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OBJECTIVE: Parkinson's disease (PD) is increasingly recognized for its non-motor symptoms, among which emotional disturbances and sleep disorders frequently co-occur. The commonality of neuroanatomical underpinnings for these symptoms is not fully understood. This study is intended to investigate the differences in gray matter volume (GMV) between PD patients with anxiety (A-PD) and those without anxiety (NA-PD). Additionally, it seeks to uncover the interplay between GMV variations and the manifestations of anxiety and sleep quality. METHODS: A total of 37 A-PD patients, 43 NA-PD patients, and 36 healthy controls (HCs) were recruited, all of whom underwent voxel-based morphometry (VBM) analysis. Group differences in GMV were assessed using analysis of covariance (ANCOVA). Partial correlation between GMV, anxiety symptom, and sleep quality were analyzed. Mediation analysis explored the mediating role of the volume of GMV-distinct brain regions on the relationship between sleep quality and anxiety within the PD patient cohort. RESULTS: A-PD patients showed significantly lower GMV in the fusiform gyrus (FG) and right inferior temporal gyrus (ITG) compared to HCs and NA-PD patients. GMV in these regions correlated negatively with Hamilton Anxiety Rating Scale (HAMA) scores (right ITG: r = -0.690, p < 0.001; left FG: r = -0.509, p < 0.001; right FG: r = -0.576, p < 0.001) and positively with sleep quality in PD patients (right ITG: r = 0.592, p < 0.001; left FG: r = 0.356, p = 0.001; right FG: r = 0.470, p < 0.001). Mediation analysis revealed that GMV in the FG and right ITG mediated the relationship between sleep quality and anxiety symptoms, with substantial effect sizes accounted for by the right ITG (25.74%) and FG (left: 11.90%, right: 15.59%). CONCLUSION: This study has shed further light on the relationship between sleep disturbances and anxiety symptoms in PD patients. Given the pivotal roles of the FG and the ITG in facial recognition and the recognition of emotion-related facial expressions, our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.
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Ansiedade , Substância Cinzenta , Imageamento por Ressonância Magnética , Doença de Parkinson , Qualidade do Sono , Humanos , Doença de Parkinson/patologia , Doença de Parkinson/psicologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Ansiedade/patologia , Ansiedade/psicologia , Ansiedade/diagnóstico por imagem , Idoso , Transtornos do Sono-Vigília/patologia , Transtornos do Sono-Vigília/psicologia , Tamanho do ÓrgãoRESUMO
Background: In the 21st century, as globalization accelerates and global public health crises occur, the One Health approach, guided by the holistic thinking of human-animal-environment and emphasizing interdisciplinary collaboration to address global health issues, has been strongly advocated by the international community. An immediate requirement exists for the creation of an assessment tool to foster One Health initiatives on both global and national scales. Methods: Built upon extensive expert consultations and dialogues, this follow-up study enhances the 2022 global One Health index (GOHI) indicator system. The GOHI framework is enriched by covering three indices, e.g. external drivers index (EDI), intrinsic drivers index (IDI), and core drivers index (CDI). The comprehensive indicator system incorporates 13 key indicators, 50 indicators, and 170 sub I-indicators, utilizing a fuzzy analytic hierarchy process to ascertain the weight for each indicator. Weighted and summed, the EDI, IDI, and CDI scores contribute to the computation of the overall GOHI 2022 score. By comparing the ranking and the overall scores among the seven regions and across 160 countries/territories, we have not only derived an overall profile of the GOHI 2022 scores, but also assessed the GOHI framework. We also compared rankings of indicators and sub I-indicators to provide greater clarity on the strengths and weaknesses of each region within the One Health domains. Results: The GOHI 2022 performance reveals significant disparities between countries/territories ranged from 39.03 to 70.61. The global average score of the GOHI 2022 is 54.82. The average score for EDI, IDI, and CDI are 46.57, 58.01, and 57.25, respectively. In terms of global rankings, countries from North America, Europe and Central Asia, East Asia and Pacific present higher scores. In terms of One Health domains of CDI, the lowest scores are observed in antimicrobial resistance (median: 43.09), followed by food security (median: 53.78), governance (median: 54.77), climate change (median: 64.12) and zoonotic diseases (median: 69.23). Globally, the scores of GOHI vary spatially, with the highest score in North America while lowest in sub-Saharan Africa. In addition, evidence shows associations between the socio-demographic profile of countries/territories and their GOHI performance in certain One Health scenarios. Conclusion: The objective of GOHI is to guide impactful strategies for enhancing capacity building in One Health. With advanced technology and an annually updated database, intensifying efforts to refine GOHI's data-mining methodologies become imperative. The goal is to offer profound insights into disparities and progressions in practical One Health implementation, particularly in anticipation of future pandemics.
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The effects of wind erosion, one of the crucial causes of soil desertification in the world, on the terrestrial ecosystem are well known. However, ecosystem responses regarding soil microbial carbon metabolism to sand deposition caused by wind erosion, a crucial driver of biogeochemical cycles, remain largely unclear. In this study, we collected soil samples from typical aeolian deposition farmland in the Songnen Plain of China to evaluate the effects of sand deposition on soil properties, microbial communities, and carbon metabolism function. We also determined the reads number of carbon metabolism-related genes by high-throughput sequencing technologies and evaluated the association between sand deposition and them. The results showed that long-term sand deposition resulted in soil infertile, roughness, and dryness. The impacts of sand deposition on topsoil were more severe than on deep soil. The diversity of soil microbial communities was significantly reduced due to sand deposition. The relative abundances of Nitrobacteraceae, Burkholderiaceae, and Rhodanobacteraceae belonging to α-Proteobacteria significantly decreased, while the relative abundances of Streptomycetaceae and Geodermatophilaceae belonging to Actinobacteria increased. The results of the metagenomic analysis showed that the gene abundances of carbohydrate metabolism and carbohydrate-activity enzyme (GH and CBM) significantly decreased with the increase of sand deposition amount. The changes in soil microbial community structure and carbon metabolism decreased soil carbon emissions and carbon cycling in aeolian deposition farmland, which may be the essential reasons for land degradation in aeolian deposition farmland.
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Carbono , Microbiologia do Solo , Solo , Carbono/metabolismo , Carbono/análise , China , Solo/química , Ecossistema , Fazendas , Microbiota , Areia/microbiologia , Bactérias/genética , Bactérias/metabolismo , Bactérias/classificação , VentoRESUMO
The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.
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Ciliophora, an exceptionally diverse lineage of unicellular eukaryotes, exhibits a remarkable range of species richness across classes in the ciliate Tree of Life. In this study, we have acquired transcriptome and genome data from 40 representative species in seven ciliate classes. Utilizing 247 genes and 105 taxa, we devised a comprehensive phylogenomic tree for Ciliophora, encompassing over 60 % of orders and constituting the most extensive dataset of ciliate species to date. We established a robust phylogenetic framework that encompasses ambiguous taxa and the major classes within the phylum. Our findings support the monophyly of each of two subphyla (Postciliodesmatophora and Intramacronucleata), along with three subclades (Protocruzia, CONTHREEP, and SAPML) nested within Intramacronucleata, and elucidate evolutionary positions among the major classes within the phylum. Drawing on the robust ciliate Tree of Life and three constraints, we estimated the radiation of Ciliophora around 1175 Ma during the middle of the Proterozoic Eon, and most of the ciliate classes diverged from their sister lineage during the latter half of this period. Additionally, based on the time-calibrated tree and species richness pattern, we investigated net diversification rates of Ciliophora and its classes. The global net diversification rate for Ciliophora was estimated at 0.004979 species/Ma. Heterogeneity in net diversification rates was evident at the class level, with faster rates observed in Oligohymenophorea and Spirotrichea than other classes within the subclades CONTHREEP and SAPML, respectively. Notably, our analysis suggests that variations in net diversification rates, rather than clade ages, appear to contribute to the differences in species richness in Ciliophora at the class level.
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Cilióforos , Filogenia , Cilióforos/genética , Cilióforos/classificação , Transcriptoma , Evolução Molecular , Especiação GenéticaRESUMO
BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.
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Córtex Cerebral , Dor Crônica , Dor Lombar , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Dor Lombar/diagnóstico por imagem , Dor Lombar/patologia , Adulto , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Dor Crônica/diagnóstico por imagem , Dor Crônica/patologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologiaRESUMO
Background: Neuroimaging studies have suggested a pivotal role for the amygdala involvement in chronic low back pain (CLBP). However, the relationship between the amygdala subregions and CLBP has not yet been delineated. This study aimed to analyze whether the amygdala subregions were linked to the development of CLBP. Methods: A total of 45 patients with CLBP and 45 healthy controls (HCs) were included in this study. All subjects were asked to complete a three-dimensional T1-weighted magnetic resonance imaging (3D-T1 MRI) scan. FreeSurfer 7.3.2 was applied to preprocess the structural MRI images and segment the amygdala into nine subregions. Afterwards, comparisons were made between the two groups in terms of the volumes of the amygdala subregions. Correlation analysis is utilized to examine the relationship between the amygdala subregion and the scale scores, as well as the pain duration in patients with CLBP. Additionally, logistic regression was used to explore the risk of the amygdala and its subregions for CLBP. Results: In comparison to HCs, patients with CLBP exhibited a significant enlargement of the left central nucleus (Ce) and left cortical nucleus (Co). Furthermore, the increased volume of the left Ce was associated with a higher risk of CLBP. Conclusion: Our study suggests that the left Ce and left Co may be involved in the pathophysiological processes of CLBP. Moreover, the volume of the left Ce may be a biomarker for detecting the risk of CLBP.
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Understanding the relative role of dispersal dynamics and niche constraints is not only a core task in community ecology, but also becomes an important prerequisite for bioassessment. Despite the recent progress in our knowledge of community assembly in space and time, patterns and processes underlying biotic communities in alpine glacierized catchments remain mostly ignored. To fill this knowledge gap, we combined the recently proposed dispersal-niche continuum index (DNCI) with traditional constrained ordinations and idealized patterns of species distributions to unravel community assembly mechanisms of different key groups of primary producers and consumers (i.e., phytoplankton, epiphytic algae, zooplankton, macroinvertebrates, and fishes) in rivers in the Qinghai-Tibet Plateau, the World's Third Pole. We tested whether organismal groups with contrasting body sizes differed in their assembly processes, and discussed their applicability in bioassessment in alpine zones. We found that community structure of alpine river biotas was always predominantly explained in terms of dispersal dynamics and historical biogeography. These patterns are most likely the result of differences in species-specific functional attributes, the stochastic colonization-extinction dynamics driven by multi-year glacier disturbances and the repeated hydrodynamic separation among alpine catchments after the rising of the Qilian mountains. Additionally, we found that the strength of dispersal dynamics and niche constraints was partially mediated by organismal body sizes, with dispersal processes being more influential for microscopic primary producers. Finding that zooplankton and macroinvertebrate communities followed clumped species replacement structures (i.e., Clementsian gradients) supports the notion that environmental filtering also contributes to the structure of high-altitude animal communities in glacierized catchments. In terms of the applied fields, we argue that freshwater bioassessment in glacierized catchments can benefit from incorporating the metacommunity perspective and applying novel approaches to (i) detect the optimal spatial scale for species sorting and (ii) identify and eliminate the species that are sensitive to dispersal-related processes.
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Rios , Animais , Tibet , Zooplâncton/fisiologia , Zooplâncton/classificação , Invertebrados/fisiologia , Camada de Gelo , Peixes/fisiologia , Ecossistema , Organismos Aquáticos , Biota , Fitoplâncton/fisiologia , Biodiversidade , Distribuição AnimalRESUMO
Protists, a highly diverse group of microscopic eukaryotic organisms distinct from fungi, animals and plants, exert crucial roles within the earth's biosphere. However, the genomes of only a small fraction of known protist species have been published and made publicly accessible. To address this constraint, the Protist 10 000 Genomes Project (P10K) was initiated, implementing a specialized pipeline for single-cell genome/transcriptome assembly, decontamination and annotation of protists. The resultant P10K database (https://ngdc.cncb.ac.cn/p10k/) serves as a comprehensive platform, collating and disseminating genome sequences and annotations from diverse protist groups. Currently, the P10K database has incorporated 2959 genomes and transcriptomes, including 1101 newly sequenced datasets by P10K and 1858 publicly available datasets. Notably, it covers 45% of the protist orders, with a significant representation (53% coverage) of ciliates, featuring nearly a thousand genomes/transcriptomes. Intriguingly, analysis of the unique codon table usage among ciliates has revealed differences compared to the NCBI taxonomy system, suggesting a need to revise the codon tables used for these species. Collectively, the P10K database serves as a valuable repository of genetic resources for protist research and aims to expand its collection by incorporating more sequenced data and advanced analysis tools to benefit protist studies worldwide.
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Bases de Dados Genéticas , Eucariotos , Fungos , Genoma , Animais , Códon , Eucariotos/genética , Fungos/genética , Plantas/genéticaRESUMO
The aim of this study is to improve the utilization of phosphorus (P) in soil, and to study the effects of phosphate-solubilizing bacteria (PSB) on P fractions and bacterial communities. In this experiment, we reduced the amount of P fertilizer by 30 % and 40 % respectively to studied the effects of combined application of bacterial fertilizers on soil microbial community and phosphate transformation process under different fertilization rates. The results showed that the application of PSB affected the transformation process of different P fractions. PSB had the most significant impact on organic phosphorus (p < 0.05). Correlation analysis showed that the abundance of bacteria was significantly correlated to the P fractions, indicating that the application of PSB had affected the bacterial community structure. In addition, Structural Equation Model (SEM) analysis showed that there was a causal relationship between the various visual variables. SEM confirmed the response relationship between bacterial communities and P components. Based on these results, we concluded that the application of PSB increased the sensitivity of P components, especially Olsen-P and MBP, to soil microorganisms. The application of PSB is an effective method to improve P utilization.
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Microbial communities are essential components of aquatic ecosystems and are widely employed for the detection, protection, and restoration of water ecosystems. The polyurethane foam unit (PFU) method, an effective and widely used environmental monitoring technique, has been improved with the eDNA-PFU method, offering efficiency, rapidity, and standardization advantages. This research aimed to explore the colonization process of microbial communities within PFUs using eDNA-PFU technology. To achieve this, we conducted ten-day monitoring and sequencing of microbial communities within PFUs in a stable and controlled artificial aquatic ecosystem, comparing them with water environmental samples (eDNA samples). Results showed 1065 genera in eDNA-PFU and 1059 in eDNA, with eDNA-PFU detecting 99.95% of eDNA-identified species. Additionally, the diversity indices of bacteria and eukaryotes in both methods showed similar trends over time in the colonization process; however, relative abundance differed. We further analyzed the colonization dynamics of microbes in eDNA-PFU and identified four clusters with varying colonization speeds. Notably, we found differences in colonization rates between bacteria and eukaryotes. Furthermore, the Molecular Ecological Networks (MEN) showed that the network in eDNA-PFU was more modular, forming a unique microbial community differentiated from the aquatic environment. In conclusion, this study, using eDNA-PFU, comprehensively explored microbial colonization and interrelationships in a controlled mesocosm system, providing foundational data and reference standards for its application in aquatic ecosystem monitoring and beyond.
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BACKGROUND: Food systems instantiate the complex interdependencies across humans, physical environments, and other organisms. Applying One Health approaches for agri-food system transformation, which adopts integrated and unifying approaches to optimize the overall health of humans, animals, plants, and environments, is crucial to enhance the sustainability of food systems. This study develops a potential assessment tool, named the global One Health index-Food Security (GOHI-FS), aiming to evaluate food security performance across countries/territories from One Health perspective and identify relevant gaps that need to be improved for sustainable food systems. METHODS: We comprehensively reviewed existing frameworks and elements of food security. The indicator framework of GOHI-FS was conceptualized following the structure-process-outcome model and confirmed by expert advisory. Publicly available data in 2020 was collected for each indicator. The weighting strategy was determined by the Fuzzy Analytical Hierarchy Process. The data for each indicator was normalized and aggregated by weighted arithmetic mean. Linear regressions were performed to evaluate the associations of GOHI-FS with health and social-economic indicators. RESULTS: The GOHI-FS includes 5 first-level indicators, 19 second-level indicators and 45 third-level indicators. There were 146 countries/territories enrolled for evaluation. The highest average score of first-level indicators was Nutrition (69.8) and the lowest was Government Support and Response (31.3). There was regional heterogeneity of GOHI-FS scores. Higher median scores with interquartile range (IQR) were shown in North America (median: 76.1, IQR: 75.5-76.7), followed by Europe and Central Asia (median: 66.9, IQR: 60.1-74.3), East Asia and the Pacific (median: 60.6, IQR: 55.5-68.7), Latin America and the Caribbean (median: 60.2, IQR: 57.8-65.0), Middle East and North Africa (median: 56.6, IQR: 52.0-62.8), South Asia (median: 51.1, IQR: 46.7-53.8), and sub-Saharan Africa (median: 41.4, IQR: 37.2-46.5). We also found significant associations between GOHI-FS and GDP per capita, socio-demographic index, health expenditure and life expectancy. CONCLUSIONS: GOHI-FS is a potential assessment tool to understand the gaps in food security across countries/territories under the One Health concept. The pilot findings suggest notable gaps for sub-Saharan Africa in numerous aspects. Broad actions are needed globally to promote government support and response for food security.
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Saúde Única , Animais , Humanos , Ásia Meridional , Meio Ambiente , Europa (Continente) , GovernoRESUMO
Ciliates are a large group of ubiquitous and highly diverse single-celled eukaryotes that play an essential role in the functioning of microbial food webs. However, their genomic diversity is far from clear due to the need to develop cultivation methods for most species, so most research is based on wild organisms that almost invariably contain contaminants. Here we establish an integrated Genome Decontamination Pipeline (iGDP) that combines homology search, telomere reads-assisted and clustering approaches to filter contaminated ciliate genome assemblies from wild specimens. We benchmarked the performance of iGDP using genomic data from a contaminated ciliate culture and the results showed that iGDP could recall 91.9% of the target sequences with 96.9% precision. We also used a synthetic dataset to offer guidelines for the application of iGDP in the removal of various groups of contaminants. Compared with several popular metagenome binning tools, iGDP could show better performance. To further validate the effectiveness of iGDP on real-world data, we applied it to decontaminate genome assemblies of three wild ciliate specimens and obtained their genomes with high quality comparable to that of previously well-studied model ciliate genomes. It is anticipated that the newly generated genomes and the established iGDP method will be valuable community resources for detailed studies on ciliate biodiversity, phylogeny, ecology and evolution. The pipeline (https://github.com/GWang2022/iGDP) can be implemented automatically to reduce manual filtering and classification and may be further developed to apply to other microeukaryotes.
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Descontaminação , Genômica , Metagenoma , Filogenia , EucariotosRESUMO
Limited data are available on the prevalence of prescription opioid use among patients with cardiac conditions who were exposed to increased risks of cardiac events including myocardial failure and cardiac arrest. According to the U.S. National Health Interview Survey, we evaluated the prevalence of opioid use in patients with cardiac conditions who reported prescription opioid use in the past 12 months and 3 months in 2019 and 2020, respectively, and further estimated the prevalence of opioid use for acute pain or chronic pain. We also analyzed the stratified prevalence by demographical characteristics. Our results showed that there was no statistically significant change in the prevalence of opioid use in the past 12 months (26.5% in 2019 vs. 25.7% in 2020) or the past 3 months (66.6% in 2019 vs. 62.5% in 2020) before and during the COVID-19 pandemic. However, there was a significant decline in the prevalence of opioid use for acute pain, from 64.2% (95% confidence interval [CI] 57.6% to 70.3%) in 2019 to 49.6% (95% CI 40.1% to 59.0%) in 2020 (P = 0.012), particularly in the subgroups of men, non-Hispanic white people, adults with education below high school, those with an income-to-poverty ratio ranging from 1.0 to 1.9, and those covered with health insurance. Our findings suggest that monitoring opioid use in the era of living with COVID-19 is important, which will help inform healthcare providers to develop care strategies to reduce health loss for vulnerable individuals.
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Dor Aguda , COVID-19 , Cardiopatias , Transtornos Relacionados ao Uso de Opioides , Masculino , Humanos , Adulto , Analgésicos Opioides/uso terapêutico , Dor Aguda/induzido quimicamente , Dor Aguda/tratamento farmacológico , Dor Aguda/epidemiologia , Prevalência , Pandemias , COVID-19/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Cardiopatias/epidemiologiaRESUMO
The giant single-celled eukaryote, Spirostomum, exhibits one of the fastest movements in the biological world. This ultrafast contraction is dependent on Ca2+ rather than ATP and therefore differs to the actin-myosin system in muscle. We obtained the high-quality genome of Spirostomum minus from which we identified the key molecular components of its contractile apparatus, including two major Ca2+ binding proteins (Spasmin 1 and 2) and two giant proteins (GSBP1 and GSBP2), which act as the backbone and allow for the binding of hundreds of spasmins. The evidence suggests that the GSBP-spasmin protein complex is the functional unit of the mesh-like contractile fibrillar system, which, coupled with various other subcellular structures, provides the mechanism for repetitive ultrafast cell contraction and extension. These findings improve our understanding of the Ca2+-dependent ultrafast movement and provide a blueprint for future biomimicry, design, and construction of this kind of micromachine.
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Actinas , Cilióforos , Miosinas , Contração Muscular/fisiologiaRESUMO
BACKGROUND: More effective targeted therapy and new combination regimens are needed for Acute myeloid leukemia (AML), owing to the unsatisfactory long-term prognosis of the disease. Here, we investigated the synergistic effect and the mechanism of a histone deacetylase inhibitor, Chidamide in combination with Cladribine, a purine nucleoside antimetabolite analog in the disease. METHODS: Cell counting kit-8 assays and Chou-Talalay's combination index were used to examine the synergistic effect of Chidamide and Cladribine on AML cell lines (U937, THP-1, and MV4-11) and primary AML cells. PI and Annexin-V/PI assays were used to detect the cell cycle effect and apoptosis effect, respectively. Global transcriptome analysis, RT-qPCR, c-MYC Knockdown, western blotting, co-immunoprecipitation, and chromatin immunoprecipitation assays were employed to explore the molecule mechanisms. RESULTS: The combination of Chidamide with Cladribine showed a significant increase in cell proliferation arrest, the G0/G1 phase arrest, and apoptosis compared to the single drug control in AML cell lines along with upregulated p21Waf1/Cip1 expression and downregulated CDK2/Cyclin E2 complex, and elevated cleaved caspase-9, caspase-3, and PARP. The combination significantly suppresses the c-MYC expression in AML cells, and c-MYC knockdown significantly increased the sensitivity of U937 cells to the combination compared to single drug control. Moreover, we observed HDAC2 interacts with c-Myc in AML cells, and we further identified that c-Myc binds to the promoter region of RCC1 that also could be suppressed by the combination through c-Myc-dependent. Consistently, a positive correlation of RCC1 with c-MYC was observed in the AML patient cohort. Also, RCC1 and HDAC2 high expression are associated with poor survival in AML patients. Finally, we also observed the combination significantly suppresses cell growth and induces the apoptosis of primary cells in AML patients with AML1-ETO fusion, c-KIT mutation, MLL-AF6 fusion, FLT3-ITD mutation, and in a CMML-BP patient with complex karyotype. CONCLUSIONS: Our results demonstrated the synergistic effect of Chidamide with Cladribine on cell growth arrest, cell cycle arrest, and apoptosis in AML and primary cells with genetic defects by targeting HDAC2/c-Myc/RCC1 signaling in AML. Our data provide experimental evidence for the undergoing clinical trial (Clinical Trial ID: NCT05330364) of Chidamide plus Cladribine as a new potential regimen in AML.
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Cu/Zn superoxide dismutase 1 (SOD1) has a high propensity to misfold and form abnormal aggregates when it is subjected to oxidative stress or carries mutations associated with amyotrophic lateral sclerosis. However, the transition from functional soluble SOD1 protein to aggregated SOD1 protein is not completely clear. Here, we propose that liquid-liquid phase separation (LLPS) represents a biophysical process that converts soluble SOD1 into aggregated SOD1. We determined that SOD1 undergoes LLPS in vitro and cells under oxidative stress. Abnormal oxidation of SOD1 induces maturation of droplets formed by LLPS, eventually leading to protein aggregation and fibrosis, and involves residues Cys111 and Trp32. Additionally, we found that pathological mutations in SOD1 associated with ALS alter the morphology and material state of the droplets and promote the transformation of SOD1 to solid-like oligomers which are toxic to nerve cells. Furthermore, the fibrous aggregates formed by both pathways have a concentration-dependent toxicity effect on nerve cells. Thus, these combined results strongly indicate that LLPS may play a major role in pathological SOD1 aggregation, contributing to pathogenesis in ALS.
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Esclerose Lateral Amiotrófica , Superóxido Dismutase-1 , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Mutação , Dobramento de Proteína , Superóxido Dismutase-1/química , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Transição de FaseRESUMO
Soil contamination by polycyclic aromatic hydrocarbons (PAHs) is an increasing problem in many countries, impacting the ecological environment's sustainable development. This study investigated the effects of fluoranthene (Fla) on soil aggregate stability. A possible mechanism for the interaction of Fla with soil aggregates was proposed by characterizing the aggregate structure. The results showed that Fla significantly improved the aggregate stability in the concentration range of 0-30.0 mg/kg. The content of macro-aggregates reached the maximum value at 10 mg/kg of Fla, which increased by 24.25% compared with the control group, while the content of large-aggregates decreased by 12.11%. Meanwhile, the mean weight diameter (MWD) and geometric mean diameter (GMD) increased by 56.63% and 37.66%, respectively. However, the macro-aggregates zeta potential value and specific surface area (SSA) decreased by 12.68% and 13.61%, respectively. The cracks of macro-aggregates were also significantly reduced. In addition, Fla-based free radicals were detected on the macro-aggregates. The absorption peak of the C-O group significantly increased, indicating that Fla may be covalently bound to the aggregates by aromatic ether bonds, which is a possible mechanism for the interaction between Fla and aggregates. This study provides theoretical support for revealing the effects of PAHs on soil.
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Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo/química , Fluorenos , Poluentes do Solo/análiseRESUMO
The Peritrichia is a speciose and morphologically distinctive assemblage of ciliated protists that was first observed by Antonie van Leeuwenhoek over 340 years ago. In the last two decades, the phylogenetic relationships of this group have been increasingly debated as morphological and molecular analyses have generated contrasting conclusions, mainly owing to limited sampling. In the present study, we performed expanded phylogenetic analyses of 152 sessilid peritrichs collected from 14 different provinces of China and 141 SSU rDNA peritrich sequences from GenBank. The results of the analyses revealed new divergent relationships between and within major clades that challenge the morphological classification of this group including, (1) the recovery of four major phylogenetically divergent clades in the monophyletic order Sessilida, (2) aboral structures such as the stalk and spasmoneme were evolutionary labile, (3) the stalk or/and spasmoneme was lost in each divergent clade indicating that parallel evolution occurred in sessilid peritrichs and (4) the life cycle and habit drive the diversity of aboral structures as well as diversification and evolution in peritrichs.
Assuntos
Cilióforos , Oligoimenóforos , Filogenia , DNA de Protozoário/genética , DNA Ribossômico/genéticaRESUMO
INTRODUCTION: Maternal vitamin D deficiency (VDD) is associated with intrauterine growth restriction (IUGR), but the exact mechanism remains unclear. Here we explored the mechanism through which VDD induced IUGR. METHODS: Female SD rats were fed a control normal diet (VD > 800 IU/Kg) or VDD diet (VD: 0 IU/Kg) for 8 weeks. Then, females were mated with 12-week-old male SD rats, and fetal and placental tissue were collected on the gestational day 13 (GD13) or 18 (GD18) to analyze the effects of VDD on pregnancy outcome and embryonic development. In vitro, the VDR gene of HTR-8/SVneo cells was knocked down to establish VDD model. Then, HTR-8/SVneo cells were treated with the MST1/2 inhibitor XMU-MP-1 or 0.1 µM/L calcitriol for 24 h (h). The mechanism of Hippo-YAP signaling pathway in VDD-induced placental dysplasia was further investigated by western blot, invasion assay, wound healing assay and Hoechst/PI staining. RESULTS: The IUGR of the pregnant rats in the VDD group was significant, the placental structure and function were damaged, and there was an obvious inflammatory response, accompanied by a significant increase in the level of the transcription co-activator YAP phosphorylation. In vitro, VDD significantly inhibited the migratory and invasive abilities of HTR-8/SVneo cells, accompanied by decreased EMT capacity and increased apoptosis. When intervening with XMU-MP-1 in advance, we found that the effects of VDD were neutralized by Hippo-YAP signaling blocker. DISCUSSION: Maternal VDD causes placental dysplasia and IUGR, and these abnormal changes may be associated with the activation of Hippo-YAP signaling pathway.