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Acid Sphingomyelinase has been reported to increase tissue ceramide and thereby mediate hHcy-induced glomerular NLRP3 inflammasome activation, inflammation, and sclerosis. In the present study, we tested whether somatic podocyte-specific silencing of Smpd1 gene attenuates hHcy-induced NLRP3 inflammasome activation and associated exosome release in podocytes and thereby suppresses glomerular inflammatory response and injury. In vivo, somatic podocyte-specific Smpd1 gene silencing almost blocked hHcy-induced glomerular NLRP3 inflammasome activation in Podocremice compared to control littermates. By nanoparticle tracking analysis, floxed Smpd1 shRNA transfection was found to abrogate hHcy-induced elevation of urinary exosome excretion in Podocremice. In addition, Smpd1 gene silencing in podocytes prevented hHcy-induced immune cell infiltration into glomeruli, proteinuria, and glomerular sclerosis in Podocremice. In cell studies, we also confirmed that Smpd1 gene knockout or silencing prevented Hcy-induced elevation of exosome release in the primary cultures of podocyte isolated from Smpd1-/-mice or podocytes of Podocremice transfected with floxed Smpd1 shRNA compared to WT/WT podocytes. Smpd1 gene overexpression amplified Hcy-induced exosome secretion from podocytes of Smpd1trg/Podocremice, which was remarkably attenuated by transfection of floxed Smpd1 shRNA. Mechanistically, Hcy-induced elevation of exosome release from podocytes was blocked by ASM inhibitor, but not by NLRP3 inflammasome inhibitors. Super-resolution microscopy also showed that ASM inhibitor, but not NLRP3 inflammasome inhibitors, prevented the inhibition of lysosome-multivesicular body interaction by Hcy in podocytes. In conclusion, our findings suggest that ASM in podocytes plays a crucial role in the control of NLRP3 inflammasome activation and exosome release.

Salt lake brine is a complex salt-water system under natural environment. Although many models can express the thermodynamic properties and phase equilibrium of electrolyte aqueous solution, the multi-temperature characteristics and predictability are still the goals of model development. In this study, a comprehensive thermodynamic model system is re-established based on the eNRTL model and some improvements: (1) new expression of long-range electrostatic term with symmetrical reference state is proposed to handle the electrolyte solution covering entire concentration range; (2) the temperature dependence of the binary interaction parameters is formulated with a Gibbs Helmholtz expression containing three temperature coefficients, the liquid parameters, which associated with Gibbs energy, enthalpy, and heat capacity contribution; and (3) liquid parameters and solid species data are regressed from properties and solubility data at full temperature range. Together the activity coefficient model, property models and parameters of liquid and solid offer a comprehensive thermodynamic model system for the typical bittern of MgCl2–CaCl2–H2O binary and ternary systems, and it shows excellent agreement with the literature data for the ternary and binary systems. The successful prediction of complete phase diagram of ternary system shows that the model has the ability to deal with high concentration and high non-ideality system, and the ability to extrapolate the temperature.

Lysosomal acid ceramidase (Ac) has been shown to be critical for ceramide hydrolysis and regulation of lysosome function and cellular homeostasis. In the present study, we generated a knockout mouse strain (Asah1fl/fl/PodoCre) with a podocyte-specific deletion of the α subunit (main catalytic subunit) of Ac. Although no significant morphologic changes in glomeruli were observed in these mice under light microscope, severe proteinuria and albuminuria were found in these podocyte-specific knockout mice compared with control genotype littermates. Transmission electron microscopic analysis showed that podocytes of the knockout mice had distinctive foot process effacement and microvillus formation. These functional and morphologic changes indicate the development of nephrotic syndrome in mice bearing the Asah1podocyte-specific gene deletion. Ceramide accumulation determined by liquid chromatography–tandem mass spectrometry was demonstrated in isolated glomeruli of Asah1fl/fl/PodoCremice compared with their littermates. By crossbreeding Asah1fl/fl/PodoCremice with Smpd1−/−mice, we also produced a double knockout strain, Smpd1−/−/Asah1fl/fl/PodoCre, that also lacks Smpd1, the acid sphingomyelinase that hydrolyzes sphingomyelin to ceramide. These mice exhibited significantly lower levels of glomerular ceramide with decreased podocyte injury compared with Asah1fl/fl/PodoCremice. These results strongly suggest that lysosomal Ac in podocytes is essential for the maintenance of the structural and functional integrity of podocytes.

The comprehensive utilization and environment-friendliness of processes for recovering fresh water or valuable salt from seawater, salt-lakes, or mineral deposits are of utmost importance for sustainable development. One primitive sustainable process for recovering salt from sodium-sulfate-type brine in Yuncheng salt lake had been considered one of the greatest inventions of ancient China, however, the replaced process of mass extraction of single Na2SO4in recent years, has reduced a large amount of residual brine. In this research, relying on the salt-forming diagram in the non-equilibrium state, the technical secrets of ancient salt processes were uncovered, and a new comprehensive utilization system was proposed and tested experimentally. The new system includes a vacuum salt-making process and a normal pressure kieserite process, which can gradually eliminate the existed waste liquid and aid in the sustainable development of the Yuncheng salt-lake. The continuous experiment of salt-making process running stably in the double salt region without double salt formation, which proves the feasibility of salt-forming diagram applied in industrial process. Thus salt-forming diagram would be extremely valuable to industry process design and control, especially, the treatment of concentrated brine.

The renal medulla, considered critical for the regulation of salt and water balance and long-term blood pressure control, is enriched in anandamide and two of its major metabolizing enzymes, cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH). Infusion of anandamide (15, 30, and 60 nmol·min−1·kg−1) into the renal medulla of C57BL/6J mice stimulated diuresis and salt excretion in a COX-2- but not COX-1-dependent manner. To determine whether endogenous endocannabinoids in the renal medulla can elicit similar effects, the effects of intramedullary isopropyl dodecyl fluorophosphate (IDFP), which inhibits the two major endocannabinoid hydrolases, were studied. IDFP treatment increased the urine formation rate and sodium excretion in a COX-2- but not COX-1-dependent manner. Neither anandamide nor IDFP affected the glomerular filtration rate. Neither systemic (0.625 mg·kg−1·30 min−1iv) nor intramedullary (15 nmol·min−1·kg−1·30 min−1) IDFP pretreatment before intramedullary anandamide (15–30 nmol·min−1·kg−1) strictly blocked effects of anandamide, suggesting that hydrolysis of anandamide was not necessary for its diuretic effect. Intramedullary IDFP had no effect on renal blood flow but stimulated renal medullary blood flow. The effects of IDFP on urine flow rate and medullary blood flow were FAAH-dependent as demonstrated using FAAH knockout mice. Analysis of mouse urinary PGE2concentrations by HPLC-electrospray ionization tandem mass spectrometry showed that IDFP treatment decreased urinary PGE2. These data are consistent with a role of FAAH and endogenous anandamide acting through a COX-2-dependent metabolite to regulate diuresis and salt excretion in the mouse kidney.

The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and glomerular sclerosis during hyperhomocysteinemia (hHcys). However, it remains unclear whether the NLRP3 inflammasome can be a therapeutic target for treatment of hHcys-induced kidney injury. Given that DHA metabolites-resolvins have potent anti-inflammatory effects, the present study tested whether the prototype, resolvin D1 (RvD1), and 17S-hydroxy DHA (17S-HDHA), an intermediate product, abrogate hHcys-induced podocyte injury by targeting the NLRP3 inflammasome. In vitro, confocal microscopy demonstrated that 17S-HDHA (100 nM) and RvD1 (60 nM) prevented Hcys-induced formation of NLRP3 inflammasomes, as shown by reduced colocalization of NLRP3 with apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) or caspase-1. Both DHA metabolites inhibited Hcys-induced caspase-1 activation and interleukin-1β production. However, DHA had no significant effect on these Hcys-induced changes in podocytes. In vivo, DHA lipoxygenase metabolites substantially inhibited podocyte NLRP3 inflammasome formation and activation and consequent glomerular sclerosis in mice with hHcys. Mechanistically, RvD1 and 17S-HDHA were shown to suppress Hcys-induced formation of lipid raft redox signaling platforms and subsequent O2·−production in podocytes. It is concluded that inhibition of NLRP3 inflammasome activation is one of the important mechanisms mediating the beneficial action of RvD1 and 17S-HDHA on Hcys-induced podocyte injury and glomerular sclerosis

Bimetallic gold–strontium catalysts were prepared and assessed for the effect of a Sr(ii) additive on the catalytic performance of gold-based catalysts for acetylene hydrochlorination, combined with characterization using N2adsorption/desorption, thermogravimetric analysis, temperature-programmed reduction/desorption, powder X-ray diffraction, transmission electron microscopy, atomic absorption spectrophotometry and X-ray photoelectron spectroscopy. The optimal catalytic performance is obtained over an Au1Sr(ii)1/AC catalyst with acetylene conversion of 87.7% and selectivity for VCM of 99.8%, after 20 h on stream under the conditions of a temperature of 180 °C, a C2H2gas hourly space velocity (GHSV) of 762 h−1, and a feed volume ratio HCl/C2H2of 1.15, which is an increase of 24.3% compared with acetylene conversion of 63.4% after 20 h on stream under the same conditions over a monometallic Au/AC catalyst. It is indicated that the addition of Sr(ii) can disperse the Au species well and inhibit carbon deposition on the catalyst surface; the Sr(ii) additive can enhance the adsorption of the two reactants, acetylene and hydrogen chloride, on the catalyst and inhibit the reduction of Au3+to Au0during the preparation and reaction, consequently enhancing the catalytic activity and long-term stability of gold-based catalysts.

Gold–cerium oxide catalysts were prepared to study the effects of cerium oxide additives on the catalytic performance of gold catalysts for acetylene hydrochlorination, using activated carbon as the support. The optimal catalytic performance is achieved over the 1Au–5CeO2/AC catalyst with an acetylene conversion of 98.4% and a selectivity to vinyl chloride monomer (VCM) of 99.9% after 20 h on stream under the conditions of 180 °C, C2H2gas hourly space velocity (GHSV) of 852 h−1and HCl/C2H2feed volume ratio of 1.15. It is indicated that the addition of cerium oxide can make active Au species uniformly dispersed and improve the adsorption properties of reactants on the catalysts, but also suppress the reduction of active gold species and inhibit coke deposition on the catalyst surfaces during the reaction. Characterization was carried out using transmission electron microscopy, Raman spectroscopy, N2adsorption/desorption analysis, thermogravimetric analysis, temperature-programmed reduction, temperature-programmed desorption, powder X-ray diffraction, atomic absorption spectroscopy and X-ray photoelectron spectroscopy.

Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation in podocytes is reportedly associated with enhanced release of exosomes containing NLRP3 inflammasome products from these cells during hyperhomocysteinemia (hHcy). We examined the possible role of increased exosome secretion during podocyte NLRP3 inflammasome activation in the glomerular inflammatory response. We tested whether exosome biogenesis and lysosome function are involved in the regulation of exosome release from podocytes during hHcy in mice and upon stimulation of homocysteine (Hcy) in podocytes. By nanoparticle tracking analysis, treatments of mice with amitriptyline (acid sphingomyelinase inhibitor), GW4869 (exosome biogenesis inhibitor), and rapamycin (lysosome function enhancer) were found to inhibit elevated urinary exosomes during hHcy. By examining NLRP3 inflammasome activation in glomeruli during hHcy, amitriptyline (but not GW4869 and rapamycin) was shown to have an inhibitory effect. However, all treatments attenuated glomerular inflammation and injury during hHcy. In cell studies, we showed that Hcy treatment stimulated exosome release from podocytes, which was prevented by amitriptyline, GW4869, and rapamycin. Structured illumination microscopy revealed that Hcy inhibited lysosome–multivesicular body interactions in podocytes, which was prevented by amitriptyline or rapamycin but not GW4869. It is concluded that activation of exosome biogenesis and dysregulated lysosome function are critically implicated in the enhancement of exosome release from podocytes leading to glomerular inflammation and injury during hHcy.