CRISPR/Cas9 targeting of passenger single nucleotide variants in haploinsufficient or essential genes expands cancer therapy prospects.

CRISPR/Cas9 technology has effectively targeted cancer-specific oncogenic hotspot mutations or insertion-deletions. However, their limited prevalence in tumors restricts their application. We propose a novel approach targeting passenger single nucleotide variants (SNVs) in haploinsufficient or essential genes to broaden therapeutic options. By disrupting haploinsufficient or essential genes through the cleavage of DNA in the SNV region using CRISPR/Cas9, we achieved the selective elimination of cancer cells without affecting normal cells. We found that, on average, 44.8% of solid cancer patients are eligible for our approach, a substantial increase compared to the 14.4% of patients with CRISPR/Cas9-applicable oncogenic hotspot mutations. Through in vitro and in vivo experiments, we validated our strategy by targeting a passenger mutation in the essential ribosomal gene RRP9 and haploinsufficient gene SMG6. This demonstrates the potential of our strategy to selectively eliminate cancer cells and expand therapeutic opportunities.

Juglone Suppresses LPS-induced Inflammatory Responses and NLRP3 Activation in Macrophages.

The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome has been implicated in a variety of diseases, including atherosclerosis, neurodegenerative diseases, and infectious diseases. Thus, inhibitors of NLRP3 inflammasome have emerged as promising approaches to treat inflammation-related diseases. The aim of this study was to explore the effects of juglone (5-hydroxyl-1,4-naphthoquinone) on NLRP3 inflammasome activation. The inhibitory effects of juglone on nitric oxide (NO) production were assessed in lipopolysaccharide (LPS)-stimulated J774.1 cells by Griess assay, while its effects on reactive oxygen species (ROS) and NLRP3 ATPase activity were assessed. The expression levels of NLRP3, caspase-1, and pro-inflammatory cytokines (IL-1ß, IL-18) and cytotoxicity of juglone in J774.1 cells were also determined. Juglone was non-toxic in J774.1 cells when used at 10 µM (p < 0.01). Juglone treatment inhibited the production of ROS and NO. The levels of NLRP3 and cleaved caspase-1, as well as the secretion of IL-1ß and IL-18, were decreased by treatment with juglone in a concentration-dependent manner. Juglone also inhibited the ATPase activities of NLRP3 in LPS/ATP-stimulated J774.1 macrophages. Our results suggested that juglone could inhibit inflammatory cytokine production and NLRP3 inflammasome activation in macrophages, and should be considered as a therapeutic strategy for inflammation-related diseases.

Snow-Ice-Inspired Approach for Growth of Amorphous Silicon Nanotips.

The growth of one-dimensional nanostructures without a metal catalyst via a simple solution method is of considerable interest due to its practical applications. In this study, the growth of amorphous silicon (a-Si) nanotips was investigated using an aqueous solution dropped onto the Si substrate, followed by drying at room temperature or below for 24 h, resulting in the formation of a-Si nanotips on the Si substrate. Typically, the a-Si nanotips were up to 1.6 µm long, with average top and middle diameters of 30 and 80 nm, respectively, and contained no metal catalyst in their structure. The growth of a-Si nanotips can be explained in terms of the liquid-solid mechanism, where the supercritical Si solution (liquid) generated on the Si substrate (after reaction with the aqueous solution) promotes the nucleation of solid Si (acting as seeds) on the roughened surface, followed by surface diffusion of Si atoms along the side wall of the Si seeds. This is very similar to the phenomenon observed in the growth of snow ice crystals in nature. When photoexcited at 265 nm, the a-Si nanotips showed blue luminescence at around 435 nm (2.85 eV), indicating feasible applicability of the nanotips in optoelectronic functional devices.