Cardioprotection by SGLT2 Inhibitors—Does It All Come Down to Na+?

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are emerging as a new treatment strategy for heart failure with reduced ejection fraction (HFrEF) and—depending on the wistfully awaited results of two clinical trials (DELIVER and EMPEROR-Preserved)—may be the first drug class to improve cardiovascular outcomes in patients suffering from heart failure with preserved ejection fraction (HFpEF). Proposed mechanisms of action of this class of drugs are diverse and include metabolic and hemodynamic effects as well as effects on inflammation, neurohumoral activation, and intracellular ion homeostasis. In this review we focus on the growing body of evidence for SGLT2i-mediated effects on cardiac intracellular Na⁺ as an upstream mechanism. Therefore, we will first give a short overview of physiological cardiomyocyte Na⁺ handling and its deterioration in heart failure. On this basis we discuss the salutary effects of SGLT2i on Na⁺ homeostasis by influencing NHE1 activity, late I_Na as well as CaMKII activity. Finally, we highlight the potential relevance of these effects for systolic and diastolic dysfunction as well as arrhythmogenesis.     

Electrical conductivity and P-wave velocity in rock samples from high-temperature Icelandic geothermal fields

Measurements of electrical conductivity and P-wave velocity of seven rock samples were made in the laboratory under inferred in situ conditions. The samples were collected from smectite and chlorite alteration zones in boreholes from the Krafla and Hengill, Iceland, geothermal areas. The measurements were done in the 25–250 °C range, with pore pressure and confining pressure equal to inferred in situ hydrostatic and lithostatic pressures, respectively. Conductivity increases linearly with temperature over the 30–170 °C range; that rise is considerably smaller above 170 °C. Time-dependent effects on conductivity occur above approximately 100 °C. These effects may be related to ion exchange between the clay minerals or the Stern layer, and the pore fluid. The temperature coefficient of conductivity is found to be considerably higher than attributed to pore fluid conduction alone, indicating interface conduction in an electrical double layer on the mineral-water interface in the pores. The results also show that there is no distinction in electrical conduction mechanism in the smectite and chlorite alteration zones; both are dominated by interface conductivity under in situ conditions. The sharp decrease in conductivity at the top of the chlorite alteration zone, commonly observed in resistivity surveys in high-temperature geothermal systems, is most likely due to the lower cation exchange capacity of chlorite compared to that of smectite.     

Atmospheric SO2 emissions since the late 1800s change organic sulfur forms in humic substance extracts of soils

Atmospheric SO2 emissions in the UK and globally increased 6- and 20-fold, respectively, from the mid-1800s to the 1960s resulting in increased S deposition, acid rain, and concurrent acidification of terrestrial and aquatic ecosystems. Structural analyses using synchrotron-based X-ray near-edge spectroscopy (XANES) on humic substance extracts of archived samples from the Rothamsted Park Grass Experiment reveal a significant (R2 = -0.58; P < 0.05; N = 7) shift in soil organic sulfur (S) forms, from reduced to more oxidized organic S between 1876 and 1981, even though soil total S contents remained relatively constant. Over the last 30 years, a decrease in emissions and consequent S deposition has again corresponded with a change of organic S structures of humic extracts-reverting in the direction of their early industrial composition. However, the observed reversal lagged behind reductions in emissions by 19 years, which was computed using cross correlations between time series data (R2 = 0.66; P = 0.0024; N = 11). Presently, the ratio of oxidized-to-reduced organic S in humic substance extracts is nearly double that of early industrial times at identical SO2 emission loads. The significant and persistent structural changes of organic S in humic substances as a response to SO2 emissions and S deposition may have effects on recuperation of soils and surface waters from acidification.     

Energy balance and emissions associated with biochar sequestration and pyrolysis bioenergy production

The implications for greenhouse gas emissions of optimizing a slow pyrolysis-based bioenergy system for biochar and energy production rather than solely for energy production were assessed. Scenarios for feedstock production were examined using a life-cycle approach. We considered both purpose grown bioenergy crops (BEC) and the use of crop wastes (CW) as feedstocks. The BEC scenarios involved a change from growing winter wheat to purpose grown miscanthus, switchgrass, and corn as bioenergy crops. The CW scenarios consider both corn stover and winter wheat straw as feedstocks. Our findings show that the avoided emissions are between 2 and 5 times greater when biochar is applied to agricultural land (2--19 Mg CO2 ha(-1) y(-1)) than used solely for fossil energy offsets. 41--64% of these emission reductions are related to the retention of C in biochar, the rest to offsetting fossil fuel use for energy, fertilizer savings, and avoided soil emissions other than CO2. Despite a reduction in energy output of approximately 30% where the slow pyrolysis technology is optimized to produce biochar for land application, the energy produced per unit energy input at 2--7 MJ/MJ is greater than that of comparable technologies such as ethanol from corn. The C emissions per MWh of electricity production range from 91-360 kg CO2 MWh(-1), before accounting for C offset due to the use of biochar are considerably below the lifecycle emissions associated with fossil fuel use for electricity generation (600-900 kg CO2 MWh(-1)). Low-temperature slow pyrolysis offers an energetically efficient strategy for bioenergy production, and the land application of biochar reduces greenhouse emissions to a greater extent than when the biochar is used to offset fossil fuel emissions.     

Cold tack of urea formaldehyde resins as an important factor in plywood production

The ability of urea formaldehyde (UF) resins to develop cold tack is needed in plywood production during pre-pressing in a cold press to ensure that the veneers stick together, can be transported, and fit into a multi-daylight hot press. The influence of defined factors on the cold tack was analyzed by determining the tensile shear strength of uncured birch veneers bonded with UF resin, and the statistically significant impact factors were determined. The factors tested were lay-up time, resin amount, resin age, moisture content, veneer temperature and pre-press time. Moisture content and veneer temperature had the highest impact on the cold tack of UF resins. A negative impact of high moisture content on the tensile shear strength and therefore on the cold tack of UF resins was proven as well as a positive impact of a comparably high (30 °C) veneer temperature. Lay-up time and pre-press time showed a minor impact on the tensile shear strength. Models were created using Design-Expert software to calculate the optimum operation conditions for cold tack.     

The sol–gel transition temperature of skim milk concentrated by microfiltration as affected by pH and protein content

This study aimed at determining sol–gel transition temperatures of microfiltered skim milk retentates for different protein levels (6, 8 and 10% (w/w)) and a wide pH range (native pH to 4.6) by means of small‐amplitude oscillatory shear rheology. For a pH of 5.4 to 5.0, the sol–gel transition temperatures decreased significantly with increasing protein content, which did not differ for pH 4.8 and 4.6. The sol–gel transition temperatures of retentates with 10% (w/w) protein at pH 5.4 and 4.6 were 58.4 °C and 10.9 °C, respectively.