Invited for the cover of this issue are Eliška Procházková, Ondřej Baszczyňski, and colleagues at IOCB (Prague) and Charles University (Prague). The image depicts phosphorus‐based, double‐cargo, ...self‐immolative linkers capable of releasing both cargos sequentially after activation by light. Read the full text of the article at 10.1002/chem.202101805.
“The most significant result of this study is the development of a new class of phosphate‐based linkers, which can release two structurally different phenolic cargos in several adjustable modes. This option may be useful in designing drug delivery strategies or developing new innovative materials.” Read more about the story behind the cover in the Cover Profile and about the research itself on page 12763 ff. (DOI: 10.1002/chem.202101805).
Phosphorus‐based self‐immolative linkers activated by light sequentially release two phenolic cargos. Structurally modifying the lactate spacer responsible for self‐immolation allows adjustable cargo ...release, ranging from minutes to days. The cargo release rate can be additionally tuned by varying the cargos. NMR spectroscopy coupled to UV light illumination enabled us to track and characterize products released during the self‐immolation process. More information can be found in the Full Paper by E. Procházková, O. Baszczyňski, et al. (DOI: 10.1002/chem.202101805).
To prevent the decay of satsuma mandarin fruit during the distribution process, we investigated the effect of ultraviolet-C (UV-C) irradiation and temperature treatment (TT) on scoparone (a ...phytoalexin) production in fruits. To this end, the fruits were maintained at 20°C for 24 h following irradiation, and then the scoparone content was measured after export to Singapore by sea freight or after domestic storage. The scoparone content in the flavedo of TT fruits significantly increased for 24 h after UV-C irradiation, compared with that in the flavedo of non-TT fruits. In fruits exported in reefer containers (0°C), the scoparone content in the TT fruits was 59.1 μg·g−1FW, whereas that in non-TT fruits was 15.1 μg·g−1FW. The domestically stored fruits showed similar trends to those of the exported fruits. The scoparone content in domestically stored fruits was higher than that in the exported fruits because the storage temperature was higher than the temperature in the reefer container used for export. There was a significant difference in the decay rate between UV-C-irradiated and non-irradiated fruits. These results showed that UV-C irradiation was effective in reducing the decay of fruits exported by sea, and TT before storage induced scoparone production in the flavedo, even under cold storage.
Recombinant adeno-associated viruses (AAVs) are commonly used gene delivery vehicles for neuroscience research. They have two engineerable features: the capsid (outer protein shell) and cargo ...(encapsulated genome). These features can be modified to enhance cell type or tissue tropism and control transgene expression, respectively. Several engineered AAV capsids with unique tropisms have been identified, including variants with enhanced central nervous system transduction, cell type specificity, and retrograde transport in neurons. Pairing these AAVs with modern gene regulatory elements and state-of-the-art reporter, sensor, and effector cargo enables highly specific transgene expression for anatomical and functional analyses of brain cells and circuits. Here, we discuss recent advances that provide a comprehensive (capsid and cargo) AAV toolkit for genetic access to molecularly defined brain cell types.
DNA nanotechnology has provided new strategies and platforms for cargo delivery. However, DNA‐based nanostructures utilized for cargo delivery have mainly focused on static structures and passive ...targeting. Here, inspired by honeybee's natural reaction to hazards, a melittin loaded tetrahedron framework nucleic acid (tFNA) nanostructure, for active targeting therapy as a “nanobee” is developed. Upon exposure to target proteins on the cell membrane, the tFNA exoskeleton goes through conformation change, leading to the selective release of melittin from the exoskeleton and the consequent selective lethal effect. As a result, the active targeting of the nanobee to tumor cells is achieved. At the same concentrations of melittin, the nanobee exhibits significantly higher and more selective cytotoxicity against target cells than free melittin molecules, whereas the inactive nanobee shows neglectable lethal effect. Notably, the complete encapsulation of melittin in the tFNA exoskeleton is confirmed by the combination of experimental screening and molecular dynamic analysis, which is proposed to be the origin of the minimized off‐target effects of nanobee. This nanobee concept offers a strategy that may be extended to various dynamic stimuli‐responsive cargo delivery systems, to enhance cargo stability and decrease severe off‐target effects.
Inspired by the honeybee's natural reaction to hazards, a framework nucleic acid (FNA) nanostructure‐based nanobee is fabricated for active melittin delivery. To minimize the off‐target effects, a combination of experimental screening and MD analysis is employed to ensure stable melittin encapsulation into the stimuli‐responsive FNA exoskeleton. Active targeting therapy is achieved with the thus fabricated nanobee in vivo.
Small hydrophilic drugs are widely used for systemic administration, but they suffer from poor absorption and fast clearance. Their nanoencapsulation can improve biodistribution, targeted delivery, ...and pharmaceutical efficacy. Hydrophilics are effectively encapsulated in compartmented particles, such as liposomes or extracellular vesicles, which are biocompatible but poorly customizable. Polymeric vectors can form compartmental structures, also being functionalizable. Here, we report a system composed of polymeric stabilized reversed micelles for hydrophilic drugs encapsulation. We optimized the preparation procedure, and calculated the critical micellar concentration. Then, we developed a strategy for stabilization that improves micelle stability upon dilution. We tested the drug loading and delivery capabilities with creatine as a drug molecule. Prepared stabilized reversed micelles had a size of around 130 nm and a negative z-potential around -16 mV, making them functional as a drug carrier. The creatine cargo increased micelle size and depended on the loading conditions. The higher amount of loaded creatine was around 60 μg/mg of particles. Delivery tests indicated full release within three days in micelles with the lower cargo, while higher loadings can provide a sustained release for longer times. Obtained results are interesting and encouraging to test the same system with different drug cargoes.
The core problem of a multimodal transportation system is integrating various transportation modes into a cohesive, efficient, and user-friendly network. This study introduces a novel centralized ...load concentration approach for regions facing geographic challenges. The principal aim is improving multimodal transportation systems by mitigating CO2 emissions and improving operational efficiency. This will significantly reduce high logistics costs and the environmental impact caused by greenhouse gas emissions, particularly in land transportation, aligning with the global sustainable development goals and offering a promising path towards a more sustainable future. The proposed method implicates direct cargo transportation from its origin to the export ports without passing through intermediate centers. The mathematical model determines the most efficient means of transportation for each route, considering variables such as distance, volume, and type of cargo. Research results indicate that multiple hubs may not be necessary in scenarios with high freight concentration, which could streamline transportation and logistics operations. The modal preferences vary depending on regional dynamics and cargo characteristics, with rail and sea transport emerging as preferable options in specific circumstances, outperforming road transport. The proposed model shows reductions in logistics costs and CO2 emissions compared to road-focused scenarios. This study provides an adaptable framework for optimizing multimodal transportation systems in regions with similar geographic and logistical attributes. It offers a versatile solution to various contexts and needs. Lastly, the strategic integration of multiple modes of transportation is fundamental to improving efficiency and sustainability.
During marine transport of coal commodities, cargo slip or liquefaction failure scenarios within the hold may occur under cyclic ship motions. The resulting cargo shift affects the vessel stability, ...and subsequently endangers goods and crews on board the vessel. This study aims to investigate the coal cargo stability under marine transport conditions. A suite of six coal samples was selected to undertake a series of undrained cyclic triaxial tests to investigate their liquefaction resistance. Results were subsequently compared to the liquefaction threshold advised by International Maritime Organisation. It was suggested that finer coals were observed to be more susceptible to liquefaction. In addition, discrete element modelling of the coal cargoes was conducted to study the cargo slip susceptibility. Calibration was performed to ensure materials modelled in the numerical program reflected the physical behaviours. Results indicated coarser coal samples with lower moisture contents exhibited cargo slip failures under nominated rolling ship motion. Nevertheless, resulting centre of gravity shift from cargo slip exhibited negligible effect on the cargo stability. Outcomes of this study provided important safety guidelines on marine transportation of coal commodities.
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