The changes of cardiac energy metabolism with sodium-glucose transporter 2 inhibitor therapy

Background/aimsTo investigate the specific effects of s odium-glucose transporter 2 inhibitor (SGLT2i) on cardiac energy metabolism.MethodsA systematic literature search was conducted in eight databases. The retrieved studies were screened according to the inclusion and exclusion criteria, and relevant information was extracted according to the purpose of the study. Two researchers independently screened the studies, extracted information, and assessed article quality.ResultsThe results of the 34 included studies (including 10 clinical and 24 animal studies) showed that SGLT2i inhibited cardiac glucose uptake and glycolysis, but promoted fatty acid (FA) metabolism in most disease states. SGLT2i upregulated ketone metabolism, improved the structure and functions of myocardial mitochondria, alleviated oxidative stress of cardiomyocytes in all literatures. SGLT2i increased cardiac glucose oxidation in diabetes mellitus (DM) and cardiac FA metabolism in heart failure (HF). However, the regulatory effects of SGLT2i on cardiac FA metabolism in DM and cardiac glucose oxidation in HF varied with disease types, stages, and intervention duration of SGLT2i.ConclusionSGLT2i improved the efficiency of cardiac energy production by regulating FA, glucose and ketone metabolism, improving mitochondria structure and functions, and decreasing oxidative stress of cardiomyocytes under pathological conditions. Thus, SGLT2i is deemed to exert a benign regulatory effect on cardiac metabolic disorders in various diseases.Systematic review registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023484295)

Bioengineered human tissue regeneration and repair using endogenous stem cells

We describe a general approach to produce bone and cartilaginous structures utilizing the self-regenerative capacity of the intercostal rib space to treat a deformed metacarpophalangeal joint and microtia. Anatomically precise 3D molds were positioned on the perichondro-periosteal or perichondral flap of the intercostal rib without any other exogenous elements. We find anatomically precise metacarpal head and auricle constructs within the implanted molds after 6 months. The regenerated metacarpal head was used successfully to surgically repair the deformed metacarpophalangeal joint. Auricle reconstructive surgery in five unilateral microtia patients yielded good aesthetic and functional results. Long-term follow-up revealed the auricle constructs were safe and stable. Single-cell RNA sequencing analysis reveal early infiltration of a cell population consistent with mesenchymal stem cells, followed by IL-8-stimulated differentiation into chondrocytes. Our results demonstrate the repair and regeneration of tissues using only endogenous factors and a viable treatment strategy for bone and tissue structural defects.</p

Nasal valve angle or nasal valve groove: Which is more suitable to describe a normal anatomic structure?

The size of the nasal valve angle is often used to assess nasal ventilation. A larger angle of the nasal valve is believed to be more conducive for ventilation, and a small angle is considered unfavorable. However, in more than 30 years of clinical practice, we have experienced that some patients with a normal nasal valve angle have relatively severe subjective or objective nasal ventilation obstruction. By studying the computed tomography data of these patients, we found that the tips of their nasal valves were at a sharp angle, while those of healthy individuals were in an arc shape. A sharp angle at the tip of the nasal valve, therefore, is a risk factor for obstructed nasal ventilation. Herein, we propose that the term “nasal valve groove” may be a more appropriate descriptor for the normal internal nasal valve anatomy, and we hope that more rhinoplasty surgeons will pay attention to how the shape of the tip affects nasal ventilation

Optimization of the Process Parameters of Fully Mechanized Top-Coal Caving in Thick-Seam Coal Using BP Neural Networks

The method of fully mechanized top-coal caving mining has become the main method of mining thick-seam coal. The process parameters of fully mechanized caving will affect the recovery rate and gangue content of top coal. Through numerical simulation software, the top-coal recovery rate and gangue content, under different fully mechanized caving process parameters, were simulated, and the influence law of different fully mechanized caving process parameters on top-coal recovery rate and gangue content was obtained. A decision model for top-coal caving process parameters was established with a BP neural network, and the optimal top-coal caving parameters were obtained for the actual situation of a working face. On this basis, a in-lab similarity simulation test of the particle material was carried out. The results show that the top-coal recovery rate and gangue content were 86.56% and 3.45%, respectively, and the coal caving effect was good. A BP neural network was used to study the decisions optimizing fully mechanized caving process parameters, which effectively improved the decision-making efficiency thereabout and provided a basis for realizing intelligent, fully mechanized caving mining

Strontium measurements and sea surface temperatures of corals from Xisha Island, South China Sea

A Porites coral collected from Xisha Island, South China Sea, represents a skeleton secreted in the period from 1906 to 1994. The Sr contents of the coral vary linearly with the instrument-measured sea-surface temperature (SST), giving a Sr thermometer: SST = -1.9658 x Sr + 193.26. The reconstructed SST data show that the late 20th century was warmer (about 1°C) than the early 20th century and that two cooling (1915/1916 and 1947/1948) and three warming (1935/1936, 1960/1961, and 1976/1977) shifts occurred in the century. The temperature shifts are more pronounced for winters, implying a close effect of the west Pacific warm pool and Asian monsoon and suggesting that the former is a primary force controlling the climatic system of the region. Results of this study and previously published data indicate a close link of temperature shifts between the boreal summer and the austral winter or the boreal winter and the austral summer. The annual SST anomalies in the South China Sea and the South Pacific reveal the existence of harmonic but opposite SST variations between the two regions. On the decadal scale the comparative annual SST anomalies for the South China Sea and for the equatorial west Pacific show a similarity in temperature variations, implying that the South China Sea climate is coherent with climatic regime of the tropical west Pacific

Functional and developmental changes in the inner hair cell ribbon synapses caused by Myosin VI knockout and deafness-inducing point mutation

Abstract Hearing loss is one of the most common neurosensory disorders in humans, and above half of hearing loss is caused by gene mutations. Among more than 100 genes that cause non-syndromic hearing loss, myosin VI (MYO6) is typical in terms of the complexity of underlying mechanisms, which are not well understood. In this study, we used both knock-out (Myo6 −/−) and point mutation (Myo6 C442Y ) mice as animal models, performed whole-cell patch-clamp recording and capacitance measurement in the inner hair cells (IHCs) in the cochlea, and sought to reveal potential functional and developmental changes in their ribbon synapses. In Myo6 −/− cochleae of both before (P8-10) and after hearing onset (P18-20), exocytosis from IHCs, measured in whole-cell capacitance change (ΔCm), was significantly reduced, Ca2+ current amplitude (ICa) was unchanged, but Ca2+ voltage dependency was differently altered, causing significant increase in Ca2+ influx in mature IHCs but not in immature IHCs. In immature IHCs of Myo6 C442Y/C442Y cochleae, neither ΔCm nor ICa was altered, but both were reduced in mature IHCs of the same animal model. Furthermore, while the reduction of exocytosis was caused by a combination of the slower rate of depleting readily releasable (RRP) pool of synaptic vesicles and slower sustained release rate (SRR) in Myo6 −/− immature IHCs, it was likely due to smaller RRP and slower SRR in mature IHCs of both animal models. These results expand our understanding of the mechanisms of deafness caused by MYO6 mutations, and provide a solid theoretical and scientific basis for the diagnosis and treatment of deafness

Research on the Optimization of Cutting Path of Cantilever Roadheader in Large Section Excavation

Coal is an important resource for China and even for the whole world. With the improvement of mechanization, automation and intelligence of coal mining equipment in China, there has been an imbalance between the speed of mining and of excavating. Adopting efficient cutting paths is beneficial to improving roadway excavation efficiency and alleviating the imbalance between mining and excavation. In this paper, taking the 12307 belt roadway of Wangjialing Coal Mine as the research background, the geomechanical parameters and distribution characteristics of the surrounding rock were observed and studied, and the test results of in-situ stress, surrounding rock structure and surrounding rock strength were obtained. Based on the test results, a numerical model was established, and the stress and displacement distribution law of the surrounding rock of the roadway under different cutting paths were analyzed, and two optimal cutting paths were proposed based on the actual situation, and industrial tests were carried out. The test results show that using the &ldquo;snake&rdquo; cutting path from bottom to top, the roadway section forming effect is good, and a single cycle excavation takes 34 min, which verified the effectiveness of the cutting path design. On the basis of specific engineering geological conditions, excavation equipment and technology, combined with experimental testing, numerical simulation and other methods, the roadway excavation cutting path can be optimized, and the research results can provide a reference for the design of cutting paths for coal mine excavation roadways with the same geological conditions

Zircon U–Pb–Hf isotopes and geochemistry analyses of the Huyu igneous rocks in northwestern Beijing, China: possible new evidence for the initial destruction of the North China Craton

<p>The timing and extent of cratonic destruction are crucial to understanding the crustal evolution of the North China Craton (NCC). Zircon U–Pb–Hf isotope data and the whole-rock major and trace element characteristics of the Huyu igneous rocks in northwestern Beijing, China, provide possible new evidence for the initial destruction of the NCC. The igneous rocks occur as several sills and dikes, including lamprophyre, monzonite porphyry, and aplite. The lamprophyres have high Mg^# and K₂O contents. The monzonite porphyries have high Mg^#, high K₂O contents, and negative <i>ε</i>_Hf(<i>t</i>) values with zircon U–Pb ages of 225.5–227.7 Ma. These two types of rocks are both enriched in large ion lithosphere elements (LILEs) and light rare earth elements (LREEs) but are depleted in high field strength elements (HFSEs) and high rare earth elements (HREEs) and have almost no Eu anomalies and relatively high total rare earth element (ΣREE) contents. In contrast, the aplites exhibit high silica and K₂O contents, low MgO contents, and more negative <i>ε</i>_Hf(<i>t</i>) values with a zircon U–Pb age of 206.2 Ma. The aplites are also enriched in LILEs and LREEs but are depleted in HFSEs and HREEs, with strongly negative Eu, Ti, P, La, Ce, and Sr anomalies and relatively low ΣREE contents. These results indicate that the lamprophyres and monzonite porphyries represent a continuous cogenetic magma evolution series after melt derived from an enriched metasomatized lithospheric mantle experienced crust assimilation and fractional crystallization. The aplites were produced by the fractional crystallization of low-Mg parental magma derived from melting of the ancient Archaean crust. The occurrence of the Huyu intrusive rocks with many other plutons of similar ages on the northern margin of the NCC suggests that the northern NCC entered an intraplate extensional tectonic environment in the Late Triassic.</p