LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis

The regenerative potential of cardiomyocytes in adult mammals is limited. Previous studies reported that cardiomyocyte proliferation is suppressed by AMP-activated protein kinase (AMPK). The role of liver kinase B1 (LKB1), as the major upstream kinase for AMPK, on cardiomyocyte proliferation is unclear. In this study, we found that the LKB1 levels rapidly increased after birth. With loss- and gain-of-function study, our data demonstrated that LKB1 levels negatively correlate with cardiomyocyte proliferation. We next identified Yes-associated protein (YAP) as the downstream effector of LKB1 using high-throughput RNA sequencing. Our results also demonstrated that AMPK plays an essential role in Lkb1 knockdown-induced cardiomyocyte proliferation. Importantly, deactivated AMPK abolished the LKB1-mediated regulation of YAP nuclear translocation and cardiomyocyte proliferation. Thus, our findings suggested the role of LKB1-AMPK-YAP axis during cardiomyocyte proliferation, which could be used as a potential target for inducing cardiac regeneration after injury

Research on Coal Mine Goaf Restoration Based on Stability of Overlying Rocks and Numerical Simulation Analysis: A Case Study of Jingmen Garden Expo Park

Goaf restoration is an important part of urban space management. With mining of coal resources, appearance of goaf and subsidence areas causes serious geological disasters and environmental and ecological problems, which significantly affect urban safety, development, and construction. Therefore, repair of goafs is crucial. In this study, the goaf of Jingmen Garden Expo Park was taken as an example. Through acquisition of engineering geological condition parameters and data on the goaf combined with the mechanical parameters selected for the site, the deformation mechanism of the overlying strata of the goaf was analyzed, and a numerical model of the goaf was established. On this basis, FLAC(3D) was used for numerical simulation to evaluate the stability of the goaf; the suitability of the site was evaluated and divided, and the ecological restoration model of the goaf in Jingmen Garden Expo Park was studied. The results showed that different degrees of ecological restoration and construction of various facilities and buildings could be carried out in the goaf. Based on the varying degrees of stability in the goaf, an appropriate restoration path is suggested according to the suitability of these different degrees. The green, innovative, and sustainable restoration design of the goaf can be carried out according to these restoration paths in order to establish a green ecological system in Jingmen Garden Expo Park

Ecological spatial network optimization of carbon sink patches for enhanced carbon sink in Wuhan Metropolitan Area, China

Achieving carbon neutrality through increasing carbon sinks is a crucial strategy for reaching long-term climate objectives. During rapid urbanization, the degradation of vegetation structure and quantity in fragmented patches leads to the reduction of the carbon sink capacity. Establishing the well-design ecological spatial network is crucial for improving the carbon sink capacity. This study focuses on enhancing the carbon sink capacity in the Wuhan Metropolitan Area (WMA) through a four-step approach–identification, construction, assessment, and optimization–to improve the ecological spatial structure of carbon sink patches and increase carbon sink capacity. The results show that we initially built 27 carbon sink patches and 52 networks, prioritizing 15 core networks. Due to the low connectivity between the Western and other regions, we added 18 steppingstones and 12 networks to enhance overall connectivity and stability of spatial network. Verification shows that our scheme benefits the connectivity and stability of whole ecological network of WMA, and increases the total carbon sink by 11.17 Mt CO2. This research enriches methods for increasing carbon sinks in urban areas and provides theoretical support for achieving carbon neutrality

Energy Release Characteristics and Reaction Mechanism of PTFE/Al/Bi2O3 Reactive Materials under Drop-Hammer Test

To obtain the influence of the Bi2O3 particle content of a PTFE/Al/Bi2O3 reactive material (later referred to as PAB) on its shock-induced chemical reaction (SICR) characteristics, five kinds of PAB with different Bi2O3 contents were prepared; the reaction process in a drop-hammer test, recorded using a high-speed camera, was analyzed. The ignition and reaction mechanisms of PAB under mechanical impact were analyzed based on the thermochemical reaction characteristics and the microstructure. The results show that with an increase in Bi2O3 content, the shock-induced chemical reaction duration and the sensitivity of PAB increase, and then decrease. When the Bi2O3 content is 9%, the impact sensitivity is the highest and the reaction duration is the longest. The heating at the crack tip is responsible for PAB ignition under long-pulse low-velocity impact. During ignition, PAB undergoes several physicochemical changes such as the melting of PTFE, a PTFE/Bi2O3 reaction, an Al/Bi2O3 reaction, pyrolysis of the melted PTFE, and a C2F4/Al reaction; moreover, the presence of Bi2O3 decreases the excitation threshold of the reactive material, which facilitates the propagation of the reaction and improves the degree of the reaction and overall energy release of the reactive material

Functionalized ZnO@TiO₂ nanorod array film loaded with ZnIn₀.₂₅Cu₀.₀₂S₁.₃₉₅ solid-solution : synthesis, characterization and enhanced visible light driven water splitting

We have designed a novel semiconductor core/layer nanostructure of a uniform ZnO@TiO₂ nanorod array modified with a ZnIn₀.₂₅Cu₀.₀₂S₁.₃₉₅ solid-solution on the surface via a facile hydrothermal synthesis. This novel nanostructure combines the merits of all components and meets the requirements of photovoltaic system application. An intimate PN heterojunction is formed from the ZnO@TiO₂ nanorod and polymetallic sulphide solid-solution, which is remarkably beneficial for the effective visible light absorption and rapid charge carrier separation. The nanostructures exhibit higher photocurrent and incident photon to electron conversion efficiency (IPCE) under no bias potential versus the Ag/AgCl electrode. We also analyzed the interface and photoelectrochemical characteristics of the nanostructure and revealed the kinetic process of the electron and hole transmission. In addition, the photoanode test shows the hydrogen production capability of the nanostructures from solar water splitting. These results verified that the ZnO and TiO₂ can be sensitized by the polymetallic sulfide for UV-Vis light driven energy conversion. Importantly, the approach we used to design the photoanode enables the development of micro-nano electronic devices with enhanced performance.11 page(s

Down-regulation of AMPK/PPARδ signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes

AIMS: Exposure to maternal diabetes is associated with increased prevalence of hypertension in the offspring. The mechanisms underlying the prenatal programming of hypertension remain unclear. Because endoplasmic reticulum (ER) stress plays a key role in vascular endothelial dysfunction in hypertension, we investigated whether aberrant ER stress causes endothelial dysfunction and high blood pressure in the offspring of dams with diabetes. METHODS AND RESULTS: Pregnant Sprague-Dawley rats were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at Day 0 of gestation. Compared with control mother offspring (CMO), the diabetic mother offspring (DMO) had higher blood pressure and impaired endothelium-dependent relaxation in mesenteric arteries, accompanied by decreased AMPK phosphorylation and PPARδ expression, increased ER stress markers, and reactive oxygen species (ROS) levels. The inhibition of ER stress reversed these aberrant changes in DMO. Ex vivo treatment of mesenteric arteries with an AMPK agonist (A769662) or a PPARδ agonist (GW1516) improved the impaired EDR in DMO and reversed the tunicamycin-induced ER stress, ROS production, and EDR impairment in mesenteric arteries from CMO. The effects of A769662 were abolished by co-treatment with GSK0660 (PPARδ antagonist), whereas the effects of GW1516 were unaffected by Compound C (AMPK inhibitor). CONCLUSION: These results suggest an abnormal foetal programming of vascular endothelial function in offspring of rats with maternal diabetes that is associated with increased ER stress, which can be ascribed to down-regulation of AMPK/PPARδ signalling cascade