Signal regulatory protein alpha initiates cachexia through muscle to adipose tissue crosstalk

BACKGROUND: Muscle wasting from chronic kidney disease (CKD) or from defective insulin signalling results in morbidity and, ultimately, mortality. We have identified an endogenous mediator of insulin resistance, signal regulatory protein alpha (SIRPα), which leads to cachexia in mice and is associated with cachexia in patients with CKD. METHODS: We assessed insulin signalling and mechanisms causing muscle atrophy plus white adipose tissue (WAT) metabolism in mouse models of CKD or acute diabetes (streptozotocin treatment). We then examined these factors in mice with global knockout (KO) of SIRPα and sought mediators of metabolic responses in muscle and adipose tissues of mice with either muscle-specific or adipose tissue-specific KO of SIRPα. Metabolic responses were confirmed in primary cultures of adipose cells. RESULTS: In mice with CKD, SIRPα expression was increased in WAT (three-fold, P \u3c 0.05), and this was associated with precursors of cachexia: \u27pathologic browning\u27, thermogenesis, and a two-fold activation of protein kinase A (P \u3c 0.05 vs. control mice) plus loss of adipose tissue mass. In contrast, mice with SIRPα global KO and CKD or acute diabetes experienced improved insulin signalling and activation of pAkt plus \u27physiologic browning\u27 of WAT. These mice avoided losses of muscle and adipose tissues and experienced a 31% improvement in survival (P \u3c 0.05) than did wild-type mice with CKD. In muscle-specific SIRPα KO mice with CKD, we uncovered that serum SIRPα levels (P \u3c 0.05) were suppressed and were associated with improved insulin signalling both in skeletal muscles and in WAT. These changes were accompanied by physiologic WAT browning. However, in adipose-specific SIRPα KO mice with CKD, levels of serum SIRPα were increased over two-fold (P \u3c 0.05), while muscle losses were minimally inhibited. Clinical implications of SIRPα signalling are suggested by our findings that include increased SIRPα expression in muscle and adipose tissues (P \u3c 0.05 vs. healthy controls) plus higher SIRPα levels in the serum of patients with CKD (2.4-fold, P=0.000017 vs. healthy controls). CONCLUSIONS: Our results show that SIRPα plays an important role as an anti-insulin mediator regulating pathways to cachexia. In muscle-specific SIRPα KO, changes in SIRPα serum levels seem to improve insulin signalling in muscle and WAT, suggesting crosstalk between muscle and adipose tissue. Therefore, targeting SIRPα may prevent cachexia in patients with CKD or acute diabetes

Multifunctional Lateral Transition-Metal Disulfides Heterojunctions

The intrinsic spin-dependent transport properties of two types of lateral VS2|MoS2 heterojunctions are systematically investigated using first-principles calculations, and their various nanodevices with novel properties are designed. The lateral VS2|MoS2 heterojunction diodes show a perfect rectifying effect and are promising for the applications of Schottky diodes. A large spin-polarization ratio is observed for the A-type device and pure spin-mediated current is then realized. The gate voltage significantly tunes the current and rectification ratio of their field-effect transistors (FETs). In addition, they all have sensitive photoresponse to blue light, and could be used as photodetector and photovoltaic device. Moreover, they generate the effective thermally-driven current when a temperature gratitude appears between the two terminals, suggesting them as potential thermoelectric materials. Hence, the lateral VS2|MoS2 heterojunctions show a multifunctional nature and have various potential applications in spintronics, optoelectronics, and spin caloritronics

SIRPα Mediates IGF1 Receptor in Cardiomyopathy Induced by Chronic Kidney Disease

BACKGROUND: Chronic kidney disease (CKD) is characterized by increased myocardial mass despite near-normal blood pressure, suggesting the presence of a separate trigger. A potential driver is SIRPα (signal regulatory protein alpha)-a mediator impairing insulin signaling. The objective of this study is to assess the role of circulating SIRPα in CKD-induced adverse cardiac remodeling. METHODS: SIRPα expression was evaluated in mouse models and patients with CKD. Specifically, mutant, muscle-specific, or cardiac muscle-specific SIRPα KO (knockout) mice were examined after subtotal nephrectomy. Cardiac function was assessed by echocardiography. Metabolic responses were confirmed in cultured muscle cells or cardiomyocytes. RESULTS: We demonstrate that SIRPα regulates myocardial insulin/IGF1R (insulin growth factor-1 receptor) signaling in CKD. First, in the serum of both mice and patients, SIRPα was robustly secreted in response to CKD. Second, cardiac muscle upregulation of SIRPα was associated with impaired insulin/IGF1R signaling, myocardial dysfunction, and fibrosis. However, both global and cardiac muscle-specific SIRPα KO mice displayed improved cardiac function when compared with control mice with CKD. Third, both muscle-specific or cardiac muscle-specific SIRPα KO mice did not significantly activate fetal genes and maintained insulin/IGF1R signaling with suppressed fibrosis despite the presence of CKD. Importantly, SIRPα directly interacted with IGF1R. Next, rSIRPα (recombinant SIRPα) protein was introduced into muscle-specific SIRPα KO mice reestablishing the insulin/IGF1R signaling activity. Additionally, overexpression of SIRPα in myoblasts and cardiomyocytes impaired pAKT (phosphorylation of AKT) and insulin/IGF1R signaling. Furthermore, myotubes and cardiomyocytes, but not adipocytes treated with high glucose or cardiomyocytes treated with uremic toxins, stimulated secretion of SIRPα in culture media, suggesting these cells are the origin of circulating SIRPα in CKD. Both intracellular and extracellular SIRPα exert biologically synergistic effects impairing intracellular myocardial insulin/IGF1R signaling. CONCLUSIONS: Myokine SIRPα expression impairs insulin/IGF1R functions in cardiac muscle, affecting cardiometabolic signaling pathways. Circulating SIRPα constitutes an important readout of insulin resistance in CKD-induced cardiomyopathy

Anomalous Circulation Patterns in Association with Summertime Regional Daily Precipitation Extremes over Northeast China

Based on the NCEP/NCAR daily reanalysis product, NOAA monthly sea surface temperature (SST) dataset, and daily precipitation data collected at observational stations provided by Meteorological Information Center of China Meteorological Administration, the present study analyzes characteristic circulation anomalies conducive to regional extreme daily precipitation in the summer over Northeast China. Results indicate that 26 extreme precipitation events occurred during the 36-year period of 1979–2014. The precipitation threshold for the 99th percentile is 22.2 mm/d, and the maximum extreme daily precipitation occurred in Liaoning Province. When extreme precipitation occurs, Northeast China is located to the southeast of an anomalous cyclonic circulation and northwest of an anomalous anticyclonic circulation, where a strong convergence zone is formed in the lower troposphere. The low-level convergence and upper-level divergence as well as the baroclinic circulation structure are favorable for the development of extreme daily precipitation. Meanwhile, there exist two symmetrical meridional circulations to the north and south of Northeast China. The two meridional circulations share the same ascending branch, which is conducive to the occurrence of precipitation. Located in the strong convergence zone to the southeast of the abnormal cyclonic circulation and northwest of the abnormal anticyclonic circulation, huge amounts of water vapor from the Inner Mongolia, Russia, the Japan Sea, and the mid-high latitudes of the Northwest Pacific are transported to Northeast China, providing sufficient water vapor condition for the occurrence of extreme daily precipitation in this region. In addition, daily extreme precipitation in Northeast China is also closely related to the accumulation and convergence of disturbance energy in Northeast China. It may also be related to the abnormal SST distribution that is high in the north and low in the south. Corresponding to extreme daily precipitation, SST anomaly in the Pacific Ocean is roughly characterized by the feature of “positive-north and negative- south” with the equator as the boundary

Numerical study of the electronic structure, elastic and optical properties of defect quaternary semiconductor CuGaSnSe4

The electronic structure, elastic and optical properties of the defect quaternary semiconductor CuGaSnSe4 in I4¯ structure are systematically investigated using first-principles calculations. We summarize and discuss some of the studies on CuGaSnSe4 in partially ordered chalcopyrite structure and find that there are three atomic arrangements so far, but it is still uncertain which is the most stable. Through detailed simulation and comparison with the corresponding literature, we get three models and predict that M1 model should be the most stable. The band structure and optical properties of compound CuGaSnSe4, including dielectric constant, refractive index and absorption spectrum, are drawn for a more intuitive understanding. The elastic constants are also calculated, which not only prove that CuGaSnSe4 in I4¯ structure is stable naturally but also help solve the problem of no data to accurately predict axial thermal expansion coefficients. The calculated values of the zero frequency dielectric constant and refractive index are comparable to those of the corresponding chalcopyrite structure but slightly larger. Keywords: Defect quaternary CuGaSnSe4, Elastic properties, Optical propertie

Defect-regulated charge carrier dynamics in two-dimensional ZnO/MoS2 heterostructure

Van der Waals ZnO/MoS2 heterostructure has been experimentally demonstrated as one of the potential candidates for photocatalyst, however, the charge carrier dynamics upon photoexcitation still remains unclear. By using nonadiabatic molecular dynamics simulations, we mainly focus on the influences of interfacial point defects on photogenerated charge separation in the ZnO/MoS2. The results reveal that oxygen vacancy in ZnO layer can induce a higher hole transfer efficiency compared to the pristine ZnO/MoS2, which attributes to the enhanced nonadiabatic coupling, originating from an out-of-plane vibration mode of S atoms, a decreased energy gap for intralayer hole transfer and stronger energy state oscillation. Alternatively, S vacancy in MoS2 introducing additional energy states in the band gap of ZnO/MoS2, serves as charge carrier recombination channels, and significantly reduces charge carrier lifetime, while doping O atom in S vacancy can compensate this effect. This study provides helpful guidance to design functional devices for solar energy photovoltaic conversion, based on two-dimensional ZnO/MoS2 heterostructures

Image steganography based on digital holography and saliency map

International audienc

Monolayer Sc₂CO₂: A Promising Candidate as a SO₂ Gas Sensor or Capturer

Toxic gaseous SO₂ adsorption on O-terminated M₂CO₂ (M = Sc, Hf, Zr, and Ti) monolayers has been studied by means of first-principle calculations. It is demonstrated that monolayer Sc₂CO₂ is most preferred for the SO₂ molecule with suitable adsorption strength and apparent charge transfer. Moreover, the electronic conductivity of Sc₂CO₂ displays a sharp increase after the adsorption of SO₂. In particular, the adsorption strength of SO₂ on Sc₂CO₂ can be further enhanced or weakened by applying tensile strains or controlling external electronic fields, which is greatly desirable to realize the capture or reversible release of toxic SO₂ gas. These distinctive features endow the Sc₂CO₂ monolayer with high selectivity and sensitivity as a potential candidate for SO₂ gas sensor, as well as efficient control for gaseous SO₂ capture