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1.
Nature ; 626(7999): 565-573, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297123

RESUMO

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.


Assuntos
Estudos de Coortes , Interação Gene-Ambiente , Variação Genética , Genoma Humano , Fenótipo , Efeitos Tardios da Exposição Pré-Natal , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Ácidos e Sais Biliares/metabolismo , China/etnologia , Cordocentese , Feto/embriologia , Ganho de Peso na Gestação , Lipídeos/sangue , Exposição Materna , Parto , Estudos Prospectivos , Genoma Humano/genética , Variação Genética/genética
2.
Hepatology ; 79(3): 589-605, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37695548

RESUMO

BACKGROUND AND AIMS: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging. APPROACH AND RESULTS: We carried out single-cell RNA sequencing on mouse liver tissues at 4 different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2+ macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2+ macrophages presented a senescence-associated secretory phenotype and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1ß and TNF-α, Cxcl2+ macrophages stimulated neutrophil extracellular traps formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2+ macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples. CONCLUSIONS: This in-depth study illustrates that the mechanism of Cxcl2+ macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis and provides a potential therapeutic strategy for age-related liver injury.


Assuntos
Fígado , Neutrófilos , Camundongos , Animais , Recém-Nascido , Humanos , Idoso , Quimiocina CXCL2 , Macrófagos , Envelhecimento
3.
Chem Soc Rev ; 53(4): 2056-2098, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38214051

RESUMO

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

4.
Plant J ; 116(3): 804-822, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37522556

RESUMO

Vegetative shade causes an array of morphological changes in plants called shade avoidance syndrome, which includes hypocotyl and petiole elongation, leaf hyponasty, reduced leaf growth, early flowering and rapid senescence. Here, we show that loss-of-function mutations in HISTONE DEACETYLASE 9 (HDA9) attenuated the shade-induced hypocotyl elongation in Arabidopsis. However, the hda9 cotyledons and petioles under shade were not significantly different from those in wild-type, suggesting a specific function of HDA9 in hypocotyl elongation in response to shade. HDA9 expression levels were stable under shade and its protein was ubiquitously detected in cotyledon, hypocotyl and root. Organ-specific transcriptome analysis unraveled that shade induced a set of auxin-responsive genes, such as SMALL AUXIN UPREGULATED RNAs (SAURs) and AUXIN/INDOLE-3-ACETIC ACIDs (AUX/IAAs) and their induction was impaired in hda9-1 hypocotyls. In addition, HDA9 binding to loci of SAUR15/65, IAA5/6/19 and ACS4 was increased under shade. The genetic and organ-specific gene expression analyses further revealed that HDA9 may cooperate with PHYTOCHROME-INTERACTING FACTOR 4/7 in the regulation of shade-induced hypocotyl elongation. Furthermore, HDA9 and PIF7 proteins were found to interact together and thus it is suggested that PIF7 may recruit HDA9 to regulate the shade/auxin responsive genes in response to shade. Overall, our study unravels that HDA9 can work as one component of a hypocotyl-specific transcriptional regulatory machinery that activates the auxin response at the hypocotyl leading to the elongation of this organ under shade.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Hipocótilo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Regulação da Expressão Gênica de Plantas , Luz , Proteínas de Ligação a DNA/genética
5.
J Am Chem Soc ; 146(28): 19303-19309, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38970779

RESUMO

Sulfur hexafluoride (SF6) is extensively employed in the power industry. However, its emissions significantly contribute to the greenhouse effect. The direct recovery of high purity SF6 from industrial waste gases would benefit its sustainable use, yet this represents a considerable challenge. Herein, we report the enrichment of SF6 from SF6/N2 mixtures via adsorptive separation in a stable Co(II)-pyrazolate MOF BUT-53 (BUT: Beijing University of Technology), which features dynamic molecular traps. BUT-53 exhibits an excellent SF6 adsorption uptake of 2.82 mmol/g at 0.1 bar and 298 K, as well as an unprecedented SF6/N2 (10:90) selectivity of 2485. Besides, the remarkable SF6/N2 selectivity of BUT-53 enables recovery of high purity (>99.9%) SF6 from a low concentration (10%) mixture through a breakthrough experiment. The excellent SF6/N2 separation efficiency was also well maintained under humid conditions (RH = 90%) over multiple cycles. Molecular simulation, single-crystal diffraction, and adsorption kinetics studies elucidate the associated adsorption mechanism and water tolerance.

6.
J Am Chem Soc ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39376039

RESUMO

Transformation between oxidation states is widespread in transition metal coordination chemistry and biochemistry, typically occurring in solution. However, air-induced oxidation in porous crystalline solids with retention of crystallinity is rare due to the dearth of materials with high structural stability that are inherently redox active. Herein, we report a new family of such materials, four isostructural cobalt-pyrazolate frameworks of face-centered cubic, fcu, topology, fcu-L-Co, that are sustained by Co8 molecular building blocks (MBBs) and dipyrazolate ligands, L. fcu-L-Co were observed to spontaneously transform from Co(II)8 to Co(III)8 MBBs in air with retention of crystallinity, marking the first such instance in metal-organic frameworks (MOFs). This transformation can also be achieved through water vapor sorption cycling, heating, or chemical oxidation. The reverse reactions were conducted by exposure of fcu-L-Co(III) to aqueous hydrazine. fcu-L-Co(II) exhibited high gravimetric water vapor uptakes of 0.55-0.68 g g-1 at 30% relative humidity (RH), while in fcu-L-Co(III) the inflection point shifted to lower RH and framework stability improved. Insight into the transformation between fcu-L-Co(II) and fcu-L-Co(III) was gained from single crystal X-ray diffraction and in situ spectroscopy. Overall, the crystal engineering approach we adopted has afforded a new family of MOFs that exhibit cobalt redox chemistry in a confined space coupled with high porosity.

7.
Mol Cancer ; 23(1): 185, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232758

RESUMO

The spatial arrangement of immune cells within the tumor microenvironment (TME) and their interactions play critical roles in the initiation and development of cancer. Several advanced technologies such as imaging mass cytometry (IMC) providing the immunological landscape of the TME with single-cell resolution. In this study, we develop a new method to quantify the spatial proximity between different cell types based on single-cell spatial data. Using this method on IMC data from 416 lung adenocarcinoma patients, we show that the proximity between different cell types is more correlated with patient prognosis compared to the traditional features such immune cell density and fractions. Consistent with previous reports, our results validate that proximity of T helper (Th) and B cells to cancer cells is associated with survival benefits. More importantly, we discover that the proximity of M2 macrophages to multiple immune cells is associated with poor prognosis. When Th/B cells are stratified into M2-distal and M2-proximal, the abundance of the former but not the latter category of Th/B cells is correlated with enhanced patient survival. Additionally, the abundance of M2-distal and M2-proximal cytotoxic T cells (Tc) is respectively associated with good and poor prognosis. Our results indicate that the prognostic effect of Th, Tc, and B cells in the tumor microenvironment is modulated by the nearby M2 macrophages. The proposed new method proposed can be readily applied to all single-cell spatial data for revealing functional impact of immune cell interactions.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Macrófagos , Microambiente Tumoral , Humanos , Prognóstico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/metabolismo , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos B/metabolismo , Análise de Célula Única/métodos
8.
Int J Cancer ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874435

RESUMO

Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients having poor prognoses. Identifying these patients is crucial for treatment management and strategic decisions. In this study, we developed a novel computational framework to define prognostic gene signatures by selecting genes with expression driven by clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of 22 genes and evaluated in five independent datasets. The CGS provided significant prognostic values after adjusting for well-established factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). Importantly, CGS demonstrated higher performance in identifying high-risk patients compared to the GEP70 and SKY92 signatures recommended for prognostic stratification of MM. CGS can further stratify patients into subgroups with significantly differential prognoses when applied to the high- and low-risk groups identified by GEP70 and SKY92. Additionally, CGS scores are significantly associated with patient response to dexamethasone, a commonly used treatment for MM. In summary, we proposed a computational framework that requires only gene expression data to identify CGSs for prognosis prediction. CGS provides a useful biomarker for improving prognostic stratification in MM, especially for identifying the highest-risk patients.

9.
Mol Biol Evol ; 40(5)2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37183780

RESUMO

In the same way that a phylogeny summarizes the evolutionary history of species, a cell lineage tree describes the process of clonal expansion, in which gene expression differences between cells naturally accrue as a result of stochastic partitioning and imperfect expression control. How is functional homeostasis, a key factor in the biological function of any population of cells, maintained in the face of such continuous accumulation of transcriptomic heterogeneity remains largely unresolved. To answer this question, we experimentally determined the single-cell transcriptomes and lineage relationships of up to 50% cells in single-HEK293-seeded colonies. Phylogenetic comparative analyses of the single-cell transcriptomes on the cell lineage tree revealed three lines of evidence for the constrained accumulation of transcriptome heterogeneity among cells, including rapid saturation of transcriptomic heterogeneity upon four cell divisions, reduced expression differences within subtrees closer to expression boundaries, and cofluctuations among genes. Our analyses showcased the applicability of phylogenetic comparative methods in cell lineage trees, demonstrated the constrained accumulation of transcriptomic heterogeneity, and provided novel insight into the functional homeostasis of cell populations.


Assuntos
Evolução Biológica , Transcriptoma , Humanos , Filogenia , Células HEK293 , Perfilação da Expressão Gênica
10.
Br J Haematol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137931

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic and molecular aberrations, enhancing the accuracy of prognostic evaluations compared to conventional MYC biomarkers. Our results indicate that MYCSS significantly refines prognostic accuracy beyond that of conventional MYC biomarkers focused on genetic aberrations. More importantly, we found that nearly 50% of patients identified as high risk by traditional MYC metrics actually share similar survival prospects with those having no MYC aberrations. These patients may benefit from standard GCB-based therapies rather than more aggressive treatments. MYCSS provides a robust signature that identifies high-risk patients, aiding in the precision treatment of DLBCL, and minimizing the potential for overtreatment.

11.
Oncologist ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250742

RESUMO

In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research.

12.
Anal Chem ; 96(29): 11853-11861, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-38989993

RESUMO

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 109, which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.


Assuntos
Proteínas de Transporte , Ouro , Humanos , Imunoensaio/métodos , Proteínas de Transporte/sangue , Ouro/química , Limite de Detecção , Colorimetria/métodos , Nanopartículas Metálicas/química , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/sangue , Análise Espectral Raman/métodos
13.
BMC Med ; 22(1): 407, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304842

RESUMO

BACKGROUND: Kidney transplantation is the optimal renal replacement therapy for children with end-stage renal disease; however, delayed graft function (DGF), a common post-operative complication, may negatively impact the long-term outcomes of both the graft and the pediatric recipient. However, there is limited research on DGF in pediatric kidney transplant recipients. This study aims to develop a predictive model for the risk of DGF occurrence after pediatric kidney transplantation by integrating donor and recipient characteristics and utilizing machine learning algorithms, ultimately providing guidance for clinical decision-making. METHODS: This single-center retrospective cohort study includes all recipients under 18 years of age who underwent single-donor kidney transplantation at our hospital between 2016 and 2023, along with their corresponding donors. Demographic, clinical, and laboratory examination data were collected from both donors and recipients. Univariate logistic regression models and differential analysis were employed to identify features associated with DGF. Subsequently, a risk score for predicting DGF occurrence (DGF-RS) was constructed based on machine learning combinations. Model performance was evaluated using the receiver operating characteristic curves, decision curve analysis (DCA), and other methods. RESULTS: The study included a total of 140 pediatric kidney transplant recipients, among whom 37 (26.4%) developed DGF. Univariate analysis revealed that high-density lipoprotein cholesterol (HDLC), donor after circulatory death (DCD), warm ischemia time (WIT), cold ischemia time (CIT), gender match, and donor creatinine were significantly associated with DGF (P < 0.05). Based on these six features, the random forest model (mtry = 5, 75%p) exhibited the best predictive performance among 97 machine learning models, with the area under the curve values reaching 0.983, 1, and 0.905 for the entire cohort, training set, and validation set, respectively. This model significantly outperformed single indicators. The DCA curve confirmed the clinical utility of this model. CONCLUSIONS: In this study, we developed a machine learning-based predictive model for DGF following pediatric kidney transplantation, termed DGF-RS, which integrates both donor and recipient characteristics. The model demonstrated excellent predictive accuracy and provides essential guidance for clinical decision-making. These findings contribute to our understanding of the pathogenesis of DGF.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Aprendizado de Máquina , Doadores de Tecidos , Humanos , Transplante de Rim/efeitos adversos , Feminino , Masculino , Criança , Estudos Retrospectivos , Adolescente , Pré-Escolar , Lactente
14.
Small ; : e2405436, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221638

RESUMO

The overuse of antibiotics poses a serious threat to human health and ecosystems. Therefore, the development of high-performance antibiotic removal materials has attracted increasing attention. However, the adsorption and removal of trace amounts of antibiotics in aqueous systems still face significant challenges. Taking tetracycline (TC) as a representative antibiotic and based on its structural characteristics, a series of TC adsorbents are prepared by grafting alkyl groups to the framework of MIL-101(Cr). The adsorptive capacity of the modified materials for tetracycline markedly surpasses that of MIL-101(Cr), with MIL-101-dod achieving the best adsorption performance. MIL-101-dod demonstrated an outstanding ability to adsorb tetracycline at low concentrations, where a 5.0 mg sample of MIL-101-dod can reduce the concentration of a 90 mL 5 ppm tetracycline solution to below 1 ppb, significantly superior to other sorbents. XPS and IR tests indicate that MIL-101-dod has multiple weak interactions with tetracycline molecules, including C─H…O and C─H…π. This work provides theoretical and experimental support for the development of adsorbents for low-concentration antibiotics.

15.
J Magn Reson Imaging ; 59(3): 1034-1042, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37272790

RESUMO

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.


Assuntos
Hepatoblastoma , Neoplasias Hepáticas , Masculino , Criança , Humanos , Pré-Escolar , Lactente , Hepatoblastoma/tratamento farmacológico , Hepatoblastoma/patologia , Hepatoblastoma/cirurgia , Terapia Neoadjuvante , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Veias Hepáticas , Sensibilidade e Especificidade , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias
16.
Eur Radiol ; 34(8): 4883-4896, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38189980

RESUMO

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.


Assuntos
Displasia Arritmogênica Ventricular Direita , Ventrículos do Coração , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/complicações , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Estudos Prospectivos , Fractais , Adulto , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Morte Súbita Cardíaca
17.
Inflamm Res ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39377802

RESUMO

OBJECTIVE: This study sought to investigate the cellular and molecular alterations during the injury and recovery periods of ALI and develop effective treatments for ALI. METHODS: Pulmonary histology at 1, 3, 6, and 9 days after lipopolysaccharide administration mice were assessed. An unbiased single-cell RNA sequencing was performed in alveoli tissues from injury (day 3) and recovery (day 6) mice after lipopolysaccharide administration. The roles of Fpr2 and Dpp4 in ALI were assessed. RESULTS: The most severe lung injury occurred on day 3, followed by recovery entirely on day 9 after lipopolysaccharide administration. The numbers of Il1a+ neutrophils, monocytes/macrophages, and Cd4+ and Cd8+ T cells significantly increased at day 3 after LPS administration; subsequently, the number of Il1a+ neutrophils greatly decreased, the numbers of monocytes/macrophages and Cd4+ and Cd8+ T cells continuously increased, and the number of resident alveolar macrophages significantly increased at day 6. The interactions between monocytes/macrophages and pneumocytes during the injury period were enhanced by the Cxcl10/Dpp4 pair, and inhibiting Dpp4 improved ALI significantly, while inhibiting Fpr2 did not. CONCLUSIONS: Our results offer valuable insights into the cellular and molecular mechanisms underlying its progression and identify Dpp4 as an effective therapeutic target for ALI.

18.
Infection ; 52(4): 1553-1561, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38733459

RESUMO

PURPOSE: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. METHODS: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. RESULTS: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. CONCLUSION: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.


Assuntos
Complicações Infecciosas na Gravidez , Resultado da Gravidez , Nascimento Prematuro , Humanos , Feminino , Gravidez , Adulto , Estudos de Coortes , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Recém-Nascido , Resultado da Gravidez/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Adulto Jovem , Fatores de Risco , Infecções Urinárias/epidemiologia , Austrália/epidemiologia , Recém-Nascido de Baixo Peso
19.
Inorg Chem ; 63(16): 7412-7421, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38600810

RESUMO

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

20.
Inorg Chem ; 63(25): 11860-11869, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38861347

RESUMO

The newly reported crystalline phosphorus nanosheets (cryst-P NSs) exhibit promising features for industrial applications, including outstanding air-water stability and facile large-scale production. However, their complex crystallization impedes a priori tailoring. Herein, the temporal evolution of cryst-P NSs was investigated with the optimized synthesis parameters. The occurrence of self-assembly and solid-state rearrangement unveiled the existence of an intermediate phase as the bulk crystalline precursor and the predominance of nonclassical crystallization pathway(s). With the upgraded synthesis protocol simultaneously strengthening the merits of cryst-P NSs, their catalytic performances were evaluated in various electro- and/or photocatalytic reactions spanning hydrogen and oxygen evolution, full water splitting, CO2 reduction, and organic pollutant decomposition. Superior catalytic activities and orders of magnitude longer lifetimes were consistently discerned compared with the widely employed black phosphorus nanosheets with similar size and thickness. The exciting discoveries in both fundamental crystallization and catalytic applications drastically thrust the comprehension of elemental phosphorus, shedding light on the encouraging capabilities of solvothermal synthesis strategies in the design and systematic tailoring of phosphorus materials.

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