Search Results (68)

Alzheimer’s disease (AD) is a catastrophic neurodegenerative disorder marked by progressive decline of cognitive function, memory loss, and neuronal death. Its pathology is characterized by the formation of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles from tau hyperphosphorylation. Despite extensive research, current treatments are limited to symptomatic relief and are associated with significant side effects. This accentuates the critical need for alternative therapeutic strategies with potent neuroprotective effects and minimal toxicity. This study investigates the neuroprotective potential of glycyrrhizic acid, as the precise molecular mechanisms by which it might improve AD pathology remain poorly understood. Using an Aβ₄₂-induced IMR-32 cell model of AD, our research revealed that Aβ₄₂ treatment caused significant protein alterations associated with AD pathology, mitochondrial dysfunction, cell cycle re-entry, and synaptic activity. Co-treatment with glycyrrhizic acid not only restored these protein levels, but also mitigated the hyperactivation of several key signaling pathways and rescued neurons from apoptosis. These findings suggest that glycyrrhizic acid exerts neuroprotective effects by preventing mitochondrial dysfunction and apoptosis via modulation of critical signaling pathways. This study provides strong evidence for glycyrrhizic acid’s neuroprotective properties in AD, paving the way for further research into its potential as a promising therapeutic agent for Alzheimer’s disease. Full article

During the reentry terminal flight of lifting-body Reusable Launch Vehicles (RLVs) propelled by liquid fuel, the sloshing of liquid propellent presents new features that, if neglected, could lead to adverse flight oscillations or even worse. This paper focuses on liquid sloshing coupled flight dynamics, sloshing effect prediction, and the suppression of adverse flight oscillations. First, a transfer function model for unsteady aerodynamics is improved and applied to describe the sloshing force effect, being included in the rigid–liquid control coupled flight dynamics model. The frequency domain analysis results show that liquid sloshing tends to degrade the closed-loop stability margin of the vehicle and even induce less damped oscillations, which can be predicted through the frequency characteristics with the sloshing force effect included. Furthermore, three suppression control measures to mitigate adverse oscillation are addressed, which include enhancing the trajectory-tracking loop damping, separating the frequencies of the rigid body motion and the liquid sloshing, and especially introducing a compensation loop to counteract the sloshing effect. Simulations demonstrate that all the provided approaches help mitigate the sloshing effect, while the compensation control with sloshing frequency characteristics included works best. Full article

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion. Full article

Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including baricitinib, ritlecitinib, and durvalumab, restore immune balance and permit anagen reentry. In androgenetic alopecia (AGA), excess dihydrotestosterone and androgen receptor signaling increase DKK1 and prostaglandin D2, suppress Wnt and β-catenin activity, and drive follicular miniaturization. Combination approaches utilizing low-dose oral minoxidil, platelet-rich plasma, exosome formulations, and low-level light therapy enhance vascularization, improve mitochondrial function, and reactivate metabolism, collectively supporting sustained regrowth. Elucidation of intracellular axes such as JAK/STAT, Wnt/BMP, AMPK/mTOR, and mitochondrial redox regulation provides a mechanistic basis for rational, multimodal intervention. Advances in stem cell organoids, biomaterial scaffolds, and exosome-based therapeutics extend treatment from suppression toward structural follicle reconstruction. Recognition of microbiome and mitochondria crosstalk underscores the need to maintain microbial homeostasis and redox stability for durable regeneration. This review synthesizes molecular and preclinical advances in AA and AGA, outlining intersecting signaling networks and regenerative interfaces that define a framework for precision and sustained follicular regeneration. Full article

A barrier Lyapunov function-based command filtered output feedback controller is proposed for the roll control of moving-mass actuated reentry vehicles challenged by strong nonlinearities, state constraints, and unmeasurable states. First, a barrier Lyapunov function is constructed to guarantee strict adherence to the position and velocity constraints of the movable mass. Next, a state observer is designed to estimate the immeasurable states, while command filtering technology with a compensation mechanism is employed to circumvent the differential explosion problem in backstepping design. The stability of the closed-loop system and the boundedness of all signals are rigorously proven via Lyapunov stability theory. Finally, numerical simulations are conducted to demonstrate the performance of the proposed controller. Full article

Background/Objectives: Tau protein, a central player in Alzheimer’s disease (AD) pathology, is classically known for its role in microtubule stabilisation. However, accumulating evidence indicates that tau also localises to the neuronal nucleus, particularly the nucleolus, where it may regulate chromatin organisation and transcription. In this study, we investigated whether different phosphorylation states of nuclear tau display age- and disease-dependent patterns, with a specific focus on the AT8 epitope (phospho-Ser202/Thr205). Methods: We analysed nuclear tau epitopes (Tau-1, AT8, PHF1, T181, and S262) by indirect immunofluorescence in SK-N-BE neuroblastoma cells under proliferative and retinoic acid-induced differentiated conditions and in post-mortem hippocampal CA1 neurons from foetal, young, aged, and AD brains. Other functional markers (UBTF, Ki67, fibrillarin and acetylated histone H4) were used to assess nuclear organisation and function. Results: Compared with the other epitopes, AT8 was unique in showing dynamic nuclear localisation: absent in proliferating cells but present after differentiation, abundant in young neurons, and significantly reduced in aged and AD samples. Nuclear AT8 co-localised with Ki67, and its decline was associated with neuronal cell cycle re-entry and nucleolar disorganisation. Conclusions: Among multiple nuclear tau epitopes, AT8 was the only one displaying age- and disease-related changes, and its reduction during ageing and AD correlates with nuclear stress, aberrant cell cycle activity, and neuronal vulnerability. Loss of nuclear AT8 may therefore represent an early marker of dysfunction in ageing and AD brains. Full article

This comprehensive review explores the critical roles of microRNAs (miRNAS) in cardiovascular diseases, emphasizing their regulatory functions in gene expression and their involvement in disease progression. miRNAS are small, evolutionarily conserved non-coding RNAs that regulate gene expression post-transcriptionally and play essential roles in various cardiac conditions, including fibrosis, cardiac remodeling, apoptosis, ischemia/reperfusion injury, hypertrophy, heart failure, arrhythmias, coronary artery disease (CAD), congenital heart diseases (CHDs), cardiomyopathies, and valvular heart disease (VHD). miRNAS are increasingly recognized as sensitive and specific biomarkers for early diagnosis, disease monitoring, and evaluation of therapeutic responses across the cardiovascular disease spectrum. Ischemia/reperfusion injury leads to significant cardiac damage through elevated oxidative stress, mitochondrial dysfunction, and apoptosis. CAD, a major contributor to global morbidity and mortality, is primarily driven by atherosclerosis and chronic inflammation. Cardiac hypertrophy is initially an adaptive response to stress but may progress to heart failure if sustained. Arrhythmias arise from electrical disturbances such as reentry, abnormal automaticity, and triggered activity. Heart failure is a complex and progressive syndrome marked by poor prognosis and increasing global prevalence. VHD involves intricate molecular alterations, including myocardial fibrosis and calcification, which contribute to disease progression and adverse outcomes. Cardiomyopathies—including hypertrophic, dilated, restrictive, and arrhythmogenic forms—are influenced by genetic mutations, systemic diseases, and disrupted molecular signaling. CHDs, the most common congenital malformations, stem from structural abnormalities in cardiac development and remain a major cause of infant morbidity and mortality. Novel therapeutic methods, such as antisense oligonucleotides, miR mimics, and exosome-based delivery mechanisms, demonstrate the translational promise of miRNAs in the realm of personalized cardiovascular medicine. However, issues such as small sample sizes, inconsistent results, interspecies differences, and delivery challenges restrict the clinical application of miRNA-based therapies. This review integrates mechanistic insights, critiques the quality of available evidence, and identifies translational shortcomings. It highlights the diagnostic, prognostic, and therapeutic potential of miRNAs in reshaping cardiovascular disease treatment. Full article

Adult cardiomyocytes (CMs) lose their proliferative capacity shortly after birth, posing a major challenge for cardiac repair following injury such as myocardial infarction (MI). Despite significant advances over the past decade, many strategies for promoting cardiac regeneration have faced limitations, underscoring the need to identify novel molecular pathways and targets. Pyruvate kinase muscle isoform 2 (PKM2), a key metabolic enzyme, has emerged as a compelling candidate in this context due to its multifaceted roles in cellular metabolism, proliferation, redox balance, angiogenesis, and master gene regulator in repair. Recent studies highlight the critical function of PKM2 in cardiac repair and regeneration. PKM2 not only promotes the proliferation of CMs but also protects the heart from oxidative stress by redirecting glycolytic intermediates toward the pentose phosphate pathway (PPP), thereby increasing nicotinamide adenine dinucleotide phosphate (NADPH) levels, reducing reactive oxygen species (ROS), and minimizing DNA damage. Moreover, PKM2 interacts with key signaling molecules, including β-catenin, hypoxia-inducible factor 1α (HIF-1a), and checkpoint kinase 1 (CHK1), to promote CM cell cycle reentry, angiogenesis, and enhanced cell survival. Collectively, these multifaceted actions highlight PKM2 as both a metabolic and signaling hub in cardiac repair by promoting myocardial remuscularization, protection, and revascularization and position PKM2 as a promising therapeutic. This review explores the diverse roles of PKM2 in myocardial repair and discusses its potential as a novel avenue for advancing regenerative therapies in cardiovascular medicine. Full article

The adult heart has a limited ability to regenerate, which is partly due to the structural and metabolic specialization that cardiomyocytes (CMs) acquire during postnatal maturation. In this review, we explore how cytoskeletal remodeling, metabolic reprogramming, and interactions with the extracellular matrix (ECM) regulate CM maturation, proliferation, and the potential for regeneration. We describe how the assembly of microtubules, actin filaments, and sarcomeric structures is essential for developing contractile function, but also creates structural barriers that prevent cell division. Recent studies show that disassembling these cytoskeletal components, along with activating signaling pathways such as Hippo-YAP, Wnt, and NRG1/ErbB4, can promote CM dedifferentiation and re-entry into the cell cycle. Metabolic shifts also play a critical role. A return from oxidative phosphorylation to glycolysis also leads to CM dedifferentiation and proliferation. In addition, changes in ECM composition and mechanical signaling affect cytoskeletal dynamics and regenerative capacity. Understanding how these structural, metabolic, and signaling networks work together opens the door to new approaches for restoring heart function after injury. Full article

This paper presents the design and implementation of a guidance algorithm for the re-entry vehicle ReFEx (Reusability Flight Experiment). This algorithm aims at correcting for the dispersion in position and velocity after separation from the launcher, by updating the trajectory. The need for this update is driven by the expected divergence from the nominal trajectory at separation, due to the use of an unguided launcher. The transcription of the problem into an optimal control problem is used as a baseline for verification purposes. This algorithm consists of a simplification of the optimal control problem, reducing the profiles of the control variables to a finite set of control parameters. Combining this problem reduction with a function that propagates the trajectory from the initial state, this approach is able to transform the problem into an unconstrained optimization problem. This paper shows that this simplification is able to find solutions of similar quality to the full optimal control approach. The resulting algorithm is proven real-time capable by deploying it into a hardware equivalent of the on-board computer. In addition, a strategy to diverge during flight to an alternative target if the nominal one cannot be reached is appended to the algorithm. Full article

Aiming at the problem of poor autonomy and weak time performance of reentry trajectory planning for Reusable Launch Vehicle (RLV), an online reentry trajectory planning and guidance method based on Twin Delayed Deep Deterministic Policy Gradient (TD3) is proposed. In view of the advantage that the drag acceleration can be quickly measured by the airborne inertial navigation equipment, the reference profile adopts the design of the drag acceleration–velocity profile in the reentry corridor. In order to prevent the problem of trajectory angle jump caused by the unsmooth turning point of the section, the section form adopts the form of four multiple functions to ensure the smooth connection of the turning point. Secondly, considering the advantages of the TD3 dual Critic network structure and delay update mechanism to suppress strategy overestimation, the TD3 algorithm framework is used to train multiple strategy networks offline and output profile parameters. Finally, considering the reentry uncertainty and the guidance error caused by the limitation of the bank angle reversal amplitude during lateral guidance, the networks are invoked online many times to solve the profile parameters in real time and update the profile periodically to ensure the rapidity and autonomy of the guidance command generation. The TD3 strategy networks are trained offline and invoked online many times so that the cumulative error in the previous guidance period can be eliminated when the algorithm is called again each time, and the online rapid generation and update of the reentry trajectory is realized, which effectively improves the accuracy and computational efficiency of the landing point. Full article

Chronic total occlusions (CTOs), defined as complete coronary artery blockages persisting for over three months, are frequently encountered in up to 25% of coronary angiograms. Although percutaneous coronary intervention (PCI) for CTO remains technically challenging, advancements in guidewires, microcatheters, re-entry devices, and intravascular imaging, along with the expertise of specialized operators, have significantly improved procedural success rates, now exceeding 90% in expert centers. While recent evidence, such as the SYNTAX II study, emphasizes the importance of complete revascularization, over half of CTO cases continue to be managed conservatively with optimal medical therapy (OMT), partly due to the limited high-quality randomized evidence supporting revascularization. Observational studies have demonstrated that successful CTO-PCI is associated with improved angina relief, quality of life, left ventricular function, and possibly long-term survival. Extended observational follow-up, such as the Korean and Canadian registries, suggests long-term reductions in cardiac and all-cause mortality with CTO revascularization. However, randomized controlled trials (RCTs) have primarily shown symptomatic benefit, with no consistent reduction in major adverse cardiac events (MACE) or mortality, likely due to limited sample sizes, short follow-up, and treatment crossovers. Various strategies, including the hybrid algorithm, guide CTO interventions by balancing antegrade and retrograde techniques based on lesion complexity. Imaging modalities such as coronary CT angiography and intravascular ultrasound play a pivotal role in planning and optimizing these procedures. Future innovations, such as real-time fusion imaging of CCTA with coronary angiography, may enhance lesion visualization and guidewire navigation. While current guidelines recommend CTO-PCI in selected symptomatic patients with demonstrable ischemia or viable myocardium, the decision should be individualized, incorporating anatomical feasibility, comorbidities, patient preferences, and input from a multidisciplinary Heart Team. Looking ahead, adequately powered RCTs with extended follow-up are essential to determine the long-term clinical impact of CTO-PCI on hard outcomes such as mortality and myocardial infarction. Full article

Hypersonic morphing vehicles (HMVs), renowned for their adaptive structural reconfiguration and cross-domain maneuverability, confront formidable reentry guidance challenges under multiple no-fly zones, stringent path constraints, and nonlinear dynamics exacerbated by morphing-induced aerodynamic uncertainties. To address these issues, this study proposes a hierarchical framework integrating an A-based energy-optimal waypoint planner, a deep deterministic policy gradient (DDPG)-driven morphing policy network, and a quasi-equilibrium glide condition (QEGC) guidance law with continuous sliding mode control. The A* algorithm generates heuristic trajectories circumventing no-fly zones, reducing the evaluation function by 6.2% compared to greedy methods, while DDPG optimizes sweep angles to minimize velocity loss and terminal errors (0.09 km position, 0.01 m/s velocity). The QEGC law ensures robust longitudinal-lateral tracking via smooth hyperbolic tangent switching. Simulations demonstrate generalization across diverse targets (terminal errors < 0.24 km) and robustness under Monte Carlo deviations (0.263 ± 0.184 km range, −12.7 ± 42.93 m/s velocity). This work bridges global trajectory planning with real-time morphing adaptation, advancing intelligent HMV control. Future research will extend this framework to ascent/dive phases and optimize its computational efficiency for onboard deployment. Full article

This paper proposes a global, predefined time control method based on a predefined time disturbance observer to address the issues of wide flight airspace, large aerodynamic deviations, and high precision requirements for the entire process of aerospace aircraft re-entry. Firstly, this method proposes an adjustable predefined time nonsingular sliding mode disturbance observer, which can not only accurately estimate the modeling uncertainty and external aerodynamic disturbances of the aerospace aircraft, but also quickly converge while suppressing chattering. Then, based on the disturbance observation results, combined with a new performance function and nonsingular predefined-time sliding mode, a global predefined-time controller suitable for any order system was designed. Unlike existing methods that can only ensure that the initial deviation converges to the deviation boundary within a predefined time and then remains within the deviation boundary, it can ensure that any deviation generated within the error boundary also converges within the predefined time. Finally, the effectiveness and superiority of the proposed control scheme were verified through comparative simulation. Full article

With its unique environment and strategic value, the near space (NS) has become the focus of global scientific and technological, military, and commercial fields. Aiming at the problem of communication interruption when the aircraft re-enters the atmosphere, to ensure the needs of communication, navigation, and telemetry, tracking, and command (TT&C), this paper proposes an overall integration of communication, navigation, and TT&C (ICNT) signals scheme based on the K/Ka frequency band. Firstly, the K/Ka frequency band is selected according to the ITU frequency division, high-speed communication requirements, advantages of space-based over-the-horizon relay, overcoming the blackout problem, and the development trend of high frequencies. Secondly, the influence of the physical characteristics of the NS on ICNT is analyzed through simulation. The results show that when the K/Ka signal is transmitted in the NS, the path loss changes significantly with the elevation angle. The bottom layer loss at an elevation angle of 90° is between 143.5 and 150.5 dB, and the top layer loss is between 157.5 and 164.4 dB; the maximum attenuation of the bottom layer and the top layer at an elevation angle of 0° is close to 180 dB and 187 dB, respectively. In terms of rainfall attenuation, when a 30 GHz signal passes through a 100 km rain area under moderate rain conditions, the horizontal and vertical polarization losses reach 225 dB and 185 dB, respectively, and the rainfall attenuation increases with the increase in frequency. For gas absorption, the loss of water vapor is higher than that of oxygen molecules; when a 30 GHz signal is transmitted for 100 km, the loss of water vapor is 17 dB, while that of oxygen is 2 dB. The loss of clouds and fog is relatively small, less than 1 dB. Increasing the frequency and the antenna elevation angle can reduce the atmospheric scintillation. In addition, factors such as the plasma sheath and multipath also affect the signal propagation. In terms of modulation technology, the constant envelope signal shows an advantage in spectral efficiency; the new integrated signal obtained by integrating communication, navigation, and TT&C signals into a single K/Ka frequency point has excellent characteristics in the simulation of power spectral density (PSD) and autocorrelation function (ACF), verifying the feasibility of the scheme. The proposed ICNT scheme is expected to provide an innovative solution example for the communication, navigation, and TT&C requirements of NS vehicles during the re-entry phase. Full article