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A nonlinear holographic technique is capable of processing optical information in the newly generated optical frequencies, enabling fascinating functions in laser display, security storage, and image recognition. One popular nonlinear hologram is based on a periodically poled lithium niobate (LN) crystal. However, due to the limitations of traditional fabrication techniques, the pixel size of the LN hologram is typically several micrometers, resulting in a limited field-of-voew (FOV) of several degrees. Here, we experimentally demonstrate an ultra-high-resolution LN hologram by using the laser poling technique. The minimal pixel size reaches 200 nm, and the FOV is extended above 120° in our experiments. The image distortions at large view angles are effectively suppressed through the Fourier transform. The FOV is further improved by combining multiple diffraction orders of SH fields. The ultimate FOV under our configuration is decided by a Fresnel transmission. Our results pave the way for expanding the applications of nonlinear holography to wide-view imaging and display.
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Interferon-γ (IFN-γ) is an important cytokine in tissue homeostasis and immune response, while studies about it in antibody-mediated rejection (ABMR) are very limited. This study aims to comprehensively elucidate the role of IFN-γ in ABMR after renal transplantation. In six renal transplantation cohorts, the IFN-γ responses (IFNGR) biological process was consistently top up-regulated in ABMR compared to stable renal function or even T cell-mediated rejection in both allografts and peripheral blood. According to single-cell analysis, IFNGR levels were found to be broadly elevated in most cell types in allografts and peripheral blood with ABMR. In allografts with ABMR, M1 macrophages had the highest IFNGR levels and were heavily infiltrated, while kidney resident M2 macrophages were nearly absent. In peripheral blood, CD14+ monocytes had the top IFNGR level and were significantly increased in ABMR. Immunofluorescence assay showed that levels of IFN-γ and M1 macrophages were sharply elevated in allografts with ABMR than non-rejection. Importantly, the IFNGR level in allografts was identified as a strong risk factor for long-term renal graft survival. Together, this study systematically analyzed multi-omics from thirteen independent cohorts and identified IFN-γ and IFNGR as determinants of ABMR and clinical outcomes in patients after renal transplantation.
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Trasplante de Riñón , Humanos , Anticuerpos , Rechazo de Injerto/etiología , Interferón gamma , Factores de RiesgoRESUMEN
Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDRΔIEC) abolished the therapeutic effect of lithocholic acid on MMF-induced GI toxicity. Impressively, we discovered that paricalcitol, a Food and Drug Administration-approved VDR agonist that has been used in clinics for years, could effectively alleviate MMF-induced GI toxicity. Our study reveals a previously unrecognized mechanism of gut microbiota, BAs, and VDR signaling in MMF-induced GI side effects, offering potential therapeutic strategies for clinics.
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Ácidos y Sales Biliares , Microbioma Gastrointestinal , Ácido Micofenólico , Receptores de Calcitriol , Animales , Ácido Micofenólico/farmacología , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Receptores de Calcitriol/metabolismo , Ácidos y Sales Biliares/metabolismo , Inmunosupresores , Ratones Endogámicos C57BL , Masculino , Enfermedades Gastrointestinales/inducido químicamente , Ácido Litocólico , HumanosRESUMEN
The role of disulfidptosis in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated disulfidptosis-related biomarkers for KIRC prognosis prediction and individualized treatment. KIRC patients were clustered by disulfidptosis profiles. Differential expression analysis, survival models, and machine learning were used to construct the disulfidptosis-related prognostic signature (DRPS). Characterizations of the tumor immune microenvironment, genetic drivers, drug sensitivity, and immunotherapy response were explored according to the DRPS risk stratification. Markers included in the signature were validated using single-cell, spatial transcriptomics, quantitative RT-qPCR, and immunohistochemistry. In the discovery cohort, we unveiled two clusters of KIRC patients that differed significantly in disulfidptosis regulator expressions and overall survival (OS). After multiple feature selection steps, a DRPS prognostic model with four features (CHAC1, COL7A1, FOXM1, SHOX2) was constructed and validated. Combined with clinical factors, the model demonstrated robust performance in the discovery and external validation cohorts (5-year AUC = 0.793 and 0.846, respectively). KIRC patients with high-risk scores are characterized by inferior OS, less tumor purity, and increased infiltrations of fibroblasts, M1 macrophages, and B cells. High-risk patients also have higher frequencies of BAP1 and AHNAK2 mutation. Besides, the correlation between the DRPS score and the chemotherapy-response signature indicated the potential effect of Gefitinib for high-risk patients. Among the signature genes, FOXM1 is highly expressed in cycling tumor cells and exhibits spatial aggregation, while others are expressed sparsely within tumor samples. The DRPS model enables improved clinical management and personalized KIRC therapy. The identified biomarkers and immune characteristics offer new mechanistic insight into disulfidptosis in KIRC.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Neoplasias Renales , Medicina de Precisión , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , TranscriptomaRESUMEN
BACKGROUND: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated. METHODS: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients. RESULTS: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects. CONCLUSIONS: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.
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Biomarcadores de Tumor , Neoplasias , Factores de Transcripción , Femenino , Humanos , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/diagnóstico , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/diagnóstico , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/diagnóstico , Neoplasias/mortalidad , Neoplasias/patología , Pronóstico , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.
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Glomerulonefritis por IGA , Humanos , Leflunamida/efectos adversos , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/inducido químicamente , Inmunosupresores/efectos adversos , Corticoesteroides/uso terapéutico , Corticoesteroides/farmacología , Tasa de Filtración GlomerularRESUMEN
A dual-mode fluorescence/visual aptasensor was developed for straightforward and accurate determination of aflatoxin B1 (AFB1) based on an Au/metal-organic framework (Au/MOF) composite. Aptamer-modified Au/Fe3O4 (Apt/Au/Fe3O4) served as the recognition element, and Au/MOF modified with complementary chains and 3,3',5,5'-tetramethylbenzidine (cDNA/TMB/Au/MOF) acted as the fluorescence and visual probes. These components are integrated to form conjugates (Apt/Au/Fe3O4-cDNA/TMB/Au/MOF). Upon the introduction of AFB1, some cDNA/TMB/Au/MOF dissociated from Apt/Au/Fe3O4, enabling the use of detached probes for visual detection. The undecomposed conjugates were isolated magnetically for use in fluorescence detection. As the AFB1 concentration increases, the visual signal intensifies and fluorescence intensity diminishes. Thus, the proposed aptasensor achieves the simultaneous fluorescence and visual determination of AFB1, obviating the need for material and reagent substitutions. The detection limits were established at 0.07 ng mL-1 for the fluorescence mode and 0.08 ng mL-1 for the visual mode. The effectiveness of the aptasensor was further validated by quantifying AFB1 in real samples.
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Aflatoxina B1 , Aptámeros de Nucleótidos , Técnicas Biosensibles , Oro , Límite de Detección , Estructuras Metalorgánicas , Nanocompuestos , Aflatoxina B1/análisis , Oro/química , Aptámeros de Nucleótidos/química , Estructuras Metalorgánicas/química , Técnicas Biosensibles/métodos , Nanocompuestos/química , Espectrometría de Fluorescencia/métodos , Bencidinas/química , Contaminación de Alimentos/análisis , Fluorescencia , Colorantes Fluorescentes/químicaRESUMEN
Spatiotemporal vortices (STOVs) are a new, to the best of our knowledge, type of structured light in which the optical phase circulates in space-time. In this work, we propose to generate STOVs via second harmonic generation in lithium niobate nonlinear photonic crystals (NPCs) with a linearly chirped Gaussian pulse as the fundamental wave. The structural function of the NPC is derived by the inverse design method. Numerical simulations of the intensity and phase profiles of the generated second harmonic waves are performed with both the amplitude-phase-modulated and the simplified binary-phase-modulated NPCs. We anticipate our study will be valuable for the experimental generation and manipulation of STOVs in NPCs.
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Effective integration of optical modes within chip-scale devices is critical to realize functional light emission, as it offers abundant physics and a versatile ability to control the mode evolution. Here, we present an efficient approach to achieve switchable emission by flexibly controlling supermode states in a doubly-coupled-ring system with four guided modes. The lasing conditions, which rely on the system's Hamiltonian, are revealed to yield multiple supermode states, including an exceptional-point state, a (quasi-)dark state, and a bright state. By freely engineering the coupling rate via phase-change material, the proposed system allows the generation of any desired states, enabling switchable and multifunctional emissions in fixed on-chip structures. Beyond the manipulation of various supermode emission states, our work presents a promising path toward the development of multifunctional integrated photonic devices, which may have applications in light storage, optical isolation, sensing, and so on.
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Ingeniería , FotonesRESUMEN
Screening for prostate cancer (PCa) using prostate-specific antigen (PSA) is common. This study aimed to identify potential nutritional variables associated with PSA levels and develop a PCa risk prediction model. A total of 5,725 participants from the 2001-2010 National Health and Nutrition Examination Survey (NHANES) database were recruited and divided into discovery and validation sets. Three machine learning (ML) algorithms were performed in discovery set to select features associated with a high-risk PSA level. Age, red blood cell (RBC), blood cholesterol, blood lead, and prognostic nutritional index (PNI) were overlapping important contributors among the three ML models. Furthermore, the relationship between the selected variables and the high-risk PSA level was verified using weighted logistic regression models and restricted cubic spline (RCS) curves. After adjustment, age and blood lead were significantly positively associated with high-risk PSA, while PNI was significantly negatively associated with high-risk PSA. A nomogram including age, RBC, blood cholesterol, and PNI was constructed for predicting the PCa risk according to PSA levels, and the area under the receiver operating characteristic curve (AUROC) of discovery and validation sets was 0.755 and 0.756, respectively. The constructed nomogram may be used for targeted PSA testing and cancer screening in community healthcare.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Estudios Transversales , Encuestas Nutricionales , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiología , ColesterolRESUMEN
BACKGROUND AND OBJECTIVE: There is uncertainty about the beneficial effects of exercise intervention for kidney transplant recipients. The purpose of our meta-analysis is to estimate the efficacy of exercise intervention in kidney transplant recipients. METHODS: A database search according to the PICOS framework was performed for all published randomized, double-blind, placebo-controlled trials (RCTs) about exercise intervention for kidney transplant recipients. The databases involved include PubMed, Embase, and Cochrane Library. RESULTS: A total of 16 RCTs (involving 827 patients) in compliance with inclusion criteria were included in our study. The results demonstrated that adequate exercise intervention improved statistically in creatinine clearance [mean difference (MD) = - 0.29, 95% confidence interval (CI) - 0.46 to - 0.11, p = 0.001], serum urea (MD = - 21.57, 95% CI - 35.84 to - 7.29, p = 0.003), VO2 peak (MD = 3.20, 95% CI 1.97-4.43, p < 0.00001), high-density lipoprotein-cholesterol (HDL-C) (MD = 0.21, 95% CI 0.04-0.37, p = 0.01), 60-s sit to stand test (60-STS) (MD = 14.47, 95% CI 8.89-20.04, p < 0.00001), 6-min walk distance (6-MWD) (MD = 91.87, 95% CI 38.34-145.39, p = 0.0008), and 6-min walk test (6-MWT) (MD = 44.08, 95% CI 20.30-67.87, p = 0.0003) of patients after kidney transplantation. No between-groups differences (p > 0.05) were observed for anthropometric characteristics, body composition, serum cytokine levels, and quality of life short form-36 questionnaire (SF-36). CONCLUSIONS: In kidney transplant recipients, appropriate exercise intervention improved renal function, cardiopulmonary function, physical performance. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022357574.
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Trasplante de Riñón , Humanos , Calidad de Vida , Ejercicio Físico , Terapia por Ejercicio/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Multidrug-resistant tuberculosis (MDR-TB) continues to spread worldwide and remains one of the leading causes of death among infectious diseases. The enoyl-acyl carrier protein reductase (InhA) belongs to FAS-II family and is essential for the formation of the Mycobacterium tuberculosis cell wall. Recent years, InhA direct inhibitors have been extensively studied to overcome MDR-TB. However, there are still no inhibitors that have entered clinical research. Here, the ensemble docking-based virtual screening along with biological assay were used to identify potent InhA direct inhibitors from Chembridge, Chemdiv, and Specs. Ultimately, 34 compounds were purchased and first assayed for the binding affinity, of which four compounds can bind InhA well with KD values ranging from 48.4 to 56.2 µM. Among them, compound 9,222,034 has the best inhibitory activity against InhA enzyme with an IC50 value of 18.05 µM. In addition, the molecular dynamic simulation and binding free energy calculation indicate that the identified compounds bind to InhA with "extended" conformation. Residue energy decomposition shows that residues such as Tyr158, Met161, and Met191 have higher energy contributions in the binding of compounds. By analyzing the binding modes, we found that these compounds can bind to a hydrophobic sub-pocket formed by residues Tyr158, Phe149, Ile215, Leu218, etc., resulting in extensive van der Waals interactions. In summary, this study proposed an efficient strategy for discovering InhA direct inhibitors through ensemble docking-based virtual screening, and finally identified four active compounds with new skeletons, which can provide valuable information for the discovery and optimization of InhA direct inhibitors.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/química , Simulación de Dinámica Molecular , Conformación Molecular , Proteínas Bacterianas/química , Simulación del Acoplamiento Molecular , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/químicaRESUMEN
The monkeypox outbreak has become a global public health emergency. The lack of valid and safe medicine is a crucial obstacle hindering the extermination of orthopoxvirus infections. The identification of potential inhibitors from natural products, including Traditional Chinese Medicine (TCM), by molecular modeling could expand the arsenal of antiviral chemotherapeutic agents. Monkeypox DNA topoisomerase I (TOP1) is a highly conserved viral DNA repair enzyme with a small size and low homology to human proteins. The protein model of viral DNA TOP1 was obtained by homology modeling. The reliability of the TOP1 model was validated by analyzing its Ramachandran plot and by determining the compatibility of the 3D model with its sequence using the Verify 3D and PROCHECK services. In order to identify potential inhibitors of TOP1, an integrated library of 4103 natural products was screened via Glide docking. Surface Plasmon Resonance (SPR) was further implemented to assay the complex binding affinity. Molecular dynamics simulations (100 ns) were combined with molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) computations to reveal the binding mechanisms of the complex. As a result, three natural compounds were highlighted as potential inhibitors via docking-based virtual screening. Rosmarinic acid, myricitrin, quercitrin, and ofloxacin can bind TOP1 with KD values of 2.16 µM, 3.54 µM, 4.77 µM, and 5.46 µM, respectively, indicating a good inhibitory effect against MPXV. The MM/PBSA calculations revealed that rosmarinic acid had the lowest binding free energy at -16.18 kcal/mol. Myricitrin had a binding free energy of -13.87 kcal/mol, quercitrin had a binding free energy of -9.40 kcal/mol, and ofloxacin had a binding free energy of -9.64 kcal/mol. The outputs (RMSD/RMSF/Rg/SASA) also indicated that the systems were well-behaved towards the complex. The selected compounds formed several key hydrogen bonds with TOP1 residues (TYR274, LYS167, GLY132, LYS133, etc.) via the binding mode analysis. TYR274 was predicted to be a pivotal residue for compound interactions in the binding pocket of TOP1. The results of the enrichment analyses illustrated the potential pharmacological networks of rosmarinic acid. The molecular modeling approach may be acceptable for the identification and design of novel poxvirus inhibitors; however, further studies are warranted to evaluate their therapeutic potential.
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Antivirales , Productos Biológicos , Monkeypox virus , ADN-Topoisomerasas de Tipo I , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Monkeypox virus/efectos de los fármacos , Ofloxacino , Reproducibilidad de los Resultados , Antivirales/química , Ácido RosmarínicoRESUMEN
Endothelial-to-mesenchymal transition (EndMT) plays a critical role in the flow-induced vascular remodeling process, such as pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). NBL1 (neuroblastoma suppressor of tumorigenicity 1) is a secreted glycoprotein that has been implicated in CHD-PAH by aggravating the phenotypic transformation of smooth muscle cells. However, the underlying mechanisms regarding the interplay between NBL1 and endothelial cells in CHD-PAH remain to be fully elucidated. Thus, we aimed to identify the potential effect of NBL1 on EndMT using a novel flow-associated PAH model with Nbl1 knockout rats. The phenotype of EndMT was detected using RNA sequencing and further examined using western blotting and immunostaining of pulmonary arteries. Our observations demonstrated that the novel strategy of Nbl1 knockout effectively attenuated flow-associated PAH through downregulation of EndMT to some extent. Mechanistic experiments were established on human pulmonary artery endothelial cells to confirm that EndMT was induced by NBL1 in vitro. After 7 days' stimulation with NBL1, concentrations of EndMT-related biomarkers and downstream transcription factors were quantified using RNA sequencing, western blotting, and immunocytochemistry. Both in vitro and in vivo experiments supported the imbalance of increased TGF-ß (transforming growth factor-ß) and dysregulation of BMP (bone morphogenetic protein) signaling by NBL1. Blocking the canonical TGF-ß pathway efficiently preserved endothelial function upon NBL1 stimulation. These data suggested that NBL1 aggravated flow-associated PAH by inducing EndMT via the TGF-ß and BMP signaling pathway. Thus, antagonizing NBL1 and rebalancing TGF-ß and BMP signaling may be a suitable therapeutic target for CHD-PAH.
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Cardiopatías Congénitas , Neuroblastoma , Hipertensión Arterial Pulmonar , Ratas , Humanos , Animales , Células Endoteliales/metabolismo , Transición Epitelial-Mesenquimal , Hipertensión Pulmonar Primaria Familiar/metabolismo , Neuroblastoma/metabolismo , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
Non-Hermitian optics has emerged as a feasible and versatile platform to explore many extraordinary wave phenomena and novel applications. However, owing to ineluctable systematic errors, the constructed non-Hermitian phenomena could be easily broken, thus leading to a compromising performance in practice. Here we theoretically proposed a dynamically tunable mechanism through GST-based phase-change material (PCM) to achieve a reconfigurable non-Hermitian system, which is robust to access the chiral exceptional point (EP). Assisted by PCM that provides tunable coupling efficiency, the effective Hamiltonian of the studied doubly-coupled-ring-based non-Hermitian system can be effectively modulated to resist the external perturbations, thus enabling the reconfigurable chiral EP and a tunable non-reciprocal transmission. Moreover, such tunable properties are nonvolatile and require no static power consumption. With these superior performances, our findings pave a promising way for reconfigurable non-Hermitian photonic devices, which may find applications in tunable on-chip sensors, isolators and so on.
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High-dimensional maximally entangled orbital angular momentum (OAM) states are a promising resource for enhancing information capacity and robustness in quantum communication. However, it still lacks an effective method to increase the state dimensionality. Here, we theoretically propose an efficient scheme to generate maximally entangled OAM states of ultrahigh dimensionality by manipulating the radial components of a Laguerre-Gaussian (LG) pump beam. By optimizing the complex amplitudes of multiple radial modes of the LG pump light, one can feasibly achieve 101-dimensional OAM-based maximally entangled states. Our scheme has potential applications in high capacity quantum communication networks.
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In recent years, Controlling Nutritional Status (CONUT) Score has become widely recognized as a novel index to evaluate the survival in urological neoplasms patients, especially with renal cell carcinoma (RCC) and upper tract urothelial carcinoma (UTUC). The aim of this meta-analysis is to evaluate the prognostic value of CONUT score in patients with RCC and UTUC. PubMed, Web of Science and Embase were searched for data on the association between CONUT score and RCC/UTUC prognosis up to July 29, 2021. Duplicates were excluded, and inclusion/exclusion criteria were applied to all abstracts. We sorted out relevant studies and extracted the risk ratios (RRs) and its 95% confidence interval (CI) for recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The relationship between gender and survival outcomes was analyzed using univariate cox regression. We analyzed seven studies including 5410 patients in the meta-analysis. A high CONUT score was associated with poor 5-year RFS (RR = 1.27, 95% CI = 1.13-1.43, P = 0.0001), CSS (RR = 1.22, 95% CI = 1.07-1.39, P = 0.003) and OS (RR = 1.24, 95% CI = 1.10-1.41, P = 0.0005). As a result, the association between CONUT score and survival was statistically significant. In addition, gender was not related to survival outcomes. Our results show that the CONUT score is associated with RCC and UTUC outcomes and can serve as a readily available biomarker for managing this disease.
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Carcinoma de Células Renales , Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/cirugía , Estado Nutricional , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare disease that mostly occurs in younger people and is located in the lungs in the general population. We report a rare case of adrenal IMT in a patient with HIV infection, which is believed to be the first of its kind worldwide. CASE PRESENTATION: We present a rare case of a 44-year-old man with HIV infection who was diagnosed with adrenal IMT. The patient refused regular highly active antiretroviral therapy 13 years ago until he was admitted to hospital after an adrenal mass was found. The patient underwent successful computed-tomography-guided needle biopsy, and pathological analysis showed fibroblastic-myofibroblastic proliferation with inflammatory infiltration, which confirmed a diagnosis of IMT. We failed to perform complete resection of the tumor because of its diffuse invasion. The patient was complicated with severe multiple pulmonary infections postoperatively because of immunodeficiency, which eventually caused his death 2 months later. CONCLUSION: Differential diagnosis of IMT is difficult, and tumor biopsy is an essential means of diagnosis. Surgical resection is preferred for both adrenal and HIV-related IMTs. Conservative treatment should be considered when there are technical difficulties with complete resection, and most patients have achieved good outcomes. However, more cases and longer follow-up are warranted to confirm long-term outcomes of HIV-related IMT.
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Neoplasias de las Glándulas Suprarrenales , Granuloma de Células Plasmáticas , Infecciones por VIH , Masculino , Humanos , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Diagnóstico Diferencial , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/cirugía , Granuloma de Células Plasmáticas/patología , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/cirugíaRESUMEN
BACKGROUND: Severe mitral regurgitation (MR) is associated with progressive heart failure and impairment of survival. Degenerative MR accounts for most MV repair surgeries. Conventional mitral valve repair surgery requires cardiopulmonary bypass and is associated with significant morbidity and risks. Transapical beating-heart mitral valve repair by artificial chordae implantation with transesophageal echocardiography (TEE) guidance has the potential to significantly reduce surgical morbidity. We report the first-in-human experience of degenerative MR repair using a novel artificial chordae implantation device (MitralstitchTM system). METHODS: Ten patients with severe MR underwent transapical artificial chordae implantation using MitralstitchTM system. The procedure was performed through a small left thoracotomy under general anesthesia and TEE guidance. Patients underwent transthoracic echocardiography and other assessments during the follow-up. RESULTS: All 10 patients with an average age of 63.7 ± 9.6 years successfully received transapical artificial chordae implantation. Their MR reduced from severe to none or trace in five patients, mild in five patients before discharge. Five patients received one artificial chordal implantation, four patients received two, and one patient received three and edge-to-edge repair by locking two of them. The safety and efficacy endpoint were achieved in all patients at 1-month follow-up. At 1-year follow-up, six patients had mild MR, three patients had moderate MR, one patient had recurrence of severe MR and underwent surgical repair. CONCLUSIONS: The results of this first-in-human study show safety and feasibility of transapical mitral valve repair using MitralStitch system. Patient selection and technical refinement are crucial to improve the outcomes.
Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Prolapso de la Válvula Mitral , Anciano , Cuerdas Tendinosas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Persona de Mediana Edad , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/complicaciones , Insuficiencia de la Válvula Mitral/cirugía , Prolapso de la Válvula Mitral/cirugía , Resultado del TratamientoRESUMEN
Conventional molecularly imprinted polymers (MIP)-based electrochemical sensors are generally susceptible to the changes of personal operation, electrode surface, and solution conditions. Herein, a ratiometric strategy was employed through introducing Cu2O nanoparticles (NPs) as inner reference probe to realize the reliable detection of diethylstilbestrol (DES). MIP film was prepared by electropolymerization of 1H-pyrrole-3-carboxylicacid in the presence of DES on carbon nanotubes/cuprous oxide/titanium carbide (CNT/Cu2O NPs/Ti3C2Tx) modified electrodes. The Ti3C2Tx with accordion-like structure not only possessed good electrical conductivity, but also facilitated the immobilization of Cu2O NPs, which contributed to stabilizing the signal. CNT was introduced to further improve the sensitivity of the sensor. Under optimum conditions, the MIP/CNT/Cu2O NPs/Ti3C2Tx electrochemical sensors showed a broad linear response range of 0.01 to 70 µM, and a low detection limit of 6 nM (S/N = 3). Moreover, the sensor was applied to detect DES in real samples including lake water, milk, and pork, and the recoveries for spiked standard were 88-112%. Thus, this work provides a new way for reliable DES detection.