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Tumor-derived extracellular vesicles are important mediators of cell-to-cell communication during tumorigenesis. Here, we demonstrated that hepatocellular carcinoma (HCC)-derived ectosomes remodel the tumor microenvironment to facilitate HCC progression in an ectosomal PKM2-dependent manner. HCC-derived ectosomal PKM2 induced not only metabolic reprogramming in monocytes but also STAT3 phosphorylation in the nucleus to upregulate differentiation-associated transcription factors, leading to monocyte-to-macrophage differentiation and tumor microenvironment remodeling. In HCC cells, sumoylation of PKM2 induced its plasma membrane targeting and subsequent ectosomal excretion via interactions with ARRDC1. The PKM2-ARRDC1 association in HCC was reinforced by macrophage-secreted cytokines/chemokines in a CCL1-CCR8 axis-dependent manner, further facilitating PKM2 excretion from HCC cells to form a feedforward regulatory loop for tumorigenesis. In the clinic, ectosomal PKM2 was clearly detected in the plasma of HCC patients. This study highlights a mechanism by which ectosomal PKM2 remodels the tumor microenvironment and reveals ectosomal PKM2 as a potential diagnostic marker for HCC.
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Proteínas de Transporte/metabolismo , Micropartículas Derivadas de Células/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Micropartículas Derivadas de Células/genética , Micropartículas Derivadas de Células/patologia , Quimiocina CCL1/metabolismo , Progressão da Doença , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Monócitos/metabolismo , Prognóstico , Fator de Transcrição STAT3/metabolismo , Hormônios Tireóideos/genética , Microambiente Tumoral , Proteínas de Ligação a Hormônio da TireoideRESUMO
Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPß, a rate-limiting enzyme in FAO. Although TPß activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPß association results in Nur77 self-sacrifice to protect TPß from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPß interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.
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Melanoma/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Animais , Sobrevivência Celular/fisiologia , Ácidos Graxos/metabolismo , Glucose/metabolismo , Células HEK293 , Humanos , Metabolismo dos Lipídeos , Melanoma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , Subunidade beta da Proteína Mitocondrial Trifuncional/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Doxorubicin is an effective chemotherapy drug for treating various types of cancer. However, lethal cardiotoxicity severely limits its clinical use. Recent evidence has indicated that aberrant activation of the cytosolic DNA-sensing cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING (stimulator of interferon genes) pathway plays a critical role in cardiovascular destruction. Here, we investigate the involvement of this mechanism in doxorubicin-induced cardiotoxicity (DIC). METHODS: Mice were treated with low-dose doxorubicin to induce chronic DIC. The role of the cGAS-STING pathway in DIC was evaluated in cGAS-deficiency (cGAS-/-), Sting-deficiency (Sting-/-), and interferon regulatory factor 3 (Irf3)-deficiency (Irf3-/-) mice. Endothelial cell (EC)-specific conditional Sting deficiency (Stingflox/flox/Cdh5-CreERT) mice were used to assess the importance of this pathway in ECs during DIC. We also examined the direct effects of the cGAS-STING pathway on nicotinamide adenine dinucleotide (NAD) homeostasis in vitro and in vivo. RESULTS: In the chronic DIC model, we observed significant activation of the cGAS-STING pathway in cardiac ECs. Global cGAS, Sting, and Irf3 deficiency all markedly ameliorated DIC. EC-specific Sting deficiency significantly prevented DIC and endothelial dysfunction. Mechanistically, doxorubicin activated the cardiac EC cGAS-STING pathway and its target, IRF3, which directly induced CD38 expression. In cardiac ECs, the cGAS-STING pathway caused a reduction in NAD levels and subsequent mitochondrial dysfunction via the intracellular NAD glycohydrolase (NADase) activity of CD38. Furthermore, the cardiac EC cGAS-STING pathway also regulates NAD homeostasis and mitochondrial bioenergetics in cardiomyocytes through the ecto-NADase activity of CD38. We also demonstrated that pharmacological inhibition of TANK-binding kinase 1 or CD38 effectively ameliorated DIC without compromising the anticancer effects of doxorubicin. CONCLUSIONS: Our findings indicate a critical role of the cardiac EC cGAS-STING pathway in DIC. The cGAS-STING pathway may represent a novel therapeutic target for preventing DIC.
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Cardiotoxicidade , Transdução de Sinais , Camundongos , Animais , NAD/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Doxorrubicina/toxicidadeRESUMO
The oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are core steps of various energy conversion and storage systems. However, their sluggish reaction kinetics, i.e., the demanding multielectron transfer processes, still render OER/ORR catalysts less efficient for practical applications. Moreover, the complexity of the catalyst-electrolyte interface makes a comprehensive understanding of the intrinsic OER/ORR mechanisms challenging. Fortunately, recent advances of in situ/operando characterization techniques have facilitated the kinetic monitoring of catalysts under reaction conditions. Here we provide selected highlights of recent in situ/operando mechanistic studies of OER/ORR catalysts with the main emphasis placed on heterogeneous systems (primarily discussing first-row transition metals which operate under basic conditions), followed by a brief outlook on molecular catalysts. Key sections in this review are focused on determination of the true active species, identification of the active sites, and monitoring of the reactive intermediates. For in-depth insights into the above factors, a short overview of the metrics for accurate characterizations of OER/ORR catalysts is provided. A combination of the obtained time-resolved reaction information and reliable activity data will then guide the rational design of new catalysts. Strategies such as optimizing the restructuring process as well as overcoming the adsorption-energy scaling relations will be discussed. Finally, pending current challenges and prospects toward the understanding and development of efficient heterogeneous catalysts and selected homogeneous catalysts are presented.
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Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs. non-ICU admission). A recently introduced alpha-index identified the 30 most predictive genetic variants. DERGA algorithm, which employs multiple classification algorithms, determined the optimal pattern of these key variants, resulting in 97% accuracy for predicting disease outcome. Individual variations ranged from 40 to 161 variants per patient, with 977 total variants detected. This study demonstrates the utility of alpha-index in ranking a substantial number of genetic variants. This approach enables the implementation of well-established classification algorithms that effectively determine the relevance of genetic variants in predicting outcomes with high accuracy.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/genética , Inteligência Artificial , AlgoritmosRESUMO
The effective separation of aromatic and aliphatic hydrocarbons remains a notable challenge in the petrochemical industry. Herein, we report a self-healing three-dimensional B â N-based hydrogen-bonded organic framework (HOF), BN-HOF-1, constructed from discrete B â N inclusive dimers through weak C-H···F and C-H···N hydrogen-bonding interactions. To make use of the specific recognition of the B â N inclusive dimers for the toluene molecules and the reversible ad/desorption nature of this novel HOF, BN-HOF-1 can exclusively recognize and separate toluene from the mixtures of toluene-methylcyclohexane, thus generating 99.6% pure toluene from its mixtures after gentle heating, the recorded value among any reported materials for toluene purification. After the toluene molecules were released from the framework, it becomes the condensed BN-HOF-1a, which can be further reused for the highly selective recognition and purification of toluene from its binary mixtures, through the reversible structural recovery back to BN-HOF-1. Single-crystal X-ray diffraction and molecular modeling studies reveal that the high specific toluene recognition is attributed to the complementary electrostatic potential between the host B â N inclusive dimers and the guest toluene, while the self-healing and recovery nature of this HOF is attributed to weak intermolecular hydrogen-bonding interactions.
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Broadband room-temperature photodetection has become a pressing need as application requirements for communication, imaging, spectroscopy, and sensing have evolved. Topological insulators (TIs) have narrow bandgap structures with a wide absorption spectral response range, which should meet the requirements of broadband detection. However, owing to their high carrier concentration and low carrier mobility resulting in poor noise equivalent power (NEP), they are generally considered unsuitable for photodetection. Here, InBiTe3 alloy nanosheet formed by doping In2Te3 into Bi2Te3(≈ 1:1) is utilized, effectively improving carrier mobility by over ten times while maintaining a narrow bandgap structure, to fabricate a broadband photodetector covering a wide response range from visible to millimeter wave (MMW). Under the synergistic multi-mechanism of the photoelectric effect in the visible-infrared region and the electromagnetic-induced potential well (EIW) effect in Terahertz band, the performance of NEP = 75 pW Hz-1/2 and response time τ ≈100 µs in visible to infrared band and the performance of NEP = 6.7 × 10-3 pW Hz-1/2, τ ≈8 µs in Terahertz region are achieved. The results demonstrate the promising prospects of topological insulator alloy (like InBiTe3) nanosheet in optoelectronic detection applications and provide a direction for the research into high-performance broadband photoelectric detectors via TIs.
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BACKGROUND: Minimally invasive sub-lobectomy is sufficient in treating small early-stage non-small cell lung cancer (NSCLC). However, comparison of the feasibility and oncologic efficacy between robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in performing sub-lobectomy for early-stage NSCLC patients age 80 years or older is scarce. METHODS: Octogenarians with clinical stage IA NSCLC (tumor size, ≤ 2 cm) undergoing minimally invasive wedge resection or segmentectomy at Shanghai Chest Hospital from 2011 to 2020 were retrospectively reviewed from a prospectively maintained database. Propensity score-matching (PSM) with a RATS versus VATS ratio of 1:4 was performed. Perioperative and long-term outcomes were analyzed. RESULTS: The study identified 594 patients (48 RATS and 546 VATS patients), and PSM resulted in 45 cases in the RATS group and 180 cases in the VATS group. The RATS patients experienced less intraoperative bleeding (60 mL [interquartile range (IQR), 50-100 mL] vs. 80 mL [IQR, 50-100 mL]; P = 0.027) and a shorter postoperative hospital stay (4 days [IQR, 3-5 days] vs. 5 days [IQR, 4-6 days]; P = 0.041) than the VATS patients. The two surgical approaches were comparable concerning other perioperative outcomes and postoperative complications (20.00% vs. 26.11%; P = 0.396). Additionally, during a median follow-up period of 66 months, RATS and VATS achieved comparable 5-year overall survival (90.48% vs. 87.93%; P = 0.891), recurrence-free survival (83.37% vs. 83.18%; P = 0.782), and cumulative incidence of death. Further subgroup comparison also demonstrated comparable long-term outcomes between the two approaches. Finally, multivariate Cox analysis indicated that the surgical approach was not independently correlated with long-term outcomes. CONCLUSIONS: The RATS approach shortened the postoperative hospital stay, reduced intraoperative bleeding by a statistically notable but clinically insignificant amount, and achieved long-term outcomes comparable with VATS in performing sub-lobectomy for octogenarians with early-stage small NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Robótica , Idoso de 80 Anos ou mais , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Octogenários , Pontuação de Propensão , Pneumonectomia , China , Cirurgia Torácica Vídeoassistida/métodosRESUMO
OBJECTIVE: Bone mineral density (BMD) is typically reduced in patients with female athlete triad (FAT) and anorexia nervosa (AN). However, bone health in most patients with functional hypothalamic amenorrhoea (FHA), who may not suffer from severe energy deficiency, has not received adequate attention in clinical practice. This study aimed to investigate BMD and its association with clinical and endocrine features in individuals with FHA and to provide clinical evidence for improving bone loss and preventing osteoporosis in FHA. DESIGN: To assess the bone status of patients with FHA and investigate its association with various clinical and endocrinological characteristics. PATIENTS: We retrospectively analysed 80 patients with FHA who attended the Obstetrics and Gynecology Hospital of Fudan University from January 2022 to March 2023. MEASUREMENTS: The levels of reproductive hormones, including luteinising hormone (LH), follicle-stimulating hormone, oestradiol (E2 ) and total testosterone (TT), were examined at the time of initial diagnosis, and a body composition analyser was used to measure body fat percentage (BF%), lean body mass (LBM) and segmental muscle/fat. Dual-emission X-ray absorptiometry was used to measure lumbar spine BMD and femoral neck BMD in patients with FHA, and the Z score was calculated. RESULTS: The study cohort consisted of 80 female patients with FHA. The average age of the patients was 24.64 ± 6.02 years, and their body mass index (BMI) was 19.47 ± 2.86 kg/m2 . The duration of weight loss was 12 (6, 24) months, while the duration of oligo/amenorrhoea was 12 (4.5, 24) months. The mean degree of weight loss was 18.39 ± 9.53%. Low BMD were present in 15% of patients with FHA at the lumbar spine and/or femoral neck; 12.5% and 10% had low bone mass at the lumbar spine and femoral neck, respectively. The low bone mass group experienced a longer period of weight loss than the normal group [24 (16.5, 60) vs. 12 (4.5, 24) months, p = .037]. In addition, the abnormal group had a lower BMR (basal metabolic rate, BMR) [1158 ± 85 vs. 1231 ± 91 kcal/day, p = .011] and lower bone mineral content [2.15 ± 0.26 vs. 2.43 ± 0.31 kg, p = .009] than the normal group. Both LBMD and femoral neck BMD (Fn BMD) were positively correlated with BMI, BF%, LBM, and regional muscle/fat mass (all p < .05). There was also a positive correlation between LBMD and basal LH levels (p = .009) and waist-to-hip ratio (p = .034), whereas Fn BMD was positively correlated with TT levels (p = .029). Multiple linear regression analysis showed that LBM was positively associated with LBMD (ß = .007, 95% confidence interval [CI] = 0.004-0.009, p < .001), while trunk muscle mass was positively associated with Fn BMD (ß = .046, 95% CI = 0.013-0.080, p = .008). CONCLUSION: Fifteen percent of the patients with FHA exhibited low bone mass, a condition associated with prolonged weight loss. The basal LH and TT levels showed positive correlations with LBMD and Fn BMD, respectively. Meanwhile, BMR levels, BMI, BF%, and muscle mass were all positively correlated with LBMD and Fn BMD. Clinically, we should be attentive to suboptimal bone health in patients with FHA and take early screening, diagnosis and intervention measures, especially appropriate muscle mass gain, to prevent the onset of osteoporosis and fragility fractures in the long term.
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Densidade Óssea , Osteoporose , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Densidade Óssea/fisiologia , Amenorreia , Estudos Retrospectivos , Absorciometria de Fóton , Composição Corporal/fisiologia , Colo do Fêmur , Testosterona , Redução de PesoRESUMO
Optical metasurfaces offer high-efficiency and flexible wavefront shaping for near-eye displays, especially in wideband waveguide couplers accommodating RGB primary colors. By leveraging the resonance characteristics of sub-wavelength periodic nanostructures, metasurfaces surpass the limitations of traditional optics that rely on multiple components and mediums. In this study, we propose adjustment of the imaginary parts of the material refractive indices as a new method to achieve balanced first-order diffraction efficiencies among RGB colors over a wide field of view (FOV) in an in-coupling metasurface waveguide coupler. Physical mechanism is investigated deeply and systematically in theory. It is found that nanostructure resonances deflect the wavefront and Poynting vector, significantly enhancing first-order diffraction efficiency, while resonance-enhanced absorption plays a crucial role in balancing the diffraction efficiency of RGB primary colors. First experimental demonstration well confirms the practical feasibility of this method and a uniform first-order diffraction efficiency of approximately 20% is achieved among RGB colors across a FOV as large as â¼30° over a single-piece glass substrate. This research provides insights into the design and mechanisms of metasurface waveguide couplers, advancing our understanding of metasurface-based RGB displays and facilitating further advancements in this field.
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High power and high brightness laser lighting puts forward new requirements for phosphor converters such as high luminous efficiency, high thermal conductivity and high saturation threshold due to the severe thermal effect. The structure design of phosphor converters is proposed as what we believe to be a novel strategy for less heat production and more heat conduction. In this work, the rod-shaped YAG:Ce phosphor ceramics (PCs) and disc-shaped YAG:Ce PCs as control group were fabricated by the gel casting and vacuum sintering, to comparatively study the luminescence performance for LD lighting, on the premise that the total number of transverse Ce3+ ions and the volume of samples from two comparison groups were same. All rod YAG:Ce PCs with low Ce3+ concentration exhibited the high luminous efficiency and better thermal stability than YAG:Ce discs with high Ce3+ concentration. Under the laser power density of 47.8 W/mm2, the luminous saturation was never observed in all rod-shaped YAG:Ce PCs. The high luminous efficacy of 245â¼274 lm/W, CRI of 56.3â¼59.5 and CCT of 4509â¼4478â K were achieved. More importantly, due to the extremely low Ce3+ doping concentration (0.01 at%), rod-shaped ceramics based LDs devices showed the excellent thermal performance and their surface temperatures were even below 30.5 °C surprisingly under the laser power density of 20.3 W·mm-2 (2 W). These results indicate that the rod shape of phosphor converter is a promising structure engineering for high power laser lighting.
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Lu3Al5O12:Ce (LuAG:Ce) phosphor ceramics (PCs) with the excellent thermal stability and high saturation threshold are considered as the best green-fluorescent converters for high-power laser diodes (LDs) lighting. In this study, the effects of sintering additives and sintering processes on the transmittance and microstructure of LuAG:Ce PCs were systematically studied, and the luminescence performance of ceramics with different transmittance was compared. LuAG:Ce PCs with the transmittance of 80% (@800â nm, 1.5 mm) were obtained by using 0.1 wt.% MgO and 0.5 wt.% TEOS as sintering additives, combined with optimized vacuum pre-sintering and hot isostatic pressing. Compared to the non-HIP samples, the transmittance had increased by 11%. The microstructure of ceramics indicated that high transparency was closely related to the decrease in intergranular pores. Notably, the luminous efficiency of 253 lm/W and its saturation thresholds of > 46 W/mm2 were obtained simultaneously in green-emitting LDs devices. Moreover, under 3W laser irradiation, highly transparent ceramics had the low surface temperature of 66.4 °C, indicating the good heat dissipation performance. The observed high luminous efficiency and high saturation threshold of LuAG:Ce PCs were attributed to fewer pores and oxygen vacancies. Therefore, this work proves that highly transparent LuAG:Ce PCs are promising green-fluorescent converters for high-power LDs lighting.
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BACKGROUND: A consensus on normal atrial deformation measurements by feature-tracking cardiac MRI remained absent. PURPOSE: Provide reference ranges for atrial strain parameters in normal subjects, evaluating the influence of field strength and analysis software on the measurements. STUDY TYPE: Meta-analysis. POPULATION: 2708 subjects from 42 studies undergoing cardiac MRI. ASSESSMENT: A systematic search was conducted from database (PubMed, Web of Science, ScienceDirect, and EMBASE) inception through August 2023. The random-effects model was used to pool the means of biatrial strain parameters. Heterogeneity and clinical variable effects were assessed. Strain measurements among different field strengths and analysis software were compared. STATISTICAL TESTS: The inverse-variance method, Cochrane Q statistic, and I2 value, meta-regression analysis, and ANOVA were used; P < 0.05 was considered statistically significant. RESULTS: The pooled means of left atrial (LA) total strain (εs), passive strain (εe), and active strain (εa) were 37.46%, 22.73%, and 16.24%, respectively, and the pooled means of LA total strain rate (SRs), passive strain rate (SRe), and active strain rate (SRa) were 1.66, -1.95, and -1.83, indicating significant heterogeneity. The pooled means of right atrial (RA) εs, εe, and εa were 44.87%, 26.05%, and 18.83%. RA SRs, SRe, and SRa were 1.66, -1.95, and -1.83, respectively. The meta-regression identified age as significantly associated with LA εs, εe and SRe, field strength was associated with LA SRa (all P < 0.05). ANOVA revealed differences in LA εa and SRa among different analysis software and in LA εs and all LA strain rates (all P < 0.05) among field strengths. No significant differences were identified in RA strain across analysis software (RA strain: P = 0.145-0.749; RA strain rates: P = 0.073-0.744) and field strengths (RA strain: P = 0.641-0.794; RA strain rates: P = 0.204-0.458). DATA CONCLUSION: This study demonstrated the pooled reference values of biatrial strain. Age, analysis software, and field strength were attributed to differences in LA strain, whereas RA strain showed consistency across different field strengths and analysis software. Limited study subjects may account for the absence of influence on RA strain. TECHNICAL EFFICACY: Stage 5.
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OBJECTIVES: Parametric mapping constitutes a novel cardiac magnetic resonance (CMR) technique enabling quantitative assessment of pathologic alterations of left ventricular (LV) myocardium. This study aimed to investigate the clinical utility of mapping techniques with and without contrast agent compared to standard CMR to predict adverse LV remodeling following acute myocardial infarction (AMI). MATERIALS AND METHODS: A post hoc analysis was performed on sixty-four consecutively enrolled patients (57 ± 12 years, 54 men) with first-time reperfused AMI. Baseline CMR was obtained at 8 ± 5 days post-AMI, and follow-up CMR at 6 ± 1.4 months. T1/T2 mapping, T2-weighted, and late gadolinium enhancement (LGE) acquisitions were performed at baseline and cine imaging was used to determine adverse LV remodeling, defined as end-diastolic volume increase by 20% at 6 months. RESULTS: A total of 11 (17%) patients developed adverse LV remodeling. At baseline, patients with LV remodeling showed larger edema (30 ± 11 vs. 22 ± 10%LV; p < 0.05), infarct size (24 ± 11 vs. 14 ± 8%LV; p < 0.001), extracellular volume (ECVinfarct; 63 ± 12 vs. 47 ± 11%; p < 0.001), and native T2infarct (95 ± 16 vs. 78 ± 17 ms; p < 0.01). ECVinfarct and infarct size by LGE were the best predictors of LV remodeling with areas under the curve (AUCs) of 0.843 and 0.789, respectively (all p < 0.01). Native T1infarct had the lowest AUC of 0.549 (p = 0.668) and was inferior to edema size by T2-weighted imaging (AUC = 0.720; p < 0.05) and native T2infarct (AUC = 0.766; p < 0.01). CONCLUSION: In this study, ECVinfarct and infarct size by LGE were the best predictors for the development of LV remodeling within 6 months after AMI, with a better discriminative performance than non-contrast mapping CMR. CLINICAL RELEVANCE STATEMENT: This study demonstrates the predictive value of contrast-enhanced and non-contrast as well as conventional and novel CMR techniques for the development of LV remodeling following AMI, which might help define precise CMR endpoints in experimental and clinical myocardial infarction trials. KEY POINTS: ⢠Multiparametric CMR provides insights into left ventricular remodeling at 6 months following an acute myocardial infarction. ⢠Extracellular volume fraction and infarct size are the best predictors for adverse left ventricular remodeling. ⢠Contrast-enhanced T1 mapping has a better predictive performance than non-contrast standard CMR and T1/T2 mapping.
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Meios de Contraste , Infarto do Miocárdio , Masculino , Humanos , Meios de Contraste/farmacologia , Remodelação Ventricular , Imagem Cinética por Ressonância Magnética/métodos , Valor Preditivo dos Testes , Gadolínio , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Imageamento por Ressonância Magnética , Miocárdio/patologia , Edema/patologia , Função Ventricular EsquerdaRESUMO
OBJECTIVE: To determine the influence of arterial hypertension (AHT), sex, and the interaction between both left- and right ventricular (LV, RV) morphology, function, and tissue characteristics. METHODS: The Hamburg City Health Study (HCHS) is a population-based, prospective, monocentric study. 1972 individuals without a history of cardiac diseases/ interventions underwent 3 T cardiac MR imaging (CMR). Generalized linear models were conducted, including AHT, sex (and the interaction if significant), age, body mass index, place of birth, diabetes mellitus, smoking, hyperlipoproteinemia, atrial fibrillation, and medication. RESULTS: Of 1972 subjects, 68% suffered from AHT. 42% with AHT and 49% controls were female. Females overall showed a higher ejection fraction (EF) (LV: regression coefficient +2.4% [95% confidence interval: 1.7; 3.1]), lower volumes and LV mass (-19.8% [-21.3; -18.5]), and prolonged native septal T1 (+22.1 ms [18.3; 25.9])/T2 relaxation times (+1.1 ms [0.9; 1.3]) (all p < 0.001) compared to males. Subjects with AHT showed a higher EF (LV: +1.2% [0.3; 2.0], p = 0.009) and LV mass (+6.6% [4.3; 9.0], p < 0.001) than controls. The interaction between sex and AHT influenced mapping. After excluding segments with LGE, males (-0.7 ms [-1.0; -0.3 | ) and females with AHT (-1.1 ms [-1.6; -0.6]) showed shorter T2 relaxation times than the sex-respective controls (p < 0.001), but the effect was stronger in females. CONCLUSION: In the HCHS, female and male subjects with AHT likewise showed a higher EF and LV mass than controls, independent of sex. However, differences in tissue characteristics between subjects with AHT and controls appeared to be sex-specific. CLINICAL RELEVANCE STATEMENT: The interaction between sex and cardiac risk factors is an underestimated factor that should be considered when comparing tissue characteristics between hypertensive subjects and controls, and when establishing cut-off values for normal and pathological relaxation times. KEY POINTS: There are sex-dependent differences in arterial hypertension, but it is unclear if cardiac MR parameters are sex-specific. Differences in cardiac MR parameters between hypertensive subjects and healthy controls appeared to be sex-specific for tissue characteristics. Sex needs to be considered when comparing tissue characteristics in patients with arterial hypertension to healthy controls.
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A surface enhanced Raman scattering (SERS) substrate of porous rod-shaped ferric oxide (Fe2O3) combined with silver nanoparticles (Ag NPs) and black phosphorus (Fe2O3/Ag/BP) was fabricated to detect the persistent organic pollutants (POPs) at low concentration. The organic pollutant Rhodamine 6G (R6G) was used as the probe molecule to study the performances of Fe2O3/Ag/BP, and 4-chlorobiphenyl (PCB-3) was the target of detection. The limit of detection (LOD) of R6G based on this novel SERS substrate Fe2O3/Ag/BP was as low as 1.0 × 10-15M, which was five orders of magnitude lower than that of Fe2O3/Ag (10-10M). The enhancement factor (EF) of Fe2O3/Ag/BP was 6.44 × 108, which was 3.1 times higher than that of porous rod-shaped Fe2O3/Ag (2.08 × 108). The Raman signal of R6G based on Fe2O3/Ag/BP had a good homogeneity, and the relative standard deviation (RSD) of Raman signal intensities of R6G at 1643 cm-1was only 5.97%. Furthermore, the Fe2O3/Ag/BP substrate exhibited a recyclability through the photocatalytic degradation of R6G. The LOD of PCB-3 based on Fe2O3/Ag/BP was 10-9M. Besides, Fe2O3/Ag/BP had a high SERS activity even it was kept in a centrifuge tube without requiring complicated treatment. These results highlight the potential application of Fe2O3/Ag/BP for ultra-trace detection of POPs in the environment.
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Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4â or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.
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Manejo de Espécimes , Urinálise , Humanos , Animais , Suínos , Reprodutibilidade dos Testes , Padrões de Referência , Detecção do Abuso de SubstânciasRESUMO
AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q-test was performed to detect heterogeneity. The MR-Egger regression intercept and MR pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to test potential horizontal pleiotropy. Leave-one-out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta-analysis. RESULTS: We confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014. CONCLUSIONS: The demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut-oral and oral-gut axes.
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Microbioma Gastrointestinal , Periodontite , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Causalidade , Periodontite/genéticaRESUMO
Structured beams have attracted increasing interest in free-space and fiber-based optical communications. Underwater wireless optical communication (UWOC) is becoming a prospective technique in marine exploration. We investigated UWOC performance using different representative structured beams. The transmission performances of the Gaussian, Bessel-Gaussian (BG), Ince-Gaussian (IG), and radially polarized Gaussian (RPG) beams were experimentally demonstrated and evaluated in underwater channels subjected to thermal gradient. The experimental results show that the BG, IG, and RPG perform better against the thermal gradient. Compared with the Gaussian beams, the beam wanders of BG, IG, and RPG beams under the thermal gradient have been reduced by 56.9%, 8.2%, and 59%, the scintillation indices have been decreased by 12.8%, 17.3%, and 28.9%, and the BER performance of the BG, IG, and RPG beams have been improved by â¼5.5, â¼3.7, and â¼5.2d B at the forward error correction threshold (FEC threshold). Based on the above results, the RPG beam is a more promising light source for UWOC. The experimental results provide a promising beam choice for UWOC.
RESUMO
The Gerchberg-Saxton (GS) algorithm has been extensively employed in computational holography and beam shaping with the advantages of quick iteration speed and high energy utilization. However, the GS algorithm is prone to trapping into local optima and not reaching ideal outcomes, leading to poor shaping quality. In this paper, a method of random disturbance superposition (RDS) was proposed to feedback GS amplitude, which could stably and universally achieve over 95% high uniformity shaping of multiple beams without other complex operations. In light of this, this paper also covered how this technique affected energy utilization. It has been discovered that the introduction of perturbation could decrease the energy utilization. By analyzing the mechanism, a phase value replacement (PVR) method was proposed, which could effectively improve energy utilization without reducing uniformity. Finally, the simulation results were experimentally validated and met expectations very well. This method helps to accurately control the energy distribution of multiple beams and has a driving effect on laser precision processing technology.