the potential benefit of early screening and intervention for OSA in women with PCOS.