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Amyloid proteins, which are considered ‘villains’ in many neurodegenerative diseases, form enigmatic pathological strains that underlie disease pathogenesis and progression. Recent technical advances in cryogenic electron microscopy and solid-state NMR spectroscopy have enabled the high-resolution structures of full-length amyloid fibrils to be determined, initiating an era in which we have the opportunity to gain atomic-level structural understanding of pathogenic protein aggregation in neurodegenerative diseases. In this Review, we aim to explain the clinicopathological heterogeneity of neurodegenerative diseases by considering the polymorphic structures of amyloid fibrils. We decipher the structural basis for the generation of fibril polymorphs, how the fibril polymorphs differ in different disease contexts and how conformational changes alter the pathology caused by amyloid proteins during disease progression. Finally, we evaluate how this knowledge might aid clinical diagnostic and therapeutic strategies to treat neurodegenerative diseases.Pathological forms of amyloid proteins, such as tau and α-synuclein, are thought to drive neurodegeneration. Li and Liu describe how techniques that reveal high-resolution protein structures can provide insight into polymorphic amyloid fibril formation and the relationships between amyloid protein conformation and disease.

The rapid spread and high death rates of the COVID-19 pandemic resulted in massive panic and anxiety all over the world. People rely heavily on media for information-seeking during the period of social isolation. This study aimed to explore the relationship between media exposure and anxiety, and highlighted the underlying mechanisms mediated by the media vicarious traumatization effect. A total of 1118 Chinese citizens participated in the online survey, who were from 30 provinces in mainland China. Results showed that all four types of media (official media, commercial media, social media, and overseas media) cause vicarious traumatization to their audiences to different degrees. It was also found that the impact of media exposure on anxiety was mediated by media vicarious traumatization: there were full mediation effects for commercial media exposure and overseas media exposure, while there were indirect-only mediation effects for official media exposure and social media exposure. Audiences staying in cities with a relatively severe pandemic were more susceptible to the vicarious traumatization caused by commercial media compared to those staying in Hubei. This study expanded the concept and application of vicarious traumatization to the mediated context, and the findings provided insightful advice to media practitioners in the face of major crisis.

Alzheimer’s disease (AD), a neurodegenerative disease, is characterized by the presence of extracellular amyloid-β (Aβ) aggregates and intracellular neurofibrillary tangles formed by hyperphosphorylated tau as pathological features and the cognitive decline as main clinical features. An important cellular correlation of cognitive decline in AD is synapse loss. Soluble Aβ oligomer has been proposed to be a crucial early event leading to synapse dysfunction in AD. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function have been suggested in the pathogenesis of AD. Astrocytes may contribute to synapse dysfunction at an early stage of AD by participating in Aβ metabolism, brain inflammatory response, and synaptic regulation. While mesenchymal stem cells can inhibit astrogliosis, and promote nonreactive astrocytes. They can also induce direct regeneration of neurons and synapses. In this review, we describe the role of mesenchymal stem cells and underlying mechanisms in regulating astrocytes-related Aβ metabolism, neuroinflammation and synapse dysfunction in early AD, exploring the open questions in this field.

Since the industrial revolution, it has been assumed that fossil-fuel combustions dominate increasing nitrogen oxide (NO x ) emissions. However, it remains uncertain to the actual contribution of the non-fossil fuel NO x to total NO x emissions. Natural N isotopes of NO 3 − in precipitation (δ 15 N w-NO3− ) have been widely employed for tracing atmospheric NO x sources. Here, we compiled global δ 15 N w-NO3− observations to evaluate the relative importance of fossil and non-fossil fuel NO x emissions. We found that regional differences in human activities directly influenced spatial-temporal patterns of δ 15 N w-NO3− variations. Further, isotope mass-balance and bottom-up calculations suggest that the non-fossil fuel NO x accounts for 55 ± 7% of total NO x emissions, reaching up to 21.6 ± 16.6Mt yr −1 in East Asia, 7.4 ± 5.5Mt yr −1 in Europe, and 21.8 ± 18.5Mt yr −1 in North America, respectively. These results reveal the importance of non-fossil fuel NO x emissions and provide direct evidence for making strategies on mitigating atmospheric NO x pollution. This study investigates in the importance of non-fossil fuel NO x emissions in the surface-earth-nitrogen cycle. The study shows how changes of regional human activities directly influence δ 15 N signatures of deposited NO x to terrestrial environments and that emissions have largely been underestimated.

Cysteine protease cathepsins have traditionally been considered as lysosome-restricted proteases that mediate proteolysis of unwanted proteins. However, studies from the past decade demonstrate that these proteases are localized not only in acidic compartments (endosomes and lysosomes), where they participate in intracellular protein degradation, but also in the extracellular milieu, plasma membrane, cytosol, nucleus, and nuclear membrane, where they mediate extracellular matrix protein degradation, cell signalling, and protein processing and trafficking through the plasma and nuclear membranes and between intracellular organelles. Studies in experimental disease models and on cathepsin-selective inhibitors, as well as plasma and tissue biomarker data from animal models and humans, have verified the participation of cysteinyl cathepsins in the pathogenesis of many cardiovascular diseases, including atherosclerosis, myocardial infarction, cardiac hypertrophy, cardiomyopathy, abdominal aortic aneurysms, and hypertension. Clinical trials of cathepsin inhibitors in chronic inflammatory diseases suggest the utility of these inhibitors for the treatment of cardiovascular diseases and associated complications. Moreover, development of cell transfer technologies that enable ex vivo cell treatment with cathepsin inhibitors might limit the unwanted systemic effects of cathepsin inhibition and provide new avenues for targeting cysteinyl cathepsins. In this Review, we summarize the available evidence implicating cysteinyl cathepsins in the pathogenesis of cardiovascular diseases, discuss their potential as biomarkers of disease progression, and explore the potential of cathepsin inhibitors for the treatment of cardiovascular diseases.

Amyloid aggregation, which disrupts protein homeostasis, is a common pathological event occurring in human neurodegenerative diseases (NDs). Numerous evidences have shown that the structural diversity, so-called polymorphism, is decisive to the amyloid pathology and is closely associated with the onset, progression, and phenotype of ND. But how could one protein form so many stable structures? Recently, atomic structural evidence has been rapidly mounting to depict the involvement of chemical modifications in the amyloid fibril formation. In this Perspective, we aim to present a hierarchical regulation of chemical modifications including covalent post-translational modifications (PTMs) and noncovalent cofactor binding in governing the polymorphic amyloid formation, based mainly on the latest α-synuclein and Tau fibril structures. We hope to emphasize the determinant role of chemical modifications in amyloid assembly and pathology and to evoke chemical biological approaches to lead the fundamental and therapeutic research on protein amyloid state and the associated NDs. This Perspective summarizes the recent advances in the structural diversity of amyloid fibrils and discusses the roles of post-translational modifications and chemical cofactors in the conformational determination of fibril polymorphs.

Gasdermin D (GSDMD)-mediated pyroptosis and downstream inflammation are important self-protection mechanisms against stimuli and infections. Hosts can defend against intracellular bacterial infections by inducing cell pyroptosis, which triggers the clearance of pathogens. However, pyroptosis is a double-edged sword. Numerous studies have revealed the relationship between abnormal GSDMD activation and various inflammatory diseases, including sepsis, coronavirus disease 2019 (COVID-19), neurodegenerative diseases, nonalcoholic steatohepatitis (NASH), inflammatory bowel disease (IBD), and malignant tumors. GSDMD, a key pyroptosis-executing protein, is linked to inflammatory signal transduction, activation of various inflammasomes, and the release of downstream inflammatory cytokines. Thus, inhibiting GSDMD activation is considered an effective strategy for treating related inflammatory diseases. The study of the mechanism of GSDMD activation, the formation of GSDMD membrane pores, and the regulatory strategy of GSDMD-mediated pyroptosis is currently a hot topic. Moreover, studies of the structure of caspase-GSDMD complexes and more in-depth molecular mechanisms provide multiple strategies for the development of GSDMD inhibitors. This review will mainly discuss the structures of GSDMD and GSDMD pores, activation pathways, GSDMD-mediated diseases, and the development of GSDMD inhibitors.

Current digital media art interactive devices are difficult to adapt to complex environments due to fixed perception mechanisms, and are easily affected by noise interference and low light, resulting in reduced recognition accuracy and interaction delay, affecting the immersive experience. This study constructs a perception and sharing optimization mechanism for digital media art interactive devices driven by adaptive Artificial Intelligence (AI). A multi-channel data fusion perception network is proposed, and the Transformer encoder is used to fuse Red-Green-Blue (RGB) image, infrared depth map, and speech spectrum map features to improve perception robustness. A user behavior temporal modeling module based on Bidirectional Graph Recurrent Transformer (Bi-GRT) is designed to achieve dynamic recognition of continuous actions, gestures, and speech emotions. Environmental simulation and adaptive control mechanisms are applied, and reinforcement learning is combined to dynamically adjust sensor parameters to adapt to environmental changes. A multi-user interactive sharing framework is constructed through federated learning to ensure privacy while improving model consistency. Finally, a real-time feedback optimization and content rendering collaborative engine is developed to achieve dynamic scheduling and optimization of multi-dimensional output content based on Graph Attention Network (Bi-GRT). Experiments show that the system has an accuracy rate of over 80% in multi-action sample recognition; the environmental adaptability achieves a response delay of 210 ms in a noisy environment; the sequence similarity of each terminal in federated learning is above 0.91; the user immersion peak is 9.2 points, Compared with existing systems, this framework has achieved breakthrough progress in environmental adaptability, multi-user collaboration, and privacy protection, providing a quantifiable performance improvement path for digital media art interactive devices.

ObjectivesThe purpose of this review is to identify the theoretical framework of implementation science in the intensive care unit (ICU), the determinants affecting implementation results, the intervention guided by a theoretical framework and the assessment of implementation effectiveness based on implementation science to guide further advancement of the implementation of evidence in the field of ICU.DesignThe scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) Scoping Review Methodology Group’s guidance and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. The study protocol was registered with the International Prospective Registry of Systematic Reviews on 15 December 2024 (registration number: CRD42024614246).Data sourcesWe searched the following databases and sources: PubMed, Web of Science, Cochrane Library and EBSCO.Eligibility criteriaWe included studies exploring the implementation science in the ICU that were published in English language.Data extraction and synthesisTwo researchers conducted the literature search by referring to the search strategies, and one researcher removed duplicates using EndNote. Two independent investigators screened the retrieved studies based on their titles and abstracts using eligibility criteria. Subsequently, the same two researchers conducted a full-text screening.Results13 articles were included: 8 qualitative studies, 3 mixed studies, 1 quasi-experimental study and 1 prospective observational study. Regarding the implementation of the theoretical framework for research, seven studies applied the consolidated framework for implementation research (CFIR), two studies applied the research implementation in health services framework (i-PARIHS) and one each of the research into the translating research into practice model, the exploration, preparation, implementation, sustain, the reach, effectiveness, adoption, implementation and maintenance model and the behaviour change wheel. The CFIR was the most applied in the ICU, followed by the i-PARIHS. The literature demonstrated how implementation science is used and how it can reduce the gap between evidence and practice.ConclusionStrategies to support the implementation of accelerated evidence-based practice in the ICU are important, and more researchers need to conduct implementation science studies of the ICU to facilitate the translation of evidence and improve the quality of nursing practice in the future.

The Karakoram fault (KKF) is an important strike‐slip boundary for accommodating deformation following the India‐Asia collision. However, whether the deformation is confined to the crust or whether it extends into the mantle remains highly debated. Here, we show that the KKF is overwhelmingly dominated by crustal degassing related to a 4He‐ and CO2‐rich fluid reservoir (for example, He contents up to ∼1.0–1.6 vol.%; 3He/4He = 0.027 ± 0.013 RA (1σ, n = 47); CO2/N2 up to 3.7–57.8). Crustal‐scale active deformation driven by strike‐slip faulting could mobilize 4He and CO2 from the fault zone rocks, which subsequently accumulate in the hydrothermal system. The KKF may have limited fluid connections to the mantle, and if any, the accumulated crustal fluids would efficiently dilute the uprising mantle fluids. In both cases, crustal deformation is evidently the first‐order response to strike‐slip faulting. Plain Language Summary Bubbling hot springs are common in fault zones along which Earth's lithosphere cracks. Chemical and isotopic compositions of spring gases can offer key information on the subsurface connectivity of the deep‐rooting faults that is not easily visible. To assess whether the Karakoram fault (KKF) in western Tibetan Plateau is developing in the crust or extends into deeper mantle, we studied the origin and transport of spring gases and found that the KKF is overwhelmingly dominated by degassing of a crustal fluid reservoir that contains high amounts of helium (He) and CO2. This could be attributed to He‐CO2 mobilization of deforming and fracturing fault zone rocks at crustal depths, suggesting that the KKF is primarily developing in the crust and may have limited fluid connections to the mantle. Key Points New He isotope data show that southern Karakoram fault (KKF) is overwhelmingly dominated by degassing of crustal fluids A crustal 4He‐ and CO2‐rich fluid reservoir is identified and linked to crustal‐scale active deformation driven by strike‐slip faulting KKF may have limited fluid connections to the mantle and requires further evaluation based on He isotope and seismic data