Nitric oxide (NO) is a gaseous signaling molecule and effector in various biological processes. In mammalian cells, NO is produced by a family of NO synthases (NOS). Three NOS isoforms have been identified as: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). In addition to NO, NOS also produces superoxide anion. This phenomenon is named NOS uncoupling as superoxide generation mainly occurs when NOS is not coupled with its cofactor or substrate. nNOS was first found to produce superoxide under L-arginine depletion condition. Further studies demonstrated that superoxide production is a general feature of all three NOS isoforms. In particular, superoxide generated from uncoupled eNOS has been found to play critical roles in the process of various cardiovascular diseases. Although NOS was first found to produce superoxide only when uncoupled with its cofactor or substrate, recent studies reveal that oxygen reduction to superoxide is an intrinsic process amid NO synthesis. Tetrahydrobiopterin plays a controlling role in preventing superoxide release from the eNOS oxygenase domain. Besides tetrahydrobiopterin, the regulation of eNOS uncoupling by the interactions with other proteins, protein phosphorylation, S-glutathionylation, and endogenous L-arginine derivatives, will be discussed in this review.

Extracellular matrix (ECM) material with good biological activity is essential to simulate cell growth microenvironment, induce cell infiltration and angiogenesis, and promote the repair of large area acute skin wound. In this study, tilapia skin acellular dermal matrix (TADM) was prepared to simulate ECM microenvironment, which can promote substantial area acute wound healing in rats. The main component of TADM is type I collagen, which has good physical and chemical properties, biological activity and cell adhesion. TADM is a form of biomaterial with low immunogenicity, low risk of prion infection and lower economic cost than other related materials such as mammalian collagen biomaterials. Our results show that TADM can guide cell infiltration, angiogenesis, regulate the expression and secretion of inflammatory and skin repair correlated factors to promote tissue healing.

Programmable RNA editing tools enable the reversible correction of mutant transcripts, reducing the potential risk associated with permanent genetic changes associated with the use of DNA editing tools. However, the potential of these RNA tools to treat disease remains unknown. Here, we evaluated RNA correction therapy with Cas13-based RNA base editors in the myosin VI p.C442Y heterozygous mutation ( Myo6 C442Y/+ ) mouse model that recapitulated the phenotypes of human dominant-inherited deafness. We first screened several variants of Cas13-based RNA base editors and guide RNAs (gRNAs) targeting Myo6 C442Y in cultured cells and found that mini dCas13X.1-based adenosine base editor (mxABE), composed of truncated Cas13X.1 and the RNA editing enzyme adenosine deaminase acting on RNA 2 deaminase domain variant (ADAR2dd E488Q ), exhibited both high efficiency of A > G conversion and low frequency of off-target edits. Single adeno-associated virus (AAV)–mediated delivery of mxABE in the cochlea corrected the mutated Myo6 C442Y to Myo6 WT allele in homozygous Myo6 C442Y/C442Y mice and resulted in increased Myo6 WT allele in the injected cochlea of Myo6 C442Y/+ mice. The treatment rescued auditory function, including auditory brainstem response and distortion product otoacoustic emission up to 3 months after AAV-mxABE- Myo6 injection in Myo6 C442Y/+ mice. We also observed increased survival rate of hair cells and decreased degeneration of hair bundle morphology in the treated compared to untreated control ears. These findings provide a proof-of-concept study for RNA editing tools as a therapeutic treatment for various semidominant forms of hearing loss and other diseases.

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Dialyzed tilapia skin collagen sponge (DTSCS) and self-assembled tilapia skin collagen sponge (STSCS) were prepared by freeze-drying. The raw components used in the fabrication of DTSCS and STSCS were separated and purified from tilapia fish skin. It is anticipated that these collagen sponges could be developed into medical dressings for hemostasis and wound healing. The aim of the present research was to explore the possibility of DTSCS and STSCS as medical dressings and compare their differences by scanning electron microscopy (SEM), water absorption measurement, differential scanning calorimetry (DSC), measurement of porosity, cytotoxicity, hemolysis, in vivo biocompatibility, and evaluation of hemostatic performance and wound healing. The results indicate that DTSCS and STSCS are suitable materials for use in medical applications with a loose and porous structure, high water absorption, high porosity, and high thermal stability. The materials also displayed good biocompatibility, including excellent blood compatibility, a lack of cytotoxicity, with no apparent rejection following implantation. STSCS exhibited rapid hemostasis and promoted healing, with slightly greater efficacy than DTSCS. The hemostatic properties and promotion of healing in DTSCS was similar to that of commercial bovine collagen sponge. Therefore, DTSCS and STSCS both represented excellent potential candidate materials for use as hemostatic agents and wound dressings.

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The introduction of 11α-hydroxy to 13-ethyl-gon-4-ene-3,17-dione (GD) by microbial transformation is a key step in the synthesis of oral contraceptive desogestrel, while low substrate solubility and uptake into cells are tough problems influencing biotransformation efficiency greatly. Nano-liposome technique was used in the hydroxylation of GD by Metarhizium anisopliae. The substrate GD was processed to be GD-loaded nano-liposomes (GNLs) with high stability and encapsulation efficiency, and then applied in microbial hydroxylation by M. anisopliae. The results proved that the yield of the main product 11α-hydroxy-13-ethyl-gon-4-ene-3,17-dione (HGD) tripled compared to regular solvent dimethylformamide dispersion method at 2 g/l of substrate feeding concentration, and the HGD conversion rate showed no obvious reduction when the substrate feeding concentration increased from 2 to 6 g/l, which indicated the improvement of GNL addition method on biotransformation. Furthermore, the main byproduct changed from 6β-hydroxy derivative of GD (with similar polarity to HGD) to 6β,11α-dihydroxy derivative, which benefits the following purification of HGD from fermentation broth. These advantages suggest a great potential for the application of nano-liposome technique in microbial steroid transformation.