Autophagy in Human Diseases

Immune Activation in Brain Aging and Neurodegeneration: Too Much or Too Little?

Degradation of microplastics in the natural environment: A comprehensive review on process, mechanism, influencing factor and leaching behavior.

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results. Abbreviation: 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Försterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green™ SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.

Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis.

Failure of many engineering systems usually results from a gradual and irreversible accumulation of damage, a degradation process. Most degradation processes can be monitored using sensor technology. The resulting degradation signals are usually correlated with the degradation process. A system is considered to have failed once its degradation signal reaches a prespecified failure threshold. This paper considers a replacement problem for components whose degradation process can be monitored using dedicated sensors. First, we present a stochastic degradation modeling framework that characterizes, in real time, the path of a component's degradation signal. These signals are used to predict the evolution of the component's degradation state. Next, we formulate a single-unit replacement problem as a Markov decision process and utilize the real-time signal observations to determine a replacement policy. We focus on exponentially increasing degradation signals and show that the optimal replacement policy for this class of problems is a monotonically nondecreasing control limit policy. Finally, the model is used to determine an optimal replacement policy by utilizing vibration-based degradation signals from a rotating machinery application.

An SW-ELM Based Remaining Useful Life Prognostic Approach for Aircraft Engines

Non-isothermal degradation of bisphenol A diglycidyl ether diacrylate-based polymers

The TSA degradation process of cement-based materials in the electrical field environment

The remaining useful life (RUL) prediction is one of the most important tasks in the prognostics and health management of industrial equipment. The statistical model-based method is widely used for RUL prediction, but it depends on sufficient prior knowledge and appropriate degradation assumptions, which limits its use in the case of the complexity degradation process or insufficient prior knowledge. Motivated by this, we propose a hybrid model to describe the degradation process, which is composed of some given degradation models. This can be conducive to describing complex degradation trajectories and further improving the flexibility of the degradation model. Then, a sparsity mechanism is proposed to automatically fuse these candidate degradation models based on the sparse variational Bayesian method. As a result, we can find the most appropriate degradation mechanism for a given degradation process without sufficient prior knowledge. To the best of the authors' knowledge, it is the first time to use such a fusion mechanism to describe the complex degradation process. A numerical example, a practical example, and three public datasets are used to verify the effectiveness and merits of the proposed method.

BackgroundFatigue is a prevalent and debilitating symptom in many chronic conditions, including immune-mediated inflammatory diseases (IMIDs) and neurodegenerative diseases (NDDs). Fatigue often fluctuates significantly within and between days, yet traditional patient-reported outcomes (PROs) typically rely on recall periods of a week or more, potentially missing these short-term variations. The development of digital tools, such as electronic diaries (eDiaries), offers a unique opportunity to collect granular, real-time data. However, the feasibility, adherence, and comparability of eDiary-based assessments to established PROs require further investigation.ObjectiveThis study aimed to evaluate the feasibility and acceptability of using a high-frequency eDiary to capture intraday variability in fatigue and to compare eDiary data with scores obtained from the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), a validated weekly recall PRO.MethodsData were collected from 159 participants enrolled in the IDEA-FAST (Identifying Digital Endpoints to Assess Fatigue, Sleep and Activities in Daily Living in Neurodegenerative Disorders and Immune-Mediated Inflammatory Diseases) feasibility study; a 4-week prospective observational study conducted at 4 European centers. Participants included individuals with NDDs (n=39), IMIDs (n=78), and healthy volunteers (n=42). Participants used an eDiary to report their physical and mental fatigue levels up to 4 times daily on a 7-point Likert scale (0=low and 6=high). Adherence was calculated as the proportion of completed eDiary entries relative to the total expected entries. Correlations between averaged eDiary scores and weekly FACIT-F scores were analyzed.ResultsAdherence to the eDiary protocol was 5505/8880 (61.99%) overall, varying by cohort, with the highest adherence (1117/1200, 93.07%) observed in the primary Sjögren syndrome cohort and the lowest adherence in the Parkinson disease (410/960, 42.7%) and Huntington disease (320/720, 44.4%) cohorts. The average adherence was 430/1680 (43.45%) in the NDD cohorts and 3367/4560 (73.84%) in the IMID cohorts. Fatigue levels showed clear diurnal variation, with significantly higher fatigue reported in the evening compared to the morning (P<.001). A moderate correlation (Spearman=0.46, P<.001) was observed between eDiary fatigue scores and FACIT-F scores, with stronger cohort-specific associations for certain FACIT-F items. These results indicate that eDiaries provide complementary insights to weekly PROs by capturing intraday fluctuations in fatigue.ConclusionsThis study demonstrates the feasibility, acceptability, and validity of using high-frequency eDiaries to assess fatigue in chronic conditions. By effectively detecting intra- and interday fatigue variations, eDiaries complement traditional PROs such as FACIT-F, offering a more nuanced understanding of fatigue patterns. Future research should explore optimized eDiary protocols to balance participant burden with data granularity.

Free radicals and antioxidants in diseases associated with immune dysfunction, inflammatory process, and aberrant metabolism Free radicals, primarily composed of reactive oxygen species (ROS) and reactive nitrogen species (RNS), can originate within the body through normal cell metabolism or external factors like medication and radiation. These free radicals serve a dual role in living organisms, acting as toxic and protective agents. Free radicals play critical roles as signaling molecules at lower to moderate concentrations. However, when antioxidant defenses are compromised, excessive free radicals can lead to oxidative stress (OS) or endoplasmic reticulum (ER) stress. Oxidative stress primarily stems from impaired mitochondria and phagocytes, two major sources of free radicals and oxidants, ultimately causing damage to biomolecules such as DNA, proteins, and lipids. Recent research findings unequivocally link the overproduction of free radicals to immune and metabolic diseases, including type 2 diabetes, neurodegenerative diseases, and cancer. Patients with these conditions exhibit elevated levels of mitochondrial ROS, reinforcing this connection. Consequently, significant efforts have been directed toward developing effective interventions to mitigate these free radical-induced reactions. These interventions encompass dietary restrictions and antioxidant therapies to reduce oxidative stress and alleviate the associated disease states. This Research Topic was designed to gather papers centered on the involvement of immune, inflammatory, and metabolic dysfunction in human diseases, focusing on the role of free radicals and antioxidants in these dysfunctions. Additionally, the topic highlighted innovative therapeutic approaches for scavenging free radicals and mitigating their Frontiers in Endocrinology frontiersin.org 01

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In vivo quantification of hydrogen gas concentration in bone marrow surrounding magnesium fracture fixation hardware using an electrochemical hydrogen gas sensor

ABSTRACTLithium‐ion batteries (LIBs) have revolutionized energy storage technologies, yet their performance, safety, and durability remain constrained by complex degradation processes that limit their ability to meet growing demands. Addressing these challenges requires a deep understanding of the underlying mechanisms. Liquid cell transmission electron microscopy (LC‐TEM), has emerged as a transformative platform for probing dynamic electrochemical processes, offering direct, multiscale insights from the crystal lattice to the full cell. Continuous advances in LC architectures, together with cutting‐edge TEM capabilities, have positioned LC‐TEM at the forefront of investigations of LIB degradation. Nevertheless, intrinsic challenges associated with liquid environments and individual cell architecture continue to limit the ability to resolve deeper details of degradation processes, creating a critical bottleneck. This review provides an overview of LIB performance challenges, recent TEM progress, and the evolution of LC‐TEM designs, emphasizing their strengths, limitations, and applications across key LIB materials. Emerging directions such as advanced microfabrication, correlative imaging, and machine learning integration are highlighted as promising pathways to expand the technique's reach and overcome current constraints. Finally, strategies are proposed to bridge in situ observations with macroscopic battery behavior. The review outlines that these emerging directions extend benefits beyond LIBs to other electrochemical and functional materials.

Change point detection of health stage and remaining useful lifetime prediction for electro-mechanical brake unit on trains