Mechanism research of elastic fixation promoting fracture healing based on proteomics and fracture microenvironment.

Aims: This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels. Methods: A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process. Results: Mean callus volume was larger in the elastic fixation group (1,755 mm3 (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm3 (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion: Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN.

The association between physical activity and positive affect in adolescents: the chain mediating role of psychological resilience and regulatory emotional self-efficacy.

Previous studies have indicated the positive impact of physical activity on positive affect in adolescents. However, the psychological mechanism is still under-explored. The current study aims to investigate the mediating role of psychological resilience and regulatory emotional self-efficacy on the relationship between physical activity and positive affect. This cross-sectional study recruited 580 adolescents (280 females, 12 to 16 years old). All participants completed the measures of the Physical Activity Questionnaire for Adolescents (PAQ-A), the Positive and Negative Affect Scale (PANAS), the Connor-Davidson Resilience Scale, and the Regulatory Emotional Self-Efficacy Questionnaire. Results showed that the association between physical activity and positive affect was significant in adolescents. Psychological resilience played a mediating role between physical activity and positive affect. The chain mediation effect of psychological resilience and regulatory emotional self-efficacy on the relationship between physical activity and positive affect was significant. These results indicated that physical activity could positively impact adolescents' positive affect through psychological resilience and regulatory emotional self-efficacy. Our findings highlighted the importance of physical activity on positive affect on adolescents, which would benefit the mental health of this population.

Syndecan-3 inhibits LPS-induced Inflammation of Bovine Mammary Epithelial Cells through the NF-κB Signal Transduction Pathway.

In mastitis, excessive inflammation caused by lipopolysaccharide (LPS) is an important factor leading to mammary tissue damage. Therefore, exploring the regulatory factors that can inhibit the widespread inflammation caused by LPS is crucial. Syndecan-3 (SDC3) has been found to play an active role in anti-inflammatory infection by inhibiting leukocyte adhesion, reducing the accumulation of inflammatory products, such as reactive oxygen species, and competing with chemokines; however, the role and regulatory mechanism of SDC3 in mastitis remains unknown. Therefore, this study aimed to reveal the effect of SDC3 on LPS-induced inflammation in bovine mammary epithelial cells (BMECs) and explore its possible molecular mechanisms. First, we constructed a BMEC inflammatory model. It was found that cells stimulated with 10 µg/mL LPS for 24 h strongly induced the expression of inflammatory cytokines and had no toxic effect on cells, which was the best condition to simulate the BMECs inflammatory response in vitro. Subsequently, we used overexpression and RNAi interference, Real Time Quantitative PCR (RT-qPCR), and Western blot assays to explore the effects of SDC3 on LPS-induced inflammatory factors and their mechanisms. The results showed that overexpression of SDC3 could inhibit the transcriptional levels of inflammatory cytokines IL-6, IL-1ß, and TNFα induced by LPS and inhibit the activation of the NF-κB inflammatory pathway by inhibiting the expression of NF-κB p50 and p-IκBα and promoting the expression of IκBα. Our results suggest that SDC3 inhibits the LPS-induced inflammatory response of BMECs through the NF-κB pathway, in which NF-κB p50 may be an important target of SDC3. These findings lay the foundation for elucidating the molecular regulatory mechanisms of dairy cow mastitis.

Phlorotannin Alleviates Liver Injury by Regulating Redox Balance, Apoptosis, and Ferroptosis of Broilers under Heat Stress.

Heat stress (HS) poses a great challenge to the poultry industry by inducing oxidative damage to the liver, endangering the health and production of broilers. As an important type of seaweed polyphenols, phlorotannin has been shown to have antioxidant properties. The present study evaluated the protective effects of dietary phlorotannin on HS-induced liver injury in broilers based on oxidative damage parameters. A total of 108 twenty-one days old male Arbor Acres plus (AA+) broilers were randomly divided into three groups: TN group (thermoneutral, 24 ± 1 °C, fed with basal diet), HS group (HS, 33 ± 1 °C for 8 h/day, fed with basal diet), and HS + phlorotannin group (HS + 600 mg/kg phlorotannin). Each group has six replicate cages with six birds per cage. The feeding experiment lasted 21 days. At the termination of the feeding experiment (42 days old), samples were collected for analysis of morphological and biochemical features. The results showed that HS decreased the liver index, serum albumin (ALB) content, hepatic antioxidant enzymes activities of catalase (CAT), total superoxide dismutase (T-SOD), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) (p < 0.05), while increasing the hepatic histopathology score, apoptosis rate, and malondialdehyde (MDA) content (p < 0.05) in 42-day-old broilers. Compared with the HS group, dietary phlorotannin improved the activities of antioxidant enzymes (GST and GSH-Px) but decreased the histopathology score and apoptosis rate in the liver (p < 0.05). Moreover, HS down-regulated hepatic mRNA expression of CAT1, NQO1, HO-1, and SLC7A11 (p < 0.05), while up-regulated hepatic mRNA expression of Keap1, MafG, IκBα, NF-κB P65, IFN-γ, TFR1, ACSL4, Bax, and Caspase-9 (p < 0.05). Compared with HS group, dietary phlorotannin up-regulated hepatic mRNA expression of Nrf2, CAT1, MafF, GSTT1, NQO1, HO-1, GCLC, GPX1, TNF-α, Fpn1, and SLC7A11 (p < 0.05), while down-regulated hepatic mRNA expression of IκBα, Bax, Caspase-9, and TFR1 (p < 0.05). In conclusion, dietary supplementation of 600 mg/kg phlorotannin could alleviate HS-induced liver injury via regulating oxidative status, apoptosis, and ferroptosis in broilers; these roles of phlorotannin might be associated with the regulation of the Nrf2 signaling pathway.

Ternary Moral Empathy Model from the Perspective of Intersubjective Phenomenology.

The phenomenon of empathy is an intersubjective process of feeling and a particular form of intentionality. Moral empathy refers to a type of empathy that can trigger moral action, with the embodied intersubjectivity laying the foundation for its emergence. This paper attempts to propose a comprehensive theoretical model of moral empathy from the perspective of intersubjective phenomenology, which includes the following. (1) The moral dimension of perceptual empathy: at the subpersonal, unconscious, and perceptual-motor level, embodied empathic practices are essential for the formation of moral consciousness and the emergence of moral empathy. (2) The moral dimension of situational empathy: following the development of shared attention mechanisms, children can direct towards the intentional objects of others through embodied situational cues to perceive the psychological state of others and generate the moral empathy of "ought", leading to dyadic morality that promotes cooperative behavior. (3) The moral dimension of narrative empathy: the narrative practices of moral empathy refer to the processes by which children could perceive and understand the moral situation of characters within an embodied narrative structure, subsequently generate prosocial motives such as empathic concern, and then accept the "objective" moral norms of the group consciousness embedded in the narrative.

Prenatal diagnosis of monozygotic twins with phenotypic differences in chromosome 17q12 deletion syndrome.

We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non-genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis: A network meta-analysis.

BACKGROUND: Currently, traditional Chinese medicine (TCM) formulas are commonly being used as adjunctive therapy for ulcerative colitis in China. Network meta-analysis, a quantitative and comprehensive analytical method, can systematically compare the effects of different adjunctive treatment options for ulcerative colitis, providing scientific evidence for clinical decision-making. AIM: To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis (UC) in clinical practice through a network meta-analysis. METHODS: Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1, 2022. Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard. The methodological quality of the studies was assessed using ReviewManager (RevMan) 5.4, and a funnel plot was constructed to test for publication bias. ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures. RESULTS: A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study. The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients. Adjuvant treatment with Baitouweng decoction (BTWT) showed a significant effect [mean difference = 36.22, 95% confidence interval (CI): 7.63 to 65.76]. For the reduction of tumor necrosis factor in patients with UC, adjunctive therapy with BTWT (mean difference = -9.55, 95%CI: -17.89 to -1.41), Shenlingbaizhu powder [SLBZS; odds ratio (OR) = 0.19, 95%CI: 0.08 to 0.39], and Shaoyao decoction (OR = -23.02, 95%CI: -33.64 to -13.14) was effective. Shaoyao decoction was more effective than BTWT (OR = 0.12, 95%CI: 0.03 to 0.39), SLBZS (OR = 0.19, 95%CI: 0.08 to 0. 39), and Xi Lei powder (OR = 0.34, 95%CI: 0.13 to 0.81) in reducing tumor necrosis factor and the recurrence rate of UC. CONCLUSION: TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Osteoporosis treatment: current drugs and future developments.

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.

Molecularly imprinted polymer-based electrochemical sensor for rapid detection of masked deoxynivalenol with Mn-doped CeO2 nanozyme as signal amplifier.

Deoxynivalenol-3-glucoside (D3G), the masked form of the important mycotoxin deoxynivalenol (DON), displays potential toxicity but is difficult to control owing to the lack of rapid detection methods. Herein, an innovative molecularly imprinted polymer (MIP)-based electrochemical sensor was developed for the rapid detection of D3G. MIP, an efficient recognition element for D3G, was electropolymerized using o-phenylenediamine based on a surface functional monomer-directing strategy for the first time. CeO2, which contains both Ce3+ and Ce4+ oxidation states, was introduced as a nanozyme to catalyze H2O2 reduction, while Mn doping generated more oxygen vacancies and considerably improved the catalytic activity. Mn-CeO2 also served as a promising substrate material because of its large surface area and excellent conductivity. Under optimal conditions, a good linear relationship was observed for D3G detection over the concentration range of 0.01-50 ng/mL. The proposed sensor could detect D3G down to 0.003 ng/mL with excellent selectivity, even distinguishing its precursor DON in complex samples. The sensor exhibited acceptable stability with high reproducibility and accuracy, and could successfully determine D3G in grain samples. To the best of our knowledge, this is the first electrochemical sensing platform for rapid D3G detection that can easily be expanded to other masked mycotoxins.

Lipid Regulatory Element Interact with CD44 on Mitochondrial Bioenergetics in Bovine Adipocyte Differentiation and Lipometabolism.

The CD44 gene is a critical factor in animal physiological processes and has been shown to affect insulin resistance and fat accumulation in mammals. Nevertheless, little research has been conducted on its precise functions in lipid metabolism and adipogenic differentiation in beef cattle. This study analyzed the expression of CD44 and miR-199a-3p during bovine preadipocyte differentiation. The luciferase reporter assay demonstrated that CD44 was a direct target of miR-199a-3p. Increased accumulation of lipid droplets and triglyceride levels, altered fatty acid metabolism, and accelerated preadipocyte differentiation were all caused by the upregulation of miR-199a-3p or a reduction in CD44 expression. CD44 knockdown upregulated the expression of adipocyte-specific genes (LPL and FABP4) and altered the levels of lipid metabolites (SOPC, l-arginine, and heptadecanoic acid). Multiomics highlights enriched pathways involved in energy metabolism (MAPK, cAMP, and calcium signaling) and shifts in mitochondrial respiration and glycolysis, indicating that CD44 plays a regulatory role in lipid metabolism. The findings show that intracellular lipolysis, glycolysis, mitochondrial respiration, fat deposition, and lipid droplet composition are all impacted by miR-199a-3p, which modulates CD44 in bovine adipocytes.

Effects of malnutrition on disease severity and adverse outcomes in idiopathic pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. METHODS: A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. RESULTS: During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P < 0.001) identified these patient groups better than the GNRI. All three malnutrition tools were associated with well-validated variables that reflected IPAH severity, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide level. The CONUT score exhibited better predictive ability than both the GNRI (ΔAUC = 0.059, P < 0.001) and PNI (ΔAUC = 0.095, P < 0.001) for adverse outcomes and significantly improved reclassification and discrimination beyond the ESC risk score. Multivariable Cox regression analysis indicated that only the CONUT score (hazard ratio = 1.363, 95% confidence interval 1.147, 1.619 per 1.0-standard deviation increment, P < 0.001) independently predicted adverse outcomes. CONCLUSIONS: The malnutrition status was associated with disease severity in patients with IPAH. The CONUT score provided additional information regarding the risk of clinically worsening events, making it a meaningful risk stratification tool for these patients.

A multifunctional gingival retraction cord with antibacterial and hemostasis properties based on Chitosan/Propolis/Tranexamic acid for dental treatment.

A novel gingival retraction cord named P/TA@CSy was prepared using chitosan yarns (CSy) loaded with tranexamic acid (TA) and Propolis (P). P/TA@CSy has good toughness with a breaking strength of 41.3 Pa, benefiting from the twisting structure and Propolis coating. A short coagulation time of 456 s was achieved for P/TA@CSy because of the potent blood absorption ability from the effective attachment of tranexamic acid. Moreover, excellent antibacterial ability was obtained with the antibacterial rates against E. coli of 94.73 %, S. aureus of 99.99 % and S. mutans of 99.99 %, contributing to Propolis's antibacterial ability. In addition, suppression of the expression of pro-inflammatory cytokines (IL-6 and TNF-α) was found, which could prevent wound infection. P/TA@CSy displayed excellent cytocompatibility with the cell activity of 100 % after 24 h. Therefore, P/TA@CSy could rapidly respond to gingival hemostasis and infection prevention, showing excellent potential in dental treatment.

Spatiotemporal Regulation of Cell Fate in Living Systems Using Photoactivatable Artificial DNA Membraneless Organelles.

Coacervates formed by liquid-liquid phase separation emerge as important biomimetic models for studying the dynamic behaviors of membraneless organelles and synchronously motivating the creation of smart architectures with the regulation of cell fate. Despite continuous progress, it remains challenging to balance the trade-offs among structural stability, versatility, and molecular communication for regulation of cell fate and systemic investigation in a complex physiological system. Herein, we present a self-stabilizing and fastener-bound gain-of-function methodology to create a new type of synthetic DNA membraneless organelle (MO) with high stability and controlled bioactivity on the basis of DNA coacervates. Specifically, long single-strand DNA generated by rolling circle amplification (RCA) is selected as the scaffold that assembles into membraneless coacervates via phase separation. Intriguingly, the as-formed DNA MO can recruit RCA byproducts and other components to achieve self-stabilization, nanoscale condensation, and function encoding. As a proof of concept, photoactivatable DNA MO is constructed and successfully employed for time-dependent accumulation and spatiotemporal management of cancer in a mouse model. This study offers new, important insights into synthetic membraneless organelles for the basic understanding and manipulation of important life processes.

Predicting Kawasaki disease shock syndrome in children.

Background: Kawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD. Methods: The clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68). Results: In the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets. Conclusion: Here we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.

Optimization of High-Activity earthworm fibrinolytic enzyme extraction methods and protein component analysis.

OBJECTIVE: Optimize the extraction process of earthworm fibrinolytic enzyme. METHODS: Chinese common earthworms underwent a series of purification processes, including grinding, salting out, hydrophobic medium chromatography, ammonium sulfate precipitation, and ion exchange chromatography, to obtain purified earthworm fibrinolytic enzyme. RESULTS: Utilizing Pheretima aspergillum as the starting material, we discovered that the specific activity of lumbrokinase extracted via ammonium sulfate precipitation was 58 U/mg, noticeably surpassing that achieved through heat precipitation and ethanol precipitation methods. After undergoing two rounds of chromatographic separations employing hydrophobic affinity chromatography and anion exchange chromatography, the specific activity of the lumbrokinase protein soared to 9267 U/mg, significantly exceeding the 3,178 U/mg specific activity attained through industrial extraction methods. DISCUSSION: The development of a novel crude extraction method for lumbrokinase protein can significantly boost its activity and purity. The discovery of a high-efficiency purification method and the identification of protein components within highly active lumbrokinase pave the way for further investigations into these proteins.

Intelligent Gas Detection: g-C3N4/Polypyrrole Decorated Alginate Paper as Smart Selective NH3/NO2 Sensors at Room Temperature.

Chemiresistive NH3/NO2 sensors are attracting considerable attention for use in air-conditioning systems. However, the existing sensors suffer from cross-sensitivity, detection limit, and power consumption, owing to the inadequate charge-transfer ability of gas-sensing materials. Herein, we develop a flexible NH3/NO2 sensor based on graphitic carbon nitride/polypyrrole decorated alginate paper (AP@g-CN/PPy). The flexible sensor can work at room temperature and exhibits a positive response of 23-246% and a negative response of 37-262% toward 0.1-5 ppm of NH3 and NO2, which is ∼4.5 times and ∼7.0 times higher than a pristine PPy sensor. Moreover, the sensor exhibits flexibility, reproducibility, long-term stability, anti-interference, and high resilience to humidity, indicating its promising potential in real applications. Using the 9 feature parameters extracted from the transient response, a matched deep learning model was developed to achieve qualitative recognition of different types of gases with distinguished decision boundaries. This work not only provides an alternative gas-sensing material for dual NH3/NO2 sensing but also establishes an intelligent strategy to identify hazardous gases under an interfering atmosphere.

Usefulness of risk assessment tools in predicting hemodynamic outcome after balloon pulmonary angioplasty: a comparative analysis.

OBJECTIVES: Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA. METHODS: In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up. RESULTS: The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009-0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96). CONCLUSION: Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA.

Promotional effects of In(PO3)3 on the high catalytic activity of CuO-In(PO3)3/C for the CO2 reduction reaction.

The construction of Cu-In bi-component catalysts is an effective strategy to enhance the electrocatalytic properties towards the CO2 reduction reaction (CO2RR). However, realizing the co-promotion of In and heteroatom P on the electrocatalytic performance is still a challenge due to the poor selectivity of metal phosphides. Herein, a novel bi-component catalyst (CuO-In(PO3)3/C) was successfully synthesized via a facile one-pot reaction to realize the integration of Cu, In, and P species for the enhancement of electrocatalysis. In particular, the as-obtained nanorod-like Cu-In(PO3)3/C exhibits superior electrocatalysis towards the CO2RR, with the highest Faraday efficiency of CO (FECO) of 88.5% at -0.586 V. Furthermore, Cu-In(PO3)3/C shows better activity, selectivity, and stability in the CO2RR; in particular, the total current density can reach 178.09 mA cm-2 at -0.886 V in 2.0 M KOH solution when a flow cell is employed. This work provides a reliable method for simplifying the synthesis of novel Cu-based catalysts and exploits the application of heteroatom P in the field of efficient CO2RR.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.