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Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and maladaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors...

BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo...

Distant metastasis of hepatocellular carcinoma (HCC) mediated by hematogenous dissemination is a leading cause of HCC-related deaths. The inflammatory response of vascular endothelial cells facilitates this process by promoting the adhesion and invasion of tumor cells in the circulatory system. While the regulation of this inflammation-mediated metastasis through upregulation of adhesion molecules and disruption of intercellular junctions has been well established, the contribution of hemodynamics to this process remains poorly understood due to the lack of a suitable vascular flow model for investigation...

Alcohol use disorder (AUD) remains a major public health concern. The dynorphin (DYN)/κ-opioid receptor (KOP) system is involved in actions of alcohol, particularly its withdrawal-associated negative affective states. This study tested the ability of LY2444296, a selective, short-acting, KOP antagonist, to decrease alcohol self-administration in dependent male and female Wistar rats at 8 h abstinence. Animals were trained to orally self-administer 10% alcohol (30 min/day for 21 sessions) and were made dependent via chronic intermittent alcohol vapor exposure for 6 weeks or exposed to air (nondependent)...

In the work, we prove the presence of chaotic dynamics, for suitable values of the model parameters, for the discrete-time system, composed of two coupled logistic maps, as formulated in Yousefi et al. [Discrete Dyn. Nat. Soc. 5, 161-177 (2000)], which describes two interdependent economies, characterized by two competitive markets each, with a demand link between them. In particular, we rely on the SAP (Stretching Along the Paths) method, based on a stretching relation for maps defined on sets homeomorphic to the unit square and expanding the paths along one direction...

Valvular endothelial cells (VECs) derived from human induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for tissue engineering heart valves (TEHVs); however, they are limited by their low differentiation efficiency and immature function. In our study, we applied unidirectional shear stress to promote hiPSCs differentiation into valvular endothelial-like cells (VELs). Compared to the static group, shear stress efficiently promoted the differentiation and functional maturation of hiPSC-VELs, as demonstrated by the efficiency of endothelial differentiation reaching 98...

Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia-reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo . Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0...

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy. It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer; however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this. In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress (FSS) found in human vasculature was designed and fabricated...

To perform multiplex profiling of single cells and eliminate the risk of potential sample loss caused by centrifugation, we developed a microfluidic flow cytometry and mass spectrometry system (μCytoMS) to evaluate the drug uptake and induced protein expression at the single cell level. It involves a microfluidic chip for the alignment and purification of single cells followed by detection with laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). Biofunctionalized nanoprobes (BioNPs), conjugating ∼3000 6-FAM-Sgc8 aptamers on a single gold nanoparticle (AuNP) ( K d = 0...

Pathological high shear stress (HSS, 100 dyn/cm 2 ) is generated in distal pulmonary arteries (PA) (100-500 μm) in congenital heart defects and in progressive PA hypertension (PAH) with inward remodeling and luminal narrowing. Human PA endothelial cells (PAEC) were subjected to HSS versus physiologic laminar shear stress (LSS, 15 dyn/cm 2 ). Endothelial-mesenchymal transition (EndMT), a feature of PAH not previously attributed to HSS, was observed. H3K27ac peaks containing motifs for an ETS-family transcription factor (ERG) were reduced, as was ERG-Krüppel-like factors (KLF)2/4 interaction and ERG expression...

Endothelial cells (ECs) respond to concurrent stimulation by biochemical factors and wall shear stress (SS) exerted by blood flow. Disruptions in flow-induced responses can result in remodeling issues and cardiovascular diseases, but the detailed mechanisms linking flow-mechanical cues and biochemical signaling remain unclear. Activin receptor-like kinase 1 (ALK1) integrates SS and ALK1-ligand cues in ECs; ALK1 mutations cause hereditary hemorrhagic telangiectasia (HHT), marked by arteriovenous malformation (AVM) development...

Natural hemodynamic changes after balloon pulmonary artery angioplasty (BPA) in a unified state without oxygen administration in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains undetermined. This study aimed to clarify the delayed changes in the hemodynamics after BPA in patients with CTEPH. We analyzed 73 consecutive patients with CTEPH who underwent BPA between July 2014 and December 2022. We extracted and evaluated hemodynamic data of the right heart catheter without oxygen administration immediately before and after the first BPA; and immediately before the second BPA, as the "post-delayed changes" after BPA...

OBJECTIVE: To explore the mechanobiological mechanism of fluid shear force (FSF) on the protection, injury, and destruction of the structure and function of the blood-brain barrier (BBB) under normal physiological conditions, ischemic hypoperfusion, and postoperative hyperperfusion conditions. BBB is mainly composed of brain microvascular endothelial cells. Rat brain microvascular endothelial cells (rBMECs) were used as model cells to conduct the investigation. METHODS: rBMECs were seeded at a density of 1×105 cells/cm2 and incubated for 48 h...

Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices...

PURPOSE: This study examined the magnitude of physiological strain imposed by repeated maximal static and dynamic apneas through assessing a panel of stress-related biomarkers. METHODS: Eleven healthy men performed on three separate occasions (≥72-h apart): a series of five repeated maximal (i) static (STA) or (ii) dynamic apneas (DYN) or (iii) a static eupneic protocol (CTL). Venous blood samples were drawn at 30, 90, and 180-min after each protocol to determine ischaemia modified albumin (IMA), neuron-specific enolase (NSE), myoglobin, and high sensitivity cardiac troponin T (hscTnT) concentrations...

Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and mal-adaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors...

Right heart failure (RHF) is associated with poor outcomes, especially in patients undergoing left ventricular assist device (LVAD) implantation. The aim of this study was to identify predictors of RHF after LVAD implantation. Of 129 consecutive patients (mean age 56 ± 11 years, 89% male) undergoing LVAD implantation, 34 developed RHF. Compared to patients without RHF, those with RHF required longer invasive mechanical ventilation and had longer intensive care unit and hospital stays ( p < 0.01). One-year all-cause mortality was significantly higher in patients with versus without RHF after LVAD implantation (29...

Cardiovascular (CV) health can be measured using the American Health Association's Life's Simple 7 scale (ALS7). Aortic stiffness (AoS) and elasticity (AoE) can be assessed using various methods, e.g., computed tomography (CT). To measure AoE, we use aortic strain and distensibility (AoD). The aim of this study was to examine the relationship between ALS7, AoS, and AoE. The study group (SG) was composed of 96 patients (mean age 70.41 ± 8.32 years) with a BMI of 25.58 ± 3.12 kg/m2 ; 28.1% were smokers, 54...

Ventricular-vascular coupling in endurance athletes remains incompletely understood. The purpose of this study was to determine the ascending aortic impedance in endurance athletes and explore its associations with traditional cardiovascular measurements. In 15 young male endurance runners and 19 young healthy men, time-resolved (CINE) 2D phase-contrast MRI quantified the ascending aortic flow while the pressure waveform was simultaneously collected via a generalized transfer function. The aortic impedance modulus and phase were calculated in the frequency domain while characteristic impedance (ZcF) was calculated by averaging moduli between the 4th and 8th heart rate (HR) harmonics...

OBJECTIVES: Ventilator dyssynchrony may be associated with increased delivered tidal volumes (Vts) and dynamic transpulmonary pressure (ΔPL,dyn), surrogate markers of lung stress and strain, despite low Vt ventilation. However, it is unknown which types of ventilator dyssynchrony are most likely to increase these metrics or if specific ventilation or sedation strategies can mitigate this potential. DESIGN: A prospective cohort analysis to delineate the association between ten types of breaths and delivered Vt, ΔPL,dyn, and transpulmonary mechanical energy...