STR Biotech (South Korea)

Cultured meat, a sustainable alternative to conventional meat, addresses ethical and environmental challenges in livestock production. Its production relies on bovine muscle stem cells from adult muscle or fetal tissue, whose proliferation and differentiation vary with age and developmental stage. However, the molecular mechanisms underlying these variations remain unclear. RNA sequencing was performed to characterize the transcriptomic landscape of bovine muscle stem cells across developmental stages, including myogenic maturation. Differentially expressed genes and key signaling pathways regulating myogenesis were identified, and the functional impact of modulating the AKT-autophagy pathway on differentiation was assessed. Transcriptomic analysis revealed distinct age-dependent gene expression patterns. It was possible to classify cells into three categories: young undifferentiated, young differentiated, and old differentiated. Young undifferentiated-like cells exhibited upregulation of genes associated with active states during the transitions from quiescence to activation and, ultimately, to commitment, indicating that they had robust differentiation potential. In contrast, aged myogenic samples displayed gene expression profiles that acted as barriers to efficient myogenic differentiation. Notably, modulation of the AKT-autophagy pathway both facilitated the production of very mature myogenic cells and prevented spontaneous differentiation, thereby preserving differentiation capacity in vitro. These findings provide insights into age-dependent muscle stem cell differentiation and suggest strategies to optimize cultured meat production. The appropriate modulation of key signaling pathways may help us to overcome major challenges in achieving scalable and efficient cultured meat manufacturing.

Diazinon is a widely used organophosphate insecticide that persists in agricultural runoff and poses risks to aquatic ecosystems and public health.In this study, we investigated the potential of a genetically engineered cyanobacterium, Synechocystis sp.PCC 6803, for efficient diazinon removal under varying environmental conditions.A phoU mutant lacking the negative regulator of the Pho regulon was employed to maintain constitutive phosphate uptake and metabolism independent of external phosphate availability.The phoU strain exhibited sustained expression of alkaline phosphatase (ALP), resulting in ALP activity 2.5-fold higher than that of the wild-type (WT).Under different phosphate concentrations (0-1.6 mM), phoU completely degraded diazinon (20 mg/l) within 11 days, with a degradation rate constant (k) up to 2.1-fold higher than WT under phosphate-replete conditions.Concurrently, phoU accumulated intracellular polyphosphate (poly-P) at levels up to four times higher than WT.Light intensity further modulated diazinon degradation and phosphate metabolism.Under high light intensity (2000 mol photons/m 2 /s), the phoU strain showed a 2.5-fold increase in diazinon degradation rate compared to WT, accompanied by a maximum poly-P accumulation of 10.95 mg/g FCW.Correlation analysis revealed a strong positive relationship between degradation rate and poly-P accumulation, indicating that organophosphate pesticide degradation is functionally linked to intracellular phosphate metabolism.These findings demonstrate that genetic deregulation of the Pho regulon enhances both diazinon degradation and phosphate assimilation, highlighting the phoU mutant as an effective cyanobacterial platform for organophosphate pesticide bioremediation under environmentally relevant conditions.

Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants’ in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial–mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28–42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment.

Background/Objectives: Mosaicism in preimplantation embryos has important implications for embryo selection and reproductive outcomes. This study investigates the age-related frequency of mosaicism, analyzes its subtypes, and evaluates its clinical significance. Methods: A total of 36,506 blastocysts were analyzed using next-generation sequencing-based preimplantation genetic testing for aneuploidy between January 2021 and December 2023. The overall frequencies of euploid, aneuploid, mosaic, and no-call embryos were 20%, 56%, 23%, and 1%, respectively. In this study, we propose a new classification. Embryos were classified into two categories: Mosaic-A, referring to embryos identified as mosaic in standard genetic testing reports, and Mosaic-B, which includes both Mosaic-A and aneuploid embryos containing mosaicism. Results: The proportion of Mosaic-A embryos significantly decreased with maternal age (31% in women <35 years, 30% at 35-37 years, 23% at 38-40 years, 16% at 41-42 years, and 10% in women >42 years). By contrast, Mosaic-B embryos, which include Mosaic-A and aneuploid embryos with mosaicism, increased with age (46%, 49%, 53%, 56%, and 62% across the same age groups). Notably, as maternal age advanced, low-level complex mosaicism decreased, whereas high-level complex mosaicism significantly increased (p < 0.001, chi-square test for trend). Other mosaicism subtypes followed similar trends. These findings suggest that the increase in high-level complex mosaicism resulted from a higher incidence of post-zygotic mitotic errors occurring earlier in development and affecting a larger proportion of cells in older women. Conclusions: This study underscores the significance of incorporating a broader classification of mosaicism, including Mosaic-A and B, to enhance understanding of the biological behavior of mosaic embryos according to age and highlights the clinical importance of cryopreserving high-level or complex mosaic embryos for transfer in women of advanced age.

Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) have been suggested as androgen-responsive stromal cells and a potential source of CXCL12, a chemokine implicated in fibroimmune pathology, but their precise role in AGA has not been fully established. In this study, we performed single-cell transcriptomic profiling of a testosterone-induced mouse model of AGA, with or without treatment of CXCL12-neutralizing antibody, to elucidate the pathological role of CXCL12 in mediating stromal-immune interactions. Our analysis suggested that DFs are the primary androgen-responsive population driving CXCL12 expression. Autocrine CXCL12-ACKR3 signaling in DFs activated TGF-β pathways and promoted fibrotic extracellular matrix deposition. In parallel, paracrine CXCL12-CXCR4 signaling reprogrammed Sox2+Twist1+ dermal papilla cells (DPCs) and promoted the accumulation of pro-fibrotic Trem2+ macrophages, contributing to impaired hair follicle regeneration. Notably, CXCL12 blockade attenuated these stromal and immune alterations, restored the regenerative capacity of DPCs, reduced pro-fibrotic macrophage infiltration, and promoted hair regrowth. Together, these findings identify CXCL12 as a central mediator of androgen-induced fibroimmune remodeling and highlight its potential as a therapeutic target in AGA.

A BSTRACT This comprehensive review presents recent advancements in drying technologies, a fundamental aspect of drug delivery systems (NDDS) in pharmaceutical sciences. Representative drying technologies that improve the solubility, stability, and bioavailability of active pharmaceutical ingredients include spray drying, freeze-drying, supercritical fluid drying, vacuum drying, microwave drying, infrared drying, and fluidized bed drying. Spray drying excels among the mentioned technologies for lipidic drug delivery systems production, generating amorphous solid dispersion and inhalation formulations. Freeze-drying possesses well-founded benefits of maintaining the integrity of thermolabile compounds. Supercritical fluid techniques also provide a solvent-less approach to nanoparticle formulations. Newer technologies, such as microwave drying and fluidized bed drying, have improved the process efficiency, production speed, and product quality of the resulting NDDS. Finally, we sought to briefly review how and what benefits from drying technologies would be improved by integrating with other NDDS approaches, specifically through self-microemulsifying drug delivery systems to help address drug solubility or targeted therapy. Overall, the culmination and adoption of these technological advances reflect an essential change in pharmaceutical and NDDS practices; it presents opportunities for future research and engineering of NDDS developments.