Uremic toxins are considered to have a determinant pathological role in the progression of chronic kidney disease. The aim of this study was to define the putative pathological roles of the renal ...renin-angiotensin-aldosterone system (RAAS) and renal tubular epithelial-to-mesenchymal transition (EMT) in kidney fibrosis induced by (indoxyl sulfate) IS and (p-cresol sulfate) PCS.
Mouse proximal renal tubular cells (PKSV-PRs) treated with IS or PCS were used. Half-nephrectomized B-6 mice were treated with IS or PCS for 4 weeks. In the losartan treatment study, the study animal was administrated with IS+losartan or PCS+losartan for 4 weeks.
IS and PCS significantly activated the intrarenal RAAS by increasing renin, angiotensinogen, and angiotensin 1 (AT1) receptor expression, and decreasing AT2 receptor expression in vitro and in vivo. IS and PCS significantly increased transforming growth factor-β1 (TGF-β1) expression and activated the TGF-β pathway by increasing Smad2/Smad2-P, Smad3/Smad3-P, and Smad4 expression. The expression of the EMT-associated transcription factor Snail was increased by IS and PCS treatment. IS and PCS induced the phenotype of EMT-like transition in renal tubules by increasing the expression of fibronectin and α-smooth muscle actin and decreasing the expression of E-cadherin. Losartan significantly attenuated the expression of TGF-β1 and Snail, and decreased kidney fibrosis induced by IS and PCS in vivo.
Activating the renal RAAS/TGF-β pathway has an important pathological role in chronic kidney injury caused by IS and PCS. IS and PCS may increase Snail expression and induce EMT-like transition.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to inadequate insulin secretion, resistance, or both. The cardiovascular complications of DM are the leading ...cause of morbidity and mortality in diabetic patients. There are three major types of pathophysiologic cardiac remodeling including coronary artery atherosclerosis, cardiac autonomic neuropathy, and DM cardiomyopathy in patients with DM. DM cardiomyopathy is a distinct cardiomyopathy characterized by myocardial dysfunction in the absence of coronary artery disease, hypertension, and valvular heart disease. Cardiac fibrosis, defined as the excessive deposition of extracellular matrix (ECM) proteins, is a hallmark of DM cardiomyopathy. The pathophysiology of cardiac fibrosis in DM cardiomyopathy is complex and involves multiple cellular and molecular mechanisms. Cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction (HFpEF), which increases mortality and the incidence of hospitalizations. As medical technology advances, the severity of cardiac fibrosis in DM cardiomyopathy can be evaluated by non-invasive imaging modalities such as echocardiography, heart computed tomography (CT), cardiac magnetic resonance imaging (MRI), and nuclear imaging. In this review article, we will discuss the pathophysiology of cardiac fibrosis in DM cardiomyopathy, non-invasive imaging modalities to evaluate the severity of cardiac fibrosis, and therapeutic strategies for DM cardiomyopathy.
Since the onset of the coronavirus disease 2019 (COVID-19), numerous neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and ...authorized for emergency use to control the pandemic. Most COVID-19 therapeutic NAbs prevent the S1 subunit of the SARS-CoV-2 spike (S) protein from binding to the human host receptor. However, the emergence of SARS-CoV-2 immune escape variants, which possess frequent mutations on the S1 subunit, may render current NAbs ineffective. In contrast, the relatively conserved S2 subunit of the S protein can elicit NAbs with broader neutralizing potency against various SARS-CoV-2 variants. In this review, the binding specificity and functional features of SARS-CoV-2 NAbs targeting different domains of the S2 subunit are collectively discussed. The knowledge learned from the investigation of the S2-specific NAbs provides insights and potential strategies for developing antibody cocktail therapy and next-generation coronavirus vaccine.
Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being ...more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached.
The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA.
When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation.
With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA.
Universities continue to play a key role in the development of a country. As university income streams shift away from government and as the income from admissions decline under the sub-replacement ...fertility phenomenon, the efficiency of resource utilization has become an important issue for university administrators. This paper applies data envelopment analysis (DEA) and the concept of an assurance region to evaluate the relative efficiency (including aggregate, technical, and scale efficiencies) of academic departments at National Chung Cheng University in Taiwan. The input factors considered are personnel (expressed in the number of faculty-equivalent persons), operating expenses, and floor area, and the output factors are teaching (expressed in total credit hours), publications (expressed in the number of papers), and external grants. Notably, teaching quality is included by considering the classroom capacity in calculating credit hours, and publication quality is included by considering the author contribution to calculate the single-author-equivalent numbers of papers. In addition, a cluster analysis based on the efficiency decomposition to the contributions of the three outputs is applied to classify the departments into three groups. The results of this paper not only provide the department head with the relative efficiency and improvement directions for the department but also serve as a reference for resource allocation and future strategy development for the university administration.
The Paris Agreement requires countries to propose their National Determined Contributions (NDCs) and encourages companies to engage in climate action. This two-stage study explores the mutual ...influence of national and corporate carbon reduction targets and their effect on the adoption of renewable energy using Hierarchical Linear Modeling (HLM). The subjects are companies nested in the G20, engaging in the Science-Based Target initiative (SBTi) or the RE100 initiative. These empirical results show corporate targets are positively correlated to adoption of renewable energy, and development of renewable energy varies by country groups, however; national targets are insignificantly correlated. Our key findings: (1) companies which set SBTs are more willing to use renewable energy to achieve their targets but prefer power purchase agreements (PPAs) and renewable energy certificates (RECs) to investment in renewables. (2) The effect of a national-level target on corporate renewable energy use is non-significant, probably because most multinational corporations are used to compliance and their performances are likely to be better than the national deployment on climate change. We argue that an industrial energy transition to renewables is economically beneficial and needs substantial support in the form of policies or subsidies, instead of just setting targets or attracting publicity.
Clinical features of epidermal growth factor receptor (EGFR) mutations, L858R, deletions in exon 19, T790M, and insertions in exon 20, in non-small cell lung cancer (NSCLC) are well known. The ...clinical significance of other uncommon EGFR mutations, such as their association with the effectiveness of EGFR tyrosine kinase inhibitors (TKI), is not well understood. This study aimed to improve the understanding of these uncommon EGFR mutations of unknown clinical significance.
Specimens from 1,261 patients were tested for EGFR mutations. We surveyed the clinical data and the effectiveness of gefitinib and erlotinib in NSCLC patients with uncommon EGFR mutations.
Of the 1,261 patients, 627 (49.8%) had EGFR mutations. This included 258 patients with deletions in exon 19, 260 patients with L858R, 25 patients with insertions or duplications in exon 20, 6 patients with de novo T790M, and 78 (12.4%) patients with uncommon mutations. Of the 78 patients, 62 received either gefitinib or erlotinib treatment. The response rate of TKIs treatment was 48.4%, and the median progression-free survival (PFS) was 5.0 months. Mutations on G719 and L861 composed a major part (28 of 62) of uncommon mutations, and were associated with a favorable effectiveness of EGFR TKIs (response rate, 57.1%; median PFS, 6.0 months). Mutations other than G719 and L861 led to a worse response to EGFR TKIs (response rate, 20.0%; median PFS, 1.6 months).
Uncommon EGFR mutations constituted a distinct part of the whole group of EGFR mutations. Their composition was heterogeneous, and their associations with EGFR TKIs differed.
Highly‐oriented indium tin oxide nanocolumns are prepared by glancing‐angle deposition with nitrogen. The tapered column profiles, which function as a graded‐refractive‐index layer, offer superior ...antireflective characteristics. The nanostructured material serves as the conductive antireflective layer for GaAs solar cells, demonstrating a viable efficiency‐boosting strategy for next‐generation photovoltaics.
With the low latency, high transmission rate, and high reliability provided by the fifth-generation mobile communication network (5G), many applications requiring ultra-low latency and high ...reliability (uRLLC) have become a hot research topic. Among these issues, the most important is the Internet of Vehicles (IoV). To maintain the safety of vehicle drivers and road conditions, the IoV can transmit through sensors or infrastructure to maintain communication quality and transmission. However, because 5G uses millimeter waves for transmission, a large number of base stations (BS) or lightweight infrastructure will be built in 5G, which will make the overall environment more complex than 4G. The lightweight infrastructure also has to be considered together. For these reasons, in 5G, there are two mechanisms for handover, horizontal, and vertical handover; hence, it must be discussed how to handle handover to obtain the best performance for the whole network. In this paper, to address handover selection, we consider delay time, energy efficiency, load balancing, and energy consumption and formulate it as a multi-objective optimization (MOO) problem. At the same time, we propose the handover of the mobile management mechanism based on location prediction combined with heuristic algorithms. The results show that our proposed mechanism is better than the distance-based one for energy efficiency, load, and latency. It optimizes by more than about 20% at most.
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