Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD.

International audienceHighly dispersed crystalline/amorphous LiFePO4 (LFP) nanoparticles encapsulated within hollow-structured graphitic carbon were synthesized using an in situ ultracentrifugation process. Ultracentrifugation triggered an in situ sol–gel reaction that led to the formation of core–shell LFP simultaneously hybridized with fractured graphitic carbon. The structure has double cores that contain a crystalline LFP (core 1) covered by an amorphous LFP containing Fe3+ defects (core 2), which are encapsulated by graphitic carbon (shell). These core–shell LFP nanocomposites show improved Li+ diffusivity thanks to the presence of an amorphous LFP phase. This material enables ultrafast discharge rates (60 mA h g-1 at 100C and 36 mA h g-1 at 300C) as well as ultrafast charge rates (60 mA h g-1 at 100C and 36 mA h g-1 at 300C). The synthesized core–shell nanocomposites overcome the inherent one-dimensional diffusion limitation in LFP and yet deliver/store high electrochemical capacity in both ways symmetrically up to 480C. Such a high rate symmetric capacity for both charge and discharge has never been reported so far for LFP cathode materials. This offers new opportunities for designing high-energy and high-power hybrid supercapacitors

Magnesium borohydride ammonia borane, Mg-(BH 4 ) 2 (NH 3 BH 3 ) 2 , was electrochemically investigated. Impedance measurements of the mechanochemically synthesized Mg-(BH 4 ) 2 (NH 3 BH 3 ) 2 exhibited an ionic conductivity of 1.3 × 10 −5 S cm −1 at 30 °C. Electrochemical cells fabricated with Mg-(BH 4 ) 2 (NH 3 BH 3 ) 2 as the solid electrolyte demonstrated reversible Mg migration through the material, indicating its potential for use as a Mg ionic conductor in all-solid-state Mg-ion batteries.

Nanocrystalline Li3VO4 dispersed within multiwalled carbon nanotubes (MWCNTs) was prepared using an ultracentrifugation (uc) process and electrochemically characterized in Li-containing electrolyte. When charged and discharged down to 0.1 V vs Li, the material reached 330 mAh g(-1) (per composite) at an average voltage of about 1.0 V vs Li, with more than 50% capacity retention at a high current density of 20 A g(-1). This current corresponds to a nearly 500C rate (7.2 s) for a porous carbon electrode normally used in electric double-layer capacitor devices (1C = 40 mA g(-1) per activated carbon). The irreversible structure transformation during the first lithiation, assimilated as an activation process, was elucidated by careful investigation of in operando X-ray diffraction and X-ray absorption fine structure measurements. The activation process switches the reaction mechanism from a slow "two-phase" to a fast "solid-solution" in a limited voltage range (2.5-0.76 V vs Li), still keeping the capacity as high as 115 mAh g(-1) (per composite). The uc-Li3VO4 composite operated in this potential range after the activation process allows fast Li(+) intercalation/deintercalation with a small voltage hysteresis, leading to higher energy efficiency. It offers a promising alternative to replace high-rate Li4Ti5O12 electrodes in hybrid supercapacitor applications.

Objective-The role of hypercoagulability in the pathogenesis of diabetic nephropathy (DN) remains elusive. We recently reported the increased infiltration of macrophages expressing tissue factor in diabetic kidney glomeruli; tissue factor activates coagulation factor X (FX) to FXa, which in turn stimulates protease-activated receptor 2 (PAR2) and causes inflammation. Approach and Results-Here, we demonstrated that diabetes mellitus increased renal FX mRNA, urinary FXa activity, and FX expression in glomerular macrophages. Administration of an oral FXa inhibitor, edoxaban, ameliorated DN with concomitant reductions in the expression of PARs (Par1 and Par2) and of proinflammatory and profibrotic genes. Diabetes mellitus induced PAR2, and lack of Par2 ameliorated DN. FXa or PAR2 agonist increased inflammatory cytokines in endothelial cells and podocytes in vitro. Conclusions-We conclude that enhanced FXa and PAR2 exacerbate DN and that both are promising targets for preventing DN. Alleviating inflammation is probably more important than inhibiting coagulation per se when treating kidney diseases using anticoagulants.

Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.

High-energy-density and low-cost calcium (Ca) batteries have been proposed as ‘beyond-Li-ion’ electrochemical energy storage devices. However, they have seen limited progress due to challenges associated with developing electrolytes showing reductive/oxidative stabilities and high ionic conductivities. This paper describes a calcium monocarborane cluster salt in a mixed solvent as a Ca-battery electrolyte with high anodic stability (up to 4 V vs. Ca2+/Ca), high ionic conductivity (4 mS cm−1), and high Coulombic efficiency for Ca plating/stripping at room temperature. The developed electrolyte is a promising candidate for use in room-temperature rechargeable Ca batteries.

Anisotropically grown Li 3 V 2 (PO 4 ) 3 nanocrystals, which are highly dispersed and directly impregnated on the surface of a carbon nanofiber (CNF), were successfully synthesized via a two-step synthesis process: i) precipitation of nanoplated V 2 O 3 precursors (20-200 nm); ii) transformation of the V 2 O 3 precursor into Li 3 V 2 (PO 4 ) 3 nanoplates without size change. The direct attachment of the Li 3 V 2 (PO 4 ) 3 nanocrystals to the carbon surface improves the electronic conductivity and Li + diffusivity of the entire Li 3 V 2 (PO 4 ) 3 /CNF composite, simultaneously producing a mesoporous network (pore size of approximately 10 nm) that acts as an electrolyte reservoir owing to the pillar effect of the impregnated Li 3 V 2 (PO 4 ) 3 crystals. This ideal Li 3 V 2 (PO 4 ) 3 /CNF nanostructure enabled a 480C rate (7.5 seconds) discharge with 83 mA h g −1 , and 69% of capacity retention at the slowest discharge rate (1C). Such an ultrafast charge-discharge performance opens the possibility of using Li 3 V 2 (PO 4 ) 3 as a cathode material for ultrafast lithium ion batteries with a stable cycle performance over 10,000 cycles at a 10C rate, maintaining 85% of the initial capacity. In the current society, the storage of electrical energy at high charge and discharge rate is an important technological issue as it enables hybrid and plug-in hybrid electric vehicles and provides a back-up to wind and solar energies.1,2 Rechargeable lithium-ion batteries (LIBs) are considered the most advanced energy storage systems; they possess high energy but limited power compared to high-power devices such as supercapacitors.1 To further improve the performance of the LIBs, several electrode materials have been proposed and investigated so far.2-11 Commercial cells utilize the layer-structured LiCoO 2 as the positive electrode, 3 but the high cost and toxicity of cobalt prohibit its use on a large scale. Spinel-type LiMn 2 O 4 is one of the alternative materials to cobalt for high-rate use. 4 Several reports on such materials for high-rate use have been published; however, the reported discharge performance are limited within 50-150C. Owing to their easy release of oxygen, LiCoO 2 and LiMn 2 O 4 also have safety issues at overcharged states or high temperatures.3,4 Thus, to achieve a long-term and safe use of the LIBs, cathode materials other than those including layer-structured or spinel-type materials have received significant attention. Researchers have identified polyanion-type cathode materials-such as phosphate cathode materials like LiFePO 4 (LFP) 5 and Li 3 V 2 (PO 4 ) 3 (LVP)-as attractive active materials because of their high thermal stability, high cyclability, and superior safety properties provided by the stable (PO 4 ) 3− unit. 6 The presence of a phosphate with a strong P-O covalency stabilizes the antibonding M-O (M = V or Fe) energy level through an M-O-P inductive effect and generates a conveniently high redox potential for M 3+ /M 2+ . 7 In particular, monoclinic LVP has attracted much attention because o...