Macrophage accumulation is not only a characteristic hallmark but also a critical component of pulmonary artery (PA) remodeling associated with pulmonary hypertension (PH). However, the cellular and molecular mechanisms that drive vascular macrophage activation and their functional phenotype remain poorly defined. Utilizing multiple levels of in vivo (bovine and rat models of hypoxia-induced PH, together with human tissue samples) and in vitro (primary mouse, rat, and bovine macrophages, human monocytes, as well as primary human and bovine fibroblasts) approaches, we observed that adventitial fibroblasts derived from hypertensive Pas (bovine and human) regulate macrophage activation. These fibroblasts activate macrophages through paracrine IL6 and STAT3, HIF1, and C/EBPβ signaling to drive expression of genes previously implicated in chronic inflammation, tissue remodeling, and PH. This distinct fibroblast-activated macrophage phenotype was independent of IL4/IL13-STAT6 and TLR-MyD88 signaling. We found that genetic STAT3 haplodeficiency in macrophages attenuated macrophage activation while complete STAT3 deficiency increased macrophage activation through compensatory upregulation of STAT1 signaling, while deficiency in C/EBPβ or HIF1 attenuated fibroblast driven macrophage activation. These findings challenge the current paradigm of IL4/IL13-STAT6 mediated alternative macrophage activation as the sole driver of vascular remodeling in PH and uncover a crosstalk between adventitial fibroblasts and macrophages in which paracrine IL6 activated STAT3, HIF1, and C/EBPβ signaling is critical for macrophage activation and polarization. Thus, targeting IL6 signaling in macrophages by completely inhibiting C/EBPβ, HIF1a or partially inhibiting STAT3 may hold therapeutic value for treatment of PH and other inflammatory conditions characterized by increased IL6 and absent IL4/IL13 signaling.

We present a method to capture both 3D shape and spatially varying reflectance with a multi-view photometric stereo (MVPS) technique that works for general isotropic materials. Our algorithm is suitable for perspective cameras and nearby point light sources. Our data capture setup is simple, which consists of only a digital camera, some LED lights, and an optional automatic turntable. From a single viewpoint, we use a set of photometric stereo images to identify surface points with the same distance to the camera. We collect this information from multiple viewpoints and combine it with structure-from-motion to obtain a precise reconstruction of the complete 3D shape. The spatially varying isotropic bidirectional reflectance distribution function (BRDF) is captured by simultaneously inferring a set of basis BRDFs and their mixing weights at each surface point. In experiments, we demonstrate our algorithm with two different setups: a studio setup for highest precision and a desktop setup for best usability. According to our experiments, under the studio setting, the captured shapes are accurate to 0.5 millimeters and the captured reflectance has a relative root-mean-square error (RMSE) of 9%. We also quantitatively evaluate state-of-the-art MVPS on a newly collected benchmark dataset, which is publicly available for inspiring future research.

The development of simple, efficient, and biocompatible organic luminescent molecules is of great significance to the clinical transformation of biomaterials. In recent years, purely organic thermally activated delayed fluorescence (TADF) materials with an extremely small single-triplet energy gap (𝚫E ST ) have been considered as the most promising new-generation electroluminescence emitters, which is an enormous breakthrough in organic optoelectronics. By merits of the unique photophysical properties, high structure flexibility, and reduced health risks, such metal-free TADF luminophores have attracted tremendous attention in biomedical fields, including conventional fluorescence imaging, time-resolved imaging and sensing, and photodynamic therapy. However, there is currently no systematic summary of the TADF materials for biomedical applications, which is presented in this review. Besides a brief introduction of the major developments of TADF material, the typical TADF mechanisms and fundamental principles on design strategies of TADF molecules and nanomaterials are subsequently described. Importantly, a specific emphasis is placed on the discussion of TADF materials for various biomedical applications. Finally, the authors make a forecast of the remaining challenges and future developments. This review provides insightful perspectives and clear prospects towards the rapid development of TADF materials in biomedicine, which will be highly valuable to exploit new luminescent materials.

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Both Varisolve formulations produced smaller embolism bubbles than occurred with air-based microfoam. Rapid clearance of Varisolve bubbles suggests that they are so small that they do not have adequate surface area available for significant binding interactions with arteriolar endothelium. Larger air-based bubbles obstruct arteriolar vessels and block blood flow.

Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.