Arterial pulse wave velocity (PWV) is recognized as a convenient method to assess peripheral vascular stiffness. This study explored the clinical characteristics of hand PWV (hPWV) and hand pulse ...transit time (hPTT) in healthy adults (sixty males = 42.4 ± 13.9 yrs; sixty-four females = 42.8 ± 13.9 yrs) voluntarily participated in this study. The arterial pulse waveform and the anatomical distance from the radial styloid process to the tip of the middle finger of both hands were recorded in the sitting position. The hPWV was calculated as the traversed distance divided by hPTT between those two points. Male subjects showed significantly greater hPWV, systolic blood pressure, and pulse pressure than age-matched female subjects, while the hPTT was not significantly different between genders. Multiple linear regression analysis showed that gender is a common determinant of hPWV and hPTT, and that age and heart rate (HR) were negatively correlated with hPWV and hPTT, respectively. We conclude that male subjects have greater hPWV than female subjects. Ageing is associated with decreased hPWV, while increased HR is associated with a smaller hPTT. The hPWV and hPTT might be used as non-invasive indices to characterise the ageing and arterial stiffness of peripheral blood vessels.
The coronavirus disease 2019 (COVID-19) pandemic continues to burden healthcare systems worldwide. COVID-19 symptoms are highly heterogeneous, and the patient may be asymptomatic or may present with ...mild to severe or fatal symptoms. Factors, such as age, sex, and comorbidities, are key determinants of illness severity and progression. Aging is accompanied by multiple deficiencies in interferon production by dendritic cells or macrophages in response to viral infections, resulting in dysregulation of inflammatory immune responses and excess oxidative stress. Age-related dysregulation of immune function may cause a more obvious pathophysiological response to SARS-CoV-2 infection in elderly patients and may accelerate the risk of biological aging, even after recovery. For more favorable treatment outcomes, inhibiting viral replication and dampening inflammatory and oxidative responses before induction of an overt cytokine storm is crucial. Resveratrol is a potent antioxidant with antiviral activity. Herein, we describe the reasons for impaired interferon production, owing to aging, and the impact of aging on innate and adaptive immune responses to infection, which leads to inflammation distress and immunosuppression, thereby causing fulminant disease. Additionally, the molecular mechanism by which resveratrol could reverse a state of excessive basal inflammatory and oxidative stress and low antiviral immunity is discussed.
The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal ...osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines’ effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD’s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.
Aphelenchoides besseyi is a plant‐parasitic nematode (PPN) in the family Aphelenchoididae capable of infecting more than 200 plant species. A. besseyi is also a species complex with strains ...exhibiting varying pathogenicity to plants. We present the genome and annotations of six Aphelenchoides species, four of which belonged to the A. besseyi species complex. Most Aphelenchoides genomes have a size of 44.7–47.4 Mb and are among the smallest in clade IV, with the exception of A. fujianensis, which has a size of 143.8 Mb and is one of the largest. Phylogenomic analysis successfully delimited the species complex into A. oryzae and A. pseudobesseyi and revealed a reduction of transposon elements in the last common ancestor of Aphelenchoides. Synteny analyses between reference genomes indicated that three chromosomes in A. besseyi were derived from fission and fusion events. A systematic identification of horizontal gene transfer (HGT) genes across 27 representative nematodes allowed us to identify two major episodes of acquisition corresponding to the last common ancestor of clade IV or major PPNs, respectively. These genes were mostly lost and differentially retained between clades or strains. Most HGT events were acquired from bacteria, followed by fungi, and also from plants; plant HGT was especially prevalent in Bursaphelenchus mucronatus. Our results comprehensively improve the understanding of HGT in nematodes.
PurposeThis study aims to evaluate cargo and eco-efficiency of global container shipping companies (CSCs) and explore the determinants of the CSCs' efficiencies. While the former is derived from the ...CSCs' operational perspective, the latter highlights environmental issue related to carbon emission reduction.Design/methodology/approachIn the first stage, a two-stage double bootstrap approach of data envelopment analysis (DEA) is applied to derive bias-corrected cargo and eco-efficiency of the top ten global CSCs under the variable returns to scale assumption. In the second stage, ordinary least squares and truncated regression are applied to examine determinants of the CSCs' efficiencies.FindingsThe DEA results reveal that the cargo efficiency of the CSCs is higher than their eco-efficiency by about 2.6% under variable returns to scale in DEA. However, the bias-corrected results show that the difference is 2.9%. The overall average efficiencies suggest that the CSCs can improve their cargo (eco) efficiency by 6.9% (10.8%). In the second stage, the regression results show that the numbers of ship, return on assets and asset turnover ratio are significantly related to both cargo and eco-efficiencies, whereas the total fleet capacity positively affects cargo efficiency.Research limitations/implicationsThe results of this study can help the inefficient CSCs make strategic decisions to improve their performance. For example, their business experience and capacity may be contributing to their efficiencies. However, this study only focuses on the container market among the three main markets, namely, dry bulk, wet bulk and container.Originality/valueThis study highlights an environmental issue in the shipping industry. While CSCs are operating their cargo efficiently in general, they should also put green initiatives into their business operations for the long-term sustainability.
Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of ...genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.
Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary ...hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased renal phosphate excretion, resulting in potentiating bone resorption and decreased bone quantity and quality. Calcium-sensing receptors (CaSRs) are group C G-proteins and negatively regulate the parathyroid glands through (1) increasing CaSR insertion within the plasma membrane, (2) increasing 1,25-dihydroxy vitamin D3 within the kidney and parathyroid glands, (3) inhibiting fibroblast growth factor 23 (FGF23) in osteocytes, and (4) attenuating intestinal calcium absorption through Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6). Calcimimetics (CaMs) decrease PTH concentrations without elevating the serum calcium levels or extraosseous calcification through direct interaction with cell membrane CaSRs. CaMs reduce osteoclast activity by reducing stress-induced oxidative autophagy and improving Wnt-10b release, which promotes the growth of osteoblasts and subsequent mineralization. CaMs also directly promote osteoblast proliferation and survival. Consequently, bone quality may improve due to decreased bone resorption and improved bone formation. CaMs modulate cardiovascular fibrosis, calcification, and renal fibrosis through different mechanisms. Therefore, CaMs assist in treating SHPT. This narrative review focuses on the role of CaMs in renal osteodystrophy, including their mechanisms and clinical efficacy.
In microalloyed steels, interphase precipitation involves the formation of precipitates at the ferrite/austenite interface during their transformation. The study on interphase precipitation has been ...ongoing since the 1970s and remains highly relevant today. While this metallurgical approach has been applied in various products of advanced steels, its application to cold‐rolled steels is still absent. This study presents a development of cold‐rolled dual‐phase (DP) steels strengthened by interphase‐precipitated carbides. A CALPHAD‐based approach is established to facilitate austenite to ferrite transformation coupled with interphase precipitation during simulated annealing for cold‐rolled DP steels. Further experimental investigations on the effects of V and Mo optimize the alloy composition, and the corresponding nano/microstructures are validated by transmission electron microscopy (TEM) and atom probe tomography. Besides, this work further addresses the impacts of interfacial segregation and microsegregation bands on the capability of interphase precipitation in the studied steels. In summary, this work charts a new pathway for the development of cold‐rolled DP steels strengthened by interphase‐precipitated carbides, advancing the realm of high‐strength steels.
This study validates a CALPHAD‐based approach in designing a prototype of cold‐rolled dual‐phase (DP) steel with interphase precipitation. Impacts of interfacial velocity and interfacial segregation on interphase precipitation in V‐Mo microalloying steels is investigated via detailed nano/microstructural characterizations. The findings summarize design principles and challenges in the development of cold‐rolled DP steel strengthened by interphase‐precipitated carbides.
Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation ...and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.
A previous study of an animal model with tumor suppressor gene von Hippel-Lindau (VHL) conditional knockdown suggested that tissue inflammation and fibrosis play important roles in the development of ...clear-cell renal cell carcinoma (ccRCC), which is consistent with the epidemiological evidence linking inflammatory kidney disease and renal cancer. Ferroptosis and inflammation have been linked in a recent study, but the exact mechanism remains unclear. This study is aimed at investigating the mechanism of lipocalin-2- (LCN-2-) mediated ferroptosis and inflammation in vhl-mutated HK-2 cells and mouse primary proximal tubule cells (mRTCs) and the polarization of macrophage RAW 264.7 cells. Based on the levels of lipid reactive oxygen species (ROS) and the expression of glutathione peroxidase 4 (GPX4) in HK-2 cells, we observed that a VHL mutation increased ROS production and depressed GPX4 expression, whereas LCN-2 knockdown reversed these effects. Accordingly, VHL appears to affect ferroptosis in an LCN-2-dependent manner. We also revealed that LCN-2 sensitizes HK-2 cells to inflammation and macrophage RAW 264.7 cells to M1-like polarization. This study provides novel insights into the potential therapeutic target and strategy for attenuating the progression of ccRCC by revealing the role of VHL in regulating chronic inflammation within the LCN-2–ferroptosis pathway.