SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study used APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by Western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of Sirt4. Subsequently, the binding of transcription factors to Sirt4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells compared with their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.NEW & NOTEWORTHY The study reveals that in Alzheimer's disease models, SIRT4 expression increases, contributing to neuronal apoptosis and amyloid-ß deposition. Reducing SIRT4 lessens apoptosis and amyloid-ß accumulation, improving memory in mice. This process involves the mTOR pathway, regulated by STAT2 transcription factor. These findings suggest targeting the STAT2-SIRT4-mTOR axis as a potential Alzheimer's treatment strategy.

Visualization and mapping of literature on the scientific analysis of wall paintings: a bibliometric analysis from 2011 to 2021.

As non-renewable cultural heritage, wall paintings play an important role in society. To reveal the trends in the scientific analysis of mural paintings, 845 relevant research articles published from 2011 to 2021 were collected from the Web of Science database and analyzed. The VOSviewer software was adopted to map the network data of scientific publications, so that relationships among authors, countries, institutions can be displayed, and the co-occurrence of keywords and co-citation can be analyzed. The results revealed close and strong interconnections between the top authors, suggesting a considerable strong research link in this field. The cooperation between research institutions was relatively close. The most productive country of relevant publications was Italy. The leading journals for the scientific analysis of wall paintings were Journal of Raman Spectroscopy and Journal of Cultural Heritage. At present, the hotspots of scientific analysis and research on wall painting are revealing the composition, distribution, origin, and deterioration mechanism of pigments, alongside with evaluating the effects and mechanism of conservation materials and techniques. On the one hand, a possible development direction in this field is introducing more cutting-edge analysis and data processing methods. On the other hand, scientific analysis is increasingly adopted to guide the research and development of mural conservation materials.

Corrigendum to "Vanillic Acid Alleviates Acute Myocardial Hypoxia/Reoxygenation Injury by Inhibiting Oxidative Stress".

[This corrects the article DOI: 10.1155/2020/8348035.].

Vanillic Acid Alleviates Acute Myocardial Hypoxia/Reoxygenation Injury by Inhibiting Oxidative Stress.

Oxidative stress is an important factor of myocardial hypoxia/reoxygenation (H/R) injury. Our research focuses on how to reduce the cardiac toxicity caused by oxidative stress through natural plant extracts. Vanillic acid (VA) is a phenolic compound found in edible plants and rich in the roots of Angelica sinensis. Experimental studies have provided evidence for this compound's effectiveness in cardiovascular diseases; however, its mechanism is still unclear. In this study, molecular mechanisms related to the protective effects of VA were investigated in H9c2 cells in the context of H/R injury. The results showed that pretreatment with VA significantly increased cell viability and decreased the percentage of apoptotic cells, as well as lactate dehydrogenase and creatine phosphokinase activity, in the supernatant, accompanied by reduced levels of reactive oxygen species and reduced caspase-3 activity. VA pretreatment also restored mitochondrial membrane potentials. Moreover, preincubation with VA significantly attenuated mitochondrial permeability transition pore activity. VA administration upregulated adenosine monophosphate-activated protein kinase α2 (AMPKα2) protein expression, and interestingly, pretreatment with AMPKα2-siRNA lentivirus effectively attenuated the cardioprotective effects of VA in response to H/R injury.

Structural-Functional Relationships Between Eye Orbital Imaging Biomarkers and Clinical Visual Assessments.

Eye diseases and visual impairment affect millions of Americans and induce billions of dollars in annual economic burdens. Expounding upon existing knowledge of eye diseases could lead to improved treatment and disease prevention. This research investigated the relationship between structural metrics of the eye orbit and visual function measurements in a cohort of 470 patients from a retrospective study of ophthalmology records for patients (with thyroid eye disease, orbital inflammation, optic nerve edema, glaucoma, intrinsic optic nerve disease), clinical imaging, and visual function assessments. Orbital magnetic resonance imaging (MRI) and computed tomography (CT) images were retrieved and labeled in 3D using multi-atlas label fusion. Based on the 3D structures, both traditional radiology measures (e.g., Barrett index, volumetric crowding index, optic nerve length) and novel volumetric metrics were computed. Using stepwise regression, the associations between structural metrics and visual field scores (visual acuity, functional acuity, visual field, functional field, and functional vision) were assessed. Across all models, the explained variance was reasonable (R2 ~ 0.1-0.2) but highly significant (p < 0.001). Instead of analyzing a specific pathology, this study aimed to analyze data across a variety of pathologies. This approach yielded a general model for the connection between orbital structural imaging biomarkers and visual function.