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Background Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACM) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. Methods β-actin-GFP transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a co-culture system with neonatal rat ventricular myocytes (NRVMs), ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and EdU incorporation analysis. Echocardiography was used to measure cardiac function and histology was performed to determine infarction size. Results In-vitro, mononucleated and bi/multi-nucleated ACMs were able to proliferate at a similar rate (7.0%) in the co-culture. Dedifferentiation proceeded ACM proliferation, which was followed by redifferentiation. Redifferentiation was essential to endow the daughter cells with cardiomyocyte contractile function. Intercellular propagation of Ca2+ from contracting NRVMs into ACM daughter cells was required to activate the Ca2+ dependent calcineurin-nuclear factor of activated T cells signaling pathway to induce ACM redifferentiation. The properties of NRVM Ca2+ transients influenced the rate of ACM redifferentiation. Hypoxia impaired the function of gap junctions by dephosphorylating its component protein connexin 43, the major mediator of intercellular Ca2+ propagation between cardiomyocytes, thereby impairing ACM redifferentiation. In-vivo, ACM proliferation was found primarily in the MI border zone. An ischemia resistant connexin 43 mutant enhanced the redifferentiation of ACM-derived new cardiomyocytes after MI and improved cardiac function. Conclusions Mature ACMs can reenter the cell cycle and form new cardiomyocytes through a three-step process, dedifferentiation, proliferation and redifferentiation. Intercellular Ca2+ signal from neighboring functioning cardiomyocytes through gap junctions induces the redifferentiation process. This novel mechanism contributes to new cardiomyocyte formation in post-MI hearts in mammals.

Because of the internal malfunction of satellite sensors and poor atmospheric conditions such as thick cloud, the acquired remote sensing data often suffer from missing information, i.e., the data usability is greatly reduced. In this paper, a novel method of missing information reconstruction in remote sensing images is proposed. The unified spatial-temporalspectral framework based on a deep convolutional neural network (STS-CNN) employs a unified deep convolutional neural network combined with spatial-temporal-spectral supplementary information. In addition, to address the fact that most methods can only deal with a single missing information reconstruction task, the proposed approach can solve three typical missing information reconstruction tasks: 1) dead lines in Aqua MODIS band 6; 2) the Landsat ETM+ Scan Line Corrector (SLC)-off problem; and 3) thick cloud removal. It should be noted that the proposed model can use multi-source data (spatial, spectral, and temporal) as the input of the unified framework. The results of both simulated and real-data experiments demonstrate that the proposed model exhibits high effectiveness in the three missing information reconstruction tasks listed above.Index Terms-Spatial-temporal-spectral, reconstruction of missing data, deep convolutional neural network, Aqua MODIS band 6, ETM+ SLC-off, cloud removal.

A miniaturized flume experiment was carried out to measure impact forces of viscous debris flow. The flow depth (7.2-11.2 cm), velocity (2.4-5.2 m/s) and impact force were recorded during the experiment. The impact process of debris flow can be divided into three phases by analyzing the variation of impact signals and flow regime. The three phases are the sudden strong impact of the debris flow head, continuous dynamic pressure of the body and slight static pressure of the tail. The variation of impact process is consistent with the change in the flow regime. The head has strong-rapid impact pressure, which is shown as a turbulent-type flow; the body approximates to steady laminar flow. Accordingly, the process of debris flows hitting structures was simplified to a triangle shape, ignoring the pressure of the tail. In order to study the distribution of the debris flow impact force at different depths and variation of the impact process over time, the impact signals of slurry and coarse particles were separated from the original signals using wavelet analysis. The slurry's dynamic pressure signal appears to be a smooth curve, and the peak pressure is 12-34 kPa when the debris flow head hits the sensors, which is about 1.54 ± 0.36 times the continuous dynamic pressure of the debris flow body. The limit of application of the empirical parameter α in the hydraulic formula was also noted. We introduced the power function relationship of α and the Froude number of debris flows, and proposed a universal model for calculating dynamic pressure. The impact pressure of large particles has the characteristic of randomness. The mean frequency of large particles impacting the sensor is 210 ± 50-287 ± 29 times per second, and it is 336 ± 114-490 ± 69 times per second for the debris flow head, which is greater than that in the debris flow body. Peak impact pressure of particles at different flow depths is 40-160 kPa, which is 3.2 ± 1.5 times the impact pressure of the slurry at the bottom of the flow, 3.1 ± 0.9 times the flow in the middle, and 3.3 ± 0.9 times the flow at the surface. The differences in impact frequency indicate that most of the large particles concentrate in the debris flow head, and the number of particles in the debris flow head increases with height. This research supports the study of solid-liquid two phase flow mechanisms, and helps engineering design and risk assessment in debris flow prone areas.

Limb remote ischemic preconditioning (RIPC) is an effective means of protection against ischemia/reperfusion (IR)–induced injury to multiple organs. Many studies are focused on identifying endocrine mechanisms that underlie the cross-talk between muscle and RIPC-mediated organ protection. We report that RIPC releases irisin, a myokine derived from the extracellular portion of fibronectin domain–containing 5 protein (FNDC5) in skeletal muscle, to protect against injury to the lung. Human patients with neonatal respiratory distress syndrome show reduced concentrations of irisin in the serum and increased irisin concentrations in the bronchoalveolar lavage fluid, suggesting transfer of irisin from circulation to the lung under physiologic stress. In mice, application of brief periods of ischemia preconditioning stimulates release of irisin into circulation and transfer of irisin to the lung subjected to IR injury. Irisin, via lipid raft–mediated endocytosis, enters alveolar cells and targets mitochondria. Interaction between irisin and mitochondrial uncoupling protein 2 (UCP2) allows for prevention of IR-induced oxidative stress and preservation of mitochondrial function. Animal model studies show that intravenous administration of exogenous irisin protects against IR-induced injury to the lung via improvement of mitochondrial function, whereas in UCP2-deficient mice or in the presence of a UCP2 inhibitor, the protective effect of irisin is compromised. These results demonstrate that irisin is a myokine that facilitates RIPC-mediated lung protection. Targeting the action of irisin in mitochondria presents a potential therapeutic intervention for pulmonary IR injury.

Snow and glacier melting and accumulation are important processes of the hydrological cycle in the cryosphere, e.g., high‐mountain areas. Glaciers and snow cover respond to climate change notably over the Tibetan Plateau (TP) as the Earth's Third Pole where complex topography and lack of ground‐based observations result in knowledge gaps in hydrological processes and large uncertainties in model output. This study develops a snow and glacier melt model for a distributed hydrological model (Coupled Routing and Excess Storage model, CREST) using the Upper Brahmaputra River (UBR) basin in the TP as a case study. Satellite and ground‐based precipitation and land surface temperature are jointly used as model forcing. A progressive two‐stage calibration strategy is developed to derive model parameters, i.e., (1) snow melting processes (stage I) and (2) glacier melting and runoff generation and routing using multisource data (stage II). Stage‐I calibration is performed using the MODIS snow cover area (SCA) product and a blending snow water equivalent (SWE) product combined with partial in situ measurements. Stage‐II calibration is based on Gravity Recovery and Climate Experiment (GRACE) satellite‐derived total water storage (TWS) changes and streamflow observed at a gauging station of the lower reach of the UBR. Results indicate that the developed two‐stage calibration method provides more reliable streamflow, snow (both SCA and SWE), and TWS change simulations against corresponding observations than commonly used methods based on streamflow and/or SCA performance. The simulated TWS time series shows high consistency with GRACE counterparts for the study period 2003–2014, and overestimated melting rates and contributions of glacier meltwater to runoff in previous studies are improved to some degree by the developed model and calibration strategy. Snow and glacier runoff contributed 10.6% and 9.9% to the total runoff, and the depletion rate of glacier mass was ∼ −10 mm/a (∼ −2.4 Gt/a, Gt/a is gigaton (km3 of water) per year) over the UBR basin during the study period. This study is valuable in examining the impacts of climate change on hydrological processes of cryospheric regions and providing an improved approach for simulating more reliable hydrological variables over the UBR basin and potentially similar regions globally.

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