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Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.
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Doenças Autoimunes , Humanos , Citocinas , Epigenômica , Histona Desmetilases , Homeostase , Oxirredutases N-Desmetilantes , Histona Desmetilases com o Domínio Jumonji/genéticaRESUMO
Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-seq analysis, revealing widespread RBP presence in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also show strong preference for hotspots in the genome, particularly gene promoters, where their association is frequently linked to transcriptional output. Unsupervised clustering reveals extensive co-association between TFs and RBPs, as exemplified by YY1, a known RNA-dependent TF, and RBM25, an RBP involved in splicing regulation. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping, and transcription. We propose that various RBPs may enhance network interaction through harnessing regulatory RNAs to control transcription.
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Cromatina/metabolismo , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Transcrição Gênica/genética , Fator de Transcrição YY1/metabolismo , Sítios de Ligação , Regulação da Expressão Gênica , Genoma Humano/genética , Células Hep G2 , Humanos , Células K562 , Proteínas Nucleares , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas de Ligação a RNA/genética , RNA-Seq , Transcriptoma , Fator de Transcrição YY1/genéticaRESUMO
Chemerin is a processed protein that acts on G protein-coupled receptors (GPCRs) for its chemotactic and adipokine activities. The biologically active chemerin (chemerin 21-157) results from proteolytic cleavage of prochemerin and uses its C-terminal peptide containing the sequence YFPGQFAFS for receptor activation. Here we report a high-resolution cryo-electron microscopy (cryo-EM) structure of human chemerin receptor 1 (CMKLR1) bound to the C-terminal nonapeptide of chemokine (C9) in complex with Gi proteins. C9 inserts its C terminus into the binding pocket and is stabilized through hydrophobic interactions involving its Y1, F2, F6, and F8, as well as polar interactions between G4, S9, and several amino acids lining the binding pocket of CMKLR1. Microsecond scale molecular dynamics simulations support a balanced force distribution across the whole ligand-receptor interface that enhances thermodynamic stability of the captured binding pose of C9. The C9 interaction with CMKLR1 is drastically different from chemokine recognition by chemokine receptors, which follow a two-site two-step model. In contrast, C9 takes an "S"-shaped pose in the binding pocket of CMKLR1 much like angiotensin II in the AT1 receptor. Our mutagenesis and functional analyses confirmed the cryo-EM structure and key residues in the binding pocket for these interactions. Our findings provide a structural basis for chemerin recognition by CMKLR1 for the established chemotactic and adipokine activities.
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Adipocinas , Quimiocinas , Receptores de Quimiocinas , Humanos , Membrana Celular , Quimiocinas/metabolismo , Microscopia Crioeletrônica , Receptores de Quimiocinas/metabolismoRESUMO
The early stages of human development are increasingly acknowledged as pivotal in laying the groundwork for subsequent behavioral and cognitive development. Spatiotemporal (4D) brain functional atlases are important in elucidating the development of human brain functions. However, the scarcity of such atlases for early life stages stems from two primary challenges: (1) the significant noise in functional magnetic resonance imaging (fMRI) that complicates the generation of high-quality atlases for each age group, and (2) the rapid and complex changes in the early human brain that hinder the maintenance of temporal consistency in 4D atlases. This study tackles these challenges by integrating low-rank tensor learning with spectral embedding, thereby proposing a novel, data-driven 4D functional atlas generation framework based on spectral functional network learning (SFNL). This method utilizes low-rank tensor learning to capture common functional connectivity (FC) patterns across different ages, thus optimizing FCs for each age group to improve the temporal consistency of functional networks. Incorporating spectral embedding aids in mitigating potential noise in FC networks derived from fMRI data by reconstructing networks in the spectral space. Utilizing SFNL-generated functional networks enables the creation of consistent and highly qualified spatiotemporal functional atlases. The framework was applied to the developing Human Connectome Project (dHCP) dataset, generating the first neonatal 4D functional atlases with fine-grained temporal and spatial resolutions. Experimental evaluations focusing on functional homogeneity, reliability, and temporal consistency demonstrated the superiority of our framework compared to existing methods for constructing 4D atlases. Additionally, network analysis experiments, including individual identification, functional systems development, and local efficiency assessments, further corroborate the efficacy and robustness of the generated atlases. The 4D atlases and related codes will be made publicly accessible (https://github.com/zhaoyunxi/neonate-atlases).
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Atlas como Assunto , Conectoma , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Recém-Nascido , Conectoma/métodos , Masculino , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/crescimento & desenvolvimento , Lactente , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Rede Nervosa/crescimento & desenvolvimentoRESUMO
Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy of non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, based on personalized tumor DNA mutations, could elicit tumor specific T cell infiltration into the tumor site, exerting potent anti-tumor efficacy. Here, we evaluated the feasibility and safety of a new antitumor strategy by adding neoantigen vaccine to the regimen of bevacizumab and anti-PD-1 antibody. Firstly, 7 novel immunogenic neoantigen peptides were identified and developed for neoantigen vaccine (LLCvac), which can elicit strong antitumor immune response in vivo. Then, in orthotopic lung cancer model, LLCvac further combining with bevacizumab and anti-PD-1 antibody exerted a stronger antitumor effect, exhibiting significant decrease of tumor volume without obvious toxicity. Furthermore, tumor immune microenvironment assessment also showed that the proportion of neoantigen-specific T cells in blood could be induced dramatically by the combined therapy. And a large amount of neoantigen-specific Ki67-positive CD8+ T cells were found in tumor tissues, which infiltrated tumor tissues effectively to kill tumor cells expressing identified neoantigens. Overall, these results suggested that this combined therapy could safely induce robust antitumor efficacy, serving as an effective chemotherapy-free strategy for NSCLC treatment.
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Vacinas Anticâncer , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígenos de Neoplasias , Bevacizumab/uso terapêutico , Vacinas Anticâncer/farmacologia , Vacinas Anticâncer/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linfócitos T CD8-Positivos , Neoplasias Pulmonares/tratamento farmacológico , Microambiente TumoralRESUMO
The direct application of liquid marbles in electromagnetic wave (EMW) absorption is challenging due to their poor stability, susceptibility to gravitational collapse, and shaping difficulties. To address this issue, a novel strategy is proposed to incorporate liquid marble microstructures (NaCl/nano-SiO2) encapsulated in organic phases (Octadecane) into the rubber-matrix (SEBS) using the ultrasound-assisted emulsion blending method. The resulting NaCl/SiO2/Octadecane microstructures anchored to SEBS offer a substantial solid-liquid interface consisting of NaCl solution and SiO2. When subjected to an alternating electromagnetic (EM) field, the water molecules and polysorbate within SiO2 exhibit heightened responsiveness to the EM field, and the movement of Na+ and Cl- within these microstructures leads to their accumulation at the solid-liquid interface, creating an asymmetric ion distribution. This phenomenon facilitates enhanced interfacial polarization, thereby contributing to the material's EMW absorption properties. Notably, the latex with 16 wt% SEBS (E-3), exhibiting a surface morphology similar to human cell tissues, achieves complete absorption of X-band (fE = 4.20 GHz, RLmin = -33.87 dB). Moreover, the latex demonstrates light density (0.78 g cm-3) and environmental stability. This study not only highlights the predominant loss mechanism in rubber-based wave-absorbing materials but also provides valuable insights into the design of multifunctional wave-absorbing materials.
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Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.
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Criptococose , Cryptococcus , MicroRNAs , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Piroptose/genética , Cryptococcus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Criptococose/metabolismo , Criptococose/patologia , Fatores de Transcrição Kruppel-LikeRESUMO
In standard quantum weak measurements, preselection and postselection of quantum states are implemented in the same photon. Here we go beyond this restrictive setting and demonstrate that the preselection and postselection can be performed in two different photons, if the two photons are polarization entangled. The Pancharatnam-Berry phase metasurface is incorporated in the weak measurement system to perform weak coupling between probe wave function and spin observable. By introducing nonlocal weak measurement into the microscopy imaging system, it allows us to remotely switch different microscopy imaging modes of pure-phase objects, including bright-field, differential, and phase reconstruction. Furthermore, we demonstrate that the nonlocal weak-measurement scheme can prevent almost all environmental noise photons from detection and thus achieves a higher image contrast than the standard scheme at a low photon level. Our results provide the possibility to develop a quantum nonlocal weak-measurement microscope for label-free imaging of transparent biological samples.
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The latest advancements in nuclear medicine indicate that radioactive isotopes and associated metal chelators play crucial roles in the diagnosis and treatment of diseases. The development of metal chelators mainly relies on traditional trial-and-error methods, lacking rational guidance and design. In this study, we propose the structure-aware transformer (SAT) combined with molecular fingerprint (SATCMF), a novel graph transformer network framework that incorporates prior chemical knowledge to construct coordination edges and learns the interactions between chelating agents and metal ions. SATCMF is trained on stability data collected from metal ion-ligand complexes, leveraging the SAT network to extract structural features relevant to the binding of ligands with metal ions. It further integrates molecular fingerprint features to refine the prediction of the stability constants of the chelating agents and metal ions. The experimental results on benchmark data set demonstrate that SATCMF achieves state-of-the-art performance based on four different graph neural network architectures. Additionally, visualizing the learned molecular attention distribution provides interpretable insights from the prediction results, offering valuable guidance for the development of novel metal chelators.
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Quelantes , Metais , Quelantes/química , Metais/química , Redes Neurais de Computação , Ligantes , Íons/química , Complexos de Coordenação/químicaRESUMO
BACKGROUND: Limited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incorporates dietary and lifestyle factors, and the occurrence of hyperuricemia. METHODS: We conducted a cross-sectional study involving 13,636 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The oxidative balance score (OBS) was determined based on four lifestyle factors and sixteen dietary nutrients. We assessed the levels of serum uric acid (SUA) and the occurrence of hyperuricemia as outcomes. Weighted logistic regression and linear models were used for statistical analysis, using Restricted Cubic Splines (RCS) to examine potential nonlinear associations. Subgroup analysis and sensitivity assessments were performed to identify any variations and ensure the robustness of the findings. RESULTS: Higher OBS was consistently correlated with decreased SUA levels and a reduced prevalence of hyperuricemia. RCS highlighted a significant negative nonlinear association, particularly in females. Subgroup analysis revealed gender-based differences and interactive correlation, providing additional insights regarding OBS and hyperuricemia relationship. CONCLUSION: This study underscores a robust negative correlation between OBS and SUA levels as well as the incidence of hyperuricemia, emphasizing the importance of dietary and lifestyle factors. Incorporating RCS, subgroup analysis, and sensitivity assessments enhances the depth of our findings, providing valuable insights for further research.
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Dieta , Hiperuricemia , Estilo de Vida , Inquéritos Nutricionais , Ácido Úrico , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Feminino , Masculino , Estudos Transversais , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto , Ácido Úrico/sangue , Dieta/métodos , Dieta/estatística & dados numéricos , Estresse Oxidativo , Prevalência , IdosoRESUMO
INTRODUCTION: Developmental delay at an early age indicates the probability of continued problems after school age. Hypertensive disorders of pregnancy (HDP) are associated with developmental delays in offspring, with inconsistent outcomes. Neonatal outcomes vary according to HDP exposure and are relevant to development in later years. Here we aimed to clarify the relationship between HDP and developmental delay in offspring and whether neonatal outcomes mediate this association. MATERIAL AND METHODS: We used data from 5934 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study conducted in Japan between July 2013 and March 2017. The Ages and Stages Questionnaires, third edition, at 24 and 42 months of age, measured developmental delay in five areas. We performed multivariate quasi-Poisson regression and causal mediation analysis by neonatal outcomes. RESULTS: At 24 months of age, compared to offspring born from normotensive mothers, offspring born from HDP-affected mothers were more likely to experience developmental delay (risk ratio [RR] 1.29, 95% confidence interval [CI]: 1.09-1.52) in the areas of communication (RR 1.21, 95% CI: 1.00-1.45) and personal-social (RR 1.15, 95% CI: 1.03-1.28). This association was mediated by neonatal outcomes: preterm birth, neonatal asphyxia, NICU admission, and neonatal small head circumference. No association was observed between HDP and developmental delay at 42 months of age. CONCLUSIONS: Exposure to HDP during fetal life is associated with offspring developmental delay. This association is partly mediated by neonatal outcomes.
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Deficiências do Desenvolvimento , Hipertensão Induzida pela Gravidez , Humanos , Feminino , Gravidez , Deficiências do Desenvolvimento/epidemiologia , Japão/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologia , Estudos Prospectivos , Adulto , Masculino , Recém-Nascido , Pré-Escolar , Estudos de Coortes , Efeitos Tardios da Exposição Pré-Natal , Resultado da Gravidez/epidemiologiaRESUMO
Orbital angular momentum (OAM) mode division multiplexing (MDM) systems can support large-capacity and high-speed rate information transmission, in which the OAM mode conversion devices play an important role. In this paper, the mode conversion principle of magneto-optical fiber-based long-period grating (MOF-LPG) is analyzed for further developing new magneto-optical (MO) OAM mode converters, including three types of C P 01 to O A M ±1,1, O A M ±1,1 to O A M ±2,1, and O A M ±1,1 to C P 02. It is shown that the magnetic tunability of the mode converters through the propagation constants of the eigenmodes is useful for compensating for process errors and increasing the operating wavelength range. The implementation of MOF-LPGs is also discussed from the aspect of the prospective experiments.
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BACKGROUND: The cellular and molecular dynamics of human prepuce are crucial for understanding its biological and physiological functions, as well as the prevention of related genital diseases. However, the cellular compositions and heterogeneity of human prepuce at single-cell resolution are still largely unknown. Here we systematically dissected the prepuce of children and adults based on the single-cell RNA-seq data of 90,770 qualified cells. RESULTS: We identified 15 prepuce cell subtypes, including fibroblast, smooth muscle cells, T/natural killer cells, macrophages, vascular endothelial cells, and dendritic cells. The proportions of these cell types varied among different individuals as well as between children and adults. Moreover, we detected cell-type-specific gene regulatory networks (GRNs), which could contribute to the unique functions of related cell types. The GRNs were also highly dynamic between the prepuce cells of children and adults. Our cell-cell communication network analysis among different cell types revealed a set of child-specific (e.g., CD96, EPO, IFN-1, and WNT signaling pathways) and adult-specific (e.g., BMP10, NEGR, ncWNT, and NPR1 signaling pathways) signaling pathways. The variations of GRNs and cellular communications could be closely associated with prepuce development in children and prepuce maintenance in adults. CONCLUSIONS: Collectively, we systematically analyzed the cellular variations and molecular changes of the human prepuce at single-cell resolution. Our results gained insights into the heterogeneity of prepuce cells and shed light on the underlying molecular mechanisms of prepuce development and maintenance.
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Células Endoteliais , Regulação da Expressão Gênica , Adulto , Humanos , Comunicação Celular/genética , Redes Reguladoras de Genes , Análise de Célula Única , Proteínas Morfogenéticas ÓsseasRESUMO
The innovation of liquid biopsy holds great potential to revolutionise cancer management through early diagnosis and timely treatment of cancer. Integrative analysis of different tumour-derived omics data (such as genomics, epigenetics, fragmentomics, and proteomics) from body fluids for cancer detection and monitoring could outperform the analysis of single modality data alone. In this review, we focussed on the discussion of early cancer detection and molecular residual disease surveillance based on multi-omics data of blood. We summarised diverse types of tumour-derived components, current popular platforms for profiling cancer-associated signals, machine learning approaches for joint analysis of liquid biopsy data, as well as multi-omics-based early detection of cancers, molecular residual disease monitoring, and treatment response surveillance. We also discussed the challenges and future directions of multi-omics-based liquid biopsy. With the development of both experimental protocols and computational methods dedicated to liquid biopsy, the implementation of multi-omics strategies into the clinical workflow will likely benefit the clinical management of cancers including decision-making guidance and patient outcome improvement.
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Multiômica , Neoplasias , Humanos , Genômica/métodos , Proteômica , Neoplasias/patologia , Epigenômica , Biologia Computacional/métodosRESUMO
Multi-omics allows the systematic understanding of the information flow across different omics layers, while single omics can mainly reflect one aspect of the biological system. The advancement of bulk and single-cell sequencing technologies and related computational methods for multi-omics largely facilitated the development of system biology and precision medicine. Single-cell approaches have the advantage of dissecting cellular dynamics and heterogeneity, whereas traditional bulk technologies are limited to individual/population-level investigation. In this review, we first summarize the technologies for producing bulk and single-cell multi-omics data. Then, we survey the computational approaches for integrative analysis of bulk and single-cell multimodal data, respectively. Moreover, the databases and data storage for multi-omics, as well as the tools for visualizing multimodal data are summarized. We also outline the integration between bulk and single-cell data, and discuss the applications of multi-omics in precision medicine. Finally, we present the challenges and perspectives for multi-omics development.
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Biologia Computacional/métodos , Medicina de Precisão/métodos , Humanos , Análise de Célula Única/métodosRESUMO
PURPOSE: Bone health and body composition share several common mechanisms like oxidative stress and inflammation. Anthocyanins have antioxidant and anti-inflammatory properties. We have reported that anthocyanins are associated with better body composition in children, but the associations with bone health have not been elucidated. We aimed to explore the association of anthocyanins with bone mineral content (BMC) and bone mineral density (BMD) at multiple sites in children. METHODS: In this cross-sectional study, 452 Chinese children aged 6-9 years were recruited. A validated 79-item food frequency questionnaire was used to collect dietary information. BMC and BMD at multiple sites (whole body; whole body excluding head, WBEH; limbs; arms; legs) were measured by dual-energy X-ray. RESULTS: Higher dietary intake of total anthocyanidins (per one standard deviation increase) was associated with a 1.28-13.6 g (1.31-1.60%, compared to median) higher BMC at all sites and a 3.61-6.96 mg (0.65-0.90%) higher BMD at the whole body, WBEH, and arm sites after controlling for a number of possible covariates. The results were similar and more pronounced for cyanidin, but not for delphinidin and peonidin. Higher dietary intake of cyanidin (per one standard deviation increase) was associated with a 1.33-15.4 g (1.48-1.68%) higher BMC at all sites and a 4.15-7.77 mg (0.66-1.00%) higher BMD at all sites except the legs. No statistically significant associations with BMC or BMD were found for dietary intake of delphinidin and peonidin. CONCLUSIONS: Higher dietary intake of total anthocyanidins and cyanidins were associated with higher BMC and BMD in Chinese children.
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Antocianinas , Densidade Óssea , Humanos , Criança , Estudos Transversais , Antioxidantes , Ingestão de AlimentosRESUMO
Components of the cell division machinery typically function at varying cell cycle stages and intracellular locations. To dissect cellular mechanisms during the rapid division process, small-molecule probes act as complementary approaches to genetic manipulations, with advantages of temporal and in some cases spatial control and applicability to multiple model systems. This Review focuses on recent advances in chemical probes and applications to address select questions in cell division. We discuss uses of both enzyme inhibitors and chemical inducers of dimerization, as well as emerging techniques to promote future investigations. Overall, these concepts may open new research directions for applying chemical probes to advance cell biology.
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Biologia Celular , Divisão Celular/fisiologia , Animais , Ciclo Celular , Técnicas Genéticas , HumanosRESUMO
OBJECTIVES: Time of flight magnetic resonance angiography (TOF-MRA) is the primary non-invasive screening method for cerebral aneurysms. We aimed to develop a computer-aided aneurysm detection method to improve the diagnostic efficiency and accuracy, especially decrease the false positive rate. METHODS: This is a retrospective multicenter study. The dataset contained 1160 TOF-MRA examinations composed of unruptured aneurysms (n = 1096) and normal controls (n = 166) from six hospitals. A total of 1037 examinations acquired from 2013 to 2019 were used as training set; 123 examinations acquired from 2020 to 2021 were used as external test set. We proposed an equalized augmentation strategy based on aneurysm location and constructed a detection model based on dual channel SE-3D UNet. The model was trained with a 5-fold cross-validation in the training set, then tested on the external test set. RESULTS: The proposed method achieved 82.46% sensitivity on patient-level, 73.85% sensitivity on lesion-level, and 0.88 false positives per case in the external test set. The performance did not show significant differences in subgroups according to the aneurysm site (except ACA), aneurysm size (except smaller than 3 mm), or MRI scanners. The performance preceded the basic SE-3D UNet by increasing 15.79% patient-level sensitivity and decreasing 4.19 FPs/case. CONCLUSIONS: The proposed automated aneurysm detection method achieved acceptable sensitivity while controlling fairly low false positives per case. It might provide a useful auxiliary tool of cerebral aneurysms MRA screening. KEY POINTS: ⢠The need for automated cerebral aneurysms detecting is growing. ⢠The strategy of equalized augmentation based on aneurysm location and dual-channel input could improve the model performance. ⢠The retrospective multi-center study showed that the proposed automated cerebral aneurysms detection using dual-channel SE-3D UNet could achieve acceptable sensitivity while controlling a low false positive rate.
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Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/patologia , Imageamento Tridimensional/métodos , Sensibilidade e Especificidade , Imageamento por Ressonância Magnética , Angiografia por Ressonância Magnética/métodos , Angiografia Cerebral/métodos , Angiografia DigitalRESUMO
BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.
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Diabetes Gestacional , Hiperuricemia , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Diabetes Gestacional/epidemiologia , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Ácido Úrico , Estudos Retrospectivos , Resultado da Gravidez/epidemiologia , Hiperuricemia/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Aumento de Peso , Retardo do Crescimento FetalRESUMO
BACKGROUND: Bronchogenic cysts (BCs) are rare and usually asymptomatic malformations detected during imaging examinations. We aimed to investigate the clinical and imaging characteristics of patients with BCs. METHODS: We retrospectively evaluated patients who received surgery to remove their BCs from January 2015 to January 2019. Their baseline characteristics, clinical information, and imaging results were reviewed. RESULTS: Our study included 129 patients, with 57 males and 72 females and a mean age of 42.7 years old. The most common location for BCs was the mediastinum (67 patients, 51.9%). Fewer than half of the patients (53 patients, 41.1%) reported clinical symptoms, with chest pain being the most common (16 patients, 30.2%). Neck BCs were more frequently observed in young patients (P = 0.002) and were more often associated with thyroid cancer (P = 0.007). A computed tomography scan was the most commonly used method to diagnose BCs in the lung and mediastinum, whereas ultrasound was the most commonly used diagnostic method for neck BCs. The characteristic images were well-defined, thin-wall cystic lesions in varying densities. A few lesions showed small, calcified spots along the rim or cavities. CONCLUSIONS: Although most BCs were found in the mediastinum, their locations could vary in different sex and age groups. Particular attention should be paid to young patients with BCs in the neck to rule out thyroid cancer.