Hydrolytic endonucleolytic ribozyme (HYER) is programmable for sequence-specific DNA cleavage.

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg2+-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.

Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease.

Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood-brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6-RES-OPC-HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6-RES-OPC-HA nanoparticles have the potential to prevent and alleviate early AD.

Amorphization-Activated Copper Indium Core-Shell Nanoparticles for Stable Syngas Production from Electrochemical CO2 Reduction.

Electrochemical carbon dioxide reduction reaction (CO2 RR) refers to the conversion of carbon dioxide into compounds with added value through electrolysis. It is still a great challenge to design and manufacture efficient CO2 RR catalysts for desired products. Producing syngas via CO2 RR is an environmentally friendly way to reduce CO2 in the atmosphere and the dependence on fossil fuels. Herein, a new class of Cu/In2 O3 nanoparticles (NPs) with controlled phases and structures were successfully prepared as superior electrocatalysts for CO2 RR, where the CO/H2 ratios in syngas on Cu/In2 O3 NPs/C-H2 remained about 1 : 2 at a broad potential range and the total faradaic efficiency of H2 and CO always remained about 90 %. Electronic structural analysis revealed that the excellent performance was attributed to the electronic interaction between amorphous In2 O3 and Cu. This work broadens the horizons for designing and preparing fascinating electrocatalysts for CO2 RR.