Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

Application of the IoT in the Food Supply Chain─From the Perspective of Carbon Mitigation.

With the rising demands on supply chain transparency and food security, the rapid outspread of the Internet of Things (IoT) to improve logistical efficiency, and the rising penetration of sensor technology into daily life, the extensive integration of the IoT in the food sector is well anticipated. A perspective on potential life cycle trade-offs in regard to the type of integration is necessary. We conduct life cycle assessment (LCA) integrated with shelf life-food loss (SL-FL) models, showing an overall 5-fold leverage on carbon reduction, which is diet dependent and a function of income. Meat presents the highest leverage, 35 ± 11-times, owing to its high carbon footprint. Two-thirds (65%) of global sensors (1 billion) engaged in monitoring fruits and vegetables can mitigate less than 7% of the total reduced carbon emissions. Despite the expected carbon emission reductions, widespread adoption of the IoT faces multiple challenges such as high costs, difficulties in social acceptance, and regional variability in technological development. Furthermore, changes in the distribution of transportation resources and dealer service models, requirements regarding the accuracy of sensor data analysis, efficient and persistent operation of devices, development of agricultural infrastructure, and farmer education and training have all increased uncertainty. Nonetheless, the research trend in smart sensors toward smaller chips and the potential integration of machine learning or blockchain as further steps make it possible to leverage these advantages to facilitate market penetration. These insights facilitate the future optimization of the application of IoT sensors for sustainability.

Environmental impact assessment of converting flexible packaging plastic waste to pyrolysis oil and multi-walled carbon nanotubes.

A solution to low recycling rates of plastic waste is the conversion into multi-walled carbon nanotubes (MWCNTs) that have high value and can create additional revenue for plant operators. The purpose of this study was to perform a life cycle assessment (LCA) of an integrated system that involves flexible packaging plastic waste (FPPW) pyrolysis, oil upgrading, and MWCNTs production. The objectives were to determine the environmental impact of MWCNTs synthesis from non-condensable pyrolysis gases, and to assess the environmental impact of MWCNTs synthesis from different plastic fractions. Integrating MWCNTs synthesis to the plastic pyrolysis process provides various environmental benefits including, reduction of contribution towards climate change, fossil depletion, human toxicity (cancer), and ionizing radiation potentials. Sensitivity analysis of MWCNTs yields provided the range of impacts on the environment and a critical yield of >2% for most impact categories was determined. Comparison of different plastic fractions indicated that using low PET content feedstock had lesser impact on the environment, and demonstrated comparable performance to mixed virgin plastics for most impact categories. The results highlighted the versatility of the integrated pyrolysis process for treating diverse plastic waste fractions with negligible effects from the impurities present in the actual FPPW during thermal processing.

Human exposure and risk assessment of recycling incineration bottom ash for land reclamation: A showcase coupling studies of leachability, transport modeling and bioaccumulation.

Incineration bottom ash (IBA) faces challenges for its sustainable recycling due to the absence of scenario-specific risk assessment. Environmental risk assessment was carried out via a case study incorporating key factors to dominate human exposures during IBA utilization in land reclamation. Three research components echoing respective IBA leaching, exposures, and consequences were performed under a supportive framework to elaborate these interlinked key factors and unveil the potential environmental risks. IBA leachability was firstly investigated using various laboratory standard leaching methods while conducted a large-scale field trial experiment for mutual confirmation, suggesting that maximum leached amounts may be achieved when liquid to solid (L/S) ratio increases to 10. Dilution and transportation models were both developed to discriminate the mitigation of IBA leachate between two periods i.e. during and after land reclamation, suggesting that dilution rather than transportation may dominate the environmental impact for metal exposures. Metal bioaccumulation from a typical mollusk species was performed coupling the calculated dietary safety limits based on Singaporean diet intake for development of the threshold of toxicology concerns on human exposures. With such, IBA benign usage in land reclamation was also conferred in the form of distance and dilution factor.

Sex differences in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

Sex differences in vascular physiology and pathophysiology: estrogen and androgen signaling in health and disease.

Sex differences between women and men are often overlooked and underappreciated when studying the cardiovascular system. It has been long assumed that men and women are physiologically similar, and this notion has resulted in women being clinically evaluated and treated for cardiovascular pathophysiological complications as men. Currently, there is increased recognition of fundamental sex differences in cardiovascular function, anatomy, cell signaling, and pathophysiology. The National Institutes of Health have enacted guidelines expressly to gain knowledge about ways the sexes differ in both normal function and diseases at the various research levels (molecular, cellular, tissue, and organ system). Greater understanding of these sex differences will be used to steer future directions in the biomedical sciences and translational and clinical research. This review describes sex-based differences in the physiology and pathophysiology of the vasculature, with a special emphasis on sex steroid receptor (estrogen and androgen receptor) signaling and their potential impact on vascular function in health and diseases (e.g., atherosclerosis, hypertension, peripheral artery disease, abdominal aortic aneurysms, cerebral aneurysms, and stroke).

Modeling active capping efficacy. 1. Metal and organometal contaminated sediment remediation.

Cd, Cr, Pb, Ag, As, Ba, Hg, CH3Hg, and CN transport through sand, granular activated carbon (GAC), organoclay, shredded tires, and apatite caps was modeled by deterministic and Monte Carlo methods. Time to 10% breakthrough, 30 and 100 yr cumulative release were metrics of effectiveness. Effective caps prevented above-cap concentrations from exceeding USEPA acute criteria at 100 yr assuming below-cap concentrations at solubility. Sand caps performed best under diffusion due to the greater diffusive path length. Apatite had the best advective performance for Cd, Cr, and Pb. Organoclay performed best for Ag, As, Ba, CH3Hg, and CN. Organoclay and apatite were equally effective for Hg. Monte Carlo analysis was used to determine output sensitivity. Sand was effective under diffusion for Cr within the 50% confidence interval (CI), for Cd and Pb (75% CI), and for As, Hg, and CH3Hg (95% CI). Under diffusion and advection, apatite was effective for Cd, Pb, and Hg (75% CI) and organoclay was effective for Hg and CH3Hg (50% CI). GAC and shredded tires performed relatively poorly. Although no single cap is a panacea, apatite and organoclay have the broadest range of effectiveness. Cap performance is most sensitive to the partitioning coefficient and hydraulic conductivity, indicating the importance of accurate site-specific measurement for these parameters.