CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We ...initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.
In the past decades, the physicochemical properties of electron donor–acceptor, EDA, complexes (also called charge-transfer, CT, complexes) have been extensively studied, although their synthetic ...applications have been somewhat limited. However, in recent years, this scenario has started to change as an increasing number of examples have been reported. In this regard, this review aims to present and discuss the main aspects associated with the physicochemical properties of these complexes and a selection of synthetic photochemical applications in organic chemistry.
Summary
Background
Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD.
Aims
To investigate the ...performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD.
Methods
Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non‐invasive markers were compared to histology as the gold standard.
Results
Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50‐0.88), 0.87 (0.77‐0.79) and 0.82 (0.70‐0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86‐1.00), 0.81 (0.69‐0.92) and 0.89 (0.77‐1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068).
Conclusions
Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.
Linked content
This article is linked to Ferraioli paper. To view this article visit https://doi.org/10.1111/apt.14501.
Targeting antioxidants to mitochondria is considered a promising strategy to prevent cellular senescence and skin ageing. In this study, we investigate whether four hydroxybenzoic acid-based ...mitochondria-targeted antioxidants (MitoBENs, MB1-4) could be used as potential active ingredients to prevent senescence in skin cells. Firstly, we evaluated the chemical stability, cytotoxicity, genotoxicity and mitochondrial toxicity of all compounds. We followed this by testing the antioxidant protective capacity of the two less toxic compounds on human skin fibroblasts. We then assessed the effects of the best hit on senescence, inflammation and mitochondrial remodeling on a 3D skin cell model, while also testing its mutagenic potential. Cytotoxicity and mitochondrial toxicity rankings were produced: MB3 < MB4 ≃ MB1 < MB2 and MB3 < MB1 < MB4 < MB2, respectively. These results suggest that pyrogallol-based compounds (MB2 and MB4) have lower cytotoxicity. The pyrogallol derivative, MB2, containing a 6-carbon spacer, showed a more potent antioxidant protective activity against hydrogen peroxide cytotoxicity. In a 3D skin cell model, MB2 also decreased transcripts related to senescence. In sum, MB2’s biological safety profile, good chemical stability and lack of mutagenicity, combined with its anti-senescence effect, converts MB2 into a good candidate for further development as an active ingredient for skin anti-ageing products.
Oleanolic (OA), ursolic (UA), and betulinic (BA) acids are three triterpenic acids (TAs) with potential effects for treatment of type 2 diabetes (T2DM). Mechanistic studies showed that these TAs act ...as hypoglycemic and antiobesity agents mainly through (i) reducing the absorption of glucose; (ii) decreasing endogenous glucose production; (iii) increasing insulin sensitivity; (iv) improving lipid homeostasis; and (v) promoting body weight regulation. Besides these promising beneficial effects, it is believed that OA, UA, and BA protect against diabetes-related comorbidities due to their antiatherogenic, anti-inflammatory, and antioxidant properties. We also highlight the protective effect of OA, UA, and BA against oxidative damage, which may be very relevant for the treatment and/or prevention of T2DM. In the present review, we provide an integrative description of the antidiabetic properties of OA, UA, and BA, evaluating the potential use of these TAs as food supplements or pharmaceutical agents to prevent and/or treat T2DM.
Green and lean paradigms have been adopted by companies in order to manage their relationships with suppliers in a supply chain management context, but nearly always separately and with little ...understanding of their influence on company performance. This paper proposes a theoretical framework for the analysis of the influence of green and lean upstream supply chain management practices on the sustainable development of businesses. To attend this objective, a set of performance measures covering economic (operational cost, environmental cost, and inventory cost), environmental (business wastage, green image, and CO 2 emission), and social (corruption risk, supplier screening and local supplier) perspectives is proposed. An explanatory case study was conducted at a Portuguese automaker to test qualitatively the validity of the proposed theoretical framework. From the case study, a model is suggested, which encompasses the relationships between green and lean upstream supply chain practices and sustainable business development.
Epiphyte communities comprise important components of many forest ecosystems in terms of biomass and diversity, but little is known regarding trade-offs that underlie diversity and structure in these ...communities or the impact that microclimate has on epiphyte trait allocation. We measured 22 functional traits in vascular epiphyte communities across six sites that span a microclimatic gradient in a tropical montane cloud forest region in Costa Rica. We quantified traits that relate to carbon and nitrogen allocation, gas exchange, water storage, and drought tolerance. Functional diversity was high in all but the lowest elevation site where drought likely limits the success of certain species with particular trait combinations. For most traits, variation was explained by relationships with other traits, rather than differences in microclimate across sites. Although there were significant differences in microclimate, epiphyte abundance, and diversity, we found substantial overlap in multivariate trait space across five of the sites. We found significant correlations between functional traits, many of which related to water storage (leaf water content, leaf thickness, hydrenchymal thickness), drought tolerance (turgor loss point), and carbon allocation (specific leaf area, leaf dry matter content). This suite of trait correlations suggests that the epiphyte community has evolved functional strategies along with a drought avoidance versus drought tolerance continuum where leaf succulence emerged as a pivotal overall trait.
Recently models have attempted to integrate the functional relationships of fat mass (FM) and fat-free mass (FFM) with the control of human energy intake (EI). Cross-sectional evidence suggests that ...at or close to EB, FFM is positively related to hunger and EI, whereas FM either shows a weak negative or no association with ad libitum EI. Further analysis suggests that the effects of FFM and FM on EI may be mediated by resting metabolic rate (RMR). These studies suggest that energy turnover is associated with EI and the largest determinant of energy requirements in most humans is FFM. During chronic positive EBs both FM and FFM expand (but disproportionately so), increasing energy demands. There is little evidence that an expanding FM exerts strong negative feedback on longer term EI. However, during chronic negative EBs FM, FFM and RMR all decrease but appetite increases. Some studies suggest that proportionate loss of FFM during weight loss predicts subsequent weight regain. Taken together these lines of evidence suggest that changes in the size and functional integrity of FFM may influence appetite and EI. Increases in FFM associated with either weight gain or high levels of exercise may 'pull' EI upwards but energy deficits that decrease FFM may exert a distinct drive on appetite. The current paper discusses how FM and FFM relationships influence appetite regulation, and how size, structure and functional integrity of FFM may drive EI in humans (i) at EB (ii) during positive EB and (iii) during negative EB.
Common bean (
) can efficiently fix atmospheric nitrogen when associated with Rhizobia. However, drought stress impairs plant metabolic processes, especially the biological nitrogen fixation (BNF). ...Here, we assessed transcriptional responses in nodules of two common bean genotypes to drought stress under BNF reliance. The RNA-Seq analysis yielded a total of 81,489,262 and 72,497,478 high quality reads for Negro Argel and BAT 477 genotypes, respectively. The reads were mapped to the
reference genome and expression analysis identified 145 and 1451 differentially expressed genes (DEGs) for Negro Argel and BAT 477 genotypes, respectively. Although BAT 477 had more DEGs, both genotypes shared certain drought-responsive genes, including an up-regulated heat shock protein (HSP) and a down-regulated peroxidase, indicating shared pathways activated during drought in nodule tissue. Functional analysis using MapMan software highlighted the up-regulation of genes involved in abiotic stress responses, such as HSPs and specific transcription factors (TFs), in both genotypes. There was a significant down-regulation in metabolic pathways related to antioxidant protection, hormone signaling, metabolism, and transcriptional regulation. To validate these findings, we conducted RT-qPCR experiments for ten DEGs in nodules from both genotypes, for which the expression profile was confirmed, thus reinforcing their functional relevance in the nodule responses to drought stress during BNF. BAT 477 genotype exhibited more pronounced response to drought, characterized by a high number of DEGs. The strong down-regulation of DEGs leads to transcriptional disturbances in several pathways related to stress acclimation such as hormone and antioxidant metabolism. Additionally, we identified several genes that are known to play key roles in enhancing drought tolerance, such as HSPs and crucial TFs. Our results provide new insights into the transcriptional responses in root-nodules, an underexplored tissue of plants mainly under drought conditions. This research paves the way for potential improvements in plant-bacteria interactions, contributing to common bean adaptations in the face of challenging environmental conditions.
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