Author Correction: Densely vascularized thick 3D tissue shows enhanced protein secretion constructed with intermittent positive pressure
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Organoids in the oral and maxillofacial region: present and future
The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.
Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men
Dietary protein restriction increases energy expenditure and enhances insulin sensitivity in mice. However, the effects of a eucaloric protein-restricted diet in healthy humans remain unexplored. Here, we show in lean, healthy men that a protein-restricted diet meeting the minimum protein requirements for 5 weeks necessitates an increase in energy intake to uphold body weight, regardless of whether proteins are replaced with fats or carbohydrates. Upon reverting to the customary higher protein intake in the following 5 weeks, energy requirements return to baseline levels, thus preventing weight gain. We also show that fasting plasma FGF21 levels increase during protein restriction. Proteomic analysis of human white adipose tissue and in FGF21-knockout mice reveal alterations in key components of the electron transport chain within white adipose tissue mitochondria. Notably, in male mice, these changes appear to be dependent on FGF21. In conclusion, we demonstrate that maintaining body weight during dietary protein restriction in healthy, lean men requires a higher energy intake, partially driven by FGF21-mediated mitochondrial adaptations in adipose tissue.
Direct observation of the topological pruning in silica glass network; the key for realizing extreme transparency
The optical transparency of silica glass significantly improves when subjected to compression at its melting temperature. Using a rare hydrostatic iso-pressure apparatus capable of reaching 0.98 GPa at 1800 °C with Ar gas as the pressure medium, we obtained centimeter-sized glass samples, allowing us to measure various properties. Both the density and refractive index increased with pressure, while the refractive index dispersion decreased monotonically. However, Rayleigh scattering intensity, and small ring structures show a minimum around 0.8 GPa. High-energy X-ray scattering analysis indicates that the short-range structure, around 4 Å, governs the monotonic trends in the averaged physical properties, such as density and refractive index. In contrast, non-monotonic changes are observed with the disappearance of intermediate-range order at around 8 Å. This simplification of structural ordering is crucial for achieving extreme transparency in silica glass. The effect of suppression of the 8 Å order is well explained by the predicted topological pruning phenomenon, where large voids and small unstable ring structures vanish, leading to the minimal light scattering under high pressure. Our experimental findings also reveal that the optimal pressure for achieving this transparency is much lower than previously predicted, which makes the process more feasible for mass-production applications.
Measurement of phospholipid lateral diffusion at high pressure by in situ magic-angle spinning NMR spectroscopy
The development of experimental methodologies that enable investigations of biochemistry at high pressure promises to yield significant advances in our understanding of life on Earth and its origins. Here, we introduce a method for studying lipid membranes at thermodynamic conditions relevant for life at deep sea hydrothermal vents. Using in situ high pressure magic-angle spinning solid state nuclear magnetic resonance spectroscopy (NMR), we measure changes in the fluidity of model microbial membranes at pressures up to 28 MPa. We find that the fluid-phase lateral diffusion of phospholipids at high pressure is significantly affected by the stoichiometric ratio of lipids in the membrane. Our results were facilitated by an accessible pressurization strategy that we have developed to enable routine preparation of solid state NMR rotors to pressures of 30 MPa or greater.
Blood pressure elevations post-lenvatinib treatment in hepatocellular carcinoma: a potential marker for better prognosis
Lenvatinib is a tyrosine kinase inhibitor that effectively inhibits vascular endothelial growth factor signaling and is used for treating hepatocellular carcinoma. However, angiogenesis inhibitors often cause hypertension. Although lenvatinib-induced hypertension has been proposed as a potential surrogate marker for better prognosis, studies on blood pressure elevations and outcomes following lenvatinib initiation are limited. This study included 67 patients who underwent lenvatinib therapy at the Department of Gastroenterology, Kagoshima University Hospital, between May 2018 and December 2023. The median age of the cohort was 71 years, and 82.1% of the patients were male. The median blood pressure at admission was 128/73 mmHg, which significantly increased to 136/76 mmHg the day after lenvatinib administration. Grade 3 hypertension (≥160/100 mmHg) occurred in 37.3% of patients during hospitalization. The median increase in systolic blood pressure from admission to its peak during hospitalization was 26 mmHg. Patients who experienced an increase in blood pressure of ≥26 mmHg were classified into the blood pressure elevation group, which showed a significantly lower mortality rate than that of the blood pressure non-elevation group (35.3% vs. 81.8%, log-rank p = 0.007), even after adjusting for age, sex, disease stage, performance status, and liver reserve function. This study demonstrated that patients who experienced earlier blood pressure elevation after lenvatinib administration had lower overall mortality rates. These findings suggest that blood pressure elevations after lenvatinib initiation may serve as valuable prognostic indicators in patients with cancer undergoing lenvatinib therapy.
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