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SIGNIFICANCE User friendly trypsin functionalized films were implemented to expand their potential as versatile, modular tools that can be widely exploited in the world of diagnosis of cultural heritage objects, ancient proteins, and palaeoproteomics a procedure that could be carried out by conservators or archaeologists first on-site and later analysed with standard MS techniques.Conventional magnetic resonance imaging (MRI) is not capable of detecting signal from the deep cartilage due to its short transverse relaxation time (T2). Moreover, several quantitative MRI techniques are significantly influenced by the magic angle effect. The combinations of ultrashort echo time (UTE) MRI with magnetization transfer (UTE-MT) and Adiabatic T1ρ (UTE-AdiabT1ρ) imaging allow magic angle-insensitive assessments of all regions of articular cartilage. The purpose of this study was to investigate the correlations between quantitative three-dimensional UTE MRI biomarkers and mechanical properties of human tibiofemoral cartilage specimens. In total, 40 human tibiofemoral cartilage specimens were harvested from three male and four female donors (64 ± 18 years old). Cartilage samples were scanned using a series of quantitative 3D UTE Cones T2* (UTE-T2*), T1 (UTE-T1), UTE-AdiabT1ρ, and UTE-MT sequences in a standard knee coil on a clinical 3T scanner. UTE-MT data were acquired with a series of MT powers d UTE-MT sequences were highlighted as promising surrogates for non-invasive assessment of cartilage mechanical properties. MMF from UTE-MT modeling showed the highest correlations with cartilage mechanics.Zika virus (ZikV) is a flavivirus that infects neural tissues, causing congenital microcephaly. ZikV has evolved multiple mechanisms to restrict proliferation and enhance cell death, although the underlying cellular events involved remain unclear. Here we show that the ZikV-NS5 protein interacts with host proteins at the base of the primary cilia in neural progenitor cells, causing an atypical non-genetic ciliopathy and premature neuron delamination. Furthermore, in human microcephalic fetal brain tissue, ZikV-NS5 persists at the base of the motile cilia in ependymal cells, which also exhibit a severe ciliopathy. Although the enzymatic activity of ZikV-NS5 appears to be dispensable, the amino acids Y25, K28, and K29 that are involved in NS5 oligomerization are essential for localization and interaction with components of the cilium base, promoting ciliopathy and premature neurogenesis. These findings lay the foundation for therapies that target ZikV-NS5 multimerization and prevent the developmental malformations associated with congenital Zika syndrome.Human induced pluripotent stem cells (hiPSCs) have the properties of differentiation potential and unlimited self-renewal. Developing efficient and highly safe methods to preserve hiPSCs is important due to they have demonstrated tremendous promise in disease etiology, drug discovery, and regenerative medicine applications. Traditionally, open systems for cell cryopreservation, such as conventional slow freezing and vitrification methods, were widespread application in the storage and transportation of hiPSCs. However, these two methods have such problems of low recovery rate and the risk of cross-contamination. Recently, closed systems for cell cryopreservation, such as CryoLogic Vitrification Method (CVM), were introduced to store and transport embryos. In this study, we developed a new friendly CVM by loading a small piece of hiPSCs colonies in the vitrification solution to the hook of Fiberplug to increase the cooling rate. To warm them, the CVM Fiberplug was immersed directly in a 37 °C warming solution for 1 min, and hiPSCs were then transferred to mTeSR1 medium. The result revealed that the new CVM had a high recovery rate and maintained the stemness and differentiation potential of hiPSCs. Our new CVM not only provide a safe way for hiPSCs preservation but also has a high survival rate in the storage of hiPSCs.Differential WNT and Notch signaling regulates differentiation of Lgr5+ crypt-based columnar cells (CBCs) into intestinal cell lineages. find more Recently we showed that mitochondrial activity supports CBCs, while adjacent Paneth cells (PCs) show reduced mitochondrial activity. This implies that CBC differentiation into PCs involves a metabolic transition toward downregulation of mitochondrial dependency. Here we show that Forkhead box O (FoxO) transcription factors and Notch signaling interact in determining CBC fate. In agreement with the organoid data, Foxo1/3/4 deletion in mouse intestine induces secretory cell differentiation. Importantly, we show that FOXO and Notch signaling converge on regulation of mitochondrial fission, which in turn provokes stem cell differentiation into goblet cells and PCs. Finally, scRNA-seq-based reconstruction of CBC differentiation trajectories supports the role of FOXO, Notch, and mitochondria in secretory differentiation. Together, this points at a new signaling-metabolic axis in CBC differentiation and highlights the importance of mitochondria in determining stem cell fate.The mitochondrial GTP (mtGTP)-dependent phosphoenolpyruvate (PEP) cycle couples mitochondrial PEPCK (PCK2) to pyruvate kinase (PK) in the liver and pancreatic islets to regulate glucose homeostasis. Here, small molecule PK activators accelerated the PEP cycle to improve islet function, as well as metabolic homeostasis, in preclinical rodent models of diabetes. In contrast, treatment with a PK activator did not improve insulin secretion in pck2-/- mice. Unlike other clinical secretagogues, PK activation enhanced insulin secretion but also had higher insulin content and markers of differentiation. In addition to improving insulin secretion, acute PK activation short-circuited gluconeogenesis to reduce endogenous glucose production while accelerating red blood cell glucose turnover. Four-week delivery of a PK activator in vivo remodeled PK phosphorylation, reduced liver fat, and improved hepatic and peripheral insulin sensitivity in HFD-fed rats. These data provide a preclinical rationale for PK activation to accelerate the PEP cycle to improve metabolic homeostasis and insulin sensitivity.