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1.
Nat Commun ; 15(1): 3437, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653755

RESUMO

Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.


Assuntos
Ascomicetos , Resistência à Doença , Endocitose , Flavonoides , Oryza , Fitoalexinas , Doenças das Plantas , Proteínas de Plantas , Oryza/microbiologia , Oryza/metabolismo , Oryza/efeitos dos fármacos , Oryza/genética , Doenças das Plantas/microbiologia , Endocitose/efeitos dos fármacos , Resistência à Doença/genética , Resistência à Doença/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sesquiterpenos/farmacologia , Sesquiterpenos/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Plantas Geneticamente Modificadas , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética
2.
Clin Otolaryngol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622816

RESUMO

INTRODUCTION: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). METHODS: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. RESULTS: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. CONCLUSION: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC.

3.
J Colloid Interface Sci ; 662: 807-813, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382365

RESUMO

Sunlight-driven CO2 reduction to value-added chemicals is an effective strategy to promote carbon recycling. The exploration of catalysts with efficient charge separation is crucially important for highly efficient CO2 photoreduction. In this work, the preparation of metal-cluster-based covalent organic framework (CuABD) integrated features from both metal organic frameworks (MOFs) and covalent organic frameworks (COFs) through the condensation of diamines and functionalized trinuclear copper clusters demonstrate a thoughtful design strategy. The reported yield of 1.3 mmol g-1 h-1 for formic acid (HCOOH) under simulated solar irradiation is impressive, surpassing the performance of many COF- and MOF-based catalysts previously reported. Compared to its isomorphic metal-free structure (named BDFTD) and bare trinuclear Cu cluster which present extremely poor catalytic activities, CuABD displays remarkably enhanced CO2 reduction activity. Experimental and theoretical investigations reveal that the efficient charge transfer between diamine monomer and cyclic trinuclear copper (I) units, and the electron delocalization of the π-conjugated framework are responsible for the appealing catalytic performance. In summary, the work presents a well-structured and scientifically sound exploration of a metal-cluster-based covalent organic framework for efficient CO2 reduction under sunlight.

4.
Sci Rep ; 13(1): 22326, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102161

RESUMO

Isozymes are enzymes that catalyze identical biological reactions, yet exhibit slight variations in structures and catalytic efficiency, which enables the precise adjustment of metabolism to fulfill the specific requirements of a particular tissue or stage of development. Methionine aminopeptidase (MetAP) isozymes function a critical role in cleaving N-terminal methionine from nascent proteins to generate functional proteins. In humans, two distinct MetAP types I and II have been identified, with type I further categorized into cytosolic (MetAP1) and mitochondrial (MetAP1D) variants. However, despite extensive structural studies on both bacterial and human cytosolic MetAPs, the structural information remains unavailable for human mitochondrial MetAP. This study was aimed to elucidate the high-resolution structures of human mitochondrial MetAP1D in its apo-, cobalt-, and methionine-bound states. Through a comprehensive analysis of the determined structures and a docking simulation model with mitochondrial substrate peptides, we present mechanistic insights into the cleavage process of the initiator methionine from mitochondrial proteins. Notably, despite the shared features at the active site between the cytosolic and mitochondrial MetAP type I isozymes, we identified distinct structural disparities within the active-site pocket primarily contributed by two specific loops that could play a role in accommodating specific substrates. These structural insights offer a basis for the further exploration of MetAP isozymes as critical players in cellular processes and potential therapeutic applications.


Assuntos
Aminopeptidases , Metionina , Humanos , Aminopeptidases/metabolismo , Isoenzimas , Metionina/metabolismo , Metionil Aminopeptidases/metabolismo , Racemetionina
5.
Eur Arch Psychiatry Clin Neurosci ; 273(2): 493-509, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36094570

RESUMO

Insomnia disorder (ID) and obstructive sleep apnea (OSA) are the two most prevalent sleep disorders worldwide, but the pathological mechanism has not been fully understood. Functional neuroimaging findings indicated regional abnormal neural activities existed in both diseases, but the results were inconsistent. This meta-analysis aimed to explore concordant regional functional brain changes in ID and OSA, respectively. We conducted a coordinate-based meta-analysis (CBMA) of resting-state functional magnetic resonance imaging (rs-fMRI) studies using the anisotropic effect-size seed-based d mapping (AES-SDM) approach. Studies that applied regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) or fractional ALFF (fALFF) to analyze regional spontaneous brain activities in ID or OSA were included. Meta-regressions were then applied to investigate potential associations between demographic variables and regional neural activity alterations. Significantly increased brain activities in the left superior temporal gyrus (STG.L) and right superior longitudinal fasciculus (SLF.R), as well as decreased brain activities in several right cerebral hemisphere areas were identified in ID patients. As for OSA patients, more distinct and complicated functional activation alterations were identified. Several neuroimaging alterations were functionally correlated with mean age, duration or illness severity in two patients groups revealed by meta-regressions. These functionally altered areas could be served as potential targets for non-invasive brain stimulation methods. This present meta-analysis distinguished distinct brain function changes in ID and OSA, improving our knowledge of the neuropathological mechanism of these two most common sleep disturbances, and also provided potential orientations for future clinical applications.Registration number: CRD42022301938.


Assuntos
Apneia Obstrutiva do Sono , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico por imagem
6.
Eur J Cardiothorac Surg ; 62(5)2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36149285

RESUMO

We report the case of successful biventricular repair after left ventricular rehabilitation in an infant with transposition of the great arteries with an intact ventricular septum, pulmonary stenosis, a large atrial septal defect and a borderline small left ventricle (mitral annulus z-score: -3.6). This baby presented to us at 2 months of age after having a modified Blalock-Taussig shunt at another hospital. We restricted the atrial septal defect with the child on cardiopulmonary bypass. Ten weeks later, the mitral annulus z-score increased to -1.5, and the transpulmonary peak pressure gradient increased to 87 mmHg. Subsequently, we performed the aortic root translocation. The patient is currently an active 4-year-old boy.


Assuntos
Comunicação Interatrial , Estenose da Valva Pulmonar , Transposição dos Grandes Vasos , Septo Interventricular , Artérias , Criança , Pré-Escolar , Comunicação Interatrial/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Lactente , Masculino , Estenose da Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/cirurgia , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/cirurgia
7.
J Med Internet Res ; 24(9): e39360, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-36155486

RESUMO

BACKGROUND: The incidence of Takotsubo syndrome (TTS), also known as the broken heart syndrome or stress cardiomyopathy, is increasing worldwide. The understanding of its prognosis has been progressively evolving and currently appears to be poorer than previously thought, which has attracted the attention of researchers. An attempt to recognize the awareness of this condition among the general population drove us to analyze the dissemination of this topic on TikTok, a popular short-video-based social media platform. We found a considerable number of videos on TTS on TikTok; however, the quality of the presented information remains unknown. OBJECTIVE: The aim of this study was to analyze the quality and audience engagement of TTS-related videos on TikTok. METHODS: Videos on the TikTok platform were explored on August 2, 2021 to identify those related to TTS by using 6 Chinese keywords. A total of 2549 videos were found, of which 80 met our inclusion criteria and were evaluated for their characteristics, content, quality, and reliability. The quality and reliability were rated using the DISCERN instrument and the Journal of the American Medical Association (JAMA) criteria by 2 reviewers independently, and a score was assigned. Descriptive statistics were generated, and the Kruskal-Wallis test was used for statistical analysis. Multiple linear regression was performed to evaluate the association between audience engagement and other factors such as video content, video quality, and author types. RESULTS: The scores assigned to the selected video content were low with regard to the diagnosis (0.66/2) and management (0.34/2) of TTS. The evaluated videos were found to have an average score of 36.93 out of 80 on the DISCERN instrument and 1.51 out of 4 per the JAMA criteria. None of the evaluated videos met all the JAMA criteria. The quality of the relayed information varied by source (All P<.05). TTS-related videos made by health care professionals accounted for 28% (22/80) of all the evaluated videos and had the highest DISCERN scores with an average of 40.59 out of 80. Multiple linear regression analysis showed that author types that identified as health professionals (exponentiated regression coefficient 17.48, 95% CI 2.29-133.52; P=.006) and individual science communicators (exponentiated regression coefficient 13.38, 95% CI 1.83-97.88; P=.01) were significant and independent determinants of audience engagement (in terms of the number of likes). Other author types of videos, video content, and DISCERN document scores were not associated with higher likes. CONCLUSIONS: We found that the quality of videos regarding TTS for patient education on TikTok is poor. Patients should be cautious about health-related information on TikTok. The formulation of a measure for video quality review is necessary, especially when the purpose of the published content is to educate and increase awareness on a health-related topic.


Assuntos
Mídias Sociais , Cardiomiopatia de Takotsubo , Humanos , Disseminação de Informação , Reprodutibilidade dos Testes , Cardiomiopatia de Takotsubo/diagnóstico , Gravação em Vídeo
8.
J Res Med Sci ; 27: 53, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092490

RESUMO

In recent years, some studies have evaluated the epidemiologic factors associated with breast density. However, the variant and inconsistent results exist. In addition, breast density has been proved to be a significant risk factor associated with breast cancer. Our review summarized the published studies and emphasized the crucial factors including epidemiological factors associated with breast density. In addition, we also discussed the potential reasons for the discrepant results with risk factors. To decrease the incidence and mortality rates for breast cancer, in clinical practice, breast density should be included for clinical risk models in addition to epidemiological factors, and physicians should get more concentrate on those women with risk factors and provide risk-based breast cancer screening regimens.

9.
Chem Commun (Camb) ; 58(73): 10114-10126, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36017810

RESUMO

Direct conversion of diluted CO2 to value-added chemical stocks and fuels with solar energy is an energy-saving approach to relieve global warming and realize a carbon-neutral cycle. The exploration of catalysts with both efficient CO2 adsorption and reduction ability is significant to achieving this goal. Metal-organic frameworks (MOFs) are emerging in the field of low-concentration CO2 reduction due to their highly tunable structure, high porosity, abundant active sites and excellent CO2 adsorption capacity. This highlight outlines the advantages of MOFs for low-pressure CO2 adsorption and the strategies to improve the photocatalytic performance of MOF materials at low CO2 concentrations, including the functionalization of organic ligands, regulation of metal nodes and preparation of MOF composites or derivatives. This paper aims to provide possible avenues for the rational design and development of catalysts with the ability to reduce low-concentration CO2 efficiently for practical applications.

10.
Eur Heart J Open ; 2(2): oeac009, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35919117

RESUMO

Takotsubo syndrome (TTS) is a rare cardiovascular condition characterized by reversible ventricular dysfunction and a presentation resembling that of acute myocardial infarction. An increasing number of studies has shown the association of respiratory diseases with TTS. Here, we comprehensively reviewed the literature and examined the available evidence for this association. After searching PubMed, EMBASE, and Cochrane Library databases, two investigators independently reviewed 3117 studies published through May 2021. Of these studies, 99 met the inclusion criteria (n = 108 patients). In patients with coexisting respiratory disease and TTS, the most common TTS symptom was dyspnoea (70.48%), followed by chest pain (24.76%) and syncope (2.86%). The most common type of TTS was apical, accounting for 81.13% of cases, followed by the midventricular (8.49%), basal (8.49%), and biventricular (1.89%) types. Among the TTS cases, 39.82% were associated with obstructive lung disease and 38.89% were associated with pneumonia. Coronavirus disease 2019 (COVID-19), which has been increasingly reported in patients with TTS, was identified in 29 of 42 (69.05%) patients with pneumonia. The overall mortality rate for patients admitted for respiratory disease complicated by TTS was 12.50%. Obstructive lung disease and pneumonia are the most frequently identified respiratory triggers of TTS. Medications and invasive procedures utilized in managing respiratory diseases may also contribute to the development of TTS. Furthermore, the diagnosis of TTS triggered by these conditions can be challenging due to its atypical presentation. Future prospective studies are needed to establish appropriate guidelines for managing respiratory disease with concurrent TTS.

11.
Nature ; 609(7926): 416-423, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35830882

RESUMO

RAS-MAPK signalling is fundamental for cell proliferation and is altered in most human cancers1-3. However, our mechanistic understanding of how RAS signals through RAF is still incomplete. Although studies revealed snapshots for autoinhibited and active RAF-MEK1-14-3-3 complexes4, the intermediate steps that lead to RAF activation remain unclear. The MRAS-SHOC2-PP1C holophosphatase dephosphorylates RAF at serine 259, resulting in the partial displacement of 14-3-3 and RAF-RAS association3,5,6. MRAS, SHOC2 and PP1C are mutated in rasopathies-developmental syndromes caused by aberrant MAPK pathway activation6-14-and SHOC2 itself has emerged as potential target in receptor tyrosine kinase (RTK)-RAS-driven tumours15-18. Despite its importance, structural understanding of the SHOC2 holophosphatase is lacking. Here we determine, using X-ray crystallography, the structure of the MRAS-SHOC2-PP1C complex. SHOC2 bridges PP1C and MRAS through its concave surface and enables reciprocal interactions between all three subunits. Biophysical characterization indicates a cooperative assembly driven by the MRAS GTP-bound active state, an observation that is extendible to other RAS isoforms. Our findings support the concept of a RAS-driven and multi-molecular model for RAF activation in which individual RAS-GTP molecules recruit RAF-14-3-3 and SHOC2-PP1C to produce downstream pathway activation. Importantly, we find that rasopathy and cancer mutations reside at protein-protein interfaces within the holophosphatase, resulting in enhanced affinities and function. Collectively, our findings shed light on a fundamental mechanism of RAS biology and on mechanisms of clinically observed enhanced RAS-MAPK signalling, therefore providing the structural basis for therapeutic interventions.


Assuntos
Cristalografia por Raios X , Peptídeos e Proteínas de Sinalização Intracelular , Complexos Multiproteicos , Proteína Fosfatase 1 , Proteínas ras , Proteínas 14-3-3 , Guanosina Trifosfato/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Complexos Multiproteicos/química , Mutação , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Proteína Fosfatase 1/química , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Quinases raf , Proteínas ras/química , Proteínas ras/metabolismo
12.
Inorg Chem ; 61(15): 5869-5877, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35385260

RESUMO

The design of efficient and inexpensive photocatalysts for CO2 photoreduction under visible light is of great significance for the sustainable development of the entire society. Herein, a copper-based metal-organic framework (MOF) (CUST-804) using a bulky tetraphenylethylene-tetrazole linker is synthesized and successfully used as a photocatalyst for CO2 reduction. The structural characterizations, as well as the photophysical properties, are investigated systematically. In the heterogeneous catalytic system, CUST-804 exhibits a robust CO production activity up to 2.71 mmol g-1 h-1 with excellent recyclability along with a selectivity of 82.8%, which is comparable with those of the reported copper-based MOF system. Theoretical calculations demonstrated that, among three kinds of coordinated model, only the 5-coordinated Cu site is active for CO2 reduction, in which the *COOH intermediate is stabilized and CO is readily desorbed. The results obtained herein can provide fresh insights into the realization of efficient copper-functionalized crystalline photocatalysts for CO2 reduction.

13.
Comput Struct Biotechnol J ; 20: 745-756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140891

RESUMO

Bcl-2 family kin (Bfk), also known as Bcl-2-like 15, plays an essential role in regulating apoptosis by eliciting weak pro-apoptotic responses in the gastrointestinal tract. Human Bfk is a novel Bcl-2 family protein owing to its unique domain composition involving BH2 and BH3. However, the molecular mechanism underlying the regulation of apoptosis by Bfk remains unclear. Here, we first report the crystal structure of human full-length Bfk. Surprisingly, the structure of Bfk adopts a canonical Bcl-2 fold but lacks the hydrophobic cleft, which could accommodate a BH3 domain from other Bcl-2 family proteins. Our biophysical interaction analysis proved that the full-length Bfk itself does not interact with multi-domain Bcl-2 family proteins or a BH3-containing peptide. Instead, Bfk is structurally and functionally reminiscent of Bid, a BH3-only protein in the Bcl-2 family, with similar conformations of helices α3-α5 and the specific motif in helix α5. Not only structural analyses of the full-length Bfk but also molecular dynamics simulation suggested that Bfk elicits its pro-apoptotic activity through a Bid-like apoptotic mechanism in which the BH3 domain is released upon caspase-mediated cleavage and a conformational change of the truncated form. Indeed, the BH3 peptide derived from Bfk exhibited in vitro interactions with Bcl-2, Bcl-XL, and Bak. These findings provide new insights into the molecular characteristics of Bfk and a valuable foundation for development of a new therapeutic target to control apoptosis.

14.
Nucleic Acids Res ; 50(4): 2319-2333, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35141752

RESUMO

Staphylococcus aureus is a notorious and globally distributed pathogenic bacterium. New strategies to develop novel antibiotics based on intrinsic bacterial toxin-antitoxin (TA) systems have been recently reported. Because TA systems are present only in bacteria and not in humans, these distinctive systems are attractive targets for developing antibiotics with new modes of action. S. aureus PemIK is a type II TA system, comprising the toxin protein PemK and the labile antitoxin protein PemI. Here, we determined the crystal structures of both PemK and the PemIK complex, in which PemK is neutralized by PemI. Our biochemical approaches, including fluorescence quenching and polarization assays, identified Glu20, Arg25, Thr48, Thr49, and Arg84 of PemK as being important for RNase function. Our study indicates that the active site and RNA-binding residues of PemK are covered by PemI, leading to unique conformational changes in PemK accompanied by repositioning of the loop between ß1 and ß2. These changes can interfere with RNA binding by PemK. Overall, PemK adopts particular open and closed forms for precise neutralization by PemI. This structural and functional information on PemIK will contribute to the discovery and development of novel antibiotics in the form of peptides or small molecules inhibiting direct binding between PemI and PemK.


Assuntos
Antitoxinas , Staphylococcus aureus , Antibacterianos/metabolismo , Antitoxinas/genética , Antitoxinas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , RNA/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo
15.
ACS Appl Mater Interfaces ; 14(5): 6476-6483, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35077129

RESUMO

The direct usage of CO2 in the flue gas to produce fuels or chemicals is of great significance from energy-saving and low-cost perspectives, yet it is still underexplored. Herein, we report the photoreduction of CO2 from the simulated industrial exhaust by synergistic catalysis of TEOA and a metal-free composite (COF1-g-C3N4) fabricated via covalently grafting COF1 with g-C3N4. The hydrogen bond interaction between TEOA and hydrazine units on COF1 is detected in diluted CO2, which leads to significantly enhanced light absorption in the whole visible-light region. Also, the photo-induced electrons undergo fast transfer from COF1 to g-C3N4. This kind of dynamic interface with enhanced light absorption and electron transfer effects promotes the photosynthetic yield of syngas to 165.6 µmol·g-1·h-1 with the use of simulated exhaust gas as a raw material directly. The photosynthetic yield of syngas ranks among the highest of known metal-free catalysts in diluted CO2. This work provides a general rule for designing efficient catalysts via a controlled catalytic interface and new insights into the role of TEOA in photochemical CO2 reduction.

16.
Lupus ; 30(12): 1973-1982, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34652991

RESUMO

BACKGROUND: Systemic lupus erythematosus is often accompanied with neuropsychiatric symptoms. Neuroimaging evidence indicated that microstructural white matter (WM) abnormalities play role in the neuropathological mechanism. Diffusion tensor imaging (DTI) studies allows the assessment of the microstructural integrity of WM tracts, but existing findings were inconsistent. This present study aimed to conduct a coordinate-based meta-analysis (CBMA) to identify statistical consensus of DTI studies in SLE. METHODS: Relevant studies that reported the differences of fractional anisotropy (FA) between SLE patients and healthy controls (HC) were searched systematically. Only studies reported the results in Talairach or Montreal Neurological Institute (MNI) coordinates were included. The anisotropic effect size version of signed differential mapping (AES-SDM) was applied to detect WM alterations in SLE. RESULTS: Totally, five studies with seven datasets which included 126 patients and 161 HC were identified. The pooled meta-analysis demonstrated that SLE patients exhibited significant FA reduction in the left striatum and bilateral inferior network, mainly comprised the corpus callosum (CC), bilateral inferior fronto-occipital fasciculus (IFOF), bilateral anterior thalamic projections, bilateral superior longitudinal fasciculus (SLF), left inferior longitudinal fasciculus (ILF), and left insula. No region with higher FA was identified. CONCLUSIONS: Disorders of the immune system might lead to subtle WM microstructural alterations in SLE, which might be related with cognitive deficits or emotional distress symptoms. This provides a better understanding of the pathological mechanism of microstructural brain abnormalities in SLE.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Lúpus Eritematoso Sistêmico/patologia , Substância Branca/diagnóstico por imagem , Anisotropia , Corpo Caloso/diagnóstico por imagem , Humanos , Neuroimagem
17.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445192

RESUMO

Given the functional attributes of Doublecortin-like kinase 1 (DCLK1) in tumor growth, invasion, metastasis, cell motility, and tumor stemness, it is emerging as a therapeutic target in gastrointestinal cancers. Although a series of specific or nonspecific ATP-competitive inhibitors were identified against DCLK1, different types of scaffolds that can be utilized for the development of highly selective inhibitors or structural understanding of binding specificities of the compounds remain limited. Here, we present our work to repurpose a Janus kinase 1 inhibitor, ruxolitinib as a DCLK1 inhibitor, showing micromolar binding affinity and inhibitory activity. Furthermore, to gain an insight into its interaction mode with DCLK1, a crystal structure of the ruxolitinib-complexed DCLK1 has been determined and analyzed. Ruxolitinib as a nonspecific DCLK1 inhibitor characterized in this work is anticipated to provide a starting point for the structure-guided discovery of selective DCLK1 inhibitors.


Assuntos
Antineoplásicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Antineoplásicos/química , Quinases Semelhantes a Duplacortina , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Simulação de Acoplamento Molecular , Nitrilas , Conformação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Pirazóis/química , Pirimidinas
18.
Front Endocrinol (Lausanne) ; 12: 658198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012420

RESUMO

Objective: Type 2 diabetes mellitus (T2DM) is often accompanied by cognitive decline and depressive symptoms. Numerous diffusion tensor imaging (DTI) studies revealed microstructural white matter (WM) abnormalities in T2DM but the findings were inconsistent. The present study aimed to conduct a coordinate-based meta-analysis (CBMA) to identify statistical consensus of DTI studies in T2DM. Methods: We performed a systematic search on relevant studies that reported fractional anisotropy (FA) differences between T2DM patients and healthy controls (HC). The anisotropic effect size seed-based d mapping (AES-SDM) approach was used to explore WM alterations in T2DM. A meta-regression was then used to analyze potential influences of sample characteristics on regional FA changes. Results: A total of eight studies that comprised 245 patients and 200 HC, along with 52 coordinates were extracted. The meta-analysis identified FA reductions in three clusters including the left inferior network, the corpus callosum (CC), and the left olfactory cortex. Besides, FA in the CC was negatively correlated with body mass index (BMI) in the patients group. Conclusions: T2DM could lead to subtle WM microstructural alterations, which might be associated with cognitive deficits or emotional distress symptoms. This provides a better understanding of the pathophysiology of neurodegeneration and complications in T2DM. Systematic Review Registration: Registered at PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42020218737.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Anisotropia , Índice de Massa Corporal , Cognição , Corpo Caloso/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/psicologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/anatomia & histologia , Substância Branca/fisiopatologia , Adulto Jovem
19.
Korean J Radiol ; 22(8): 1397-1415, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33987995

RESUMO

The use of pediatric cardiothoracic CT for congenital heart disease (CHD) was traditionally limited to the morphologic evaluation of the extracardiac thoracic vessels, lungs, and airways. Currently, the applications of CT have increased, owing to technological advancements in hardware and software as well as several dose-reduction measures. In the previously published part 1 of the guideline by the Asian Society of Cardiovascular Imaging Congenital Heart Disease Study Group, we reviewed the prerequisite technical knowledge for clinical applications in a user-friendly and vendor-specific manner. Herein, we present the second part of our guideline on contemporary clinical applications of pediatric cardiothoracic CT for CHD based on the consensus of experts from the Asian Society of Cardiovascular Imaging CHD Study Group. This guideline describes up-to-date clinical applications effectively in a systematic fashion.


Assuntos
Cardiopatias Congênitas , Criança , Consenso , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X
20.
ACS Appl Mater Interfaces ; 13(2): 2462-2471, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33411498

RESUMO

The rational design and construction of multifunctional electrocatalysts with high activity, low cost, and outstanding stability are highly desirable for the development of renewable energy but are still a big challenge. Bimetallic catalysts are a kind of promising candidates, like the hybrids of Co and VN nanoparticles (Co/VN). However, the inevitable aggregation during the preparation and electrochemical process lowers their reactivity and durability. Herein, small Co/VN nanoparticles (4-8 nm) embedded in porous graphitic carbon layers (Co/VN NPs@C) were obtained through the pyrolysis of metal-organic frameworks (MOFs). The synergistic effect of in situ generated Co and VN NPs together with fast electron transfer from graphitic carbon layers renders this catalyst to possess excellent trifunctional performance. More attractively, Co/VN NPs@C as both the anode and the cathode shows a low voltage of 1.58 V when the current density is up to 10 mA cm-2, exceeding most electrocatalysts based on non-noble metals. The rechargeable Zn-air batteries constructed by Co/VN NPs@C deliver high round-trip efficiency together with a peak power density of 130 mW cm-2, a specific capacity of 757 mAh g-1, and desirable stability, outperforming the traditional Zn-air batteries based on the Pt/C and RuO2 pair. This work opens a promising avenue toward constructing highly effective multifunctional electrocatalysts by designing small-sized nanoparticles with various active sites derived from MOFs.

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