Deep-learning assisted zwitterionic magnetic immunochromatographic assays for multiplex diagnosis of biomarkers.

Magnetic nanoparticle (MNP)-based immunochromatographic tests (ICTs) display long-term stability and an enhanced capability for multiplex biomarker detection, surpassing conventional gold nanoparticles (AuNPs) and fluorescence-based ICTs. In this study, we innovatively developed zwitterionic silica-coated MNPs (MNP@Si-Zwit/COOH) with outstanding antifouling capabilities and effectively utilised them for the simultaneous identification of the nucleocapsid protein (N protein) of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and influenza A/B. The carboxyl-functionalised MNPs with 10% zwitterionic ligands (MNP@Si-Zwit 10/COOH) exhibited a wide linear dynamic detection range and the most pronounced signal-to-noise ratio when used as probes in the ICT. The relative limit of detection (LOD) values were achieved in 12 min by using a magnetic assay reader (MAR), with values of 0.0062 ng/mL for SARS-CoV-2 and 0.0051 and 0.0147 ng/mL, respectively, for the N protein of influenza A and influenza B. By integrating computer vision and deep learning to enhance the image processing of immunoassay results for multiplex detection, a classification accuracy in the range of 0.9672-0.9936 was achieved for evaluating the three proteins at concentrations of 0, 0.1, 1, and 10 ng/mL. The proposed MNP-based ICT for the multiplex diagnosis of biomarkers holds substantial promise for applications in both medical institutions and self-administered diagnostic settings.

User-Centered Development of STOP (Successful Treatment for Paranoia): Material Development and Usability Testing for a Digital Therapeutic for Paranoia.

BACKGROUND: Paranoia is a highly debilitating mental health condition. One novel intervention for paranoia is cognitive bias modification for paranoia (CBM-pa). CBM-pa comes from a class of interventions that focus on manipulating interpretation bias. Here, we aimed to develop and evaluate new therapy content for CBM-pa for later use in a self-administered digital therapeutic for paranoia called STOP ("Successful Treatment of Paranoia"). OBJECTIVE: This study aimed to (1) take a user-centered approach with input from living experts, clinicians, and academics to create and evaluate paranoia-relevant item content to be used in STOP and (2) engage with living experts and the design team from a digital health care solutions company to cocreate and pilot-test the STOP mobile app prototype. METHODS: We invited 18 people with living or lived experiences of paranoia to create text exemplars of personal, everyday emotionally ambiguous scenarios that could provoke paranoid thoughts. Researchers then adapted 240 suitable exemplars into corresponding intervention items in the format commonly used for CBM training and created 240 control items for the purpose of testing STOP. Each item included newly developed, visually enriching graphics content to increase the engagement and realism of the basic text scenarios. All items were then evaluated for their paranoia severity and readability by living experts (n=8) and clinicians (n=7) and for their item length by the research team. Items were evenly distributed into six 40-item sessions based on these evaluations. Finalized items were presented in the STOP mobile app, which was co-designed with a digital health care solutions company, living or lived experts, and the academic team; user acceptance was evaluated across 2 pilot tests involving living or lived experts. RESULTS: All materials reached predefined acceptable thresholds on all rating criteria: paranoia severity (intervention items: ≥1; control items: ≤1, readability: ≥3, and length of the scenarios), and there was no systematic difference between the intervention and control group materials overall or between individual sessions within each group. For item graphics, we also found no systematic differences in users' ratings of complexity (P=.68), attractiveness (P=.15), and interest (P=.14) between intervention and control group materials. User acceptance testing of the mobile app found that it is easy to use and navigate, interactive, and helpful. CONCLUSIONS: Material development for any new digital therapeutic requires an iterative and rigorous process of testing involving multiple contributing groups. Appropriate user-centered development can create user-friendly mobile health apps, which may improve face validity and have a greater chance of being engaging and acceptable to the target end users.

Reductant-dependent DNA-templated silver nanoparticle formation kinetics.

DNA molecules have been demonstrated to be good templates for producing silver nanoparticles (AgNPs), with the advantages of well-controlled sizes, shapes, and properties. Revealing the formation kinetics of DNA-templated AgNPs is crucial for their efficient synthesis. Herein, using magnetic tweezers, we studied the reduction kinetics of the Ag+-DNA structure and the subsequent nucleation kinetics by adding NaBH4, L-ascorbic acid, and sodium citrate solutions. At [Ag+] = 0.01 mM, the addition of NaBH4 solution with the same concentration resulted in the restoration of DNA. In contrast, by increasing the [NaBH4]/[Ag+] ratio (r) to 10 and 100, the DNA extension initially decreased rapidly and then increased, indicating nucleation-dissolution kinetics. With AgNO3 solutions of higher concentrations (0.1 mM and 1 mM), direct particle nucleation and growth kinetics were observed by adding a tenfold (r = 10) or a hundredfold (r = 100) amount of NaBH4, which were evidenced by a significant reduction in DNA extension. The reductant dependence of the kinetics was further investigated. Addition of L-ascorbic acid to the DNA-Ag+ solution yielded an increase-decrease kinetics that was different from that caused by NaBH4, suggesting that nucleation was not initially favored due to the lack of sufficient Ag atoms; while sodium citrate showed a weak nucleation-promoting ability to form AgNPs. We discussed the findings within the framework of classical nucleation theory, in which the supersaturation of the Ag atom is strongly influenced by multiple factors (including the reducing ability of the reductant), resulting in different kinetics.

A sham-controlled randomised trial of pulmonary artery denervation for Group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial.

BACKGROUND: Long-term clinical outcomes after pulmonary artery denervation (PADN) in patients with Group 1 pulmonary arterial hypertension (PAH) have not been reported. AIMS: We aimed to investigate the effect of PADN on 1-year outcomes in patients with PAH. METHODS: In the multicentre PADN-CFDA trial, 128 patients with Group 1 PAH were randomly assigned to PADN plus a phosphodiesterase-5 inhibitor (PDE-5i) versus a sham PADN procedure plus a PDE-5i. The principal endpoint of interest for the present study was clinical worsening at 1 year after randomisation, the composite of worsening of PAH (increase in WHO functional class, need for additional PAH treatments or PAH-related hospitalisation), atrial septostomy, listing for lung transplantation, or all-cause death. RESULTS: One-year clinical follow-up was available in all patients. At 1 year, clinical worsening had occurred in 3 (4.8%) patients in the PADN plus PDE-5i group and in 15 patients (23.1%) in the sham plus PDE-5i group (adjusted hazard ratio: 0.17; 95% confidence interval [CI]: 0.05-0.60; p=0.006), driven by significantly increased rates of PAH-related hospitalisations, worsening functional class and the requirement for additional PAH treatments in the sham group. Results were consistent in high-risk, intermediate-risk and low-risk patients (pinteraction=0.186). Patients treated with PADN plus PDE-5i had an improvement in the between-group change in the six-minute walking distance (6MWD) from baseline to 1 year of 81.2 m (95% CI: 50.3-112.2; p<0.001) compared with PDE-5i treatment alone. CONCLUSIONS: In this multicentre sham-controlled randomised trial, PADN treatment for Group 1 PAH significantly reduced clinical worsening and improved the 6MWD during 1-year follow-up in patients treated with a PDE-5i.

Machine learning for clustering and postclosure outcome of adult CHD-PAH patients with borderline hemodynamics.

BACKGROUND: Patients with uncorrected isolated simple shunts associated pulmonary arterial hypertension (PAH) had increased mortality. Treatment strategies for borderline hemodynamics remain controversial. This study aims to investigate preclosure characteristics and its association with postclosure outcome in this group of patients. METHODS: Adults with uncorrected isolated simple shunts associated PAH were included. Peak tricuspid regurgitation velocity<2.8 m/sec with normalized cardiac structures was defined as the favorable study outcome. We applied unsupervised and supervised machine learning for clustering analysis and model constructions. RESULTS: Finally, 246 patients were included. During a median follow-up of 414days, 58.49% (62/106) of patients with pretricuspid shunts achieved favorable outcome while 32.22% (46/127) of patients with post-tricuspid shunts. In unsupervised learning, two clusters were identified in both types of shunts. Generally, the oxygen saturation, pulmonary blood flow, cardiac index, dimensions of the right and left atrium, were the major features that characterized the identified clusters. Specifically, mean right atrial pressure, right ventricular dimension, and right ventricular outflow tract helped differentiate clusters in pretricuspid shunts while age, aorta dimension, and systemic vascular resistance helped differentiate clusters for post-tricuspid shunts. Notably, cluster 1 had better postclosure outcome than cluster 2 (70.83% vs 32.55%, p < .001 for pretricuspid and 48.10% vs 16.67%, p < .001 for post-tricuspid). However, models constructed from supervised learning methods did not achieve good accuracy for predicting the postclosure outcome. CONCLUSIONS: There were two main clusters in patients with borderline hemodynamics, in which one cluster had better postclosure outcome than the other.

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial.

BACKGROUND: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients. METHODS: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months. RESULTS: In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up. CONCLUSIONS: In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.

Machine learning in a real-world PFO study: analysis of data from multi-centers in China.

PURPOSE: The association of patent foreman ovale (PFO) and cryptogenic stroke has been studied for years. Although device closure overall decreases the risk for recurrent stroke, treatment effects varied across different studies. In this study, we aimed to detect sub-clusters in post-closure PFO patients and identify potential predictors for adverse outcomes. METHODS: We analyzed patients with embolic stroke of undetermined sources and PFO from 7 centers in China. Machine learning and Cox regression analysis were used. RESULTS: Using unsupervised hierarchical clustering on principal components, two main clusters were identified and a total of 196 patients were included. The average age was 42.7 (12.37) years and 64.80% (127/196) were female. During a median follow-up of 739 days, 12 (6.9%) adverse events happened, including 6 (3.45%) recurrent stroke, 5 (2.87%) transient ischemic attack (TIA) and one death (0.6%). Compared to cluster 1 (n = 77, 39.20%), patients in cluster 2 (n = 119, 60.71%) were more likely to be male, had higher systolic and diastolic blood pressure, higher body mass index, lower high-density lipoprotein cholesterol and increased proportion of presence of atrial septal aneurysm. Using random forest survival (RFS) analysis, eight top ranking features were selected and used for prediction model construction. As a result, the RFS model outperformed the traditional Cox regression model (C-index: 0.87 vs. 0.54). CONCLUSIONS: There were 2 main clusters in post-closure PFO patients. Traditional cardiovascular profiles remain top ranking predictors for future recurrence of stroke or TIA. However, whether maximizing the management of these factors would provide extra benefits warrants further investigations.

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial.

BACKGROUND: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial. OBJECTIVES: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH. METHODS: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months. RESULTS: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up. CONCLUSIONS: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266).

The brain dynamics of trust decisions and outcome evaluation in narcissists.

Individuals with narcissism are, by definition, self-centered, focus on self-benefit, and demonstrate less prosocial behaviors. Trusting strangers is risky, as it can result in exploitation and non-reciprocation. Thus, the trust may be antagonistic to narcissism. However, how narcissists make the choice to trust remains to be elucidated. The current study examined 44 participants (22 rated high in narcissism) playing as trustors in one-shot trust games, and their electroencephalograms were recorded. Individuals high in narcissism exhibited less trust toward strangers, especially following gaining feedback for their trust. In addition, narcissists exhibited a larger N2 following distrust and a stronger negatively-valanced difference in feedback-related negativity (dFRN) after trustee feedback. Our findings provide insights into how individuals with narcissism trust strangers. The results also shed light on the temporal course of brain activity involved in trust decision-making and outcome evaluation in individuals with narcissism.

Lanthanide ions induce DNA compaction with ionic specificity.

Lanthanide (Ln) cations exhibit unique properties that include the ability to interact with DNA to form metal-DNA complexes, which are of great interest in medical, biological and nano-technological fields. Both experimental and theoretical studies have not completely addressed the interaction dynamics between lanthanide ions and DNA. The present study investigates the dynamics of the Ln3+-DNA interaction at the level of a single DNA molecule. Different DNA-metal complexes were produced by the addition of the five lanthanide ions, La3+, Ce3+, Pr3+, Tb3+, and Ho3+ to the DNA solutions. The binding dynamics indicated that the lanthanide cations can induce DNA compaction in a concentration and force-dependent manner. Ionic specificity was displayed in the single-molecule interaction dynamics, where, Ho3+ was found to be the most efficient lanthanide to cause DNA compaction, which was verified by the morphological characterization. The DNA molecules in the five Ln3+-DNA complex solutions were restored to their original length with different restoration speeds, by the addition of EDTA, and this further indicated that the Ho3+ ion had the strongest affinity toward DNA. We conclude that counterion correlation cannot solely explain the ion-dependent DNA compaction, and ionic specificity should be considered significant.

Association of nutritional status and mortality risk in patients with primary pulmonary hypertension.

Malnutrition plays a crucial role in pulmonary hypertension (PH). The prognostic nutritional index (PNI) is a reliable indicator for nutritional status assessment. However, its relationship with mortality risk in PH patients has not yet been investigated. This study analyzed data from the Patient Registry for Primary PH. PNI was calculated through albumin and lymphocyte counts. Subjects with missing data for PNI calculation were excluded. The primary endpoint was all-cause mortality. Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Of the 317 patients records available in the registry, we finally included 136 patients. The average age of the included subjects was 40.56 (14.91) years and 63.24% (86/136) were female. In our analysis of Cox regression, per 1-point increment of PNI was associated with 4% decreased risk of mortality in PH patients (age- and sex-adjusted HR: 0.96, 95% CI: 0.93-0.98, p = 0.002). We further categorized these subjects by quartiles of PNI. Compared to quartile 4, the age- and sex-adjusted HRs of death for quartiles 1, 2, and 3 were 2.39 (95% CI: 1.21-4.72, p = 0.01), 2.25 (95% CI: 1.15-4.39, p = 0.02), and 1.72 (95% CI: 0.84-3.52, p = 0.14). In addition, logistic regression analyses suggested a positive correlation of PNI with total lung capacity (ß = 0.98, p = 0.002) and forced expiratory volume in 1 min (ß = 1.53, p = 0.03). This study demonstrates that low PNI was associated with an increased risk of death in PH patients. These findings help to enlighten our understanding of the nutritional status and adverse outcomes in PH patients.

Preparation of BMP-2/PDA-BCP Bioceramic Scaffold by DLP 3D Printing and its Ability for Inducing Continuous Bone Formation.

Digital light processing (DLP)-based 3D printing is suitable to fabricate bone scaffolds with small size and high precision. However, the published literature mainly deals with the fabrication procedure and parameters of DLP printed bioceramic scaffold, but lacks the subsequent systematic biological evaluations for bone regeneration application. In this work, a biphasic calcium phosphate (BCP) macroporous scaffold was constructed by DLP-based 3D printing technique. Furthermore, bone morphogenetic protein-2 (BMP-2) was facilely incorporated into this scaffold through a facile polydopamine (PDA) modification process. The resultant scaffold presents an interconnected porous structure with pore size of ∼570 µm, compressive strength (∼3.6 MPa), and the self-assembly Ca-P/PDA nanocoating exhibited excellent sustained-release property for BMP-2. Notably, this BMP-2/PDA-BCP scaffold presents favorable effects on the adhesion, proliferation, osteogenic differentiation, and mineralization of bone marrow stromal cells (BMSCs). Furthermore, in vivo experiments conducted on rats demonstrated that the scaffolds could induce cell layer aggregation adjacent to the scaffolds and continuous new bone generation within the scaffold. Collectively, this work demonstrated that the BMP-2/PDA-BCP scaffold is of immense potential to treat small craniofacial bone defects in demand of high accuracy.

Gelatin methacryloyl-alginate core-shell microcapsules as efficient delivery platforms for prevascularized microtissues in endodontic regeneration.

Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was ∼359 µm, and that of GelMA cores was ∼278 µm. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDPSCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications. STATEMENT OF SIGNIFICANCE: Cell-laden microspheres combined with the proangiogenesis approach are promising in endodontic regeneration. We proposed GelMA-alginate core-shell microcapsules generated via the coaxial electrostatic microdroplet (CEM) method, which utilizes a double-lumen needle to allow for core-shell structures to form. The microcapsules were used for co-culturing hDPSCs and HUVECs to harvest large amounts of prevascularized microtissues, which further showed improved vascularization and pulp-like tissue regeneration in vivo. This CEM method and the microcapsule system have advantages of high-throughput generation, convenient collection, and avoid aggregation during long-term culturing. We proposed a high-effective platform for mass production of prevascularized microtissues, which exhibit great promise in the clinical transformation of endodontic regeneration and other applications in regenerative medicine.

Association between oral contraceptive use and incident heart failure.

AIMS: Oral contraceptives (OCs) are widely used in women of reproductive age, but their influences on heart failure (HF) development have yet to be reported. This study was performed to assess HF risk associated with OC use. METHODS AND RESULTS: We studied women participating in the Multi-Ethnic Study of Atherosclerosis with available data on OC use. Inverse probability of treatment weighting analyses were used to reduce baseline imbalances. Cox proportional hazards models were applied to evaluate the associations of OC use and HF risk. The primary analysis comprised a total of 3594 participants [average age 62.10 (10.24) years]. During an average follow-up of 12.45 (3.75) years, 138 incident HF occurred. In unadjusted Cox model, OC use was associated with a decreased risk of HF [hazard ratio (HR) = 0.45, 95% confidence interval (CI) 0.31-0.64, P < 0.001]. However, in multivariable-adjusted and inverse probability of treatment weighting models, the results were attenuated and became non-significant (HR = 0.96, 95% CI 0.63-1.48, P = 0.86 and HR = 0.79, 95% CI 0.45-1.40, P = 0.43, respectively). Duration of OC use was not related to increased risks of HF. When stratifying HF into subtypes, similar associations were observed. In multivariable-adjusted regression models, OC use was positively associated with left ventricular end-diastolic mass [coefficient (ß) = 3.04, P = 0.006] and stroke volume (ß = 1.76, P = 0.01 for the left ventricle; ß = 2.17, P = 0.005 for the right ventricle) but had no impact on left ventricular ejection fraction (ß = 0.09, P = 0.75) and right ventricular ejection fraction (ß = 0.33, P = 0.25). CONCLUSIONS: Oral contraceptive use in women of reproductive age does not portend increased risk of HF. However, whether the formulations or dosages differently impact this association should be further investigated.

High plasma adiponectin is associated with increased pulmonary blood flow and reduced right ventricular function in patients with pulmonary hypertension.

BACKGROUND: Adiponectin is a biomarker closely related to heart failure. However, its role in pulmonary hypertension remains unclear. In this study, we investigated the association between adiponectin and hemodynamic abnormalities, right ventricular function in patients with congenital heart disease associated pulmonary hypertension (CHD-PH). METHODS: Patients with CHD-PH were enrolled in this cross-sectional study. Linear regression analysis was performed to assess the association between adiponectin, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and different clinical parameters. Results were depicted as beta-estimates(ß) with 95%-confidence intervals (95% CI). In addition, mediation and receiver operating characteristic curve analyses were used to analyze the relationships among adiponectin, NT-proBNP and right ventricular function. RESULTS: A total of 86 CHD-PH patients were included. The overall mean adiponectin concentration was 7.9 ± 5.8 µg/ml. Log adiponectin was positively correlated with pulmonary circulation index (ß = 2.2, 95% CI 0.5, 4.0), log NT-proBNP (ß = 0.22, 95% CI 0.04, 0.41) and inversely with the tricuspid annular plane systolic excursion (TAPSE, ß = -4.7, 95% CI -8.6, - 0.8). The mediation analysis revealed the association between NT-proBNP and TAPSE was fully mediated by adiponectin (total effect c = - 5.4, 95% CI -9.4, - 1.5, p = 0.013; direct effect c' = - 3.7, 95% CI -7.5, 0.1, p = 0.067). Additionally, the efficiency of adiponectin for detecting right ventricular dysfunction was not inferior to NT-proBNP (AUC = 0.84, 95% CI 0.67-1.00 vs AUC = 0.74, 95% CI 0.51-0.97, p = 0.23). CONCLUSIONS: Adiponectin is closely correlated with pulmonary blood flow and right ventricular function and may be a valuable biomarker for disease assessment in patients with pulmonary hypertension.

The effect of the α7nAChR agonist on Wnt/ß-catenin signaling in osteoporosis.

The cholinergic pathway neurotransmitter acetylcholine (ACh) regulates the inflammatory cascade through a specific α7 nicotinic acetylcholine receptor (α7nAChR). However, the role and related mechanisms of α7nAChR in osteoporosis (OP) remain unclear. Therefore, this study aims to analyze the effects of α7nAChR on osteoblasts and related mechanisms. Mouse osteoblast MC3T3-E1 was cultured in vitro and divided into a control group and an α7nAChR agonist group (2.4 and 4.8 mg/kg.d). An MTT assay was used to detect the osteoblast activity, an ARS staining assay was used to analyze the formation of calcified nodules of osteoblasts, and an alkaline phosphatase (ALP) activity colorimetric assay was used to determine the ALP activity. Real-time PCR was performed to analyze the expression of RUNX2 and OPN mRNA. The inflammatory factor tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretions were analyzed by ELISA. The α7nAChR agonists dose-dependently promoted osteoblast proliferation, increased calcified nodules, ALP activity, RUNX2 and OPN mRNA expression, decreased inflammatory factors TNF-α and IL-6 secretion, and increased Wnt1, ß-catenin mRNA and protein expression. Compared with the control group, the differences were statistically significant (P<0.05). α7nAChR agonists can inhibit the proliferation and differentiation of osteoblasts by regulating the Wnt/ß-catenin signaling pathway, and then participate in the regulation of osteoporosis.