Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo.

Human pluripotent stem cell-derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both in vitro and in vivo organoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single-cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA-approved drug, effectively attenuated cyst formation in vivo. This in vivo organoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation.

Liquid Crystal Monomer: A Potential PPARγ Antagonist.

Liquid crystal monomers (LCMs) are a large family of artificial ingredients that have been widely used in global liquid crystal display (LCD) industries. As a major constituent in LCDs as well as the end products of e-waste dismantling, LCMs are of growing research interest with regard to their environmental occurrences and biochemical consequences. Many studies have analyzed LCMs in multiple environmental matrices, yet limited research has investigated the toxic effects upon exposure to them. In this study, we combined in silico simulation and in vitro assay validation along with omics integration analysis to achieve a comprehensive toxicity elucidation as well as a systematic mechanism interpretation of LCMs for the first time. Briefly, the high-throughput virtual screen and reporter gene assay revealed that peroxisome proliferator-activated receptor gamma (PPARγ) was significantly antagonized by certain LCMs. Besides, LCMs induced global metabolome and transcriptome dysregulation in HK2 cells. Notably, fatty acid ß-oxidation was conspicuously dysregulated, which might be mediated through multiple pathways (IL-17, TNF, and NF-kB), whereas the activation of AMPK and ligand-dependent PPARγ antagonism may play particularly important parts. This study illustrated LCMs as a potential PPARγ antagonist and explored their toxicological mode of action on the trans-omics level, which provided an insightful overview in future chemical risk assessment.

Decompartmentalisation as a simple color manipulation of plant-based marbling meat alternatives.

Recent efforts for cell-based meat cuts focus on engineering edible scaffolds, with visual cues which are key to enhancing consumer acceptance, receiving less attention Here, we employed artificial intelligence (AI)-based screening of potential plant materials and discovered that jackfruit (Artocarpus heterophyllus) has the natural structures to recapitulate marbling visuals of meat cuts. Plant tissue compositions are exploited for its differential polyphenol adsorption to produce complex marbling patterns. A one-step colour control method by varying oxidation and incubation conditions of polyphenols was developed to produce permanent meat-like colours resembling chicken, pork, and beef. The scaffold exhibits a meat-like browning behaviour when cooked and is shown to support high-density porcine myoblasts culture without masking the marbled appearance. Surveys with 78 volunteers found that marbled jackfruit scaffolds improved consumer perception of cell-based meat by ∼8%. Our approach of combining AI, tissue engineering, and sensory science unlocks the possibility of creating a range of novel cell-based meat cuts with consumer focus.