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1.
Sci Total Environ ; : 171805, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38508262

RESUMO

A pressing issue in contemporary society is the resource scarcity of phosphorus. Operating on the principle of electrochemical reactions between Mg as the anode and oxygen from air as the cathode, Mg-air batteries (MAB) have been employed to provide new prospects for phosphorus recovery in struvite form. Different phosphorus concentrations and reaction time impact struvite generation in MAB systems; however, the exact mechanism has rarely been investigated. We investigated how varying the initial phosphorus concentration and the reaction time affects phosphorus recovery, electricity generation, and the efficiency of struvite production in MAB. Additionally, we examine the impact of solid carbon sources on phosphorus transformation in sludge. The findings revealed that the incorporation of solid carbon sources facilitated the release of phosphate by changing phosphorus speciation. The electrolyte derived from the conditioned sludge filtrate exhibited a remarkable phosphorus removal efficiency of 91.7 % within 1 h, yielding the highest struvite purity of ~70 %, whereas that using raw sludge filtrate or extending the reaction time was found to be less effective, even reducing struvite formation. Furthermore, different electrolytes influence the system's ability to passivate anode, and electrolytes with higher phosphorus concentrations have better electricity production performance. The results by Visual MINTEQ model confirmed that longer reaction times and lower initial phosphorus concentrations can negatively affect struvite formation by introducing Mg3(PO4)2 and Mg(OH)2. The integration of agricultural waste as carbon sources with MAB for phosphorus recovery represents a potential methodology for struvite recuperation from sewage sludge, thereby heralding a sustainable strategy for resource recovery.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38416803

RESUMO

Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1 and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.

3.
Circ Res ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420756

RESUMO

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

4.
Insights Imaging ; 15(1): 58, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411736

RESUMO

OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. METHODS: RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan-Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. RESULTS: After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan-Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p < 0.05). CONCLUSION: RARS and RABS were independent predictors for adverse cardiac events, which could provide incremental prognostic value for conventional predictors in ARVC. CRITICAL RELEVANCE STATEMENT: We evaluated the prognostic value of right atrial strain in ARVC patients and suggested cardiologists consider RA strain as a predictive parameter when evaluating the long-term outcome of ARVC patients in order to formulate better clinical therapy. KEY POINTS: • Patients with ARVC had significantly reduced RA strain and strain rates compared with healthy participants. • Participants with lower RA reservoir and booster stains were associated with a significantly higher risk of adverse cardiac events. • RA booster and reservoir strain provide incremental value to conventional parameters.

5.
J Cardiovasc Magn Reson ; 26(1): 101005, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302000

RESUMO

BACKGROUND: The prognostic value of left ventricular (LV) myocardial trabecular complexity on cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. This study aimed to evaluate the prognostic value of LV myocardial trabecular complexity using fractal analysis in patients with DCM. METHODS: Consecutive patients with DCM who underwent CMR between March 2017 and November 2021 at two hospitals were prospectively enrolled. The primary endpoints were defined as the combination of all-cause death and heart failure hospitalization. The events of cardiac death alone were defined as the secondary endpoints.LV trabeculae complexity was quantified by measuring the fractal dimension (FD) of the endocardial border based on fractal geometry on CMR. Cox proportional hazards regression and Kaplan-Meier survival analysis were used to examine the association between variables and outcomes. The incremental prognostic value of FD was assessed in nested models. RESULTS: A total of 403 patients with DCM (49.31 ± 14.68 years, 69% male) were recruited. After a median follow-up of 43 months (interquartile range, 28-55 months), 87 and 24 patients reached the primary and secondary endpoints, respectively. Age, heart rate, New York Heart Association functional class >II, N-terminal pro-B-type natriuretic peptide, LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, presence of late gadolinium enhancement, global FD, LV mean apical FD, and LV maximal apical FD were univariably associated with the outcomes (all P < 0.05). After multivariate adjustment, LV maximal apical FD remained a significant independent predictor of outcome [hazard ratio = 1.179 (1.116, 1.246), P < 0.001]. The addition of LV maximal apical FD in the nested models added incremental prognostic value to other common clinical and imaging risk factors (all <0.001; C-statistic: 0.84-0.88, P < 0.001). CONCLUSION: LV maximal apical FD was an independent predictor of the adverse clinical outcomes in patients with DCM and provided incremental prognostic value over conventional clinical and imaging risk factors.

6.
Animals (Basel) ; 14(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338032

RESUMO

The bovine coronavirus (BCoV) KBR-1 strain, obtained from calf diarrhea samples collected in 2017, belongs to group GIIa. To attenuate this strain, it was subcultured continuously (up to 79 times) in HRT-18 cells, followed by 80-120 passages in MDBK cells. The KBR-1-p120 strain harvested from MDBK cells at passage 120 harbored 13 amino acid mutations in the spike gene. Additionally, the KBR-1-p120 strain showed a high viral titer and cytopathogenic effects in MDBK cells. Seven-day-old calves (negative for BCoV antigen and antibodies) that did not consume colostrum were orally inoculated with the attenuated candidate strain (KBR-1-p120), or with KBR-1 passaged 10 times (KBR-1-p10) in HRT-18 cells. Calves inoculated with KBR-1-p10 had a low diarrhea score, and BCoV RNA was detected at 3-7 days post-inoculation (DPI). The virus was also present in the duodenum, jejunum, and ileum at autopsy; however, calves inoculated with KBR-1-p120 had low levels of BCoV RNA in feces at 4-6 DPI, and no diarrhea. In addition, an extremely small amount of BCoV RNA was present in the jejunum and ileum at autopsy. The small intestines of calves inoculated with KBR-1-p120 were emulsified and used to infect calves two more times, but pathogenicity was not recovered. Therefore, the KBR-1-p120 strain has potential as a live vaccine candidate.

7.
Clin Exp Ophthalmol ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363022

RESUMO

The escalating incidence of diabetes mellitus has amplified the global impact of diabetic retinopathy. There are known structural and functional changes in the diabetic retina that precede the fundus photography abnormalities which currently are used to diagnose clinical diabetic retinopathy. Understanding these subclinical alterations is important for effective disease management. Histology and high-resolution clinical imaging reveal that the entire neurovascular unit, comprised of retinal vasculature, neurons and glial cells, is affected in subclinical disease. Early functional manifestations are seen in the form of blood flow and electroretinography disturbances. Structurally, there are alterations in the cellular components of vasculature, glia and the neuronal network. On clinical imaging, changes to vessel density and thickness of neuronal layers are observed. How these subclinical disturbances interact and ultimately manifest as clinical disease remains elusive. However, this knowledge reveals potential early therapeutic targets and the need for imaging modalities that can detect subclinical changes in a clinical setting.

8.
Neural Netw ; 172: 106075, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38278092

RESUMO

The SSVEP-based paradigm serves as a prevalent approach in the realm of brain-computer interface (BCI). However, the processing of multi-channel electroencephalogram (EEG) data introduces challenges due to its non-Euclidean characteristic, necessitating methodologies that account for inter-channel topological relations. In this paper, we introduce the Dynamic Decomposition Graph Convolutional Neural Network (DDGCNN) designed for the classification of SSVEP EEG signals. Our approach incorporates layerwise dynamic graphs to address the oversmoothing issue in Graph Convolutional Networks (GCNs), employing a dense connection mechanism to mitigate the gradient vanishing problem. Furthermore, we enhance the traditional linear transformation inherent in GCNs with graph dynamic fusion, thereby elevating feature extraction and adaptive aggregation capabilities. Our experimental results demonstrate the effectiveness of proposed approach in learning and extracting features from EEG topological structure. The results shown that DDGCNN outperforms other state-of-the-art (SOTA) algorithms reported on two datasets (Dataset 1: 54 subjects, 4 targets, 2 sessions; Dataset 2: 35 subjects, 40 targets). Additionally, we showcase the implementation of DDGCNN in the context of synchronized BCI robotic fish control. This work represents a significant advancement in the field of EEG signal processing for SSVEP-based BCIs. Our proposed method processes SSVEP time domain signals directly as an end-to-end system, making it easy to deploy. The code is available at https://github.com/zshubin/DDGCNN.


Assuntos
Interfaces Cérebro-Computador , Humanos , Potenciais Evocados Visuais , Redes Neurais de Computação , Algoritmos , Eletroencefalografia/métodos , Estimulação Luminosa
9.
Eur Radiol ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189980

RESUMO

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

10.
Food Res Int ; 177: 113835, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38225112

RESUMO

The work aimed to develop the multi-protein mixture of egg yolk as natural particles to stabilize high internal phase Pickering emulsions (HIPPEs) to improve the bioaccessibility of ß-carotene in the elderly. The results showed that the depletion attraction drove the adsorption of egg yolk protein particles at the oil-water interface and the formation of osmotic droplet clusters due to the attachment of particle-coated droplets in the dispersed phase, leading to kinetic blocking and stable gelation of HIPPEs. Rheological measurements showed that HIPPEs had shear thinning, low shear stress, viscoelastic properties, and structural recovery properties, which facilitated easy consumption for the elderly. The stability of HIPPEs was verified by ionic and centrifugal stability tests, demonstrating their potential for application to complex gastric environments. HIPPEs have been applied to the International Dysphagia Dietary Standardization Initiative (IDDSI) test and simulated in vitro digestion in older adults, demonstrating their safe swallowability and high ß-carotene bioaccessibility. Our findings suggest solutions for food practitioners facing the aging problem and provide new insights for preparing age-friendly foods.


Assuntos
Carboximetilcelulose Sódica , beta Caroteno , Humanos , Idoso , Emulsões/química , beta Caroteno/química , Gema de Ovo/metabolismo , Proteínas do Ovo
11.
J Magn Reson Imaging ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270242

RESUMO

BACKGROUND: The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases. PURPOSE: To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD). STUDY TYPE: Prospective outcome study. POPULATION: 207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls. FIELD STRENGTH: 3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences. ASSESSMENT: All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared. STATISTICAL TESTS: Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant. RESULTS: Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group. DATA CONCLUSION: LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

12.
J Magn Reson Imaging ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38258534

RESUMO

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is characterized by progressive myocardial fibro-fatty infiltration accompanied by trabecular disarray. Traditionally, two-dimensional (2D) instead of 3D fractal dimension (FD) analysis has been used to evaluate trabecular disarray. However, the prognostic value of trabecular disorder assessed by 3D FD measurement remains unclear. PURPOSE: To investigate the prognostic value of right ventricular trabecular complexity in ACM patients using 3D FD analysis based on cardiac MR cine images. STUDY TYPE: Retrospective. POPULATION: 85 ACM patients (mean age: 45 ± 17 years, 52 male). FIELD STRENGTH/SEQUENCE: 3.0T/cine imaging, T2-short tau inversion recovery (T2-STIR), and late gadolinium enhancement (LGE). ASSESSMENT: Using cine images, RV (right ventricular) volumetric and functional parameters were obtained. RV trabecular complexity was measured with 3D fractal analysis by box-counting method to calculate 3D-FD. Cox and logistic regression models were established to evaluate the prognostic value of 3D-FD for major adverse cardiac events (MACE). STATISTICAL TESTS: Cox regression and logistic regression to explore the prognostic value of 3D-FD. C-index, time-dependent receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) to evaluate the incremental value of 3D-FD. Intraclass correlation coefficient for interobserver variability. P < 0.05 indicated statistical significance. RESULTS: 26 MACE were recorded during the 60 month follow-up (interquartile range: 48-67 months). RV 3D-FD significantly differed between ACM patients with MACE (2.67, interquartile range: 2.51 ~ 2.81) and without (2.52, interquartile range: 2.40 ~ 2.67) and was a significant independent risk factor for MACE (hazard ratio, 1.02; 95% confidence interval: 1.01, 1.04). In addition, prognostic model fitness was significantly improved after adding 3D-FD to RV global longitudinal strain, LV involvement, and 5-year risk score separately. DATA CONCLUSION: The myocardial trabecular complexity assessed through 3D FD analysis was found associated with MACE and provided incremental prognostic value beyond conventional ACM risk factors. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

13.
Cancer Sci ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287874

RESUMO

Platinum-based therapies have revolutionized the treatment of high-grade serous ovarian cancer (HGSOC). However, high rates of disease recurrence and progression remain a major clinical concern. Impaired mitochondrial function and dysregulated reactive oxygen species (ROS), hallmarks of cancer, hold potential as therapeutic targets for selectively sensitizing cisplatin treatment. Here, we uncover an oncogenic role of the palmitoyltransferase ZDHHC12 in regulating mitochondrial function and ROS homeostasis in HGSOC cells. Analysis of The Cancer Genome Atlas (TCGA) ovarian cancer data revealed significantly elevated ZDHHC12 expression, demonstrating the strongest positive association with ROS pathways among all ZDHHC enzymes. Transcriptomic analysis of independent ovarian cancer datasets and the SNU119 cell model corroborated this association, highlighting a strong link between ZDHHC12 expression and signature pathways involving mitochondrial oxidative metabolism and ROS regulation. Knockdown of ZDHHC12 disrupted this association, leading to increased cellular complexity, ATP levels, mitochondrial activity, and both mitochondrial and cellular ROS. This dysregulation, achieved by the siRNA knockdown of ZDHHC12 or treatment with the general palmitoylation inhibitor 2BP or the fatty acid synthase inhibitor C75, significantly enhanced cisplatin cytotoxicity in 2D and 3D spheroid models of HGSOC through ROS-mediated mechanisms. Markedly, ZDHHC12 inhibition significantly augmented the anti-tumor activity of cisplatin in an ovarian cancer xenograft tumor model, as well as in an ascites-derived organoid line of platinum-resistant ovarian cancer. Our data suggest the potential of ZDHHC12 as a promising target to improve the outcome of HGSOCs in response to platinum-based chemotherapy.

15.
J Magn Reson Imaging ; 59(2): 522-532, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37203257

RESUMO

BACKGROUND: Vertical run-length nonuniformity (VRLN) is a texture feature representing heterogeneity within native T1 images and reflects the extent of cardiac fibrosis. In uremic cardiomyopathy, interstitial fibrosis was the major histological alteration. The prognostic value of VRLN in patients with end-stage renal disease (ESRD) remains unclear. PURPOSE: To evaluate the prognostic value of VRLN MRI in patients with ESRD. STUDY TYPE: Prospective. POPULATION: A total of 127 ESRD patients (30 participants in the major adverse cardiac events, MACE group). FIELD STRENGTH/SEQUENCE: 3.0 T/steady-state free precession sequence, modified Look-Locker imaging. ASSESSMENT: MRI image qualities were assessed by three independent radiologists. VRLN values were measured in the myocardium on the mid-ventricular short-axis slice of T1 mapping. Left ventricular (LV) mass, LV end-diastolic and end-systolic volume, as well as LV global strain cardiac parameters were measured. STATISTICAL TESTS: The primary endpoint was the incident of MACE from enrollment time to January 2023. MACE is a composite endpoint consisting of all-cause mortality, acute myocardial infarction, stroke, heart failure hospitalization, and life-threatening arrhythmia. Cox proportional-hazards regression was performed to test whether VRLN independently correlated with MACE. The intraclass correlation coefficients of VRLN were calculated to evaluate intraobserver and interobserver reproducibility. The C-index was computed to examine the prognostic value of VRLN. P-value <0.05 were considered statistically significant. RESULTS: Participants were followed for a median of 26 months. VRLN, age, LV end-systolic volume index, and global longitudinal strain remained significantly associated with MACE in the multivariable model. Adding VRLN to a baseline model containing clinical and conventional cardiac MRI parameters significantly improved the accuracy of the predictive model (C-index of the baseline model: 0.781 vs. the model added VRLN: 0.814). DATA CONCLUSION: VRLN is a novel marker for risk stratification toward MACE in patients with ESRD, superior to native T1 mapping and LV ejection fraction. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.


Assuntos
Cardiomiopatias , Falência Renal Crônica , Humanos , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Imageamento por Ressonância Magnética , Função Ventricular Esquerda , Volume Sistólico , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Valor Preditivo dos Testes , Imagem Cinética por Ressonância Magnética/métodos
16.
Mol Ther ; 32(2): 384-394, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38087779

RESUMO

Hematopoietic stem/progenitor cell (HSPC)-based anti-HIV-1 gene therapy holds great promise to eradicate HIV-1 or to provide long-term remission through a continuous supply of anti-HIV-1 gene-modified cells without ongoing antiretroviral therapy. However, achieving sufficient engraftment levels of anti-HIV gene-modified HSPC to provide therapeutic efficacy has been a major limitation. Here, we report an in vivo selection strategy for anti-HIV-1 gene-modified HSPC by introducing 6-thioguanine (6TG) chemoresistance through knocking down hypoxanthine-guanine phosphoribosyl transferase (HPRT) expression using RNA interference (RNAi). We developed a lentiviral vector capable of co-expressing short hairpin RNA (shRNA) against HPRT alongside two anti-HIV-1 genes: shRNA targeting HIV-1 co-receptor CCR5 and a membrane-anchored HIV-1 fusion inhibitor, C46, for efficient in vivo selection of anti-HIV-1 gene-modified human HSPC. 6TG-mediated preconditioning and in vivo selection significantly enhanced engraftment of HPRT-knockdown anti-HIV-1 gene-modified cells (>2-fold, p < 0.0001) in humanized bone marrow/liver/thymus (huBLT) mice. Viral load was significantly reduced (>1 log fold, p < 0.001) in 6TG-treated HIV-1-infected huBLT mice compared to 6TG-untreated mice. We demonstrated that 6TG-mediated preconditioning and in vivo selection considerably improved engraftment of HPRT-knockdown anti-HIV-1 gene-modified HSPC and repopulation of anti-HIV-1 gene-modified hematopoietic cells in huBLT mice, allowing for efficient HIV-1 inhibition.


Assuntos
HIV-1 , Transplante de Células-Tronco Hematopoéticas , Humanos , Camundongos , Animais , HIV-1/fisiologia , Hipoxantina Fosforribosiltransferase/genética , Hipoxantina Fosforribosiltransferase/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Medula Óssea/metabolismo , Tioguanina/metabolismo , Tioguanina/farmacologia , RNA Interferente Pequeno/genética
17.
Cell Death Dis ; 14(12): 811, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071340

RESUMO

Pancreatic cancer is highly lethal, of which 90% is pancreatic ductal adenocarcinoma (PDAC), with a 5-year survival rate of less than 12%, lacking effective treatment options and late diagnosis. Furthermore, the tumors show an intense resistance to cytotoxic chemotherapies. As autophagy is elevated in PDAC, targeting the autophagic pathway is regarded as a promising strategy for cancer treatment. Immunofluorescence and transmission electron microscopy were utilized to assess the autophagic flux. Label-free quantitative phosphoproteomics was used to figure out critically altered tyrosine phosphorylation of the proteins. Tumor-bearing mice were used to validate that SH2 TrM-(Arg)9 restrained the growth of tumor cells. SH2 TrM-(Arg)9 inhibited collagen-induced autophagy via blocking the DDR1/PYK2/ERK signaling cascades. SH2 TrM-(Arg)9 improved the sensitivity of PANC-1/GEM cells to gemcitabine (GEM). Inhibition of autophagy by SH2 TrM-(Arg)9 may synergized with chemotherapy and robusted tumor suppression in pancreatic cancer xenografts. SH2 TrM-(Arg)9 could enter into PDAC cells and blockade autophagy through inhibiting DDR1/PYK2/ERK signaling and may be a new treatment strategy for targeted therapy of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Quinase 2 de Adesão Focal/metabolismo , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Transdução de Sinais , Autofagia , Linhagem Celular Tumoral , Receptor com Domínio Discoidina 1/metabolismo
18.
Molecules ; 28(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138433

RESUMO

Biotransformation of ursonic acid (1) by two fungal strains Aspergillus ochraceus CGMCC 3.5324 and Aspergillus oryzae CGMCC 3.407 yielded thirteen new compounds (4, 5, 7-10, and 13-19), along with five recognized ones. The structural details of new compounds were determined through spectroscopic examination (NMR, IR, and HR-MS) and X-ray crystallography. Various modifications, including hydroxylation, epoxidation, lactonization, oxygen introduction, and transmethylation, were identified on the ursane core. Additionally, the anti-neuroinflammatory efficacy of these derivatives was assessed on BV-2 cells affected by lipopolysaccharides. It was observed that certain methoxylated and epoxylated derivatives (10, 16, and 19) showcased enhanced suppressive capabilities, boasting IC50 values of 8.2, 6.9, and 5.3 µM. Such ursonic acid derivatives might emerge as potential primary molecules in addressing neurodegenerative diseases.


Assuntos
Aspergillus ochraceus , Aspergillus oryzae , Aspergillus ochraceus/química , Cristalografia por Raios X , Biotransformação
19.
Vaccine ; 41(49): 7377-7386, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37973511

RESUMO

In several countries, classical swine fever (CSF) has not been detected in domestic pigs, but has been detected in wild boars, making the disease difficult to control. To overcome this problem, we inoculated pigs with a CSF live marker vaccine (Flc-LOM-BErns strain), which has "distinguish infection from vaccinated animals (DIVA)" function, to determine whether it is suitable as an oral vaccine specifically for wild boars. Pigs inoculated intramuscularly or orally with the Flc-LOM-BErns vaccine were challenged 2 or 4 weeks later, respectively, with virulent CSFV. Pigs administered the oral Flc-LOM-BErns strain (105.0 and 6.0 TCID50/dose), and those vaccinated intramuscularly (103.0 TCID50/dose), had normal numbers of leukocytes and normal body temperature. Also, they generated protective neutralizing antibodies and anti-BVDV Erns antibodies. In addition, all pigs in these groups survived, with no CSFV RNA detected in feces, spleen, or other organs. Thus, the Flc-LOM-BErns vaccine shows excellent safety and efficacy, while having DIVA function and suitability for oral inoculation.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Vacinas Virais , Suínos , Animais , Peste Suína Clássica/prevenção & controle , Vacinas Marcadoras , Anticorpos Antivirais , Vacinas Atenuadas , Sus scrofa
20.
Viruses ; 15(11)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38005843

RESUMO

From late 2013-2022, 1131 cases of porcine epidemic diarrhea (PED) were reported to the Korean Animal Health Integrated System (KAHIS). There were four major outbreaks from winter to spring (2013-2014, 2017-2018, 2018-2019, and 2021-2022), with the main outbreaks occurring in Chungnam (CN), Jeonbuk (JB), and Jeju (JJ). Analysis of the complete spike (S) gene of 140/1131 KAHIS PEDV cases nationwide confirmed that 139 belonged to the G2b genotype and 1 to the G2a genotype. Among them, two strains (K17GG1 and K17GB3) were similar to an S INDEL isolated in the United States (strain OH851), and 12 strains had deletions (nucleotides (nt) 3-99) or insertions (12 nt) within the S gene. PEDVs in JJ formed a regionally independent cluster. The substitution rates (substitutions/site/year) were as follows: 1.5952 × 10-3 in CN, 1.8065 × 10-3 in JB, and 1.5113 × 10-3 in JJ. A Bayesian skyline plot showed that the effective population size of PEDs in JJ fell from 2013-2022, whereas in CN and JB it was maintained. Genotyping of 340 Korean PEDV strains, including the 140 PEDVs in this study and 200 Korean reference strains from GenBank, revealed that only the highly pathogenic non-INDEL type (G2b) was dominant from 2020 onwards. Therefore, it is predicted that the incidence of PED will be maintained by the G2b (non-INDEL) genotype.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Suínos , Animais , Estados Unidos , Vírus da Diarreia Epidêmica Suína/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Prevalência , Teorema de Bayes , Doenças dos Suínos/epidemiologia , República da Coreia/epidemiologia , Filogenia , Glicoproteína da Espícula de Coronavírus/genética , Diarreia
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