ABSTRACT
BACKGROUND: Xenotransplantation of genetically engineered porcine organs has the potential to address the challenge of organ donor shortage. Two cases of porcine-to-human kidney xenotransplantation were performed, yet the physiological effects on the xenografts and the recipients' immune responses remain largely uncharacterized. METHODS: We performed single-cell RNA sequencing (scRNA-seq) and longitudinal RNA-seq analyses of the porcine kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal scRNA-seq of the peripheral blood mononuclear cells (PBMCs) to detect recipient immune responses across time. FINDINGS: Although no hyperacute rejection signals were detected, scRNA-seq analyses of the xenografts found evidence of endothelial cell and immune response activation, indicating early signs of antibody-mediated rejection. Tracing the cells' species origin, we found human immune cell infiltration in both xenografts. Human transcripts in the longitudinal bulk RNA-seq revealed that human immune cell infiltration and the activation of interferon-gamma-induced chemokine expression occurred by 12 and 48 h post-xenotransplantation, respectively. Concordantly, longitudinal scRNA-seq of PBMCs also revealed two phases of the recipients' immune responses at 12 and 48-53 h. Lastly, we observed global expression signatures of xenotransplantation-associated kidney tissue damage in the xenografts. Surprisingly, we detected a rapid increase of proliferative cells in both xenografts, indicating the activation of the porcine tissue repair program. CONCLUSIONS: Longitudinal and single-cell transcriptomic analyses of porcine kidneys and the recipient's PBMCs revealed time-resolved cellular dynamics of xenograft-recipient interactions during xenotransplantation. These cues can be leveraged for designing gene edits and immunosuppression regimens to optimize xenotransplantation outcomes. FUNDING: This work was supported by NIH RM1HG009491 and DP5OD033430.
Subject(s)
Graft Rejection , Kidney Transplantation , Transplantation, Heterologous , Animals , Transplantation, Heterologous/adverse effects , Transplantation, Heterologous/methods , Humans , Swine , Graft Rejection/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Single-Cell Analysis , Heterografts/immunology , RNA-Seq , Sequence Analysis, RNA , Kidney/immunology , Kidney/metabolismABSTRACT
Both linguistic and extralinguistic consultations are essential in translation practice and have been commonly investigated as an integral topic in previous studies. However, since extralinguistic information is usually longer in extent and not specifically designed for a linguistic purpose, extralinguistic consultations involve different search strategies compared with linguistic consultations. Drawing on eye-tracking and screen-recording data, this study compares linguistic and extralinguistic consultations in terms of cognitive resources allocation and information processing patterns in English-Chinese translation. It also explores the differences among 17 language learners, 20 student translators, and 21 professional translators, and the effect of extralinguistic consultation on their translation quality. The findings are as follows: (1) all participants allocate more attention and lower cognitive load to extralinguistic consultations than to linguistic consultations; (2) participants' translation experience levels and their attention allocated to extralinguistic consultation show an inverted U-shaped relationship; and (3) participants who consult extralinguistic information before drafting or devote more attention to extralinguistic consultation produce target texts with significantly higher scores.
ABSTRACT
BACKGROUND: Lipoprotein(a)[Lp(a)] has been considered as an independent risk factor for coronary artery disease (CAD). The present study aimed to evaluate the association between baseline serum Lp(a) and CAD progression determined by angiographic score. METHODS: A total of 814 patients who had undergone two or more coronary computed tomography angiography at least 6 months apart were consecutively enrolled and the coronary severity was determined by the Gensini score system. Patients were stratified into two groups according to Lp(a)>300 mg/L and Lp(a) ≤ 300 mg/L or classified as "progressors" and "non-progressors" based on the Gensini score rate of change per year. The association of continuous Lp(a) and Lp(a)>300 mg/L with CAD progression were respectively assessed by logistic regression analysis. Moreover, further evaluation of those association was performed in subgroups of the study population. RESULTS: Patients in the "progressors" group had significant higher Lp(a) levels. Furthermore, the multivariate logistic regression analysis showed that elevated Lp(a) (odds ratio [OR]: 1.451, 95% confidence interval [CI]: 1.177-1.789, p<.001) and Lp(a)>300 mg/L (OR:1.642, 95% CI:1.018-2.649, p = .042) were positively associated with CAD progression after adjusting for confounding factors. In addition, those relation seemed to be more prominent in subjects with lower body mass index (OR: 1.880, 95% CI: 1.224-2.888, p for interaction = .060). CONCLUSIONS: Elevated baseline serum Lp(a) is positively and independently associated with angiographic progression of CAD, particularly in participants with relatively low body mass index. Therefore, Lp(a) could be a potent risk factor for CAD progression, assisting in early risk stratification in cardiovascular patients.
Subject(s)
Coronary Artery Disease , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Humans , Lipoprotein(a) , Risk Factors , Severity of Illness IndexABSTRACT
Comparisons between backward and forward translation (BT, FT) have long illuminated the organization of bilingual memory, with neuroscientific evidence indicating that FT would involve greater linguistic and attentional demands. However, no study has directly assessed the functional interaction between relevant mechanisms. Against this background, we conducted the first fMRI investigation of functional connectivity (FC) differences between BT and FT. In addition to yielding lower behavioral outcomes, FT was characterized by increased FC between a core semantic hub (the left anterior temporal lobe, ATL) and key nodes of attentional and vigilance networks (left inferior frontal, left orbitofrontal, and bilateral parietal clusters). Instead, distinct FC patterns for BT emerged only between the left ATL and the right thalamus, a region implicated in automatic relaying of sensory information to cortical regions. Therefore, FT seems to involve enhanced coupling between semantic and attentional mechanisms, suggesting that asymmetries in cross-language processing reflect dynamic interactions between linguistic and domain-general systems.