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Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

The application of mine method shallow burying and undercutting method in subway and tunnel engineering is becoming more and more significant, but shallow burying and undercutting method also has its own limitations: the shallow burying and undercutting method can easily cause the subsidence of nearby surface, there is a security threat to surrounding buildings, the instability of the tunnel inside, easy to cause the collapse of construction tunnels, endangering construction safety, so ensuring construction safety becomes the key to the project. By combining the examples of the Heyi River Tunnel in Quzhou, the project focuses on the safety measures of tunnel surrounding rock, and simulates tunnel excavation with BIM technology.

National Standards HJ 636-2012 and GB 11893-89 illustrated that total nitrogen (TN) is digested with alkaline potassium persulfate and then determined using ultraviolet spectrophotometry and that total phosphorus (TP) is digested with neutral potassium persulfate and then determined using spectrophotometry. However, the analysis efficiency is low due to individual sampling and digestion for TN and TP. Based on national standard methods, a modified and effective method to respectively determine the contents of TN and total TP in one sample from trunk stem flow liquid, which would be digested once using potassium persulfate as the oxidant combined with spectrophotometry is focused on, and reported here. The results indicated that nitrogenous compounds from the sample in the alkaline potassium persulfate solution would be oxidized and decomposed into the form of NO3--N, whose absorbance is proportional to the concentration of TN under high temperature. Phosphorous compounds from the sample in the acidic potassium persulfate solution were oxidized and decomposed into the form of PO43--P, whose absorbance was proportional to the concentration of TP under high temperature. The precision (RSD, n=5) of this method for determination of the actual samples is TN < 2% and TP < 4%. The standard addition recovery rates of TN and TP are 98.0%-104.2% and 94.0%-107.0%, respectively. Therefore, two standard series and high pressure digestion twice, which were needed in the national standard methods, were modified to only one standard series and high pressure digestion once saving 50% of the sample amount and enhancing the analytical efficiency. This modified determination was proved to be effective in the analysis of samples with low contents of organic matter from stem flow liquid, due to the difficulty of digestion and interference of determination of TN and TP in those samples with high contents of organic matters under the before mentioned conditions.

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD., Introduction Progression to organ failure is marked by fibrosis and loss of architecture in solid organs, such as the kidney. In almost all progressive chronic kidney diseases (CKDs), the features [...]

With an electron-deficient rigid planar structure and excellent π–π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g−1 at 100 mA g−1 and 550 mA h g−1 at 400 mA g−1 and stable cycling with a capacity of 503 mA h g−1 after 1000 cycles at 400 mA g−1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials. [ABSTRACT FROM AUTHOR]

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o-iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B. [ABSTRACT FROM AUTHOR]

The characteristics of phase scintillation (represented by the phase scintillation indices, σφ) from GPS and Beidou are statistically analyzed using a ground‐based receiver at Zhongshan Station, Antarctica, from 2020 to 2022 for the first time. The phase scintillation of the GPS and Beidou signals present a similar pattern of occurrence. The statistical results on the occurrence morphology of phase scintillation show that the phase scintillation predominately occurs in the magnetic pre‐noon and pre‐midnight sectors. Moreover, phase scintillation performs a dependence on solar and geomagnetic activities. Furthermore, the phase scintillation also gives a seasonal variation with the maximum occurrence happened at the autumn and the minimum occurrence during the summer. Consequently, these results improve understanding of the morphological characteristics of the phase fluctuations in the less studied Antarctic region. The study also demonstrates the use of the combined data set to improve the coverage in the Antarctic region. Key Points: Morphological characteristics of phase scintillation of GPS and Beidou signals at Zhongshan station, Antarctica, for the first timeThe occurrences of phase scintillation mainly concentrated in the prenoon and pre‐midnight sectors for both signalsThe similar behaviors of phase scintillation convey the usefulness of the combined data for irregularity studies in the polar region [ABSTRACT FROM AUTHOR]