Fibrosis is the abnormal deposition of extracellular matrix, which can lead to organ dysfunction, morbidity, and death. The disease burden caused by fibrosis is substantial, and there are currently ...no therapies that can prevent or reverse fibrosis. Metabolic alterations are increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types. As a result, metabolically targeted therapies could become important strategies for fibrosis reduction. Indeed, some of the pathways targeted by antifibrotic drugs in development - such as the activation of transforming growth factor-β and the deposition of extracellular matrix - have metabolic implications. This Review summarizes the evidence to date and describes novel opportunities for the discovery and development of drugs for metabolic reprogramming, their associated challenges, and their utility in reducing fibrosis. Fibrotic therapies are potentially relevant to numerous common diseases such as cirrhosis, non-alcoholic steatohepatitis, chronic renal disease, heart failure, diabetes, idiopathic pulmonary fibrosis, and scleroderma.
Despite the advances that have been made in developing new therapeutics, cardiovascular disease remains the leading cause of worldwide mortality. Therefore, understanding the mechanisms underlying ...cardiovascular tissue injury and repair is of prime importance. Following cardiac tissue injury, the immune system has an important and complex role in driving both the acute inflammatory response and the regenerative response. This Review summarizes the role of the immune system in cardiovascular disease - focusing on the idea that the immune system evolved to promote tissue homeostasis following injury and/or infection, and that the inherent cost of this evolutionary development is unwanted inflammatory damage.
The cytoskeleton of a cell controls all the aspects of cell shape changes and motility from its physiological functions for survival to reproduction to death. The structure and dynamics of the ...cytoskeletal components: actin, microtubules, intermediate filaments, and septins - recently regarded as the fourth member of the cytoskeleton family - are conserved during evolution. Such conserved and effective control over the mechanics of the cell makes the cytoskeletal components great candidates for in vitro reconstitution and bottom-up synthetic biology studies. Here, we review the recent efforts in reconstitution of the cytoskeleton in and on membrane-enclosed biomimetic systems and argue that co-reconstitution and synergistic interplay between cytoskeletal filaments might be indispensable for efficient mechanical functionality of active minimal cells. Further, mechanical equilibrium in adherent eukaryotic cells is achieved by the formation of integrin-based focal contacts with extracellular matrix (ECM) and the transmission of stresses generated by actomyosin contraction to ECM. Therefore, a minimal mimic of such balance of forces and quasi-static kinetics of the cell by bottom-up reconstitution requires a careful construction of contractile machineries and their link with adhesive contacts. In this review, in addition to cytoskeletal crosstalk, we provide a perspective on reconstruction of cell mechanical equilibrium by reconstitution of cortical actomyosin networks in lipid membrane vesicles adhered on compliant substrates and also discuss future perspectives of this active research area.
Laser ablation in liquid (LAL) has received considerable attention over the last decade, and is gradually becoming an irreplaceable technique to synthesize nanocrystals and fabricate functional ...nanostructures because it can offer effective solutions to some challenges in the field of nanotechnology. The goal of this review is to offer a comprehensive summary of recent developments of LAL in nanocrystal synthesis and nanostructure fabrication. First, we will introduce the fundamental processes of microsecond, nanosecond, and femtosecond LAL, and how the active species act differently in plasma, cavitation bubbles, and droplets in the different LAL processes. Second, a variety of LAL-based techniques for nanomaterials synthesis and processing are presented, such as electric-, magnetic-, and temperature-field LAL, as well as electrochemically assisted LAL, pulsed laser deposition in liquid, and laser writing of nanopatterns in liquid. Third, new progress in LAL-generated nanomaterials is described. Fourth, we emphasize five applications of LAL-generated nanomaterials that have emerged recently in the fields of optics, magnetism, environment, energy, and biomedicine. Finally, we consider the core advantages of LAL, the limitations of LAL and corresponding solutions, and the future directions in this promising research area.
Highlights ► We assessed the role of autophagy in endovascular perforation SAH model. ► Autophagy has a beneficial role in early brain injury following SAH. ► This neuroprotective effect was ...associated with inhibition of apoptotic cell death. ► The mitochondrial pathway was involved in autophagy-modulated apoptosis after SAH.
Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip ...spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.
In this paper, we investigate the sources for Palu Bay tsunamis, which occurred in September 2018 after a M
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7.5 earthquake struck on a strike-slip fault. Previous land-based field studies have ...identified numerous coastal landslides as possible sources for tsunami generation. Here, we present new post-earthquake bathymetry survey data in the bay. We compare the new very detailed nearshore bathymetry with the pre-earthquake data so as to quantify the magnitudes and configurations of coastal landslides and the characteristics of landslide-generated waves. We perform numerical simulations of tsunami propagation, isolating the coastal landslides as the only sources. The results show that, although the landslide-generated waves characteristically have shorter periods than the observed tsunami waves, the combination of the waves is able to produce long waves comparable with those observed, due to the ringing effects of the trapped waves inside the bay. Therefore, we conclude that landslide-generated waves played a significant role in the tsunamis in Palu Bay. Nevertheless, it is likely that the tsunamis were caused by a combination of tectonic and landslide sources.
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