ABSTRACT
The rhesus macaque (Macaca mulatta) is a crucial experimental animal that shares many genetic, brain organizational, and behavioral characteristics with humans. A macaque brain atlas is fundamental to biomedical and evolutionary research. However, even though connectivity is vital for understanding brain functions, a connectivity-based whole-brain atlas of the macaque has not previously been made. In this study, we created a new whole-brain map, the Macaque Brainnetome Atlas (MacBNA), based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data. The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections. The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images. As a demonstrative application, the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure. The resulting resource includes: (1) the thoroughly delineated Macaque Brainnetome Atlas (MacBNA), (2) regional connectivity profiles, (3) the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset (Brainnetome-8), and (4) multi-contrast MRI, neuronal-tracing, and histological images collected from a single macaque. MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function. Therefore, it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.
Subject(s)
Brain , Macaca mulatta , Animals , Macaca mulatta/anatomy & histology , Brain/metabolism , Brain/anatomy & histology , Brain/diagnostic imaging , Humans , Connectome , Atlases as Topic , Male , Brain Mapping/methods , Diffusion Tensor Imaging/methods , Neural Pathways/anatomy & histology , Neural Pathways/metabolism , Neural Pathways/diagnostic imagingABSTRACT
Background: Nrf2 plays a pivotal role in governing the antioxidant defense system, triggering the transcription of diverse genes involved in cellular protection. Its role in mitigating oxidative damage and modulating inflammatory processes has made Nrf2 an attractive target for therapeutic interventions. Despite the growing interest in Nrf2 research, a bibliometric analysis is relatively rare. This study aimed to clarify Nrf2's role in multiple diseases, identify emerging trends and hotspots using bibliometric analysis, and provide valuable insights and potential directions for future therapeutic interventions. Methods: The Science Citation Index of Web of Science Core library from 2000 to 2022 was searched on 22 October 2022. Use Microsoft Excel, CiteSpace, Bibliometrix, and VOS viewers for data collection and visualization of research focus and trends. Results: A vast collection of 22,040 research studies on Nrf2 published between 2000 and 2022 were identified. Nrf2 research has seen significant growth globally from 2000 to 2022. China leaded in publication numbers (9,623, 43.66%), while the United States dominated in citation frequency with 261,776 citations. China Medical University was the most productive institutions (459, 2.08%). Masayuki Yamamoto topped in publications (307), while Itoh K. ranked first in citations with 3669. Free Radical Biology and Medicine was the journal with the most studies and citations on Nrf2 (613, 29,687 citations). The analysis of keyword clustering enhanced the categorization of topics and can be summarized as oxidative stress, cancer, disorders in glycolipid metabolism, inflammation, and neurological conditions. Conclusion: China and the United States are the pioneers in Nrf2 research. Recently, there has been a comprehensive exploration of Nrf2 involving both experimental and clinical aspects, as well as mechanisms and therapeutic applications. Investigating novel molecular mechanisms, including NF-κB, Ho1, and Keap1, and developing enhanced, targeted Nrf2 activators or inhibitors to uncover the interplay among cancer, glycolipid metabolic disorder, inflammation, and neurological disorders will be upcoming trends and hotspots.
ABSTRACT
Environmental cadmium (Cd) exposure is a serious public health concern, as the kidney is the primary target for Cd exposure. The present study aimed to investigate the role and underlying mechanisms of nuclear factor erythroid-derived 2-like 2 (Nrf2) in renal fibrosis induced by chronic Cd exposure. Nrf2 knockout (Nrf2-KO) mice and their wild-type littermates (Nrf2-WT) were exposed to 100 or 200 ppm Cd in drinking water for up to 16 or 24 weeks. Following the Cd exposures, Nrf2-KO mice showed elevated urinary neutrophil gelatinase-associated lipocalin (NGAL) and BUN levels compared to Nrf2-WT mice. Masson's trichrome staining and expression of fibrosis-associated proteins revealed that more severe renal fibrosis occurred in Nrf2-KO than that in Nrf2-WT mice. Renal Cd content in the Nrf2-KO mice exposed to 200 ppm Cd was lower than that in Nrf2-WT mice, which might be a consequence of the severe renal fibrosis in the Nrf2-KO mice. Mechanistic studies showed that Nrf2-KO mice exhibited higher levels of oxidative damage, lower antioxidant levels, and more regulated cell death, apoptosis in particular, than those in Nrf2-WT mice caused by Cd exposure. In conclusion, Nrf2-KO mice were more prone to develop renal fibrosis induced by chronic Cd exposure, partially due to a weakened antioxidant, detoxification capacity and increased oxidative damage.
Subject(s)
Cadmium , Kidney Diseases , NF-E2-Related Factor 2 , Animals , Mice , Antioxidants/metabolism , Cadmium/toxicity , Fibrosis/chemically induced , Kidney Diseases/chemically induced , Mice, Knockout , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative StressABSTRACT
In the past 2 years, three earthquakes of magnitude 6.0 and above occurred consecutively in Qinghai province, China, i.e., the 22 May 2021 Ms7.4 Maduo, 8 January 2022 Ms6.9 Menyuan, and 26 March 2022 Ms6.0 Delingha earthquakes. The hydrological observation instruments set up by the China Earthquake Administration allow us to study the dynamic processes in the well-aquifer systems during the establishment of criticality. Particularly, the observations played an important role in the prediction of the 8 January 2022 Ms6.9 Menyuan earthquake that was approved by the People's Government of Qinghai province. This work presents the hydrological data recorded by 7 stations to show the short-term anomalies before these earthquakes. To explore the performance of the hydrological observations in detecting earthquakes that occurred on different active tectonic blocks, we calculate the relative amplitudes of the pre-seismic changes. Results indicate that markedly pre-seismic change is found if the observation station and the detection earthquake are on the same block, and moderate change is found if they are on the adjacent blocks, while the precursor is hard to be identified if they are on the separated blocks. The variations in the hydrological responses may be caused by the strength weakening (or dilatancy) of source media. And the increased volumes in the crust can be evidenced by the changes in the geodetic time series in the same neighborhoods and during the same period, augmenting stress loading between the blocks.
ABSTRACT
Difficulties in parsing the multiaspect heterogeneity of schizophrenia (SCZ) based on current nosology highlight the need to subtype SCZ using objective biomarkers. Here, utilizing a large-scale multisite SCZ dataset, we identified and validated 2 neuroanatomical subtypes with individual-level abnormal patterns of the tensor-based morphometric measurement. Remarkably, compared with subtype 1, which showed moderate deficits of some subcortical nuclei and an enlarged striatum and cerebellum, subtype 2, which showed cerebellar atrophy and more severe subcortical nuclei atrophy, had a higher subscale score of negative symptoms, which is considered to be a core aspect of SCZ and is associated with functional outcome. Moreover, with the neuroimaging-clinic association analysis, we explored the detailed relationship between the heterogeneity of clinical symptoms and the heterogeneous abnormal neuroanatomical patterns with respect to the 2 subtypes. And the neuroimaging-transcription association analysis highlighted several potential heterogeneous biological factors that may underlie the subtypes. Our work provided an effective framework for investigating the heterogeneity of SCZ from multilevel aspects and may provide new insights for precision psychiatry.
Subject(s)
Magnetic Resonance Imaging , Schizophrenia , Humans , Magnetic Resonance Imaging/methods , Schizophrenia/diagnostic imaging , Neuroimaging , Cerebellum/diagnostic imaging , AtrophyABSTRACT
For light-emitting polymers with a deep highest occupied molecular orbital energy level used for polymer light-emitting diodes (PLEDs), the hole injection barrier and hole transport of the anode buffer layer are of vital importance for optimizing electroluminescent performance. In this study, high-work-function hole injection layers with nanotextures were achieved by modifying poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) with a perfluorinated ionomer (PFI) and n-butyl alcohol and were used to achieve a single-layer device without a hole transport layer. With such an interlayer, the PLEDs based on PPF-SO25 exhibit remarkable current efficiency over 13.0 cd A-1, which significantly outperform the devices with regular PEDOT:PSS. To our knowledge, this performance is among the best reported for single-layer blue PLEDs. The bias-dependent capacitance curves of these PLEDs suggest a nonuniform surface distribution of PFI. Our findings show that the PFI-modified PEDOT:PSS not only operates as a high-work-function hole injection layer to facilitate hole injection but also as a potential inner scattering medium for light extraction.