RESUMO
Environmental plastic fragments have been verified as byproducts of large plastic and its secondary pollutants including micro and nanoplastics. There are few quantitative studies available, but their contours have values for the weathering mechanisms. We used geometric descriptors, fractal dimensions, and Fourier descriptors to characterize field and artificial polyethylene and polypropylene samples as a means of investigating the contour characteristics. It provides a methodological framework for contour classification. Unsupervised classification was performed using self-organizing neural networks with size-invariance parameters. We revealed the isometric phenomenon of plastic fragments during fragmentation, i.e., that the degree of contour rounding and complexity increase and decrease, respectively, with decreasing fragment size. With an average error rate of 8.9 %, we can distinguish artificial samples from field samples. It was also validated by the difference in Carbonyl Index between groups. We propose a two-stage process for plastic fragmentation and give three types of contour features which were key in the description of fragmented contours, i.e., size, complexity, and rounding. Our work will improve the accuracy of characterizations regarding the weathering and fragmentation processes of certain kinds of plastic fragments. The contour parameters also have the potential to be applied in more realistic scenarios and varied polymers.
RESUMO
Herein, we report a synergistic photoredox/palladium catalytic system for the efficient enantioconvergent synthesis of axially chiral esters from racemic heterobiaryl (pseudo)halides (bromides/triflates) with CO2 and alkyl bromides under mild conditions. A wide range of axially chiral esters were obtained in good to high yields with excellent enantioselectivities. Detailed mechanistic studies unveiled that the ratio of photocatalyst and palladium catalyst exhibited significant impact on the chemo- and enantioselectivities of the reaction. Kinetic studies and control experiments supported the proposed mechanism involving cascade asymmetric carboxylation followed by SN2 substitution. The achievement of high enantioselectivity relies not only on the choice of synergistic metallaphotoredox catalysts but also on the utilization of alkyl bromides, which trap the generated chiral carboxylic anions in situ, thus preventing their immediate racemization.
RESUMO
Lightweight porous ceramics with a unique combination of superior mechanical strength and damage tolerance are in significant demand in many fields such as energy absorption, aerospace vehicles, and chemical engineering; however, it is difficult to meet these mechanical requirements with conventional porous ceramics. Here, we report a graded structure design strategy to fabricate porous ceramic nanowire networks that simultaneously possess excellent mechanical strength and energy absorption capacity. Our optimized graded nanowire networks show a compressive strength of up to 35.6 MPa at a low density of 540 mg·cm-3, giving rise to a high specific compressive strength of 65.7 kN·m·kg-1 and a high energy absorption capacity of 17.1 kJ·kg-1, owing to a homogeneous distribution of stress upon loading. These values are top performance compared to other porous ceramics, giving our materials significant potential in various engineering fields.
RESUMO
Na5YSi4O12 (NYSO) is demonstrated as a promising electrolyte with high ionic conductivity and low activation energy for practical use in solid Na-ion batteries. Solid-state NMR was employed to identify the six types of coordination of Na+ ions and migration pathway, which is vital to master working mechanism and enhance performance. The assignment of each sodium site is clearly determined from high-quality 23Na NMR spectra by the aid of Density Functional Theory calculation. Well-resolved 23Na exchangespectroscopy and electrochemical tracer exchange spectra provide the first experimental evidence to show the existence of ionic exchange between sodium at Na5 and Na6 sites, revealing that Na transport route is possibly along three-dimensional chain of open channel-Na4-open channel. Variable-temperature NMR relaxometry is developed to evaluate Na jump rates and self-diffusion coefficient to probe the sodium-ion dynamics in NYSO. Furthermore, NYSO works well as a dual ion conductor in Na and Li metal batteries with Na3V2(PO4)3 and LiFePO4 as cathodes, respectively.
RESUMO
BACKGROUND: Gemmatimonadota bacteria are widely distributed in nature, but their metabolic potential and ecological roles in marine environments are poorly understood. RESULTS: Here, we obtained 495 metagenome-assembled genomes (MAGs), and associated viruses, from coastal to deep-sea sediments around the world. We used this expanded genomic catalog to compare the protein composition and update the phylogeny of these bacteria. The marine Gemmatimonadota are phylogenetically different from those previously reported from terrestrial environments. Functional analyses of these genomes revealed these marine genotypes are capable of degradation of complex organic carbon, denitrification, sulfate reduction, and oxidizing sulfide and sulfite. Interestingly, there is widespread genetic potential for secondary metabolite biosynthesis across Gemmatimonadota, which may represent an unexplored source of novel natural products. Furthermore, viruses associated with Gemmatimonadota have the potential to "hijack" and manipulate host metabolism, including the assembly of the lipopolysaccharide in their hosts. CONCLUSIONS: This expanded genomic diversity advances our understanding of these globally distributed bacteria across a variety of ecosystems and reveals genetic distinctions between those in terrestrial and marine communities. Video Abstract.
Assuntos
Metagenoma , Filogenia , Genoma Bacteriano , Sedimentos Geológicos/microbiologia , Genômica , Água do Mar/microbiologia , Organismos Aquáticos/genética , Metabolismo Secundário , MetagenômicaRESUMO
Ultrasmall metallic nanoclusters (NCs) protected by surface ligands represent the most promising catalytic materials; yet understanding the structure and catalytic activity of these NCs remains a challenge due to dynamic evolution of their active sites under reaction conditions. Herein, we employed a single-nanoparticle collision electrochemistry method for real-time monitoring of the dynamic electrocatalytic activity of a single fully ligand-protected Au25(PPh3)10(SC2H4Ph)5Cl22+ nanocluster (Au252+ NC) at a cavity carbon nanoelectrode toward the oxygen reduction reaction (ORR). Our experimental results and computational simulations indicated that the reversible depassivation and passivation of ligands on the surface of the Au252+ NC, combined with the dynamic conformation evolution of the Au259+ core, led to a characteristic current signal that involves "ON-OFF" switches and "ON" fluctuations during the ORR process of a single Au252+ NC. Our findings reinvent the new perception and comprehension of the structure-activity correlation of NCs at the atomic level.
RESUMO
Regulator of G-protein signaling (RGS) proteins exhibit GTPase-accelerating protein activities to govern G-protein function. In the rice blast fungus Magnaporthe oryzae, there is a family of at least eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), each exhibiting distinct or shared functions in the growth, appressorium formation, and pathogenicity. MoRgs3 recently emerged as one of the crucial regulators that senses intracellular oxidation during appressorium formation. To explore this unique regulatory mechanism of MoRgs3, we identified the nucleoside diphosphate kinase MoNdk1 that interacts with MoRgs3. MoNdk1 phosphorylates MoRgs3 under induced intracellular reactive oxygen species levels, and MoRgs3 phosphorylation is required for appressorium formation and pathogenicity. In addition, we showed that MoRgs3 phosphorylation determines its interaction with MoCrn1, a coronin-like actin-binding protein homolog, which regulates MoRgs3 internalization. Finally, we provided evidence demonstrating that MoRgs3 functions in MoMagA-mediated cAMP signaling to regulate normal appressorium induction. By revealing a novel signal perception mechanism, our studies highlighted the complexity of regulation during the appressorium function and pathogenicity of the blast fungus. IMPORTANCE: We report that MoRgs3 becomes phosphorylated in an oxidative intracellular environment during the appressorium formation stage. We found that this phosphorylation is carried out by MoNdk1, a nucleoside diphosphate kinase. In addition, this phosphorylation leads to a higher binding affinity between MoRgs3 and MoCrn1, a coronin-like actin-binding protein that was implicated in the endocytic transport of several other RGS proteins of Magnaporthe oryzae. We further found that the internalization of MoRgs3 is indispensable for its GTPase-activating protein function toward the Gα subunit MoMagA. Importantly, we characterized how such cellular regulatory events coincide with cAMP signaling-regulated appressorium formation and pathogenicity in the blast fungus. Our studies uncovered a novel intracellular reactive oxygen species signal-transducing mechanism in a model pathogenic fungus with important basic and applied implications.
Assuntos
AMP Cíclico , Proteínas Fúngicas , Doenças das Plantas , Espécies Reativas de Oxigênio , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , AMP Cíclico/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Fosforilação , Doenças das Plantas/microbiologia , Oryza/microbiologia , Proteínas RGS/metabolismo , Proteínas RGS/genética , Regulação Fúngica da Expressão Gênica , Núcleosídeo-Difosfato Quinase/metabolismo , Núcleosídeo-Difosfato Quinase/genética , Ascomicetos/genética , Ascomicetos/metabolismo , Ascomicetos/patogenicidade , VirulênciaRESUMO
The microbial communities of marine seep sediments contain unexplored physiological and phylogenetic diversity. Here, we examined 30 bacterial metagenome-assembled genomes (MAGs) from cold seeps in the South China Sea, the Indian Ocean, the Scotian Basin, and the Gulf of Mexico, as well as from deep-sea hydrothermal sediments in the Guaymas Basin, Gulf of California. Phylogenetic analyses of these MAGs indicate that they form a distinct phylum-level bacterial lineage, which we propose as a new phylum, Candidatus Effluviviacota, in reference to its preferential occurrence at diverse seep areas. Based on tightly clustered high-quality MAGs, we propose two new genus-level candidatus taxa, Candidatus Effluvivivax and Candidatus Effluvibates. Genomic content analyses indicate that Candidatus Effluviviacota are chemoheterotrophs that harbor the Embden-Meyerhof-Parnas glycolysis pathway. They gain energy by fermenting organic substrates. Additionally, they display potential capabilities for the degradation of cellulose, hemicellulose, starch, xylan, and various peptides. Extracellular anaerobic respiration appears to rely on metals as electron acceptors, with electron transfer primarily mediated by multiheme cytochromes and by a flavin-based extracellular electron transfer (EET) mechanism that involves NADH-quinone oxidoreductase-demethylmenaquinone-synthesizing enzymes, uncharacterized membrane proteins, and flavin-binding proteins, also known as the NUO-DMK-EET-FMN complex. The heterogeneity within the Ca. Effluviviacota phylum suggests varying roles in energy metabolism among different genera. While NUO-DMK-EET-FMN electron transfer has been reported predominantly in Gram-positive bacteria, it is now identified in Ca. Effluviviacota as well. We detected the presence of genes associated with bacterial microcompartments in Ca. Effluviviacota, which can promote specific metabolic processes and protect the cytosol from toxic intermediates. IMPORTANCE: The newly discovered bacterial phylum Candidatus Effluviviacota is widespread across diverse seepage ecosystems, marine environments, and freshwater environments, with a notable preference for cold seeps. While maintaining an average abundance of approximately 1% in the global gene catalog of cold seep habitats, it has not hitherto been characterized. The metabolic versatility of Ca. Effluviviacota in anaerobic carbon, hydrogen, and metal cycling aligns with its prevalence in anoxic niches, with a preference for cold seep environments. Variations in metabolic potential between Ca. Effluvivivax and Ca. Effluvibates may contribute to shaping their respective habitat distributions.
Assuntos
Bactérias , Genoma Bacteriano , Sedimentos Geológicos , Metagenoma , Microbiota , Filogenia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Microbiota/genética , Sedimentos Geológicos/microbiologia , Água do Mar/microbiologia , MetagenômicaRESUMO
OBJECTIVE: To elucidate the chemical profile of Xanthocerais lignum's extracts of different polarities and their impact on rheumatoid arthritis (RA), we identified anti-RA markers and predicted their action mechanisms. METHODS: A collagen-induced arthritis rat model was established, and UPLC-Q-Exactive Orbitrap MS technology was employed to analyze and identify the chemical constituents within the alcohol extract of Xanthocerais lignum and its various extraction fractions, as well as their translocation into the bloodstream. Serum spectrum-effect correlation analysis was utilized to elucidate the pharmacodynamic material basis of Xanthocerais lignum against RA and to screen for Q-Markers. Finally, the potential anti-RA mechanisms of the Q-Markers were predicted through compound-target interaction data and validated using molecular docking techniques. RESULTS: We identified 71 compounds, with flavan-3-ols and flavanones as key components. Of these, 36 were detected in the bloodstream, including 17 original and 19 metabolized forms. Proanthocyanidin A2, dihydroquercetin, catechin, and epicatechin (plus glucuronides) showed potential anti-RA activity. These compounds, acting as Q-Markers, may modulate ERK, NF-κB, HIF-1α, and VEGF in the HIF-1 pathway. CONCLUSIONS: This research clarifies Xanthocerais lignum's pharmacodynamic material basis against RA, identifies 4 Q-Markers, and offers insights into their mechanisms, aiding quality assessment and lead compound development for RA treatment.
Assuntos
Artrite Reumatoide , Biomarcadores , Simulação de Acoplamento Molecular , Extratos Vegetais , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/sangue , Artrite Reumatoide/metabolismo , Ratos , Biomarcadores/sangue , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/sangue , Artrite Experimental/metabolismo , Masculino , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Antirreumáticos/farmacologia , Antirreumáticos/química , Antirreumáticos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The urgent need for field detection of uranium in seawater is 2-fold: to provide prompt guidance for uranium extraction and to prevent human exposure to nuclear radiation. However, current methods for this purpose are largely hindered by bulky instrumentation, high costs of developed materials, and severe matrix interferences, which limit their further application in the field. Herein, we demonstrated a portable and label-free strategy for the field detection of uranyl in seawater based on the efficient photocleavage of DNA. Further experiments confirmed the generation of ultraviolet (UV) light-induced reactive oxygen species (ROS), such as O2â¢- and â¢OH, which fragmented oligomeric DNA in the presence of uranyl and UV light. Detailed studies showed that DNA significantly enhances uranyl absorption in the UV-visible region, leading to the generation of more ROS. A fluorescence system for the selective detection of uranyl in seawater was established by immobilizing two complementary oligonucleotides with the fluorescent dye SYBR Green I. The strategy of UV-induced photocleavage offers high selectivity, excellent interference immunity, and high sensitivity for uranyl, with a detection limit of 6.8 nM. Additionally, the fluorescence can be visually detected using a 3D-printed miniaturized device integrated with a smartphone. This method has been successfully applied to the on-site detection of uranyl in seawater in 18 Chinese coastal cities and along the coast of Hainan Island within 3 min for a single sample. The sample testing and field analysis results indicate that this strategy has promising potential for real-time monitoring of trace uranyl in China's coastal waters. It is expected to be utilized for the rapid assessment of nuclear contamination and nuclear engineering construction.
Assuntos
DNA , Água do Mar , Raios Ultravioleta , Urânio , Água do Mar/análise , Água do Mar/química , DNA/análise , China , Urânio/análise , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/análise , Limite de Detecção , Processos Fotoquímicos , Diaminas , Benzotiazóis/química , Compostos Orgânicos/análise , Compostos Orgânicos/química , QuinolinasRESUMO
Introduction: We aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between. Methods: Using summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites. Results: We identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%. Discussion: Our study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.
Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Tireoidite Autoimune , Humanos , Tireoidite Autoimune/genética , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/metabolismo , Polimorfismo de Nucleotídeo Único , Predisposição Genética para DoençaRESUMO
Exosomes are 30-150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs (mRNAs, microRNAs/miRNAs, long non-coding RNAs/lncRNAs), and DNA of their parent cell. In pathological conditions, the composition of exosomes is altered, making exosomes a potential source of biomarkers for disease diagnosis. Exosomes can cross the blood-brain barrier (BBB), which is an advantage for using exosomes in the diagnosis of central nervous system (CNS) diseases. Neuropsychiatric diseases belong to the CNS diseases, and many potential diagnostic markers have been identified for neuropsychiatric diseases. Here, we review the potential diagnostic markers of exosomes in neuropsychiatric diseases and discuss the potential application of exosomal biomarkers in the early and accurate diagnosis of these diseases. Additionally, we outline the limitations and future directions of exosomes in the diagnosis of neuropsychiatric diseases.
RESUMO
Background: Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear. Objective: To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators. Methods: We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression. Results: Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency. Conclusions: Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.
RESUMO
PURPOSE: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. METHODS: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. RESULTS: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. CONCLUSIONS: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.
Assuntos
Líquido da Lavagem Broncoalveolar , Mycobacterium tuberculosis , Sequenciamento por Nanoporos , Tuberculose Pulmonar , Humanos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , China , Sequenciamento por Nanoporos/métodos , Masculino , Feminino , Líquido da Lavagem Broncoalveolar/microbiologia , Adulto , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Escarro/microbiologia , Idoso , Adulto JovemRESUMO
Rivers have been recognized as the primary conveyors of microplastics to the oceans, and seaward transport flux of riverine microplastics is an issue of global attention. However, there is a significant discrepancy in how microplastic concentration is expressed in field occurrence investigations (number concentration) and in mass flux (mass concentration). Of urgent need is to establish efficient conversion models to correlate these two important paradigms. Here, we first established an abundant environmental microplastic dataset and then employed a deep neural residual network (ResNet50) to successfully separate microplastics into fiber, fragment, and pellet shapes with 92.67% accuracy. We also used the circularity (C) parameter to represent the surface shape alteration of pellet-shaped microplastics, which always have a more uneven surface than other shapes. Furthermore, we added thickness information to two-dimensional images, which has been ignored by most prior research because labor-intensive processes were required. Eventually, a set of accurate models for microplastic mass conversion was developed, with absolute estimation errors of 7.1, 3.1, 0.2, and 0.9% for pellet (0.50 ≤ C < 0.75), pellet (0.75 ≤ C ≤ 1.00), fiber, and fragment microplastics, respectively; environmental samples have validated that this set is significantly faster (saves â¼2 h/100 MPs) and less biased (7-fold lower estimation errors) compared to previous empirical models.
Assuntos
Monitoramento Ambiental , Microplásticos , Poluentes Químicos da Água , Rios/químicaRESUMO
Resilient ceramic aerogels with a unique combination of lightweight, good high-temperature stability, high specific area, and thermal insulation properties are known for their promising applications in various fields. However, the mechanical properties of traditional ceramic aerogels are often constrained by insufficient interlocking of the building blocks. Here, we report a strategy to largely increase the interlocking degree of the building blocks by depositing a pyrolytic carbon (PyC) coating onto Si3N4 nanowires. The results show that the mechanical performances of the Si3N4 nanowire aerogels are intricately linked to the microstructure of the PyC nodes. The compression resilience of the Si3N4@PyC nanowire aerogels increases with an increase of the interlayer cross-linking in PyC. Additionally, benefiting from the excellent high-temperature stability of PyC, the Si3N4@PyC nanowire aerogels demonstrate significantly superior in situ resilience up to 1400 °C. The integrated mechanical and high-temperature properties of the Si3N4@PyC nanowire aerogels make them highly appealing for applications in harsh conditions. The facile method of manipulating the microstructure of the nodes may offer a perspective for tailoring the mechanical properties of ceramic aerogels.
RESUMO
PGC1α, a central player in mitochondrial biology, holds a complex role in the metabolic shifts seen in cancer cells. While its dysregulation is common across major cancers, its impact varies. In some cases, downregulation promotes aerobic glycolysis and progression, whereas in others, overexpression escalates respiration and aggression. PGC1α's interactions with distinct signaling pathways and transcription factors further diversify its roles, often in a tissue-specific manner. Understanding these multifaceted functions could unlock innovative therapeutic strategies. However, challenges exist in managing the metabolic adaptability of cancer cells and refining PGC1α-targeted approaches. This review aims to collate and present the current knowledge on the expression patterns, regulators, binding partners, and roles of PGC1α in diverse cancers. We examined PGC1α's tissue-specific functions and elucidated its dual nature as both a potential tumor suppressor and an oncogenic collaborator. In cancers where PGC1α is tumor-suppressive, reinstating its levels could halt cell proliferation and invasion, and make the cells more receptive to chemotherapy. In cancers where the opposite is true, halting PGC1α's upregulation can be beneficial as it promotes oxidative phosphorylation, allows cancer cells to adapt to stress, and promotes a more aggressive cancer phenotype. Thus, to target PGC1α effectively, understanding its nuanced role in each cancer subtype is indispensable. This can pave the way for significant strides in the field of oncology.
RESUMO
The Chinese sturgeon (Acipenser sinensis) is an endangered freshwater mega-fish (IUCN-red listed) that survives in the Yangtze River Basin, but the population of which has declined significantly in response to environmental pressures generated by human activities. In order to evaluate the interaction between Chinese sturgeon and microplastics (MPs) for the first time, we examined the gut and gills of historical samples (n = 27), in conjunction with the blood and mucus of live samples (n = 10), to explore the potential pathways involved in MP uptake. We detected MPs in 62.9 % of the field fish, with no significant difference between guts (mean=0.9 items/individual) and gills (mean=0.8 items/individual). The abundance of MPs in fish from 2017 was significantly higher than that from 2015 to 2016 with regards to both gills and gut samples. The size of MPs in gills was significantly smaller than those in guts, yet both contained mostly fibers (90.2 %). No MPs were confirmed in blood, however 62.5 % of mucus samples contained MPs. The MPs in mucus indicated the possibility of MPs entering Chinese sturgeons if their skins were damaged. The body size of Chinese sturgeons affected their MPs uptake by ingestion and inhalation, as less MPs were detected in the gut and gills of smaller individuals. Combining the evidence from historical and live samples, we revealed the presence of MPs in different tissues of Chinese sturgeon and their potential relevance to exposure pathways. Our work expands the understanding of multiple exposure pathways between MPs and long-lived mega-fish, while emphasizing the potential risks of long-term exposure in the field.
Assuntos
Espécies em Perigo de Extinção , Peixes , Brânquias , Microplásticos , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/análise , Peixes/metabolismo , Brânquias/metabolismo , Brânquias/química , Monitoramento Ambiental , Exposição Ambiental , Muco , ChinaRESUMO
BACKGROUND: In radiotherapy, the delineation of the gross tumor volume (GTV) in brain metastases using computed tomography (CT) simulation localization is very important. However, despite the criticality of this process, a pronounced gap exists in the availability of tools tailored for the automatic segmentation of the GTV based on CT simulation localization images. PURPOSE: This study aims to fill this gap by devising an effective tool specifically for the automatic segmentation of the GTV using CT simulation localization images. METHODS: A dual-network generative adversarial network (GAN) architecture was developed, wherein the generator focused on refining CT images for more precise delineation, and the discriminator differentiated between real and augmented images. This architecture was coupled with the Mask R-CNN model to achieve meticulous GTV segmentation. An end-to-end training process facilitated the integration between the GAN and Mask R-CNN functionalities. Furthermore, a conditional random field (CRF) was incorporated to refine the initial masks generated by the Mask R-CNN model to ensure optimal segmentation accuracy. The performance was assessed using key metrics, namely, the Dice coefficient (DSC), intersection over union (IoU), accuracy, specificity, and sensitivity. RESULTS: The GAN+Mask R-CNN+CRF integration method in this study performs well in GTV segmentation. In particular, the model has an overall average DSC of 0.819 ± 0.102 and an IoU of 0.712 ± 0.111 in the internal validation. The overall average DSC in the external validation data is 0.726 ± 0.128 and the IoU is 0.640 ± 0.136. It demonstrates favorable generalization ability. CONCLUSION: The integration of the GAN, Mask R-CNN, and CRF optimization provides a pioneering tool for the sophisticated segmentation of the GTV in brain metastases using CT simulation localization images. The method proposed in this study can provide a robust automatic segmentation approach for brain metastases in the absence of MRI.
RESUMO
Gut microbes play a vital role in the health and disease of animals, especially in relation to pathogen infections. Chinchillas, ferrets, and marmots are commonly used as important laboratory animals for infectious disease research. Here, we studied the bacterial and fungal microbiota and discovered that chinchillas had higher alpha diversity and a higher abundance of bacteria compared to marmots and ferrets by using the metabarcoding of 16S rRNA genes and ITS2, coupled with co-occurrence network analysis. The dominant microbes varied significantly among the three animal species, particularly in the gut mycobiota. In the ferrets, the feces were dominated by yeast such as Rhodotorula and Kurtzmaniella, while in the chinchillas, we found Teunomyces and Penicillium dominating, and Acaulium, Piromyces, and Kernia in the marmots. Nevertheless, the dominant bacterial genera shared some similarities, such as Clostridium and Pseudomonas across the three animal species. However, there were significant differences observed, such as Vagococcus and Ignatzschineria in the ferrets, Acinetobacter and Bacteroides in the chinchillas, and Bacteroides and Cellvibrio in the marmots. Additionally, our differential analysis revealed significant differences in classification levels among the three different animal species, as well as variations in feeding habitats that resulted in distinct contributions from the host microbiome. Therefore, our data are valuable for monitoring and evaluating the impacts of the microbiome, as well as considering potential applications.