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BACKGROUND: Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. METHODS: High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis. RESULTS: In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC. CONCLUSIONS: Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.
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Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Humanos , Carcinoma de Células Renales/genética , Empalme Alternativo , ARN Circular/genética , MicroARNs/genética , Neoplasias Renales/genética , Ribonucleoproteínas Nucleares Heterogéneas , Proteína de Unión al Tracto de Polipirimidina , Citocromo P-450 CYP1B1 , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genéticaRESUMEN
Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated. The Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) results suggested that exosomes highly expressing miR-3200-3p could inhibit Treg cell viability and promote apoptosis levels when treated with Treg cells. Detection of the senescence-associated proteins p16 INK4A and MMP3 by western blot (WB) revealed that exosomes highly expressing miR-3200-3p were able to elevate their protein expression levels. Tumour xenograft experiments demonstrated that exosomes with high miR-3200-3p expression promoted Treg cell senescence and inhibited subcutaneous tumour growth in nude mice. Dual-luciferase reporter assays and RNA pull-down assays showed that miR-3200-3p could be linked with DDB1. Overexpression of DDB1 reverses changes in DCAF1/GSTP1/ROS protein expression caused by exosomes with high miR-3200-3p expression. In conclusion, inhibition of VEGFR2 expression in tumour cells promotes the expression of miR-3200-3p in exosomes secreted by tumour cells. miR-3200-3p enters the TME through exosomes and acts on DDB1 in Treg cells to promote senescence of Treg cells to inhibit tumour progression.
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Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , MicroARNs , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Neoplasias Pulmonares/patología , Exosomas/genética , Exosomas/metabolismo , Ratones Desnudos , Senescencia de Células T , Proliferación Celular/genética , Microambiente TumoralRESUMEN
Recent advances in laser technology have enabled tremendous progress in light-induced molecular reactions, at the heart of which the breaking and formation of chemical bonds are located. Such progress has been greatly facilitated by the development of an accurate quantum-mechanical simulation method, which, however, does not necessarily accompany clear dynamical scenarios and is rather computationally heavy. Here, we develop a wave-packet surface propagation (WASP) approach to describe the molecular bond-breaking dynamics from a hybrid quantum-classical perspective. Via the introduction of quantum elements including state transitions and phase accumulations to the Newtonian propagation of the nuclear wave packet, the WASP approach naturally comes with intuitive physical scenarios and accuracies. It is carefully benchmarked with the H_{2}^{+} molecule and is shown to be capable of precisely reproducing experimental observations. The WASP method is promising for the intuitive visualization of light-induced molecular dynamics and is straightforward extensible towards complex molecules.
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BACKGROUND: Cardiac T1 mapping is valuable for evaluating myocardial fibrosis, yet its resolution and acquisition efficiency are limited, potentially obscuring visualization of small pathologies. PURPOSE: To develop a technique for high-resolution cardiac T1 mapping with a less-than-100-millisecond acquisition window based on radial MOdified Look-Locker Inversion recovery (MOLLI) and a calibrationless space-contrast-coil locally low-rank tensor (SCC-LLRT) constrained reconstruction. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Sixteen healthy subjects (age 25 ± 3 years, 44% females) and 12 patients with suspected cardiomyopathy (age 57 ± 15 years, 42% females), NiCl2-agar phantom. FIELD STRENGTH/SEQUENCE: 3-T, standard MOLLI, radial MOLLI, inversion-recovery spin-echo, late gadolinium enhancement. ASSESSMENT: SCC-LLRT was compared to a conventional locally low-rank (LLR) method through simulations using Normalized Root-Mean-Square Error (NRMSE) and Structural Similarity Index Measure (SSIM). Radial MOLLI was compared to standard MOLLI across phantom, healthy subjects, and patients. Three independent readers subjectively evaluated the quality of T1 maps using a 5-point scale (5 = best). STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient analysis, linear regression, Bland-Altman analysis. P < 0.05 was considered statistically significant. RESULTS: In simulations, SCC-LLRT demonstrated a significant improvement in NRMSE and SSIM compared to LLR. In phantom, both radial MOLLI and standard MOLLI provided consistent T1 estimates across different heart rates. In healthy subjects, radial MOLLI exhibited a significantly lower mean T1 (1115 ± 39 msec vs. 1155 ± 36 msec), similar T1 SD (74 ± 14 msec vs. 67 ± 23 msec, P = 0.20), and similar T1 reproducibility (28 ± 18 msec vs. 22 ± 15 msec, P = 0.34) compared to standard MOLLI. In patients, the proposed method significantly improved the sharpness of myocardial boundaries (4.50 ± 0.65 vs. 3.25 ± 0.43), the conspicuity of papillary muscles and fine structures (4.33 ± 0.74 vs. 3.33 ± 0.47), and artifacts (4.75 ± 0.43 vs. 3.83 ± 0.55). The reconstruction time for a single slice was 5.2 hours. DATA CONCLUSION: The proposed method enables high-resolution cardiac T1 mapping with a short acquisition window and improved image quality. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
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The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P â =â 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P â =â 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HRâ =â 6.834, 95% CI: 1.350-34.592, P â =â 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P â =â 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HRâ =â 5.911, 95% CI: 1.391-25.122, P â =â 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Factor A de Crecimiento Endotelial Vascular , Humanos , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Pronóstico , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/química , Antígeno B7-H1/sangre , Antígeno B7-H1/químicaRESUMEN
BACKGROUND: Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. METHODS: Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers' markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. RESULTS: A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers' markets with the highest number of pathogen species, totaling six and seven, respectively. CONCLUSIONS: Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.
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Insectos Vectores , Animales , Humanos , Insectos Vectores/microbiología , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/genética , China/epidemiología , Dípteros/microbiología , Virus/aislamiento & purificación , Virus/clasificación , Virus/genética , Muscidae/microbiologíaRESUMEN
To overcome the two main obstacles of large-scale application of superspreading material, self assembly is used to prepare superspreading polymer membrane (SPPM) in this work. An amphiphilic SPPM is prepared by capillary force-driven self assembly using PP melt-blown nonwovens and polyvinyl alcohol (PVA). The prepared SPPM has low preparation cost and stable performance since self assembly needs low energy consumption, and the production is thermodynamically stable. By using cryo-electron microscopy, transmission electron microscopy, X-ray photoelectron spectrum and scanning electron microscope with energy dispersive X-ray spectroscopy. It is proved that PVA is successfully assembled on the fiber surface of PP melt-blown nonwovens. The prepared SPPM has excellent spreading performance, the "spreading times" of both water and oil are less than 0.5 s. They showed much superior performance compared to traditional materials when applied in oil-water separation, seawater desalination, and ion separation. This work will definitely promote the development of self assembly, superspreading materials, and related sciences.
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Objective: To study the clinical effects of anlotinib combined with second-line chemotherapy (SLC) on immunosuppression in patients with advanced non-small cell lung cancer (NSCLC). Methods: In this retrospective study, the medical records of 106 patients with advanced NSCLC admitted to the Lianyungang First People's Hospital from November 2020 to March 2022 were retrospectively analyzed. Amongst 106 patients, 53 patients received second-line single-agent chemotherapy regimens (SLC group), and 53 patients received anlotinib combined with SLC (ASLC group). Prognosis, levels of immune cells and inflammatory cytokine, and adverse reactions were analyzed. Results: Clinical efficacy of the ASLC group was significantly higher than the SLC group (p<0.05). After treatment, patients in the ASLC group exhibited significantly higher levels of CD4+/CD8+ and CD4+ compared to those in the SLC group (p<0.05), while the difference in CD8+ level between the two groups was not statistically significant (p>0.05). After treatment, levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-8 (IL-8), interleukin-6 (IL-6) in the ASLC group were lower compared to the SLC group (p<0.05). Conclusion: In patients with advanced NSCLC, anlotinib combined with SLC is associated with higher levels of immune cells and reduced inflammatory factors. This treatment regimen, thus, can reduce immunosuppression and improve the prognosis of NSCLC patients.
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One of the major obstacles to the effective application of vascularized fruit is an insufficient understanding of the relationship between the microenvironment and neovascular homeostasis. The role of extracellular matrix stiffness in regulating the structural and functional stability of neovascularization has not yet been elucidated. This study explored the effects of matrix stiffness on neovascular homeostasis in nude mice. Dextran hydrogels with three different stiffnesses were separately combined with mouse bone marrow-derived endothelial progenitor cells (EPCs) and subcutaneously implanted into the backs of nude mice. After 14 days, neovascular homeostasis indicators in the different groups were measured. Cell autophagy levels were evaluated, and inhibitor assays were performed to explore the underlying mechanism. New blood vessels were generated in the three stiffnesses of the EPC-loaded dextran hydrogels 14 days after implantation. The newly formed vessels tended to have better structural stability in softer hydrogels. Endothelial function markers, such as endothelial nitric oxide synthase and E-selectin, were downregulated as the matrix stiffness increased. Furthermore, we found that cell autophagy levels decreased in stiffer matrices, and autophagy inhibition attenuated neovascular homeostasis. A soft matrix is conducive to maintaining neovascular homeostasis through autophagy in nude mice.
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Autofagia , Homeostasis , Neovascularización Fisiológica , Animales , Ratones , Dextranos/farmacología , Hidrogeles/química , Ratones DesnudosRESUMEN
Almost all current electrochemiluminescent reagents require real-time electrochemical stimulation to emit light. Here, we report a novel electrochemiluminescent reagent, nitrogen-deficient graphitic carbon nitride (CNx), that can emit afterglow electrochemiluminescence (ECL) after cessation of electric excitation. CNx obtained by post-thermal treatment of graphitic carbon nitride (CN) with KSCN has a cyanamide group and a nitrogen vacancy, which created defects to trap electrically injected electrons. The trapped electrons can slowly release and react with coreactants to emit light with longevity. The cathodic afterglow ECL lasts for 70 s after pulsing the CNx nanosheet (CNxNS-1.6)-modified glassy carbon electrode at -1.0 V for 20 s in 2.0 M PBS containing 1 mM K2S2O8. The afterglow ECL mechanism is revealed by investigation of its influencing factors and ECL wavelength. The discovery of afterglow ECL may open a new doorway for new significant applications of the ECL technique and provide a deeper understanding of the structure-property relationships of CN.
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PURPOSE: To propose an acceleration method for 3D variable flip-angle (VFA) T1 mapping based on a technique called shift undersampling improves parametric mapping efficiency and resolution (SUPER). METHODS: The proposed method incorporates strategies of SUPER, controlled aliasing in volumetric parallel imaging (CAIPIRINHA), and total variation-based regularization to accelerate 3D VFA T1 mapping. The k-space sampling grid of CAIPIRINHA is internally undersampled with SUPER along the contrast dimension. A proximal algorithm was developed to preserve the computational efficiency of SUPER in the presence of regularization. The regularized SUPER-CAIPIRINHA (rSUPER-CAIPIRINHA) was compared with low rank plus sparsity (L + S), reconstruction of principal component coefficient maps (REPCOM), and other SUPER-based methods via simulations and in vivo brain T1 mapping. The results were assessed quantitatively with NRMSE and structural similarity index measure (SSIM), and qualitatively by two experienced reviewers. RESULTS: rSUPER-CAIPIRINHA achieved a lower NRMSE and higher SSIM than L + S (0.11 ± 0.01 vs. 0.19 ± 0.03, p < 0.001; 0.66 ± 0.05 vs. 0.37 ± 0.03, p < 0.001) and REPCOM (0.16 ± 0.02, p < 0.001; 0.46 ± 0.04, p < 0.001). The reconstruction time of rSUPER-CAIPIRINHA was 6% of L + S and 2% of REPCOM. For the qualitative comparison, rSUPER-CAIPIRINHA showed improvement of overall image quality and reductions of artifacts and blurring, although with a lower apparent SNR. Compared with 2D SUPER-SENSE, rSUPER-CAIPIRINHA significantly reduced NRMSE (0.11 ± 0.01 vs. 0.23 ± 0.04, p < 0.001) and generated less noisy reconstructions. CONCLUSION: By incorporating SUPER, CAIPIRINHA, and regularization, rSUPER-CAIPIRINHA mitigated noise amplification, reduced artifacts and blurring, and achieved faster reconstructions compared with L + S and REPCOM. These advantages render 3D rSUPER-CAIPIRINHA VFA T1 mapping potentially useful for clinical applications.
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Imagenología Tridimensional , Imagen por Resonancia Magnética , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Aumento de la Imagen/métodos , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Conventional echo-planar imaging (EPI) uses a radiofrequency pulse for excitation and a prolonged echo train to sample k space, while off-resonance and T2 * decay effects caused by magnetic susceptibility variation accumulate within each echo, leading to geometric distortion. Multishot EPI methods, which divide k space into segments, can shorten the effective echo spacing and reduce the distortion on EPI images. But multiple shots cost longer scan time and render susceptibility to motion. In this study, we propose a new "multishot" EPI method termed pseudo multishot EPI (pmsEPI), in which phase-encoding lines are segmented as in multishot EPI but are collected within a single shot. With the magnetization divided into different pathways via interleaved excitation instead of refocusing in a single long echo train, the total phase error accumulation is reduced in each segmented acquisition, thereby improving distortion of the resultant EPI image. The performance of the pmsEPI method is demonstrated by phantom and in vivo brain experiments on a 3-T scanner. The experimental results show that the distortion displacements of pmsEPI acquisition compared with conventional EPI decrease by 50% with two pseudo shots and 66% with three pseudo shots, validating the ability of the method to obtain images with reduced distortion in a single shot, although magnetization splitting may induce more than 40% SNR loss and minor artifacts. Specifically, the ability of pmsEPI in diffusion-weighted imaging with different trajectory options is highlighted, and the flexibility is demonstrated in a single-shot blip up and down acquisition.
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Imagen de Difusión por Resonancia Magnética , Imagen Eco-Planar , Imagen Eco-Planar/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Cabeza , Movimiento (Física) , Artefactos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
We report the ionization reduction of atoms in two-color femtosecond laser fields in this joint theoretical-experimental study. For the multiphoton ionization of atoms using a 400 nm laser pulse, the ionization probability is reduced if another relatively weak 800 nm laser pulse is overlapped. Such ionization reduction consistently occurs regardless of the relative phase between the two pulses. The time-dependent Schrödinger equation simulation results indicate that with the assisted 800 nm photons the electron can be launched to Rydberg states with large angular quantum numbers, which stand off the nuclei and thus are hard to be freed in the multiphoton regime. This mechanism works for hydrogen, helium, and probably some other atoms if two-color laser fields are properly tuned.
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PURPOSE: To develop a partially interpretable neural network for joint suppression of banding and flow artifacts in non-phase-cycled bSSFP cine imaging. METHODS: A dual-stage neural network consisting of a voxel-identification (VI) sub-network and artifact-suppression (AS) sub-network is proposed. The VI sub-network provides identification of artifacts, which guides artifact suppression and improves interpretability. The AS sub-network reduces banding and flow artifacts. Short-axis cine images of 12 frequency offsets from 28 healthy subjects were used to train and test the dual-stage network. An additional 77 patients were retrospectively enrolled to evaluate its clinical generalizability. For healthy subjects, artifact suppression performance was analyzed by comparison with traditional phase cycling. The partial interpretability provided by the VI sub-network was analyzed via correlation analysis. Generalizability was evaluated for cine obtained with different sequence parameters and scanners. For patients, artifact suppression performance and partial interpretability of the network were qualitatively evaluated by 3 clinicians. Cardiac function before and after artifact suppression was assessed via left ventricular ejection fraction (LVEF). RESULTS: For the healthy subjects, visual inspection and quantitative analysis found a considerable reduction of banding and flow artifacts by the proposed network. Compared with traditional phase cycling, the proposed network improved flow artifact scores (4.57 ± 0.23 vs 3.40 ± 0.38, P = 0.002) and overall image quality (4.33 ± 0.22 vs 3.60 ± 0.38, P = 0.002). The VI sub-network well identified the location of banding and flow artifacts in the original movie and significantly correlated with the change of signal intensities in these regions. Changes of imaging parameters or the scanner did not cause a significant change of overall image quality relative to the baseline dataset, suggesting a good generalizability. For the patients, qualitative analysis showed a significant improvement of banding artifacts (4.01 ± 0.50 vs 2.77 ± 0.40, P < 0.001), flow artifacts (4.22 ± 0.38 vs 2.97 ± 0.57, P < 0.001), and image quality (3.91 ± 0.45 vs 2.60 ± 0.43, P < 0.001) relative to the original cine. The artifact suppression slightly reduced the LVEF (mean bias = -1.25%, P = 0.01). CONCLUSIONS: The dual-stage network simultaneously reduces banding and flow artifacts in bSSFP cine imaging with a partial interpretability, sparing the need for sequence modification. The method can be easily deployed in a clinical setting to identify artifacts and improve cine image quality.
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Artefactos , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Aumento de la Imagen/métodos , Estudios Retrospectivos , Volumen Sistólico , Interpretación de Imagen Asistida por Computador/métodos , Algoritmos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Función Ventricular Izquierda , Redes Neurales de la Computación , Imagen por Resonancia CinemagnéticaRESUMEN
In this study, the optical properties of poly(maleic anhydride-alt-vinyl acetate) (PMV) synthesized by different polymerization methods are studied systematically. Compared to self-stabilized precipitation polymerization (pPMV), solution polymerization produces PMV solids (sPMV) with an extraordinarily high quantum yield (QY) of 20.65%. Additionally, redissolving pPMV in good solvents (rPMV) will also help to increase QY. The rising QY of sPMV and rPMV supports the idea that good solvents will reduce the rigidity of polymer chains and promote cluster formation, which is confirmed by lower glass transition temperature (Tg ) and small angle X-ray scatterer (SAXS). The study also finds that PMV exhibits application potentials in white light-emitting diodes (WLEDs) and light conversion film.
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Anhídridos Maleicos , Solventes , Dispersión del Ángulo Pequeño , Difracción de Rayos XRESUMEN
It has been reported that particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) could induce epithelial-mesenchymal transition (EMT)- and extracellular matrix (ECM)-related pulmonary fibrosis (PF). The transcription factor Nrf2 alleviated PM2.5-induced PF by antagonizing oxidative stress. The N6-methyladenosine (m6A) modification plays a significant role in the stress response. However, the effect of m6A modification on the mechanisms of Nrf2-mediated defense against PM2.5-induced PF remained unknown. Here, we explored the role and the underlying molecular mechanisms of m6A methylation of Nrf2 mRNA in PM2.5-induced PF. We established filtered air (FA), unfiltered air (UA), and concentrated PM2.5 air (CA) group mice model and 0, 50, and 100 µg/mL PM2.5-treated 16HBE cell models. The extent of lung fibrosis in mice and fibrosis indicators were detected by histopathological analysis, immunohistochemical staining and western blotting. The molecular mechanism of m6A-modified Nrf2 was demonstrated by m6A-methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), qRT-PCR and T3 ligase-based PCR. Our data showed that PM2.5 exposure for 16 weeks could induce pulmonary fibrosis and activate Nrf2 signaling pathway. m6A methyltransferase METTL3 was upregulated after PM2.5 treatment in vivo and in vitro. Moreover, METTL3 mediated m6A modification of Nrf2 mRNA and promoted Nrf2 translation in mice and 16HBE cells after PM2.5 exposure. Mechanistically, three m6A-modified sites (1317, 1376 and 935; numbered relative to the first nucleotide of 3'UTR) of Nrf2 mRNA were identified in PM2.5-treatment 16HBE cells. Furthermore, the m6A binding proteins YTHDF1/IGF2BP1 promoted Nrf2 translation by binding to m6A residues of Nrf2 mRNA. Our results revealed the mechanism of m6A mediated Nrf2 signaling pathway against oxidative stress, which affected the development of PM2.5-induced PF.
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Fibrosis Pulmonar , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Material Particulado/toxicidad , ARN , ARN Mensajero/genéticaRESUMEN
Mammalian oocyte maturation relies on mitochondrial ATP production, but this can lead to damaging reactive oxygen species (ROS). SIRT3, a mitochondrial sirtuin, plays a critical role in regulating mitochondrial redox balance in mouse oocytes under stress; however, its specific roles in porcine oocytes remain unclear. In this study, we utilized the SIRT3 inhibitor 3-TYP to investigate SIRT3's importance in porcine oocyte maturation. Our findings revealed that SIRT3 is expressed in porcine oocytes and its inhibition leads to maturation failure. This was evident through reduced polar body extrusion, arrested cell cycle, as well as disrupted spindle organization and actin distribution. Furthermore, SIRT3 inhibition resulted in a decrease in mitochondrial DNA copy numbers, disruption of mitochondrial membrane potential, and reduced ATP levels, all indicating impaired mitochondrial function in porcine oocytes. Additionally, the primary source of damaged mitochondria was associated with decreased levels of deacetylated superoxide dismutase 2 (SOD2) after SIRT3 inhibition, which led to ROS accumulation and oxidative stress-induced apoptosis. Taken together, our results suggest that SIRT3 regulates the levels of deacetylated SOD2 to maintain redox balance and preserve mitochondrial function during porcine oocyte maturation, with potential implications for improving pig reproduction.
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Enfermedades Mitocondriales , Sirtuina 3 , Ratones , Animales , Porcinos , Especies Reactivas de Oxígeno , Sirtuina 3/genética , Sirtuina 3/metabolismo , Estrés Oxidativo , Oocitos/metabolismo , Adenosina Trifosfato/metabolismo , Enfermedades Mitocondriales/metabolismo , Mamíferos/metabolismoRESUMEN
BACKGROUND & AIMS: Cirrhotic cardiomyopathy is a major complication and cause of morbidity in end-stage primary biliary cholangitis (PBC). However, it is unclear whether there is clinically silent myocardial involvement at the early stage of PBC before cirrhosis and cardiac manifestations. This prospective, three-center, multi-modality cardiac imaging study on the early identification of myocardial impairment in PBC (EARLY-MYO-PBC) was designed to identify silent myocardial impairment in PBC patients without cardiac manifestations. METHODS: A total of 112 subjects (56 with PBC and 56 age- and sex-matched controls) undergoing cardiovascular magnetic resonance (CMR) were enrolled. Demographic, serologic, and cardiac imaging data were prospectively collected. All participants had no cardiac discomfort or previous heart disease and had normal electrocardiographic findings. RESULTS: Subclinical myocardial involvement, as evidenced by cardiac morphologic, functional, and tissue characterization changes on CMR, including hyperdynamic left ventricular (LV) ejection fraction (median, 75% in PBC patients vs 69% in controls, P = .029), subclinical myocardial edema by T2-short tau inversion recovery (21% vs 2% in controls, P = .001), elevated extracellular matrix indices (30% vs 26% in controls, P < .001), and impaired myocardial viability by positive late gadolinium enhancement (LGE) (36%), was detected in PBC patients. Importantly, a mid-wall "stripe" at the LV septum was identified as a PBC-specific LGE pattern that differs from other known cardiomyopathies. In multivariate analysis, gp210 positivity (odds ratio [OR] = 9.909, P = .010), lower hemoglobin (OR = 0.919, P = .004), and body mass index (OR = 0.638, P = .005) were independent predictors of cardiac abnormalities in PBC. CONCLUSIONS: This study demonstrates clinically silent cardiac impairment with specific CMR patterns in PBC, allowing optimal screening for early myocardial impairment and potentially timely therapies. (Trial registration no.: NCT03545672).
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Cardiomiopatías , Cirrosis Hepática Biliar , Cardiomiopatías/diagnóstico , Cardiomiopatías/patología , Medios de Contraste , Fibrosis , Gadolinio , Humanos , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/patología , Imagen por Resonancia Cinemagnética/efectos adversos , Miocardio/patología , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
In this study, an effective quadruple optimization integrated synergistic strategy is designed to fabricate quality Sb gradient-doped SnO2 /Sb2 S3 heterostructure for an efficient photoelectrochemical (PEC) cell. The experimental results and theoretical calculations reveal that i) optical absorption matching is realized by combining the anti-reflection of SnO2 and high light absorption ability of Sb2 S3 in the visible region; ii) interface reinforcement is carried out by coordinating gradient-distributed Sb in SnO2 with S in S-rich precursor of Sb2 S3 for improving the Sb2 S3 crystallization process and matching crystalline lattice of Sb:SnO2 and Sb2 S3 ; iii) ultrahigh electron mobility is achieved by making Sb gradient-doped SnO2 ; iv) carrier separation and transport are accelerated by constructing type-II heterojunction with appropriate energy level alignment and forming a high-speed electron transport channel. All of above-mentioned optimization effects are integrated into a synergistic strategy for constructing the Sb:SnO2 /Sb2 S3 photoanode, achieving a photocurrent density of 2.30 mA cm-2 , hydrogen generation rate of 30.03 µmol cm-2 h-1 , and decent working stability. Notably, this method can also be used in other large-scale fabrication processes, such as drop-casting, spray-coating, blade-coating, printing, slot-die, etc. Moreover, this universal integrated strategy paves an avenue to fabricate efficient photoelectrodes with excellent photoelectrochemical performances.
RESUMEN
PURPOSE: Respiratory motion causes mismatches between PET images of the myocardium and the corresponding cardiac MR images in cardiac integrated PET/MR. The mismatch may affect the attenuation correction and the diagnosis of non-ischemic cardiomyopathies. In this study, we present a two-stage cardiac PET and MR late gadolinium enhancement (LGE) co-registration method, which seeks to improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration using an integrated whole-body PET/MR system. METHODS: The proposed PET and LGE two-stage co-registration method was evaluated through comparison with one-stage direct co-registration and no-registration. One hundred and ninety-one slices of LGE and forty lesions were studied. Two trained nuclear medicine physicians independently assessed the displacement between LGE and PET to qualitatively evaluate the co-registration quality. The changes of the mean SUV in the normal myocardium and the LGE-enhanced lesions before and after image co-registration were measured to quantitatively evaluate the accuracy and value of image co-registration. RESULTS: The two-stage method had an improved image registration score (4.93 ± 0.89) compared with the no-registration method (3.49 ± 0.84, p value < 0.001) and the single-stage method (4.23 ± 0.81, p value < 0.001). Furthermore, the two-stage method led to increased SUV value in the myocardium (3.87 ± 2.56) compared with the no-registration method (3.14 ± 1.92, p value < 0.001) and the single-stage method (3.32 ± 2.16, p value < 0.001). The mean SUV in the LGE lesion significantly increased from 2.51 ± 2.09 to 2.85 ± 2.35 (p value < 0.001) after the two-stage co-registration. CONCLUSION: The proposed two-stage registration method significantly improved the co-registration between PET and LGE in integrated PET/MR imaging. The technique may improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration. REGISTERED NO: DF-2020-085,2020.04.30.