Search Results (6,091)

This paper examines whether genuine dwelling—understood as embodied engagement with a world that resists, endures, and exceeds human control—can occur in the metaverse. Drawing on Heidegger’s account of dwelling and Ingold’s concept of the ‘taskscape’, it argues that the metaverse is structurally unable to sustain dwelling in the full ontological sense. The argument unfolds in three steps. First, dwelling is shown to depend on friction: bodily cost, temporal irreversibility, material resistance, and exposure to mortal finitude. Second, the metaverse is interpreted as a technological and commercial project oriented toward reducing these frictions through attenuated bodily burden, reversible action, programmable environments, and artificial scarcity. Third, the paper extends the concept of the metaverse beyond immersive hardware to describe a broader condition of digitalized life in which experience becomes increasingly modifiable, personalized, and optimized. In this wider sense, the difficulty of dwelling in the metaverse is not limited to a niche technology but reveals a tendency within late-digital culture itself. The paper concludes by proposing a politics of friction: a public deliberation over which resistances are unjust and should be transformed, and which are constitutive conditions of ethical, ecological, and responsible life. Full article

Silicone rubber is an important external insulating material for composite bushings, composite insulators, and other power equipment. During long-term service, it is inevitably exposed to coupled environmental and electrical stresses, such as elevated temperature, moisture ingress, strong electric fields, and partial discharge, which may lead to hydrophobicity loss, surface chalking, crack propagation, and particle shedding. To reveal the microscopic degradation mechanism of silicone rubber under complex operating conditions, a molecular model of methyl vinyl silicone rubber was constructed using Materials Studio. A stable silicone rubber molecular structure was obtained through crosslinking, geometry optimization, and ensemble relaxation. Subsequently, a reactive molecular dynamics simulation system under coupled temperature–humidity–electric field conditions was established using LAMMPS and the ReaxFF reactive force field. Different temperature gradients, electric field intensities, and aging–recovery stages were designed to investigate the degradation behavior of silicone rubber. The evolution of the maximum carbon content, maximum silicon content, carbon-containing decomposition products, and typical small-molecule products, including H₂, H₂O, CH₄, C₂H₂, C₂H₄, and C₂H₆, was statistically analyzed. In addition, atomic trajectory tracking was performed to clarify the processes of methyl group detachment, Si-O bond cleavage, water molecule participation, and molecular chain reconstruction. The results show that high temperature mainly promotes methyl group detachment from side chains and fracture of the siloxane main chain, while a strong electric field accelerates the decomposition process and induces the transformation of long siloxane chains into shorter chains. Water molecules can react with broken siloxane chains to form hydroxyl-containing structures, making the structural degradation partially irreversible. The degradation process of silicone rubber under coupled temperature–humidity–electric field stress can be summarized as side-chain detachment, main-chain scission, water-assisted reactions, free-radical recombination, and local molecular aggregation. This study provides a molecular-level theoretical basis for aging mechanism analysis, condition assessment, and lifetime prediction of composite external insulating materials. Full article

Introduction: Teprotumumab (Tepezza^®), an insulin-like growth factor-1 receptor (IGF-1R) antagonist, is the first FDA-approved targeted therapy for thyroid eye disease (TED). While effective for reducing proptosis and inflammation, increasing post-marketing evidence has linked teprotumumab to auditory adverse events. IGF-1 signaling is essential for cochlear maintenance and neuroprotection; therefore, systemic IGF-1R inhibition presents a biologically plausible mechanism for ototoxicity. Despite growing recognition of these effects, no standardized approach exists for audiologic assessment or monitoring of patients receiving teprotumumab. This review aimed to (1) summarize proposed mechanisms and the reported spectrum of teprotumumab-related auditory effects, (2) evaluate current methods used to assess and monitor these patients, and (3) identify areas of consensus and ongoing uncertainty. Methods: An updated narrative review of the literature was conducting using PubMed, CINAHL, and Google Scholar using Boolean strings targeting teprotumumab exposure and hearing-related outcomes. Studies from 2022 onward were identified using Boolean search strings targeting teprotumumab exposure and hearing-related outcomes. Peer-reviewed English language studies reporting audiometric findings were eligible for inclusion. Results: Ten studies met inclusion criteria. Reported effects most commonly included bilateral high-frequency SNHL, tinnitus, and aural fullness, typically emerging after three to six infusions. Many cases demonstrated persistent deficits despite drug discontinuation. Baseline audiometric assessment was not uniformly reported across studies, and monitoring protocols varied considerably, with inconsistent incorporation of speech testing and immittance measures. Conclusions: Teprotumumab-associated ototoxicity is increasingly recognized and potentially irreversible. Current evidence is insufficient to guide standardized monitoring. Prospective studies are urgently needed to establish evidence-based audiologic surveillance protocols. Full article

Multiple sclerosis (MS) is a neuro-inflammatory disease characterized by demyelination in the central nervous system (CNS). Although a substantial endogenous capacity for remyelination has been demonstrated, this process is frequently incomplete and exhibits marked intra- and inter-individual heterogeneity. Several factors influence the extent of spontaneous myelin regeneration, including age, sex, disease course, and lesion localization. Oligodendrocytes (OL), derived from oligodendrocyte progenitor cells (OPCs), are the principal myelinating cells of the CNS. The regenerative cascade involves several key stages, including OPC activation, recruitment, differentiation into oligodendrocytes (OL), and myelin deposition. This process is orchestrated in a spatiotemporal manner by a complex interplay of intracellular signaling pathways, genetic determinants, and dynamic microenvironmental cues, which together balance inhibitory and pro-remyelinating influences. Several lines of evidence indicate that chronically demyelinated axons are vulnerable to degeneration, whereas successful remyelination may confer neuroprotection. These observations underscore remyelination as a promising neuroprotective therapeutic target for preventing or slowing disability progression in MS, a condition in which gradual neuroaxonal degeneration is believed to underlie irreversible disability progression. In this review, we aim to bridge the gap between fundamental biological mechanisms of remyelination and their clinical relevance. We examine recent advances in in vivo techniques for assessing remyelination and discuss how these measures correlate with clinical and disability outcomes. In addition, we review recent clinical trials of remyelination-promoting therapies and analyze the challenges that have limited their advancement beyond phase II. Overall, we seek to provide a comprehensive overview of the remyelination process from bench to bedside, highlighting both the obstacles and the therapeutic potential of remyelination strategies in MS. Full article

Background: Uridine diphosphate glucose (UDP-Glc) is one of the key substrates for the biosynthesis of gallotannins in plants. UDP-glucose dehydrogenase (UGD) catalyzes the irreversible oxidation of UDP-Glc to UDP-glucuronic acid (UDP-GlcA), thus affecting the biosynthesis and accumulation of gallotannins in the Chinese gallnut. Methods and Results: In this study, we identified three members of the RcUGD family from the Rhus chinensis genome. Protein sequence alignment revealed that all three RcUGDs possess the conserved NAD⁺ coenzyme binding motif GAGYVGG and the catalytic motif GFGGSCFQKDIL. qRT-PCR analysis revealed that the expression levels of RcUGD3 in stem and root tissues were respectively 10-fold and 13-fold greater than that in the leaves, in which gallotannin accumulation was higher. RcUGD3 expression level declined by 63% during early (24 d) gallnut development, suggesting an inverse relationship between RcUGD3 expression level and gallotannin biosynthesis. In addition, subcellular localization analysis using the tobacco transient transformation system showed that RcUGD proteins are broadly distributed throughout the cell. Moreover, an in vitro enzyme activity assay indicated that the recombinant RcUGD3 protein catalyzed UDP-Glc to produce UDP-GlcA as shown by HPLC. Taken together, our results suggested that RcUGD3 protein is responsible for UDP-Glc degradation and probably plays a regulatory role in gallotannin biosynthesis in the Chinese gallnut. Conclusions: This study lays a foundation for further elucidating the function and expression regulation mechanism of the RcUGD gene family and provides new insights for the super-accumulation mechanisms of gallotannins in Chinese gallnuts. Full article

Backfilling the industrial solid waste coal gangue into deep coal mine goafs for CO₂ geological sequestration is a crucial pathway to achieve the synergistic effect of pollution reduction and carbon mitigation. However, in complex deep geological environments, the chemical evolution of multiple mineral phases of coal gangue under gas–water–rock coupling effects and the carbon-controlling mechanism of residual total organic carbon (TOC) remain unclear. In this study, coal gangue from the goaf of the Xiaobaodang Coal Mine was used as the research object. Relying on a customized high-temperature and high-pressure reaction system to simulate the deep in situ environment (45 °C, 10 MPa), and combined with X-ray diffraction (XRD), total organic carbon determination, and isothermal CO₂ adsorption experiments, the geochemical mechanism by which inorganic minerals and organic residual carbon synergistically control the ultimate CO₂ adsorption potential was systematically revealed. The results show that the modification of the CO₂ adsorption potential of coal gangue by gas–water–rock reactions exhibits strong mineral phase differentiation. Systems rich in active silicates generate a large amount of secondary clay minerals through intense carbonation alteration, achieving a significant increase in micro–nano pores and absolute adsorption capacity. Systems rich in carbonates steadily release deep primary adsorption potential by widening mass transfer channels through mineral dissolution. In contrast, systems rich in primary clay minerals face an irreversible attenuation of adsorption space due to physical clogging of pore throats caused by fluid migration. Furthermore, the initial organic carbon content exerts a significant non-linear regulatory effect on the development of the micropore network. The physical adsorption sites provided by the high relative content of layered clay minerals (>41%), coupled with the interfacial enhancement effect exerted by a moderate organic carbon content (0.12~0.16%), constitute an optimal physicochemical synergistic enhancement network, which is the core geological reason for stimulating the ultimate carbon sequestration capacity of coal gangue. The results of this study not only enrich the multiphase interfacial thermodynamic theory of complex heterogeneous geological bodies but also provide solid theoretical support for the precise optimization of target areas and the long-term evaluation of carbon sinks in goaf CO₂ sequestration engineering. Full article

Introduction: Chemical pollution of water bodies constitutes a global problem with huge impacts on fish populations. Consequently, the assessment of the effects of contaminants, especially on the nervous system, has become essential. The zebrafish (Danio rerio) has emerged as a prominent vertebrate model in ecotoxicology and neuroscience, in large part owing to the availability of genetic resources, including a high level of genome sequencing and annotation, plus the similarity of its neuron types and neurotransmitters to other vertebrates, including humans, and its stereotyped behaviour. Objective: The main objective of this mini-review is to present a synthesis of the key behavioural assays used in zebrafish larvae to assess neurotoxicity, focusing on developmental neurotoxicity. Methodology: A literature review was conducted based on the ScienceDirect and PubMed databases, covering publications between 2000 and 2025, selecting relevant studies on larval (up to 120 hpf) behaviour and contaminant exposure. The methodology was based on the analysis of behavioural tests applied to larvae, which evaluate responses to various stimuli, including visual, acoustic, tactile, and social stimuli. Results: Established, commonly used key assays include the light/dark test and locomotor, touch, photomotor, acoustic, and social response tests. The literature results confirm that zebrafish larvae exhibit complex behavioural patterns comparable to those of higher vertebrates, making them suitable for neurobehavioural studies. Changes in locomotor behaviour, responses to stimuli, or social patterns are extremely sensitive indicators of early neurotoxic effects, often before morphological changes are observed. Furthermore, the developing nervous system is particularly sensitive to chemicals, with high potential for irreversible effects, even with short-term exposures. Conclusions: Overall, our findings demonstrate that behavioural assays in zebrafish larvae constitute an effective, sensitive, and economically viable tool for assessing the neurotoxicity of compounds, contributing to a better understanding of the mechanisms of action and advancing environmental protection and public health strategies, considering also the “one health” approach. Full article

Background: Toxoplasmosis is a prevalent zoonotic disease worldwide, affecting approximately one-third of the global human population. Primary infection with Toxoplasma gondii during pregnancy can induce miscarriage or congenital infection, leading to irreversible damage to the foetus. Moreover, reactivation of T. gondii infection in immunosuppressed individuals can result in fatal outcomes. No vaccine exists to prevent human disease caused by this parasite. Thus, a vaccine that could induce complete and lasting protection against human toxoplasmosis is an unmet need. Method: In this work, BALB/cByJ mice were intranasally immunised with a subunit vaccine consisting of T. gondii membrane proteins (TGMP) from the T. gondii Me49 strain plus CpG-oligodeoxynucleotide adjuvant (CpG). Antibody responses were analysed by ELISA, while T-cell responses were evaluated by flow cytometry. The immunogenic proteins present in TGMP were identified by mass spectrometry, and parasite burden was quantified by qPCR. Result: The results showed raised TGMP-specific serum IgG and intestinal IgA antibody levels, and parasite-specific IFN-γ-producing CD4⁺ and CD8⁺ memory T cells. Dense granule proteins (GRA) 2 and 7, surface antigen (SAG)-related sequences 25, 29B, and 34A, microneme protein (MIC) 10, toxofilin, nascent polypeptide-associated complex (NAC) domain-containing protein, and NAC subunit beta were identified as immunogenic proteins. Mice immunised with TGMP+CpG were challenged with T. gondii tachyzoites and showed a significant reduction in the parasitic burden in the peritoneal exudate, spleen, and lungs, compared to mice sham-immunised with CpG alone. Conclusions: Altogether, these results indicate that mucosal immunisation with TGMP plus CpG adjuvant is worth exploring as a vaccination approach to prevent toxoplasmosis. Full article

In 1988, plastic surgeon Lee Dellon in Annals of Plastic Surgery hypothesized that there was “A Cause for Optimism in Diabetic Neuropathy”. He noted that entrapment neuropathy is common in diabetic peripheral neuropathy (DPN) and explained that multiple sites of local nerve entrapment can also produce the classically described clinical picture of progressive and irreversible ‘length dependent axonopathy’. This observation has justified for him the use of nerve decompression (ND) surgery for beneficial treatment of DPN pain, diabetic foot ulcer (DFU), ulcer recurrences and their subsequent complications. Subsequent observational and controlled reports have consistently demonstrated post-operative benefit for these problems, but ND has not yet been widely adopted. The lack of an etiologic explanation of the physiology changes which would allow surgery to modify the metabolic disturbances of diabetes has likely been involved in such hesitance. Recent explanations that glycolysis is altered in diabetes through intensified polyol metabolism which produces swollen nerves, local peripheral entrapments and compression neuropathy now provide plausible associations of hyperglycemia with epidermal hypoxia and nutrition deficit. Recognition that nerve enlargements can create secondary fibro-osseous compressions explains the well-known association of diabetes and compression syndromes. Peripheral nerve entrapments damage small c-fibers and produce sympathetic autonomic as well as sensorimotor dysfunction. This explains the diminished skin microcirculation, epidermal hypoxia and nutrition deficit seen in diabetes, DPN, DFU and Charcot neuroarthropathy. Laboratory and clinical evidence has demonstrated that ND in diabetes rejuvenates at least two sympathetically commanded skin microcirculation processes and explains how surgery is producing beneficial results. This article recapitulates the literature which clarifies the processes by which ND surgery can modify painful DPN, DFU occurrence, ulcer healing, DFU recurrence risk, amputations after DFU healing, and bilateral pain relief after unilateral surgery. Full article

Cisplatin is a widely used platinum-based chemotherapeutic agent that often causes irreversible hair cell loss, leading to hearing impairment. To date, effective strategies for preventing cisplatin-induced ototoxicity remain limited. Corchorus olitorius L. (COL) is rich in bioactive phytochemicals with antioxidant and anti-inflammatory properties; however, the protective role of COL stem against cisplatin-induced hearing loss has not been explored. This study aimed to determine whether COL stem extract treatment could mitigate cisplatin-induced hair cell damage in the lateral line system of zebrafish. Herein, we use 7-day post-fertilization (dpf) transgenic zebrafish larvae as a high-throughput screening platform to assessed COL stem extract against cisplatin-induced hair cell injury. Endpoints included mechanotransduction (MET) function, reactive oxygen species (ROS) production, apoptotic and inflammatory responses, and locomotor behavior. Antioxidant capacity and acute toxicity were also evaluated. Pretreatment with COL stem extract preserved hair cell viability, restored MET function, reduced ROS accumulation, upregulated Nrf-2-dependent cytoprotective genes, suppressed apoptosis, and attenuated macrophage infiltration. The recovery of swimming behavior correlated with hair cell protection, confirming the phenotypic relevance. This study demonstrates, for the first time, that COL stem exerts potent otoprotective effects through antioxidative, anti-apoptotic, and anti-inflammatory mechanisms, contributes to maintain mechanosensory function and swimming behavior. The findings support COL stem as a promising candidate for otoprotection and validate zebrafish-based high-throughput screening for novel therapeutic discovery. Full article

Background and Clinical Significance: Pre-eruptive intracoronal resorption is a rare developmental anomaly resembling occlusal caries despite the absence of an external breach. Case Presentation: We report of two cases. The first case involves a 9-year-old girl with PEIR of tooth 24 that was not identified on a panoramic radiograph taken one year earlier. The lesion later became clinically evident, presenting with symptoms and discoloration, and progressed to irreversible pulpitis requiring pulpotomy. This case highlights the importance of careful interpretation of paediatric panoramic radiographs and timely intervention to preserve pulp vitality in developing permanent teeth. The second case concerns a 16-year-old girl in whom PEIR was incidentally detected on cone-beam computed tomography (CBCT) in tooth 38. As the tooth has not yet erupted, its future clinical presentation and progression remain uncertain. To the best of the authors’ knowledge, there are no published reports specifically describing PEIR in patients from the Baltic region. Conclusions: Early radiographic detection of pre-eruptive intracoronal resorption is essential to prevent pulpal involvement and improve treatment outcomes, particularly when combined with careful interpretation of routine paediatric radiographs to minimize the risk of delayed diagnosis. This case emphasizes the importance of recognizing asymptomatic disease progression and integrating multidisciplinary approach to provide individualized treatment planning. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) is a progressive, incurable condition marked by irreversible airflow limitation and systemic inflammation. Cardiovascular comorbidities, particularly pulmonary hypertension (PH), exacerbate disease severity. While cigarette smoke is a well-known trigger, non-smoking-related inflammatory pathways remain underexplored. This study investigates vascular remodeling in a murine model of inflammation induced by chronic exposure to house dust mite Farinae (HDM). Methods: Female C57BL/6 mice were sensitized with HDM in Freund’s Complete Adjuvant and challenged intranasally with HDM for six weeks. Lung inflammation, mucus hypersecretion, and vascular remodeling were evaluated via BAL, histology, immunofluorescence, echocardiography, gene expression, proteomics, and FlexiVent pulmonary function tests (FlexiVent system). Results: HDM exposure induced a mixed inflammatory response, with elevated neutrophils, monocytes, and lymphocytes in BALF. Mucus hyperproduction (increase in MUC5AC/MUC5B) and impaired lung function (reduced FEV0.1/FVC) were observed. Vascular remodeling was evidenced by increased wall thickness, α-SMA expression, and collagen deposition. Proteomic analysis revealed dysregulation of endothelial markers and protease/antiprotease imbalance. HIF1-α was significantly upregulated in lung tissue and correlated with vascular and epithelial remodeling. Conclusions: Chronic HDM exposure in mice recapitulates key features observed in subsets of COPD and PH, including inflammation-driven airway and vascular remodeling. HIF1-α emerges as a central regulator, linking hypoxia to structural changes. This model offers insights into the effect of non-smoking-related inflammatory pathways on bronchial and vascular remodeling that are potentially relevant for subgroups of COPD patients and highlights HIF1-α as a potential therapeutic target. Full article

Background: Various controversial conclusions exist regarding the reproductive toxicity of cyclophosphamide, creating uncertainties about the recovery timeline of maternal reproductive capacity and offspring health. Methods: Using a mouse model with a clinically relevant cyclophosphamide dosing regimen, we examined the recovery of female reproductive function after exposure and the long-term survival and development of their offspring. Results: Our findings revealed that cyclophosphamide exposure shortened the maternal reproductive lifespan, characterized by early fertility impairment at one week (p < 0.05), transient recovery at two weeks (p > 0.05), a subsequent decline at four weeks with further deterioration, and eventual progression to infertility at six months (p < 0.01). F1 pups from the cyclophosphamide group exhibited growth restriction, higher mortality rates, delayed pubertal onset, and impaired neurodevelopment during long-term follow-up. Although some parameters transiently improved at 2 weeks post-withdrawal, these abnormalities persisted or recurred at 4 and 8 weeks, indicating that developmental defects were not lessened by prolonging the medication withdrawal period. Conclusions: These findings demonstrate irreversible gonadotoxicity and developmental toxicity following cyclophosphamide exposure in this mouse model. Full article

Background and Clinical Significance: Giant cell arteritis (GCA) is an autoimmune vasculitis of both medium and large-sized vessels typically affecting females 50 years of age or older. Severe complications can include permanent visual loss, acute coronary syndrome, or stroke. This case will present an atypical presentation of bilateral OPN which can be a rare manifestation of GCA; Case Report: Our patient developed acute, painful worsening central vision loss progressing from right eye to left with bilateral extraocular motility restriction and magnetic resonance image (MRI) revealed bilateral, circumferential optic nerve sheath enhancement suggesting optic perineuritis (OPN). Temporal artery biopsy confirmed GCA with bilateral temporal arteritis. The patient was treated with a high dose course of corticosteroids followed by a taper and was started on upadacitinib with symptomatic improvement; Conclusions: This case underscores OPN as a rarer manifestation of giant cell arteritis that can present with bilateral painful eye movements and vision loss. Early recognition and prompt corticosteroid therapy are essential to prevent irreversible visual impairment. Full article

Convolutional neural networks (CNN) have transformed visual recognition, yet robust geometric reasoning, reliable out-of-distribution generalization, and recognition from limited data remain substantially unsolved. CNNs draw their architectural inspiration from the mammalian visual cortex, but the translation from biology to engineering was selective and, in places, imprecise, and those imprecisions have consequences that are well documented. This paper examines where the biological fidelity holds and where it gives way, grounding the analysis in formal results that predate deep learning and in recent empirical findings on CNN failure modes. We identify three diagnosable architectural limitations. First, CNNs conflate visual modalities that the biological system separates structurally at the lateral geniculate nucleus, feeding raw RGB pixels into a single undifferentiated filter bank and entangling orientation, color, and texture signals from the first layer onward. Second, CNNs repeat a spatial subsampling operation across the full depth of the network, far beyond the early visual cortex stages where it has biological warrant. Barnard and Casasent established formally in 1990 that this operation discards positional information irreversibly at every layer where it is applied, and repeating it into regions that correspond to V4 and inferotemporal cortex compounds this loss without the compensating transition to qualitatively different computations that the biological hierarchy performs. Third, the pooling-as-complex-cell analogy that motivated this design reflects a misreading of what complex cells compute. The spatiotemporal energy model formalizes complex cell behavior as geometry extraction: detecting the presence and orientation of a local edge structure robustly, abstracting over photometric accidents of contrast polarity and sub-wavelength phase that are not geometrically meaningful. Pooling is a tolerable first-stage approximation of this behavior, but as a general-purpose invariance mechanism repeated across the full depth of the network, it is attempting something categorically different, namely object-level position invariance through spatial subsampling, which achieves its goal by discarding exactly the geometric information that the energy model preserves. Treating pooling as a scalable, indefinitely repeatable implementation of complex cell behavior—rather than as a first-stage approximation with a natural biological endpoint at V3—conflates two operations that differ not in degree but in kind, and crucially it removed the principled criterion for confining the S-C operation to early visual cortex: because pooling was understood as a general-purpose invariance mechanism, the field had no architectural reason to stop repeating it. We survey how capsule networks, group-equivariant CNNs, PDE-based networks, and vision transformers each address one or two of these limitations while leaving the others intact. We propose six desiderata that a more biologically complete architecture would need to satisfy and argue that satisfying them requires treating the visual cortex’s solution as a coherent package in which each component depends on the others working correctly, rather than as a menu of independently selectable principles. Full article