ABSTRACT
Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.
Subject(s)
Carbocyanines , Infrared Rays , Mitochondria , Optical Imaging , Phototherapy , Mitochondria/metabolism , Mitochondria/drug effects , Carbocyanines/chemistry , Animals , Mice , Humans , Phototherapy/methods , Fluorescent Dyes/chemistry , Female , Mice, Inbred BALB C , Photothermal Therapy/methods , Cell Line, Tumor , DimerizationABSTRACT
Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health.
ABSTRACT
Levulinic acid, a hydrolysis product of lignocellulose, can be metabolized into important compounds in the field of medicine and pesticides by engineered strains of Saccharomyces cerevisiae. Levulinic acid, as an intermediate product widely found in the conversion process of lignocellulosic biomass, has multiple applications. However, its toxicity to Saccharomyces cerevisiae reduces its conversion efficiency, so screening Saccharomyces cerevisiae genes that can tolerate levulinic acid becomes the key. By creating a whole-genome knockout library and bioinformatics analysis, this study used the phenotypic characteristics of cells as the basis for screening and found the HMX1 gene that is highly sensitive to levulinic acid in the oxidative stress pathway. After knocking out HMX1 and treating with levulinic acid, the omics data of the strain revealed that multiple affected pathways, especially the expression of 14 genes related to the cell wall and membrane system, were significantly downregulated. The levels of acetyl-CoA and riboflavin decreased by 1.02-fold and 1.44-fold, respectively, while the content of pantothenic acid increased. These findings indicate that the cell wall-membrane system, as well as the metabolism of acetyl-CoA and riboflavin, are important in improving the resistance of Saccharomyces cerevisiae to levulinic acid. They provide theoretical support for enhancing the tolerance of microorganisms to levulinic acid, which is significant for optimizing the conversion process of lignocellulosic biomass to levulinic acid.
ABSTRACT
The MYF5 gene is first inducibly expressed in muscle cell during embryonic muscle development and plays an important role in regulating the differentiation of skeletal muscle precursors. In this study we used PCR-RFLP to investigate two pig (Sus scrofa) populations (n = 302) for two MYF5 gene polymorphisms, a previously unreported novel Met-Leu shift single nucleotide polymorphism (SNP) MYF5/Hsp92II located on exon 1 and the previously identified intron 1 MYF5/HinfI SNP. Haplotype and association analysis showed that haplotypes of the two SNPs were significantly associated with drip loss rate (DLR, p < 0.05), water holding capacity (WHC, p < 0.05), biceps femoris meat color value (MCV2, p < 0.05), biceps femoris marbling score (MM2, p < 0.01), longissimus dorsi intramuscular fat percentage (IMF, p < 0.01) and longissimus dorsi Water moisture content (WM, p < 0.01) in the population 2. However, further studies are needed to confirm these preliminary results.