Search Results (336)

Metabolic dysfunction-associated fatty liver disease (MAFLD), a recently proposed term to replace non-alcoholic fatty liver disease (NAFLD), emphasizes the critical role of metabolic dysfunction and applies broader diagnostic criteria. Diagnosis of MAFLD requires evidence of hepatic steatosis combined with obesity, type 2 diabetes mellitus, or other metabolic dysregulation conditions, all of which significantly elevate the risk of chronic kidney disease (CKD). This review discusses the pathological mechanisms of lipid accumulation and insulin resistance in MAFLD and CKD, highlighting their mechanistic connections. Specifically, ectopic fat accumulation triggered by metabolic reprogramming, oxidative stress and inflammation induced by energy overload, modified lipids, uremic toxins, and senescence, as well as insulin resistance pathways activated by pro-inflammatory factors and lipotoxic products, collectively exacerbate simultaneous hepatic and renal injury. Moreover, interactions among hyperinsulinemia, the sympathetic nervous system, the renin–angiotensin system (RAS), and altered adipokine and hepatokine profiles further amplify insulin resistance, ectopic lipid deposition, and systemic damage. Finally, the review explores potential therapeutic strategies targeting lipid metabolism, insulin sensitivity, and RAS activity, which offer promise for dual-organ protection and improved outcomes in both hepatic and renal systems. Full article

Providing long-term care for a person with Alzheimer’s disease is associated with chronic stress and emotional overload. One of the key predictors of emotional burden is the amount of time devoted to caregiving, which intensifies the experienced stress. Additional risk factors include the stage of the illness, difficulties in the care recipient’s activities of daily living, the caregiver’s neglect of their own needs, and challenging behaviours exhibited by the person receiving care. Therefore, it is essential to identify the psychological protective resources of caregivers that can buffer the impact of stress. Background/Objectives: The objective of the study was to explore the psychological mechanisms underlying the involvement of caregivers supporting individuals with Alzheimer’s disease. A moderated mediation model was employed, in which stress indirectly affects caregiver involvement through a sense of coherence, and the strength of this relationship is moderated by the amount of time devoted to caregiving. Methods: The bootstrapping method was applied using 5000 resamples within a 95% bias-corrected confidence interval. The analysis accounted for variables such as stress levels, sense of coherence, involvement in caregiving, duration of care, education, gender, age, and stage of the illness. Results: The sense of coherence mediated the relationship between stress and involvement in caring (B = 0.0063, SE = 0.0031, 95% CI [0.0012, 0.0135]), and this indirect effect was contingent upon the amount of time devoted to helping. The relationship between sense of coherence and involvement in caring was significant at the mean level (B = 0.005, SE = 0.002, 95% CI [0.0004, 0.0101]) and became stronger at high levels of time devoted to caring (+1 SD; B = 0.009, SE = 0.003, 95% CI [0.0030, 0.0148]). These results indicate that the positive association between sense of coherence and caregiver involvement increases with the amount of time spent caring. Conclusions: The results highlight the importance of strengthening caregivers’ resilience resources—such as a sense of coherence—in preventing overload. The model may serve as a foundation for developing interventions aimed at supporting caregivers’ mental health. Full article

To address poor film pickup, incomplete soil–film separation, and high soil content in conventional residual film recovery machines, this study designed a belt-tooth type residual film recovery machine. Its core component integrates flexible belts with nail-teeth, providing both overload protection and efficient conveying. EDEM simulations compared film pickup performance across tooth profiles, identifying an optimal structure. Based on the kinematics and mechanical properties of residual film, a film removal mechanism and packing device were designed, incorporating partitioned packing belts to reduce soil content rate in the collected film. Using Box–Behnken experimental design, response surface methodology analyzed the effects of machine forward speed, film-lifting tooth penetration depth, and pickup belt inclination angle. Key findings show: forward speed, belt angle, and tooth depth (descending order) primarily influence recovery rate; while tooth depth, belt angle, and forward speed primarily affect soil content rate. Multi-objective optimization in Design-Expert determined optimal parameters: 5.2 km/h speed, 44 mm tooth depth, and 75° belt angle. Field validation achieved a 90.15% recovery rate and 5.86% soil content rate. Relative errors below 2.73% confirmed the regression model’s reliability. Compared with common models, the recovery rate has increased slightly, while the soil content rate has decreased by more than 4%, meeting the technical requirements for resource recovery of residual plastic film. Full article

Poloxamer (P) 188 attenuates myocardial ischemia/reperfusion injury through cell membrane stabilization. Cell–cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia/reoxygenation (HR) injury. The mechanism of interaction with P188 still requires exploration. We examined if N(ω)-nitro-L-arginine methyl ester (LNAME), a non-specific nitric oxide (NO) synthase inhibitor, abolishes protection in the presence or absence of P188 and/or ECs. We co-cultured mouse coronary artery ECs in an insert atop mouse CMs plated at confluency on the bottom of a well. Normoxic controls remained in complete media while HR groups were exposed to 24 h hypoxia at 0.01% O₂ in serum- and glucose-free media, followed by 2 h reoxygenation in complete media. P188 (300 μM), LNAME (40 mM), or vehicle were administered upon reoxygenation. ECs at the used lower density did not decrease HR-triggered lactate dehydrogenase release or calcium overload in CMs by themselves. P188 reduced both indicators after HR by 16/18% without and by 22/25% with ECs, respectively. LNAME abrogated CM protection by P188. Neither intervention had an effect under normoxia. Our co-culture data indicates that P188 requires NO, not necessarily of endothelial origin, to elicit CM protection. Full article

Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart’s energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency. A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors—CB₁ and CB₂, α2 adrenoceptor, or 5-hydroxytryptamine receptor. Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas–liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method. Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium. The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction. Full article

Increasing climate change requires cities to adapt to changing weather conditions. New elements for decentralized stormwater management must be installed to protect the sewer system from overloading during heavy rainfall events and to keep water in the city for irrigation use. A pilot project was implemented in Leipzig in 2020, in which infiltration tree trench systems with three different designs were installed and equipped with measuring technology during a road renovation project. The catchment areas of these three tree trenches are between 215 and 300 m² each. In two of the systems, water retention was included to supply the tree with water during drought periods. The retention elements are sealed with clay in tree trench TT1 and bentonite in tree trench TT3. For tree trench TT2, no retention capacity was provided. This article presents the design, construction, and scientific monitoring of the three tree infiltration trenches. The conclusions after four years of operation from the perspective of two departments of the City of Leipzig are summarized. The tree trench TT1 with the clay pan for water storage shows the best performance in terms of water retention and tree fitness. For the next generation of such infiltration systems, improvements in the design of the street runoff inlets and the surface of the tree trench system’s interior are discussed. Full article

Glutamate is an excitatory neurotransmitter in the central nervous system (CNS) that mediates synaptic transmission. However, glutamate homeostasis among neural cells is broken in cerebral ischemia. Excessive glutamate triggers N-methyl-d-aspartate receptors (NMDARs) in postsynaptic neurons, leading to intracellular calcium (Ca²⁺) overload and excitoneurotoxicity. At this moment, L-lactate may affect NMDARs and play a protective role in cerebral ischemia. This work proposes that L-lactate regulates glutamate signaling among neural cells. But, dysregulation of L-lactate in glutamate signaling cascades contributes to glutamate excitotoxicity in cerebral ischemia. In detail, L-lactate regulates the glutamine(Gln)-glutamate cycle between astrocytes and presynaptic neurons, which triggers the astroglial L-lactate-sensitive receptor (LLR)-cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway, coordinating astroglial glutamate uptake and neuronal glutamate transmission. L-lactate mediates glutamate signaling and synaptic transmission among neural cells. In addition, L-lactate promotes the function of mitochondrial calcium uniporter complex (MCUC), which quickly depletes intracellular Ca²⁺ in postsynaptic neurons. In addition, L-lactate can promote the conversion of microglia from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype. Therefore, regulation of L-lactate in glutamate signaling in the CNS might become a preventive target for cerebral ischemia. Full article

Motorbike taxis are widely used in Yaoundé and Douala, despite their association with heightened accident risks and relatively high fares. This research combines qualitative methods, including 38 semi-structured interviews and direct field observations, with a quantitative survey of 280 motorbike taxi passengers (customers). It employs a dynamic risk approach to analyse both the factors motivating individuals to choose motorbike taxis and the strategies adopted by drivers and passengers to mitigate and prevent accidents. The findings reveal that speed, cost-effectiveness, and the limited accessibility of certain neighbourhoods to other transport options are key factors driving regular motorbike taxi use. Moreover, strategies for managing accident risks include regulating passenger positions based on gender, perceived age, or physical stature; invoking deities for protection; and passengers’ verbal interactions with drivers to ensure safer behaviour. This research also explores how overloading, a collectively tolerated deviance, is managed to avoid or minimize the impact of accidents. By addressing both risk acceptance and prevention strategies, this study provides new insights into passengers’ social perceptions, which are often overlooked in motorbike taxi research. It expands the understanding of motorbike taxi use in urban Global South transport contexts, particularly in terms of users’ risk management behaviours. Full article

Articular cartilage (AC) plays an important role in the biomechanics of synovial joints. Its task is to enable smooth movement and transfer of mechanical loads with minimised friction. AC is characterised by unique mechanical properties resulting from its complex structure, in which the dominant components are type II collagen, proteoglycans and water. Healthy articular cartilage shows elasticity in compression, viscoelastic properties, and the ability to relax stresses under the influence of cyclic loads. In response to different loading modes, it shows anisotropic and non-uniform behaviour, which translates into its cushioning and protective function for the subchondral bone. Significant changes occur in the structure and mechanical properties of cartilage with age as a result of mechanical overload or degenerative diseases, such as osteoarthritis. This results in a deterioration of the cushioning and mechanical function, which leads to progressive degradation of joint tissues. Understanding the mechanical properties of AC is crucial for developing effective diagnostic methods. Analysis of changes in mechanical properties contributes to the early detection of pathological changes. The aim of this paper is to review the current state of knowledge regarding the structure and biomechanical properties of articular cartilage, and to analyse conventional and alternative diagnostic methods in the context of their suitability for assessing the state of AC, particularly in the early stages of degenerative processes. Full article

Brain ischemia-reperfusion (IR) injury is a critical pathological process that leads to extensive neuronal death, with hippocampal pyramidal cells, particularly those in the cornu Ammonis 1 (CA1) subfield, being highly vulnerable. Until now, human olfactory mitral cell resistance to IR injury has not been directly studied, but olfactory dysfunction in humans is frequently reported in systemic vascular conditions such as ischemic heart failure and may serve as an early clinical marker of neurological or cardiovascular disease. Mitral cells, the principal neurons of the olfactory bulb (OB), exhibit remarkable resistance to IR injury, suggesting the presence of unique molecular adaptations that support their survival under ischemic stress. Several factors may contribute to the resilience of mitral cells. They have a lower susceptibility to excitotoxicity, mitigating the harmful effects of excessive glutamate signaling. Additionally, they maintain efficient calcium homeostasis, preventing calcium overload—a major trigger for cell death in vulnerable neurons. Mitral cells may also express high baseline levels of antioxidant enzymes and their activities, counteracting oxidative stress. Their robust mitochondrial function enhances energy production and reduces susceptibility to metabolic failure. Furthermore, neuroprotective signaling pathways, including phosphatidylinositol-3-kinase (PI3K)/Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), and nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated antioxidative responses, further bolster their resistance. In addition to these intrinsic mechanisms, the unique microvascular architecture and metabolic support within the olfactory bulb provide an extra layer of protection. By comparing mitral cells to ischemia-sensitive neurons, key vulnerabilities—such as oxidative stress, excitotoxicity, calcium dysregulation, and mitochondrial dysfunction—can be identified and potentially mitigated in other brain regions. Understanding these molecular determinants of neuronal survival may offer valuable insights for developing novel neuroprotective strategies to combat IR injury in highly vulnerable areas, such as the hippocampus and cortex. Full article

Alpine plants face intense ultraviolet (UV) radiation in high-altitude ecosystems, necessitating adaptive mechanisms like tyrosinase-mediated phenolic metabolism for UV protection. This study aimed to characterize the phenolic profile of Corallodiscus flabellatus (or C. flabellata) and elucidate its mechanistic interactions with tyrosinase under high-altitude environments with intense ultraviolet (UV) radiation. Two novel phenylethanoid glycosides (PhGs) and seven known compounds were isolated using silica gel, ODS, and preparative HPLC, with structures determined via NMR, HR-ESI-MS, and acid hydrolysis. Tyrosinase (EC 1.14.18.1) inhibition assays revealed divergent effects: compound 7 (containing a caffeoyl moiety) exhibited potent inhibition (IC₅₀ = 0.23 μM), comparable to arbutin, while other PhGs displayed activation or biphasic responses. Molecular docking analysis demonstrated that compound 7 stabilized tyrosinase via π-π stacking with Phe264 and Cu²⁺ coordination, whereas activating compounds likely acted as substrates. These findings elucidate the dual regulatory function of PhGs, which activate tyrosinase to counteract acute ultraviolet-induced stress and inhibit its activity to attenuate oxidative overload, thereby advancing our understanding of alpine plant adaptation mechanisms. Full article

Zinc (Zn) imbalance—deficiency or overload—is implicated in hepatocyte injury, yet its mechanisms and therapeutic strategies remain incompletely understood. This study investigated Zn dyshomeostasis-induced hepatotoxicity in AML12 hepatocytes and evaluated fisetin’s protective potential in diet-induced Zn overload C57BL/6 mice for in vivo validation. In AML12 cells, both Zn deficiency and overload impaired hepatocyte viability and promoted oxidative stress, but only overload activated autophagy and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Fisetin, a natural flavonoid with well-documented antioxidant and anti-inflammatory properties, selectively mitigated Zn overload-induced AML12 cytotoxicity and oxidative damage by enhancing autophagic flux and Nrf2 signaling without Zn chelation, while demonstrating no effect on Zn deficiency. Specifically, fisetin required autophagy to sustain Nrf2 activation, as chloroquine abolished its protective effects. In vivo, fisetin administration (200 mg/kg BW, oral gavage) alleviated Zn overload-associated weight loss and hepatic oxidative damage in mice, paralleling its in vitro effects through reinforced autophagy–Nrf2 axis activation. The autophagy-dependent Nrf2 activation mechanism highlights fisetin’s therapeutic potential for Zn-related liver disorders. Full article

The overload protection device is crucial in ensuring the orderly absorption of kinetic energy by the coupler buffer device. This paper studies an overload protection bolt with a cut-out zone. In the bolt impact experiment, a premature fracture of 10.9-grade M24 bolts was observed. Based on the analysis of the results, it was concluded that this phenomenon was caused by the mismatch between the mechanical properties of the bolts and the dynamic performance of the coupler. Building on this test, a numerical simulation model was established and subsequently validated. The width and depth of the inducing structure were selected as the research objects. Using the Latin Hypercube method, 78 sets of cut-out zone structure parameters were generated, and numerical simulations were performed on the cut-out induced bolts. The simulation results indicate that the peak force generated by the coupler collision leads to necking in the cut-out induced bolts, which consequently weakens their mechanical properties to some extent. Therefore, it is necessary to consider a strength margin when designing cut-out induced bolts. Based on the simulation results, a surrogate model was constructed, and the optimal bolt cut-out zone was obtained through optimization: a width of 17.74 mm and a depth of 1.37 mm. The surrogate model predicted a fracture force of 1894.13 kN for the bolts. An impact test was conducted to verify the performance of the optimized cut-out induced bolts. The experimental results showed that the cut-out induced bolts broke after the crush tube completed its kinetic energy absorption, with a fracture force of 1828.44 kN, which was a 3.59% difference from the predicted value of the surrogate model. After optimization, the fracture force of the cut-out induced bolts increased from 1147.5 kN to 1828.44 kN (a 59.34% improvement), while the fracture time extended from 20.9 ms to 69 ms, fully meeting the design requirements of the overload protection device. Full article

Aortic stenosis (AS) is a common and serious valvular disease in older adults, often leading to increased left ventricular mass (LVM) due to pressure overload. Excessive LVM is linked to adverse outcomes, but its sex-specific prognostic significance remains unclear. Focusing on sex-based differences, this study evaluated the left ventricular mass index (LVMi) prognostic value in patients with symptomatic severe AS. We retrospectively analyzed 531 outpatients (283 men, 248 women; mean age 74.7 years) with symptomatic but stable severe AS and no prior valve procedures. Clinical and echocardiographic data were collected between April 2020 and February 2024, with a mean follow-up of 2.67 years. A total of 165 patients (31.1%) died during follow-up, 86% from cardiovascular causes. Deceased patients had lower ejection fraction and higher LVMi. Multivariate Cox analysis identified LVMi and atrial fibrillation (AF) as independent predictors of mortality, while valve intervention predicted survival. In women, both LVMi and AF predicted mortality; valve intervention was protective. In men, only the lack of valve intervention predicted death. Elevated LVMi was a strong predictor of mortality in non-operated patients, with the most pronounced impact observed in women with severe AS. Full article

Soft anthropomorphic robotic grippers are attractive because of their inherent compliance, allowing them to adapt to the shape of grasped objects and the overload protection needed for safe human–robot interaction or gripping delicate objects with sophisticated control. The anthropomorphic design allows the gripper to benefit from the biological evolution of the human hand to create a multi-functional robotic end effector. Entirely soft grippers could be more efficient because they yield under high loads. A trending solution is a hybrid gripper combining soft and rigid elements. This work describes a prototype of an anthropomorphic, underactuated five-finger gripper with a direct pneumatic drive from soft bending actuators and an integrated resistive tactile sensor array. It is a hybrid construction with soft robotic structures and rigid skeletal elements, which reinforce the body, focus the direction of the actuator’s movement, and make the finger joints follow the forward kinematics. The hand is equipped with a resistive tactile dielectric elastomer sensor array that directly triggers the hand’s actuation in the sense of reflexes. The hand can execute precision grips with two and three fingers, as well as lateral grip and strong grip types. The softness of the actuation allows the finger to adapt to the shape of the objects. Full article