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In this work, Pt3Fe nanoparticles (Pt3Fe NPs) with the ordered internal structure and Pt-rich shells surrounded by plenty of Fe single atoms (Fe SAs) as active species (Pt3Fe NP-in-Fe SA) loaded in the carbon materials are successfully fabricated, which are abbreviated as island-in-sea structured (IISS) Pt3Fe NP-in-Fe SA catalysts. Moreover, the synergistic effect of O-bridging between Pt3Fe NPs and Fe SAs, and the ordered internal structured Pt3Fe NPs with Pt-rich shells of an optimal thickness contributes to the achievement of the local acidic environments on the surfaces of Pt3Fe NPs in the alkaline hydrogen evolution reaction (HER) and the enhancement of the desorption rate of *OH intermediate in the acidic oxygen reduction reaction (ORR). In addition, the electronic interactions between Pt3Fe NPs and dispersed Fe SAs cannot only provide efficient electrons transfer, but also prevent the aggregation and dissolution of Pt3Fe NPs. Furthermore, the overpotential and the half wave potential of the as-prepared IISS Pt3Fe NP-in-Fe SA catalysts toward the alkaline HER and toward the acidic ORR are 8 mV at a current density of 10 mA cm-2 and 0.933 V, respectively, which is 29 lower and 86 mV higher than those (37 mV and 0.847 V) of commercial Pt/C catalysts.
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BACKGROUND: Previously, we revealed noticeable dynamic fluctuations in syndecan-1 levels in the peripheral blood of post-stroke patients. We further investigated the clinical prognostic value of syndecan-1 as a biomarker of glycoprotein damage in patients with acute ischaemic stroke (AIS). METHODS: We examined 105 patients with acute large vessel occlusion in the anterior circulation, all of whom underwent mechanical thrombectomy (MT). Peripheral blood syndecan-1 levels were measured 1 day after MT, and patients were categorised into favourable and unfavourable prognostic groups based on the 90-day modified Rankin Scale (mRS) score. Additionally, we compared the clinical outcomes between groups with high and low syndecan-1 concentrations. RESULTS: The findings revealed a significantly lower syndecan-1 level in the group with an unfavourable prognosis compared to those with a favourable prognosis (p < 0.01). In the multivariable logistic regression analysis, lower syndecan-1 levels were identified as a predictor of unfavourable prognosis (odds ratio (OR) = 0.965, p = 0.001). Patients displaying low syndecan-1 expression in the peripheral blood (< 29.51 ng/mL) experienced a > twofold increase in the rates of unfavourable prognosis and mortality. CONCLUSIONS: Our study demonstrates that syndecan-1, as an emerging, easily detectable stroke biomarker, can predict the clinical outcomes of patients with AIS. After MT, low levels of syndecan-1 in the peripheral blood on the first day emerged as an independent risk factor for an unfavourable prognosis, suggesting that lower syndecan-1 levels might signify worse clinical presentation and outcomes in stroke patients undergoing this procedure.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Sindecana-1 , Humanos , Biomarcadores , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/cirurgia , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/cirurgia , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/etiologia , Sindecana-1/sangue , Sindecana-1/química , Trombectomia/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Cerebral ischemia (CI) induces a profound neuroinflammatory response, but the underlying molecular mechanism remains unclear. Exosomes from adipose-derived stem cells (ADSC-exos) have been found to play a crucial role in cell communication by transferring molecules including microRNAs (miRNAs), which have been shown to modulate the inflammatory response after CI and are viable molecular targets for altering brain function. The current study aimed to explore the contribution of ADSC-exosomal miR-21-5p to the neuroinflammation after CI. METHODS: The differentially expressed miR-21-5p in CI was screened based on literature search. The target mRNAs of miR-21-5p were predicted using online databases and verified by luciferase reporter assay. Then, BV2 cells were treated with hemin to simulate the inflammatory response after CI, and its animal model was induced using the MCAO method. Ischemia was evaluated in rats using 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining. ADSCs-exos were further isolated and identified by western blot analysis and transmission electron microscope. RESULTS: MiR-21-5p was significantly down-regulated in CI and alleviated neuropathic damage after CI by the PIK3R1/PI3K/AKT signaling axis. And miR-21-5p derived from ADSCs-exos alleviated neuroinflammation after CI via promoting microglial M2 polarization. CONCLUSION: We demonstrated that ADSC-exosomal miR-21-5p mitigated post-CI inflammatory response through the PIK3R1/PI3K/AKT signaling axis and could offer neuroprotection after CI through promoting polarization of M2 microglia.
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Modelos Animais de Doenças , Exossomos , MicroRNAs , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Exossomos/metabolismo , Exossomos/transplante , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Humanos , Linhagem Celular , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/genética , Doenças Neuroinflamatórias/metabolismo , Microglia/metabolismo , Microglia/patologia , Camundongos , Tecido Adiposo/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Pessoa de Meia-Idade , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
OBJECTIVE: Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead to high-performance blood tests towards GC diagnosis and prognosis. We attempted to develop diagnostic and prognostic models for GC based on plasma metabolic information. DESIGN: We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort and 264 participants in prospective cohort. Discovery and verification phases of diagnostic and prognostic models were conducted in retrospective cohort through machine learning and Cox regression of plasma metabolic fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, the developed diagnostic model was validated in prospective cohort by both NPELDI-MS and ultra-performance liquid chromatography-MS (UPLC-MS). RESULTS: We demonstrated the high throughput, desirable reproducibility and limited centre-specific effects of PMFs obtained through NPELDI-MS. In retrospective cohort, we achieved diagnostic performance with areas under curves (AUCs) of 0.862-0.988 in the discovery (n=1157 from 5 centres) and independent external verification dataset (n=787 from another 2 centres), through 5 different machine learning of PMFs, including neural network, ridge regression, lasso regression, support vector machine and random forest. Further, a metabolic panel consisting of 21 metabolites was constructed and identified for GC diagnosis with AUCs of 0.921-0.971 and 0.907-0.940 in the discovery and verification dataset, respectively. In the prospective study (n=264 from lead centre), both NPELDI-MS and UPLC-MS were applied to detect and validate the metabolic panel, and the diagnostic AUCs were 0.855-0.918 and 0.856-0.916, respectively. Moreover, we constructed a prognosis scoring system for GC in retrospective cohort, which can effectively predict the survival of GC patients. CONCLUSION: We developed and validated diagnostic and prognostic models for GC, which also contribute to advanced metabolic analysis towards diseases, including but not limited to GC.
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We employ the internally contracted multireference configuration interaction (icMRCI-F12) with Davidson corrections to explore the electronic states of monobromosilylene molecules (HSiBr). A total of 20 states with energy up to 8.7 eV and the corresponding 50 states after taking the spin-orbit coupling (SOC) effects into account are investigated. The spectroscopic constants of the low-lying states, as well as oscillator strengths, vertical transition energies and potential energy curves (PECs) for all the 20 spin-free states and the 50 spin-orbit-coupled states of HSiBr are presented. The results indicate that the SOC effect significantly affects the dissociation pathways and the PECs of electronic excited states of HSiBr. Based on our calculation results, the interactions between the states and the dissociation of HSiBr in the UV region are discussed. Our study sheds some light on the complex interactions and dynamics of the electronic excited states of HSiBr, which would provide valuable information for future experimental investigations.
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Podocyte injury is a major determinant of focal segmental glomerular sclerosis (FSGS) and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance for the treatment of FSGS. CLEC14A is a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family. CLEC14A is found to be expressed in vascular endothelial cells during embryogenesis and is also implicated in tumor angiogenesis. However, the current understanding of the biological functions of CLEC14A in podocyte is very limited. In this study, we found that CLEC14A was expressed in podocyte and protected against podocyte injury in mice with Adriamycin (ADR)-induced FSGS. First, we observed that CLEC14A was downregulated in mice with ADR nephropathy and renal biopsies from individuals with FSGS and other forms of podocytopathies. Moreover, CLEC14A deficiency exacerbated podocyte injury and proteinuria in mice with ADR nephropathy accompanied by enhanced inflammatory cell infiltration and inflammatory responses. In vitro, overexpression of CLEC14A in podocyte had pleiotropic protective actions, including anti-inflammatory and anti-apoptosis effects. Mechanistically, CLEC14A inhibited high-mobility group box 1 protein (HMGB1) release, at least in part by directly binding HMGB1, and suppressed HMGB1-mediated signaling, including NF-κB signaling and early growth response protein 1 (EGR1) signaling. Taken together, our findings provide new insights into the pivotal role of CLEC14A in maintaining podocyte function, indicating that CLEC14A may be an innovative therapeutic target in FSGS.
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Doxorrubicina/farmacologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Podócitos/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/fisiologia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Células Endoteliais/metabolismo , Glomerulosclerose Segmentar e Focal/metabolismo , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteinúria/metabolismo , Transdução de Sinais/fisiologiaRESUMO
We perform time-resolved polarization-dependent study on ultrafast dynamics in the A Ë 2 B2 state of NO2 . A linearly-polarized 400â nm femtosecond laser is used to resonantly pump NO2 to its first excited state A Ë 2 B2 , and the time-dependent ionic yields produced via strong field ionization at 800â nm are measured under different laser polarizations. The yield ratios measured with the lasers perpendicular and parallel to each other first decrease and then increases as the wave packet evolves on the excited state, with a minimum ratio at 180â fs delay time, which can be attributed to the evolution time in the A Ë 2 B2 state. The behavior of the time-resolved ionization in elliptically polarized laser field is also investigated and discussed.
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Gastric cancer is the fifth most frequently occurring and the fourth most lethal malignant cancer worldwide. A bioactive protein (pPe Op) from Omphalia lapidescens exhibits significant inhibitory effects on gastric cancer cells. miRNA deep sequencing analysis shows that miR-30b-5p is significantly upregulated in HGC-27 cells treated with pPe Op. Verification results show that the expression level of miR-30b-5p is significantly increased in HGC-27 cells after pPe Op treatment. Additionally, miR-30b-5p is significantly downregulated in clinical gastric cancer tissues compared to that in adjacent normal tissues. Following pPe Op treatment and/or transfection with miR-30b-5p mimic, the proliferation, migration, and invasion of HGC-27 cells are significantly impaired. Immunofluorescence microscopy shows that pPe Op and/or miR-30b-5p destroy(s) microfilaments and microstructures and inhibit(s) the formation of pseudopodia. Bioinformatics analysis, dual-luciferase reporter assay, and western blot analysis confirm that miR-30b-5p downregulates Rac1/Cdc42 expression and activation by targeting RAB22A. Available data indicate that miR-30b-5p plays an anti-gastric cancer role in mediating pPe Op. pPe Op upregulates miR-30b-5p expression, which in turn inhibits RAB22A expression, resulting in a reduction in the expression and activation of Rac1 and Cdc42 and their downstream targets, thus destroying the cytoskeletal structure and inhibiting the proliferation, migration, and invasion of cancer cells.
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MicroRNAs , Neoplasias Gástricas , Humanos , Movimento Celular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Transfecção , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Abscess of the mitral-aortic intervalvular fibrosa (MAIVF) is a rare occurrence, with its most frequently described causative associations being active or prior endocarditis, prosthetic valves, or native valves with anomalies. We report a case of infective endocarditis (IE) complicated by an abscess of the MAIVF without valvular involvement. This case highlights the importance of this rare clinical entity and of the multimodality imaging approach in reaching an accurate diagnosis and differential diagnosis. METHODS AND RESULTS: A 35-year-old male presented with fatigue and intermittent high-grade fever for a 2-week duration. IE was suspected based on a clinical exam. Transthoracic echocardiography (TTE) demonstrated heterogeneous mass with a size of about 2.9 cm × 2.3 cm coming from the MAIVF, mimicking an intracardiac mass. Color Doppler flow Imaging showed the mass without communication with the surrounding cardiovascular cavities. Cardiac computed tomography angiography (CCTA) revealed a large low-density mass without any enhancement, which was situated adjacent to the left ventricular tract with a severely compressed left atrial chamber. The patient underwent cardiac mass removal under extracorporeal circulation. During the procedure, a large abscess was found to be located in MAIVF. The postoperative course was uneventful. DISCUSSION: The abscess of MAIVF is a rare entity with a high risk of developing the pseudoaneurysm of MAIVF (p-MAIVF). The periaortic spread of the abscess is a dynamic process in which the inflammation of the deep tissue causes, in the first stage, a MAIVF thickening, which eventually progresses with the formation of an abscess, and subsequently, a pseudoaneurysm. Complications of p-MAIVF include rupture into the left atrium, aorta, or pericardial space leading to hemopericardium, tamponade, and death. The major differential diagnosis for abscess of MAIVF includes p-MAIVF an intracardiac mass. TTE plays a key role in the diagnosis and differential diagnosis of abscesses of MAIVF. CCTA can be a useful adjunct to further characterize abscess spread, three-dimensional spatial relationships with other cardiac structures for preoperative planning, as well as in the evaluation of potential complications such as coronary artery compromise and communication with the aorta, left atrium, or pericardial space. Surgical management is recommended in complicated, symptomatic patients to prevent further expansion of abscesses or pseudoaneurysms. CONCLUSION: The abscess of MAIVF is a rare complication of endocarditis and surgical trauma in the MAIVF area, TTE remains a first-line imaging modality for clinically suspected periaortic abscess or other IE complications. CCTA has a complementary role to echocardiography in identification, characterization, and preoperative planning.
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Falso Aneurisma , Endocardite Bacteriana , Endocardite , Abscesso/diagnóstico por imagem , Adulto , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Aorta , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Endocardite/complicações , Endocardite/diagnóstico por imagem , Endocardite Bacteriana/complicações , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgiaRESUMO
BACKGROUND: We report a hitherto unreported combination of pulmonary stenosis, single coronary artery anomaly and coronary sinus to left atrial communication. Our case highlights the important value of coronary computed tomographic angiography and transthoracic echocardiography for the diagnosis of such anomalies and guidance for proper management. METHODS AND RESULTS: A 64-year-old male presented chest tightness and shortness of breath for 2 days. Transthoracic echocardiography revealed a thickened pulmonary valve leaflet and subvalvular outflow tract stenosis, colour flow Doppler showed a significant accelerated blood flow in the pulmonary artery cavity originating from the subvalvular outflow tract, continuous wave Doppler revealed the transpulmonary valvular pressure gradient of 63mmHg. Computed tomographic angiography image reveals thickened pulmonary valve leaflets and subvalvular outflow tract stenosis, single coronary artery anomaly and levoatriocardinal vein. The patient underwent percutaneous pulmonary valve balloon dilatation, the post-procedural course was uneventful. DISCUSSION: Pulmonary stenosis can occur as part of more congenital cardiac malformations or as rare primary isolated pulmonary stenosis, which includes the valvular, sub-valvular, or supra-valvular pulmonary stenosis. Single coronary artery anomalies are very rare, anomalous right coronary artery originates from proximal to mid-left anterior descending coronary artery is one such single coronary artery anomaly, in most cases, it is asymptomatic, diagnosed incidentally, and a benign entity has a better prognosis except if the right coronary artery is passing between the aorta and pulmonary artery. This course of the right coronary artery anomaly is malignant. Coronary sinus to left atrial communication includes a direct or indirect communication. The direct communication is described as a partial or complete absence of the roof between the coronary sinus and left atrium, as it is well known as the unroofed coronary sinus syndrome. The indirect communication is an anomalous bridging vein communicating the coronary sinus to the left atrium, which can be distinguished from classical unroofed coronary sinus syndrome. The venous collateral channel communication between the coronary sinus to the left atrium by a bridging vein is also categorized as a variant type of unroofed coronary sinus syndrome. Understanding coronary venous variations has significant clinical implications particularly in the realm of electrophysiology. The anatomical variations can have important consequences for procedures such as biventricular pacing and trans-coronary vein ablations. CONCLUSION: Pulmonary stenosis combined with single coronary artery anomaly and bridging vein communication between the coronary sinus and the left atrium is an extremely rare. Coronary computed tomographic angiography and transthoracic echocardiographyplay an important role the diagnosis of such anomalies and guidance for clinical Treatment.
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Doença da Artéria Coronariana , Seio Coronário , Anomalias dos Vasos Coronários , Cardiopatias Congênitas , Comunicação Interatrial , Estenose da Valva Pulmonar , Constrição Patológica , Angiografia Coronária , Seio Coronário/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/cirurgia , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Comunicação Interatrial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estenose da Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/cirurgiaRESUMO
BACKGROUND: Abnormalities in drainage of the great cardiac vein (GCV) are interesting due to its rarity and likely to be underreported, with most cases found incidentally in cardiac imaging and autopsy studies. We report a case with anomalous drainage of the GCV into the LA, and the rest of the cardiac veins are draining normally. METHODS AND RESULTS: A 60-year-old male presented with heart palpitations for half a month. Electrocardiogram and laboratory tests showed no abnormalities. He was recommended for coronary computed tomography angiography (CCTA). The maximum intensity projection image of CCTA showed that the GCV draining into the left atrium, the rest of the cardiac veins, and coronary vein sinus were draining into the right atrium normally. Volume-rendered image of coronary CT angiography showed that the GCV originated in the upper third of the anterior interventricular sulcus and drained directly into the left atrium. DISCUSSION: Abnormalities in drainage of the GCV are interesting due to its rarity and likely to be underreported. Only a few cases have been reported that the aberrant drainage of the GCV, with draining into the anterior cardiac veins, the left internal thoracic vein, the superior vena cava, the right atrium, and the LA. The abnormality of GCV is an often neglected aspect of CCTA imaging, it can be better displayed in the venous phase of coronary catheter angiography. The awareness of which may be critically important for procedures that require venous access such as coronary surgery requiring retrograde cardioplegia, surgical ablation of aberrant conducting pathways, pacemaker insertion, and valves surgery. CONCLUSION: This variant of the GCV is interesting due to its rarity. CCTA has important diagnostic imaging value in abnormalities of the origin, course, and termination of the GCVs, the variant can be better displayed in the venous phase of coronary catheter angiography.
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Seio Coronário , Veia Cava Superior , Angiografia Coronária , Seio Coronário/diagnóstico por imagem , Seio Coronário/cirurgia , Drenagem , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Veia Cava Superior/anormalidades , Veia Cava Superior/diagnóstico por imagem , Veia Cava Superior/cirurgiaRESUMO
BACKGROUND: Left atrial anomalous fibromuscular cord is a rare congenital anomaly, which exists in a small proportion of the general population. Although its clinical significance remains largely unknown, it is generally considered a benign entity. We report a case of incidental finding of left atrial fibromuscular cord without structural cardiac abnormalities or hemodynamic obstruction. METHODS AND RESULTS: A-39-year-old female presented with palpitations for more than 10 years. Electrocardiogram and laboratory tests showed no unremarkable. Transthoracic echocardiography revealed an abnormal linear structure connecting the interatrial septum and the left atrial free wall, color Doppler flow imaging did not show hemodynamic obstruction. Cardiac contrast-enhanced computed tomography images showed the string-like structure associated with calcification, connecting the interatrial septum and the ridge around the orifice of the left inferior pulmonary vein. Sagittal multiplanar reconstructed image showed a dot-like structure located in the left atrial cavity. DISCUSSION: Left atrial anomalous fibromuscular cord is a rare congenital anomaly, which is also known as left atrial anomalous fibromuscular cord, left atrial false tendon, accessory chordae tendineae, or left atrial aberrant band. The clinical significance is unclear. Some cases have been reported that the fibromuscular cord, which do not have pathological significance. It has also been reported that it may be associated with supraventricular arrhythmias, patent foramen ovale, and Chiai's network. In some patients, attachment to the mitral chord can lead to mitral valve insufficiency and murmur. Nevertheless, a detailed understanding the anomalous anatomical characteristics of the anomalous cord may help us to better predict an unexpected difficulty in catheter manipulation, and potential arrhythmogenicity. CONCLUSION: Transthoracic echocardiography and cardiac computed tomography angiography have an important imaging value for the diagnosis of the left atrial anomalous fibromuscular cord, including its origin, course, or whether associated with other cardiovascular malformations.
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Cardiopatias Congênitas , Comunicação Interatrial , Insuficiência da Valva Mitral , Arritmias Cardíacas , Cordas Tendinosas/anormalidades , Feminino , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Cardiopatias Congênitas/complicações , Comunicação Interatrial/complicações , Humanos , Insuficiência da Valva Mitral/complicaçõesRESUMO
BACKGROUND: Genetic research on longevity has provided important insights into the mechanism of aging and aging-related diseases. Pinpointing import genetic variants associated with aging could provide insights for aging research. METHODS: We performed a whole-genome sequencing in 19 centenarians to establish the genetic basis of human longevity. RESULTS: Using SKAT analysis, we found 41 significantly correlated genes in centenarians as compared to control genomes. Pathway enrichment analysis of these genes showed that immune-related pathways were enriched, suggesting that immune pathways might be critically involved in aging. HLA typing was next performed based on the whole-genome sequencing data obtained. We discovered that several HLA subtypes were significantly overrepresented. CONCLUSIONS: Our study indicated a new mechanism of longevity, suggesting potential genetic variants for further study.
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Envelhecimento/genética , Povo Asiático/genética , Testes Genéticos/métodos , Variação Genética , Estudo de Associação Genômica Ampla , Sequenciamento Completo do Genoma/métodos , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoRESUMO
The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.
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Adenocarcinoma/diagnóstico , Antineoplásicos/uso terapêutico , Misturas Complexas/uso terapêutico , Neoplasias Esofágicas/diagnóstico , Junção Esofagogástrica , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/metabolismo , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Análise Serial de Tecidos , Trametes , Resultado do TratamentoRESUMO
Ultrafast time-resolved strong field ionization-photofragmentation (SFI-PF) has emerged as a useful method for investigation of dynamics of molecular cations. Here we perform a SFI-PF study on the electronic states of toluene cations. By measuring the ion yields as a function of delay time, we obtain the transients of both parent and daughter ions, which show ultrafast decays and out-of-phase oscillations. The results provide the first experimental evidence of D1-D0 ultrafast relaxation of toluene cations occurring in about 530 fs and indicate coincident resonance between the vibrational states in D1 and D0 leading to oscillations with a period of about 2.05 ps. Our study should shed some light on the ultrafast photochemistry involving complex molecular cations.
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The effects of PADI4 and GAA on the senescence of Alzheimer's cells were explored in the present work. HT22 cells were treated with Aß25-35 to establish an Alzheimer's model and were then treated with different concentrations of GAA and transfected with a siPADI4 lentiviral vector. GAA could reverse the effects of Aß25-35 on inhibiting cell viability and promoting apoptosis and senescence. siPADI4 reduced Aß25-35-induced cell viability and upregulated Aß25-35-induced cell apoptosis and senescence, as well as partially reversed the effect of GAA on cells, and these results were confirmed by detecting the expressions of senescence- and apoptosis-related proteins. In addition, siPADI4 was found to promote the phosphorylation of Akt and mTOR, which was partially reversed by GAA. In conclusion, PADI4 mediates autophagy and participates in the role of GAA monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway.
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Doença de Alzheimer/patologia , Autofagia/fisiologia , Senescência Celular/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Lanosterol/análogos & derivados , Proteína-Arginina Desiminase do Tipo 4/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Linhagem Celular , Ácidos Heptanoicos/química , Humanos , Lanosterol/química , Lanosterol/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial-mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC-823 were treated with cisplatin. Down-regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer.
Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , HumanosRESUMO
Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS). Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome. Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5-CD28- group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H- and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed.
Assuntos
Antígenos B7/metabolismo , Biomarcadores Tumorais/metabolismo , Antígenos CD28/metabolismo , Neoplasias Gástricas/mortalidade , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
Two anthracene-based complexes [Ir(pbt)2(aip)]Cl (1) and [Ir(pbt)2(aipm)]Cl (2) have been synthesized based on the ligands aip = 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline, aipm = 2-(9-anthryl)-1-methyl-imidazo[4,5-f][1,10]phenanthroline, and pbtH = 2-phenylbenzothiazole in order to explore both the influence of the substituent group R1 (R1 = H in 1 and CH3 in 2) on photo-oxidation activity and photo-oxidation-induced luminescence. Both 1H NMR spectra and ES mass spectra indicate that the anthracene moiety in complex 1 can be oxidized at room temperature upon irradiation with 365 nm light. Thus, this complex shows photo-oxidation-induced turn-on yellow luminescence. Compared to 1, complex 2 incorporates an R1 = CH3 group, resulting in very weak photo-oxidation activity. On the basis of experimental results and quantum chemical calculation, we report the differences between 1 and 2 in both photo-oxidation behavior and the related luminescence modulation and discuss the relationship between photo-oxidation activity and substituent group R1 in these complexes.
RESUMO
In this study, the effects of electro-dewatering technology applied to high-salt industrial sludge dewatering performance were investigated, in terms of ions migrations and distributions by model simulation and layered tests. The simulation results of Na+ and K+ migrations were consistent with layered experiments during electro-dewatering, where Na+ ions migrated faster than K+ ions. More than 80% Na+ ions were removed by electromigration, which would be useful in subsequent sludge utilization. The mass specific energy consumption was reduced from 350.08 to 295.88â¯kWh per ton sludge by means of piecewise voltage electro-dewatering method. This study provided insights into the soluble ions migration and distribution mechanism in electro-dewatering process, and a method to improve commercial application performance of high-salt industrial sludge electro-dewatering.