Search

Background: We sought to explore the molecular mechanisms underpinning acute lung injury (ALI) caused by poisoning with paraquat (PQ). Methods: Selection mice were intraperitoneally injected with PQ at 40 mg/kg, whereas controls were injected with sterile saline. On days 2, 7, and 14 after administration, mice were anesthetized and sacrificed, and lung tissue was removed. Lung pathological changes were observed with conventional staining techniques. Lung tissue components were assessed with tandem mass spectrometry tag technology, and differentially expressed proteins (DEPs) were bioinformatically analyzed and investigated with parallel reaction monitoring. Results: The expression of 91, 160, and 78 proteins was significantly altered at days 2, 7, and 14, respectively. Gene Ontology analyses revealed that the DEPs in the PQ-2d and PQ-7d groups were involved primarily in humoral immunity and coagulation-related reactions, whereas those in the PQ-14d group were implicated primarily in chemotactic and regulatory responses. Kyoto Encyclopedia of Genes and Genomes analyses indicated that complement and coagulation cascades were key pathways in the PQ-2d and PQ-7d groups, whereas xenobiotic metabolism by cytochrome P450 was a key pathway in the PQ-14d group. Nine proteins at PQ-2d and eight proteins at PQ-7d were validated through parallel reaction monitoring (PRM). Conclusions: PQ-induced ALI depends on over-activation of immune responses by damaged alveolar/endothelial cells, and the complement/coagulation cascade pathway plays a key role during this process. The proteins identified herein might provide new therapeutic targets or biomarkers for PQ poisoning. [ABSTRACT FROM AUTHOR]

Objective: Rapid on-site evaluation (ROSE) of respiratory cytology specimens is a critical technique for accurate and timely diagnosis of lung cancer. However, in China, limited familiarity with the Diff-Quik staining method and a shortage of trained cytopathologists hamper utilization of ROSE. Therefore, developing an improved deep learning model to assist clinicians in promptly and accurately evaluating Diff-Quik stained cytology samples during ROSE has important clinical value. Methods: Retrospectively, 116 digital images of Diff-Quik stained cytology samples were obtained from whole slide scans. These included 6 diagnostic categories - carcinoid, normal cells, adenocarcinoma, squamous cell carcinoma, non-small cell carcinoma, and small cell carcinoma. All malignant diagnoses were confirmed by histopathology and immunohistochemistry. The test image set was presented to 3 cytopathologists from different hospitals with varying levels of experience, as well as an artificial intelligence system, as single-choice questions. Results: The diagnostic accuracy of the cytopathologists correlated with their years of practice and hospital setting. The AI model demonstrated proficiency comparable to the humans. Importantly, all combinations of AI assistance and human cytopathologist increased diagnostic efficiency to varying degrees. Conclusions: This deep learning model shows promising capability as an aid for on-site diagnosis of respiratory cytology samples. However, human expertise remains essential to the diagnostic process. [ABSTRACT FROM AUTHOR]

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance [e.g., ∼2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models]. For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high-frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low-density lipoprotein receptor-deficient background (Npr2+/−;Ldlr−/−; 32 males and 18 females) were imaged at 4 and 8 wk of age. Fourteen percent of the Npr2+/−;Ldlr−/− mice exhibited features associated with aortic valve malformations, including 1) abnormal transaortic flow patterns on color Doppler (recirculation and regurgitation), 2) peak systolic flow velocities distal to the aortic valves reaching or surpassing ∼1,250 mm/s by pulsed-wave Doppler, and 3) putative fusion of cusps along commissures and abnormal movement elucidated by two-dimensional (2-D) imaging with ultrahigh temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type-0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost effective, and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models. NEW & NOTEWORTHY: We developed a high-frequency ultrasound imaging protocol for diagnosing congenital aortic valve structural abnormalities in 4-wk-old mice. Our protocol defines specific criteria to distinguish mice with abnormal aortic valves from those with normal tricuspid valves using color Doppler, pulsed-wave Doppler, and two-dimensional (2-D) imaging with ultrahigh temporal resolution. This approach enables early identification of valvular abnormalities for efficient and ethical experimental design of longitudinal studies of congenital valve diseases and associated pathologies in mice. [ABSTRACT FROM AUTHOR]

Resourceful and inexpensive seawater direct splitting omits the desalination process and effectively increases the efficiency of hydrogen energy generation. However, the development of seawater splitting is hampered by the competing selectivity challenges from anodic oxygen evolution reaction (OER) and chlorine evolution reaction and the issues of electrode corrosion. Herein, the borate anion‐intercalated NiV‐LDH nanoflakes/NiCoP nanowires heterostructures supported on Ni foam (2D/1D NiV‐BLDH/NiCoP/NF) is synthesized. Theoretical calculations show that a small amount of V atom doping in Ni(OH)2 is favorable for changing the electronic environment around Ni atoms via bridging Ni─O, which can construct Ni─O─V to accelerate electron transfer and promote catalytic activity. The borate anions (B(OH)4−) intercalation not only results in the good hydrophilicity and high OH− selectivity but also weakens the adsorption of chlorine (Cl−), which effectively restrains the chlorine evolution reaction. Thus, the component optimized NiV0.1‐BLDH/NiCoP/NF electrocatalyst only requires 268 mV overpotential to reach 100 mA cm−2 for OER in an alkaline environment. Particularly, the NiCoP/NF||NiV0.1‐BLDH/NiCoP/NF cell exhibits attractive overall water splitting performance with a low voltage of 1.46 and 1.53 V at 10 mA cm−2 in alkaline freshwater and alkaline seawater, respectively. The design strategy of this electrocatalyst provides a new avenue for seawater splitting. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV- and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy murine left and right ventricles indicated that LV-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the RV. Single-cell RNA-sequencing analysis of the two populations confirmed that Postn+ CFs were more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed a unique expansion of two less-well-characterized CF subpopulations (Igfbp3+ and Inmt+). These findings demonstrate that LV- and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform on whether LV and RV fibrosis require distinct treatments. [ABSTRACT FROM AUTHOR]

Due to the vital role of empathy in promoting prosocial behaviors and nurturing social bonds, there is a growing interest in cultivating empathy. Yet, the effectiveness of existing training methods on empathy, especially on different dimensions of empathy (i.e., affective, cognitive, motivational, and behavioral empathy), varies tremendously, and the underlying causes for this heterogeneity remain insufficiently explored. To address this issue, we categorized various training methods into three distinct approaches based on the premise that empathy can be influenced by factors associated with the subject, the object, and their relationship. Respectively, these are Subject-Oriented, Object-Oriented, and Socially Oriented approaches. To examine the effects of training and sustainability of these approaches on different dimensions of empathy, we conducted a meta-analysis encompassing 110 eligible studies with 32, 44, 39, 39, and 91 samples for affective, cognitive, motivational, behavioral, and composite empathy, respectively. Results showed that trainings produced small and unsustainable effects on affective empathy, moderate and unsustainable effects on cognitive empathy, small and sustainable effects on motivational empathy, and moderate and sustainable effects on behavioral empathy. The effects of training on composite empathy were robust but decreased over time. Among the three training approaches, Socially Oriented approaches were the most effective in improving all dimensions of empathy. Subject-Oriented and Object-Oriented approaches were effective only in improving cognitive and composite empathy. Altogether, our study offers practical guidance for selecting appropriate training approaches and proposes theoretical principles for developing optimal training strategies in both basic research and clinical applications. Public Significance Statement: Empathy is essential for building strong social connections and encouraging positive behaviors toward others. This meta-analytic review reveals that while affective empathy (emotional resonance) is hard to train, cognitive (perspective taking), motivational (caring), and behavioral empathy (empathetic actions) are more easily enhanced. Approaches aiming to improve social relationships are the most effective in enhancing empathy, offering practical insights for training on empathy in educational, clinical, and community settings to foster a more empathetic and cohesive society. [ABSTRACT FROM AUTHOR]

Background: The incidence of multiple pregnancies has increased worldwide recently and women with a twin pregnancy are at higher risk of adverse outcomes compared with women with a singleton pregnancy. It is important to understand the risk factors for adverse fetal outcomes in twin pregnancy in order to guide clinical management., Aim: To identify the independent risk factors, including maternal personal and family medical histories and first trimester ultrasound screening findings, for adverse fetal outcomes of twin pregnancy before 28 weeks of gestation., Methods: The data of 126 twin pregnancies in our hospital, including pregnancy outcomes, first trimester ultrasound screening findings and maternal medical history, were retrospectively collected. Twenty-nine women with adverse outcomes were included in the abnormal group and the remaining 97 women were included in the control group., Results: Patients in the abnormal group were more likely to be monochorionic diamniotic (13/29 vs 20/97, P = 0.009), with a higher mean pulsatility index (PI, 1.57 ± 0.55 vs 1.28 ± 0.42, P = 0.003; cutoff value: 1.393) or a higher mean resistance index (0.71 ± 0.11 vs 0.65 ± 0.11, P = 0.008; cutoff value: 0.683) or early diastolic notch of bilateral uterine arteries (UtAs, 10/29 vs 15/97, P = 0.024) or with abnormal ultrasound findings (13/29 vs 2/97, P < 0.001), compared with the control group. Monochorionic diamnioticity, higher mean PI of bilateral UtAs and abnormal ultrasound findings during first trimester screening were independent risk factors for adverse fetal outcomes ( P < 0.05)., Conclusion: First trimester ultrasound screening for twin pregnancy identifies independent risk factors and is useful for the prediction of fetal outcomes., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interests., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) afflicts over half of all patients with heart failure and is a debilitating and fatal syndrome affecting postmenopausal women more than any other demographic. This bias toward older females calls into question the significance of menopause in the development of HFpEF, but this question has not been probed in detail. In this study, we report the first investigation into the impact of ovary-intact menopause in the context of HFpEF. To replicate the human condition as faithfully as possible, vinylcyclohexene dioxide (VCD) was used to accelerate ovarian failure (AOF) in female mice while leaving the ovaries intact. HFpEF was established with a mouse model that involves two stressors typical in humans: a high-fat diet and hypertension induced from the nitric oxide synthase inhibitor N G -nitro-l-arginine methyl ester (l-NAME). In young female mice, AOF or HFpEF-associated stressors independently induced abnormal myocardial strain indicative of early subclinical systolic and diastolic cardiac dysfunction. HFpEF but not AOF was associated with elevations in systolic blood pressure. Increased myocyte size and reduced myocardial microvascular density were not observed in any group. Also, a broad panel of measurements that included echocardiography, invasive pressure measurements, histology, and serum hormones revealed no interaction between AOF and HFpEF. Interestingly, AOF did evoke a higher density of infiltrating cardiac immune cells in both healthy and HFpEF mice, suggestive of proinflammatory effects. In contrast to young mice, middle-aged "old" mice did not exhibit cardiac dysfunction from estrogen deprivation alone or from HFpEF-related stressors. NEW & NOTEWORTHY This is the first preclinical study to examine the impact of ovary-intact menopause [accelerated ovarian failure (AOF)] on HFpEF. Echocardiography of young female mice revealed early evidence of diastolic and systolic cardiac dysfunction apparent only on strain imaging in HFpEF only, AOF only, or the combination. Surprisingly, AOF did not exacerbate the HFpEF phenotype. Results in middle-aged "old" females also showed no interaction between HFpEF and AOF and, importantly, no cardiovascular impact from HFpEF or AOF.

This study reports a new methodology for right heart imaging by ultrasound in mice under right ventricular (RV) pressure overload. Pulmonary artery constriction (PAC) or sham surgeries were performed on C57BL/6 male mice at 8 wk of age. Ultrasound imaging was conducted at 2, 4, and 8 wk postsurgery using both classical and advanced ultrasound imaging modalities including electrocardiogram (ECG)-based kilohertz visualization, anatomical M-mode, and strain imaging. Based on pulsed Doppler, the PAC group demonstrated dramatically enhanced pressure gradient in the main pulmonary artery (MPA) as compared with the sham group. By the application of advanced imaging modalities in novel short-axis views of the ventricles, the PAC group demonstrated increased thickness of RV free wall, enlarged RV chamber, and reduced RV fractional shortening compared with the sham group. The PAC group also showed prolonged RV contraction, asynchronous interplay between RV and left ventricle (LV), and passive leftward motion of the interventricular septum (IVS) at early diastole. Consequently, the PAC group exhibited prolongation of LV isovolumic relaxation time, without change in LV wall thickness or systolic function. Significant correlations were found between the maximal pressure gradient in MPA measured by Doppler and the RV systolic pressure by catheterization, as well as the morphological and functional parameters of RV by ultrasound. NEW & NOTEWORTHY The established protocol overcomes the challenges in right heart imaging in mice, thoroughly elucidating the changes of RV, the dynamics of IVS, and the impact on LV and provides new insights into the pathophysiological mechanism of RV remodeling.