Search Results (413)

The junctional sarcoplasmic reticulum (jSR) is a critical organelle in cardiomyocytes, regulating calcium homeostasis and Excitation–Contraction Coupling (ECC). A quantitative understanding of its protein composition is essential for investigating cardiac physiology and related pathologies. However, isolating intact jSR vesicles, particularly those enriched in membrane proteins, remains a challenging task. Here, we describe our optimized protocol for reproducible enrichment of jSR vesicles from a single murine heart, without the use of antibodies. The protocol enables the recovery of low-abundance membrane proteins while preserving their native interactions with partners. This strategy facilitates the straightforward identification by Mass Spectrometry of highly relevant yet challenging jSR proteins, including the cardiac Ryanodine Receptor and calsequestrin. Our protocol provides a robust tool for studying the structural and stoichiometric organization of the cardiac jSR components in a widely used animal model. Full article

Focusing on the Lingshan section of Guangxi’s Pinglu Canal, this study addresses frequent waterlogging during construction under subtropical monsoon rainfall. Human disturbances alter hydrological processes, causing project delays and economic losses. We developed a coupled Storm Water Management Model (SWMM 1D hydrological) and Hydrologic Engineering Center—River Analysis System 2D (HEC-RAS 2D hydrodynamic) model. High-resolution Unmanned Aerial Vehicle—Light Detection and Ranging (UAV-LiDAR) Digital Elevation Model (DEM) delineated sub-catchments, while the Green-Ampt model quantified soil conductivity decay. Synchronized runoff data drove high-resolution HEC-RAS 2D simulations of waterlogging evolution under design storms (1–100-year return periods) and a real event (10 May 2025). Key results: Water depth exhibits nonlinear growth with return period—slow at low intensities but accelerating beyond 50-year events, particularly at temporary road junctions where embankments impede flow. Additionally, intensive intermittent rainfall causes significant ponding at excavation pit-road intersections, and optimized drainage drastically shortens recession time. The study reveals a “rapid runoff generation–restricted convergence–prolonged ponding” mechanism under construction disturbance, validates the model’s capability for complex scenarios, and provides critical data for real-time waterlogging risk prediction and drainage optimization during the canal’s construction. Full article

Voltage-gated Ca²⁺ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1–CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in skeletal muscle as multiple isoforms. The adult isoform, CaVβ1D, localizes at the triad and modulates CaV1 activity during Excitation–Contraction Coupling (ECC). In this study, we investigated the lesser-known embryonic/perinatal CaVβ1 isoforms and their roles in neuromuscular junction (NMJ) formation, maturation, and maintenance. We found that CaVβ1 isoform expression is developmentally regulated through differential promoter activation. Specifically, CaVβ1A is expressed in embryonic muscle and reactivated in denervated adult muscle, alongside the known CaVβ1E isoform. Nerve injury in adult muscle triggers a shift in promoter usage, resulting in re-expression of embryonic/perinatal Cacnb1A and Cacnb1E transcripts. Functional analyses using aneural agrin-induced AChR clustering on primary myotubes demonstrated that these isoforms contribute to NMJ formation. Additionally, their expression during early post-natal development is essential for NMJ maturation and long-term maintenance. These findings reveal previously unrecognized roles of CaVβ1 isoforms beyond VGCC regulation, highlighting their significance in neuromuscular system development and homeostasis. Full article

The junction temperature (T_j) is a key parameter reflecting the thermal behavior of Silicon carbide (SiC) MOSFETs and is essential for condition monitoring and reliability assessment in power electronic systems. However, the limited temperature sensitivity of switching characteristics makes it difficult for traditional single temperature-sensitive electrical parameters (TSEPs) to achieve accurate estimation. To address this challenge and enable practical thermal sensing applications, this study proposes an accurate, application-oriented T_j estimation method based on multivariate linear regression (MLR) using turn-off current fall time (t_fi) and fall loss (E_fi) as complementary TSEPs. First, the feasibility of using current fall time and current fall energy loss as TSEPs is demonstrated. Then, a coupled junction temperature prediction model is developed based on multivariate linear regression using t_fi and E_fi. The proposed method is experimentally validated through comparative analysis. Experimental results demonstrate that the proposed method achieves high prediction accuracy, highlighting its effectiveness and superiority in MLR approach based on the current fall phase characteristics of SiC MOSFETs. This method offers promising prospects for enhancing the condition monitoring, reliability assessment, and intelligent sensing capabilities of power electronics systems. Full article

Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development and positioning of dyads is essential in excitation–contraction (EC) coupling and, thus, beating of the heart. Three proteins, namely CMYA5, JPH2, and BIN1, are responsible for maintaining the dyadic cleft between the T-tubule and junctional sarcoplasmic reticulum (jSR). Various other dyadic proteins play integral roles in the primary function of the dyad—translating a propagating action potential (AP) into a myocardial contraction. Ca²⁺, a secondary messenger in this process, acts as an allosteric activator of the sarcomere, and its cytoplasmic concentration is regulated by the dyad. Loss-of-function mutations have been shown to result in cardiomyopathies and arrhythmias. Adeno-associated virus (AAV) gene therapy with dyad components can rescue dyadic dysfunction, which results in cardiomyopathies and arrhythmias. Overall, the dyad and its components serve as essential mediators of calcium homeostasis and excitation–contraction coupling in the mammalian heart and, when dysfunctional, result in significant cardiac dysfunction, arrhythmias, morbidity, and mortality. Full article

Inelastic electron tunneling spectroscopy (IETS) has emerged as a powerful vibrational spectroscopy technique for molecular electronic junctions, providing unique insights into molecular vibrations and electron–phonon coupling at the nanoscale. In this review, we present a comprehensive overview of IETS in molecular junctions, tracing its development from foundational principles to the latest advances. We begin with the theoretical background, detailing the mechanisms by which inelastic tunneling processes generate vibrational fingerprints of molecules, and highlighting how IETS complements optical spectroscopies by accessing electrically driven vibrational excitations. We then discuss recent progress in experimental techniques and device architectures that have broadened the applicability of IETS. Central focus is given to emerging applications of IETS over the last decade: molecular sensing (identification of chemical bonds and conformational changes in junctions), thermoelectric energy conversion (probing vibrational contributions to molecular thermopower), molecular switches and functional devices (monitoring bias-driven molecular state changes via vibrational signatures), spintronic molecular junctions (detecting spin excitations and spin–vibration interplay), and advanced data analysis approaches such as machine learning for interpreting complex tunneling spectra. Finally, we discuss current challenges, including sensitivity at room temperature, spectral interpretation, and integration into practical devices. This review aims to serve as a thorough reference for researchers in physics, chemistry, and materials science, consolidating state-of-the-art understanding of IETS in molecular junctions and its growing role in molecular-scale device characterization. Full article

Various nature-based solutions (NbS)—such as constructed wetlands, drainage ditches, and vegetated buffer strips—have recently demonstrated strong potential for mitigating pollutant transport in open channels and river systems. Numerical modeling is a widely adopted and effective approach for assessing the performance of these interventions. This study presents the first development of a two-dimensional (2D) meshless advection–diffusion model based on an Eulerian smoothed particle hydrodynamics (SPH) framework, specifically designed to simulate passive pollutant transport in open channel flows. The proposed model marks a pioneering application of the ESPH technique to environmental pollutant transport problems. It couples the 2D depth-averaged shallow water equations with an advection–diffusion equation to represent both fluid motion and pollutant concentration dynamics. A uniform particle arrangement ensures that each fluid particle interacts symmetrically with eight neighboring particles for flux computation. To represent the pollutant transport process, the dispersion coefficient is defined as the sum of molecular and turbulent diffusion components. The turbulent diffusion coefficient is calculated using a prescribed turbulent Schmidt number and the eddy viscosity obtained from a Smagorinsky-type mixing-length turbulence model. Three analytical case studies, including one-dimensional transcritical open channel flow, 2D isotropic and anisotropic diffusion in still water, and advection–diffusion in a 2D uniform flow, are employed to verify the model’s accuracy and convergence. The model demonstrates first-order convergence, with relative root mean square errors (RRMSEs) of approximately 0.2% for water depth and velocity, and 0.1–0.5% for concentration. Additionally, the model is applied to a laboratory experiment involving 2D pollutant dispersion in a 90° junction channel. The simulated results show good agreement with measured velocity and concentration distributions. These findings indicate that the developed model is a reliable and effective tool for evaluating the performance of NbS in mitigating pollutant transport in open channels and river systems. Full article

We investigate how collisional interactions between the condensate and the thermal cloud influence the distinct dynamical regimes (Josephson plasma, phase-slip-induced dissipative regime, and macroscopic quantum self-trapping) emerging in ultracold atomic Josephson junctions at non-zero subcritical temperatures. Specifically, we discuss how the self-consistent dynamical inclusion of collisional processes facilitating the exchange of particles between the condensate and the thermal cloud impacts both the condensate and the thermal currents, demonstrating that their relative importance depends on the system’s dynamical regime. Our study is performed within the full context of the Zaremba–Nikuni–Griffin (ZNG) formalism, which couples a dissipative Gross–Pitaevskii equation for the condensate dynamics to a quantum Boltzmann equation with collisional terms for the thermal cloud. In the Josephson plasma oscillation and vortex-induced dissipative regimes, collisions markedly alter dynamics at intermediate-to-high temperatures, amplifying damping in the condensate imbalance mode and inducing measurable frequency shifts. In the self-trapping regime, collisions destabilize the system even at low temperatures, prompting a transition to Josephson-like dynamics on a temperature-dependent timescale. Our results show the interplay between coherence, dissipation, and thermal effects in a Bose–Einstein condensate at a finite temperature, providing a framework for tailoring Josephson junction dynamics in experimentally accessible regimes. Full article

α-Latrotoxin stimulates neurotransmitter release by binding to a presynaptic receptor and then forming ion-permeable membrane pores and/or stimulating the receptor, latrophilin-1, or Adhesion G-protein-coupled receptor type L1 (ADGRL1). To avoid pore formation, we use the mutant α-latrotoxin (LTX^N4C), which does not form pores and only acts through ADGRL1. ADGRL1 is cleaved into an N-terminal fragment (NTF) and a C-terminal fragment (CTF), which behave as independent cell-surface proteins, reassociating upon binding LTX^N4C. We investigated the role of the NTF-CTF association in LTX^N4C action, using perfluorooctanoic acid (PFOA). We demonstrate that at low concentrations (≤100 μM) PFOA does not adversely affect ADGRL1-expressing neuroblastoma cells or inhibit LTX^N4C binding. However, it causes the dissociation of the NTF-CTF complexes, independent redistribution of the fragments on the cell surface, and their separate internalization. PFOA also promotes the dissociation of NTF-CTF complexes induced by LTX^N4C binding. When applied to mouse neuromuscular junctions, PFOA inhibits LTX^N4C-induced neurotransmitter release in a concentration-dependent manner. Our results indicate that ADGRL1 can mediate LTX^N4C signaling only while its fragments remain associated. These findings explain some aspects of receptor-dependent toxin action and contribute to a mechanistic understanding of ADGRL1 functions in neurons. Full article

Silicon carbide (SiC) half-bridge power modules are widely utilized in new energy power generation, electric vehicles, and industrial power supplies. To address the research gap in collaborative validation between electro-thermal coupling models and process reliability, this paper proposes a closed-loop methodology of “design-simulation-process-validation”. This approach integrates in-depth electro-thermal simulation (LTspice XVII/COMSOL Multiphysics 6.3) with micro/nano-packaging processes (sintering/bonding). Firstly, a multifunctional double-pulse test board was designed for the dynamic characterization of SiC devices. LTspice simulations revealed the switching characteristics under an 800 V operating condition. Subsequently, a thermal simulation model was constructed in COMSOL to quantify the module junction temperature gradient (25 °C → 80 °C). Key process parameters affecting reliability were then quantified, including conductive adhesive sintering (S820-F680, 39.3 W/m·K), high-temperature baking at 175 °C, and aluminum wire bonding (15 mil wire diameter and 500 mW ultrasonic power/500 g bonding force). Finally, a double-pulse dynamic test platform was established to capture switching transient characteristics. Experimental results demonstrated the following: (1) The packaged module successfully passed the 800 V high-voltage validation. Measured drain current (4.62 A) exhibited an error of <0.65% compared to the simulated value (4.65 A). (2) The simulated junction temperature (80 °C) was significantly below the safety threshold (175 °C). (3) Microscopic examination using a Leica IVesta 3 microscope (55× magnification) confirmed the absence of voids at the sintering and bonding interfaces. (4) Frequency-dependent dynamic characterization revealed a 6 nH parasitic inductance via Ansys Q3D 2025 R1 simulation, with experimental validation at 8.3 nH through double-pulse testing. Thermal evaluations up to 200 kHz indicated 109 °C peak temperature (below 175 °C datasheet limit) and low switching losses. This work provides a critical process benchmark for the micro/nano-manufacturing of high-density SiC modules. Full article

This paper presents a distributed optimization strategy for reactive power–voltage control in distribution networks with high photovoltaic (PV) penetration under limited sensor deployment scenarios. To address voltage violations and minimize network power losses, a novel distributed optimization framework is developed that utilizes selective nodal measurements from PV-integrated nodes and critical T-junction locations, coupled with inter-node communication for information exchange. The methodology integrates an adaptive step size algorithm within a dynamic projected primal–dual distributed optimization framework, eliminating manual parameter tuning requirements while ensuring theoretical convergence guarantees through Lyapunov stability analysis. Comprehensive validation on the IEEE 33-bus distribution test system demonstrates that the proposed strategy achieves significant performance improvements. The distributed control framework reduces measurement infrastructure requirements while maintaining near-optimal performance, demonstrating superior economic efficiency and operational reliability. These results establish the practical viability of the proposed approach for real-world distribution network applications with high renewable energy integration, providing a cost-effective solution for voltage regulation under incomplete observability conditions. Full article

Multilateral wells can effectively develop complex reservoirs at a lower cost, which, in turn, enhances the overall efficiency of oilfield exploitation. However, drilling branch wells from the main wellbore can disrupt the surrounding formation stresses, leading to secondary stress concentration at the junctions, which, in turn, causes wellbore instability. This study established a coupled analysis model for wellbore stability in branch wells by integrating seepage, stress, and damage. The model explained the instability mechanisms of branch wellbores under multi-physics coupling conditions. The results showed that during drilling, the thin, interwall section of branch wells had weak resistance to external loads, with significant stress concentration and a maximum damage factor of 0.267, making it prone to instability. As drilling time progressed, fractures in the surrounding rock mass of the wellbore continuously formed, propagated, and interconnected, causing a sharp increase in the permeability of the damaged area. The seepage direction of drilling fluid in the wellbore tended towards the severely damaged interwall section, leading to a rapid increase in pore pressure there. With increasing distance from the interwall tip, the resistance to external loads strengthened, and the formation damage factor, permeability, pore pressure, and equivalent plastic strain all gradually decreased. When the drilling fluid density increased from 1.0 g/cm³ to 1.5 g/cm³, the maximum equivalent plastic strain around the wellbore decreased from 0.041 to 0.014, a reduction of 65.8%, indicating that appropriately increasing the drilling fluid density can effectively reduce the risk of wellbore instability. Full article

This article proposes a 3D mathematical model of the influence of electrical heterogeneity of the ion exchange membrane surface on the processes of salt ion transfer in membrane systems with axial symmetry; in particular, we investigate an annular membrane disk in the form of a coupled system of Nernst–Planck–Poisson and Navier–Stokes equations in a cylindrical coordinate system. A hybrid numerical–analytical method for solving the boundary value problem is proposed, and a comparison of the results for the annular disk model obtained by the hybrid method and the independent finite element method is carried out. The areas of applicability of each of these methods are determined. The proposed model of an annular disk takes into account electroconvection, which is understood as the movement of an electrolyte solution under the action of an external electric field on an extended region of space charge formed at the solution–membrane boundary under the action of the same electric field. The main regularities and features of the occurrence and development of electroconvection associated with the electrical heterogeneity of the surface of the membrane disk of the annular membrane disk are determined; namely, it is shown that electroconvective vortices arise at the junction of the conductivity and non-conductivity regions at a certain ratio of the potential jump and angular velocity and flow down in the radial direction to the edge of the annular membrane. At a fixed potential jump greater than the limiting one, the formed electroconvective vortices gradually decrease with an increase in the angular velocity of rotation until they disappear. Conversely, at a fixed value of the angular velocity of rotation, electroconvective vortices arise at a certain potential jump, and with its subsequent increase gradually increase in size. Full article

Background: The escalating prevalence of food allergies, alongside the global call for environmentally sustainable dietary transitions, has drawn attention to plant-based dietary models—particularly those inspired by the EAT-Lancet Commission. These frameworks not only reduce reliance on animal-sourced foods, benefiting planetary health, but may also play a role in modulating immune tolerance and allergic responses. Methods: This scoping review followed PRISMA guidelines and included 53 peer-reviewed studies published between 2000 and 2024, retrieved from PubMed, Scopus, and Google Scholar. Eligible articles were classified into two thematic domains: prevention of food allergy onset (n = 31) and modulation of allergic symptoms in sensitized individuals (n = 22). Included studies comprised randomized controlled trials (n = 6), observational studies (n = 17), systematic reviews and meta-analyses (n = 11), and narrative/scoping reviews (n = 19). Results: Sustainable plant-based diets were consistently associated with a lower incidence of allergic sensitization and reduced symptom severity. These effects were partly due to the exclusion of common allergens (e.g., dairy, eggs, and shellfish) but more importantly due to immunomodulatory mechanisms. Fermentable fibers can enhance short-chain fatty acid (SCFA)-producing bacteria (e.g., Faecalibacterium prausnitzii), elevating butyrate and acetate levels, which interact with G-protein-coupled receptors 43 and 109A (GPR43 and GPR109A) to induce regulatory T cells (Tregs) and reinforce epithelial integrity via tight junction proteins such as occludin and claudin-1. Polyphenols (e.g., quercetin and luteolin) can inhibit Th2-driven inflammation by stabilizing mast cells and downregulating IL-4 and IL-1. Conclusions: Following sustainable dietary guidelines such as those proposed by the EAT-Lancet Commission may confer dual benefits: promoting environmental health and reducing the burden of allergic diseases. By emphasizing plant-based patterns rich in fiber and polyphenols, these diets support microbiota-mediated immune education, mucosal barrier function, and immunological tolerance. When properly supervised, they represent a promising tool for allergy prevention and symptom management. Larger randomized trials and long-term population studies are needed to confirm and operationalize these findings in clinical and public health contexts. Full article

Amidst the swift progression of urban expansion, transformations in land utilization have become increasingly pronounced, posing significant threats to ecosystem coherence and continuity. Establishing a well-designed ecological security pattern (ESP) framework proves essential for preserving environmental equilibrium and enhancing species diversity. This investigation centers on the Fuzhou urban agglomeration as its primary study zone, employing the patch-oriented land utilization simulation (PLUS) approach to forecast 2030 land cover modifications under environmentally conscious conditions. By integrating morphological spatial configuration assessment (MSPA) with habitat linkage evaluation, critical ecological hubs were pinpointed. Subsequent application of electrical circuit principles alongside the minimal cumulative resistance (MCR) methodology enabled the identification of vital ecological pathways and junctions, culminating in the development of a comprehensive territorial ESP framework. Key findings reveal the subsequent outcomes: (1) the main land use type in the Fuzhou metropolitan area is woodland, which accounts for over 80% of its area, and under the ecological priority scenario for 2030, woodland fragmentation was significantly improved; (2) ecological sources are mainly distributed in the northwest, northeast, and central regions, with their total area proportion increasing to 40.49% by 2030; (3) we constructed 35 ecological corridors and 42 ecological nodes, including 14 key ecological pinch points, 9 potential ecological pinch points, and 4 ecological barrier points; and (4) the final ESP formed the pattern of “three cores, three areas, multiple corridors, and multiple sources,” providing strong support for ecological protection and regional sustainable development in the Fuzhou metropolitan area. In this research, we explore the coupled methods of land use simulation and ecological network construction, offering insights for optimizing ESPs in other rapidly urbanizing areas. Full article