WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression

AbstractArterial medial calcification (AMC) is prevalent in patients with chronic kidney disease (CKD) and contributes to elevated risk of cardiovascular events and mortality. Vascular smooth muscle cells (VSMCs) to osteogenic transdifferentiation (VOT) in a high-phosphate environment is involved in the pathogenesis of AMC in CKD. WNT/β-catenin signaling is indicated to play a crucial role in osteogenesis via promoting Runx2 expression in osteoprogenitor cells, however, its role in Runx2 regulation and VOT remains incompletely clarified. In this study, Runx2 was induced and β-catenin was activated by high-phosphate in VSMCs. Two forms of active β-catenin, dephosphorylated on Ser37/Thr41 and phosphorylated on Ser675 sites, were upregulated by high-phosphate. Activation of β-catenin, through ectopic expression of stabilized β-catenin, inhibition of GSK-3β, or WNT-3A protein, induced Runx2 expression, whereas blockade of WNT/β-catenin signaling with Porcupine (PORCN) inhibitor or Dickkopf-1 (DKK1) protein inhibited Runx2 induction by high-phosphate. WNT-3A promoted osteocalcin expression and calcium deposition in VSMCs, whereas DKK1 ameliorated calcification of VSMCs induced by high-phosphate. Two functional T cell factor (TCF)/lymphoid enhancer-binding factor binding sites were identified in the promoter region of Runx2 gene in VSMCs, which interacted with TCF upon β-catenin activation. Site-directed mutation of each of them attenuated Runx2 response to β-catenin, and deletion or destruction of both of them completely abolished this responsiveness. In the aortic tunica media of rats with chronic renal failure, followed by AMC, Runx2 and β-catenin was induced, and the Runx2 mRNA level was positively associated with the abundance of phosphorylated β-catenin (Ser675). Collectively, our study suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC

Monodispersed FeS2 Electrocatalyst Anchored to Nitrogen-Doped Carbon Host for Lithium–Sulfur Batteries

Despite their high theoretical energy density, lithium–sulfur (Li–S) batteries are hindered by practical challenges including sluggish conversion kinetics and shuttle effect of polysulfides. Here, a nitrogen-doped continuous porous carbon (CPC) host anchoring monodispersed sub-10\ua0nm FeS2 nanoclusters (CPC@FeS2) is reported as an efficient catalytic matrix for sulfur cathode. This host shows strong adsorption of polysulfides, promising the inhibition of polysulfide shuttle and the promoted initial stage of catalytic conversion process. Moreover, fast lithium ion (Li-ion) diffusion and accelerated solid–solid conversion kinetics of Li2S2 to Li2S on CPC@FeS2 host guarantee boosted electrochemical kinetics for conversion process of sulfur species in Li–S cell, which gives a high utilization of sulfur under practical conditions of high loading and low electrolyte/sulfur (E/S) ratio. Therefore, the surfur cathode (S/CPC@FeS2) delivers a high specific capacity of 1459 mAh g−1 at 0.1 C, a stable cycling over 900 cycles with ultralow fading rate of 0.043% per cycle, and an enhanced rate capability compared with cathode only using carbon host. Further demonstration of this cathode in Li–S pouch cell shows a practical energy density of 372\ua0Wh kg−1 with a sulfur loading of 7.1\ua0mg cm−2 and an E/S ratio of 4\ua0\ub5L mg−1

Development and application of an amplified luminescent proximity homogeneous assay-linked immunosorbent assay for the accurate quantification of kidney injury molecule-1

Background: Kidney injury molecule-1 (Kim-1), a specific marker of kidney injury, is usually not expressed in normal kidneys or at very low levels but is highly expressed in injured renal tubular epithelial cells until the damaged cells recover completely. Therefore, we aimed to develop an efficient and highly sensitive assay to accurately quantify Kim-1 levels in human serum and urine.Methods: In this study, a novel immunoassay was developed and named amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). Anti-Kim-1 antibodies can be directly coupled to carboxyl-modified donor and acceptor beads for the rapid detection of Kim-1 by double-antibody sandwich method. Serum and urine samples for Kim-1 measurements were obtained from 129 patients with nephropathy and 17 healthy individuals.Results: The linear range of Kim-1 detected by AlphaLISA was 3.83–5000 pg/mL, the coefficients of variation of intra-assay and inter-assay batches were 3.36%–4.71% and 5.61%–11.84%, respectively, and the recovery rate was 92.31%–99.58%. No cross reactions with neutrophil gelatinase-associated lipocalin, liver-type fatty acid binding protein, and matrix metalloproteinase-3 were observed. A good correlation (R2 = 0.9086) was found between the findings of Kim-1-TRFIA and Kim-AlphaLISA for the same set of samples. In clinical trials, both serum and urine Kim-1 levels were significantly higher in patients with nephropathy than in healthy individuals, especially in patients with acute kidney injury. Furthermore, serum Kim-1 was superior to urinary Kim-1 in distinguishing between patients with nephropathy and healthy individuals.Conclusion: The developed Kim-1-AlphaLISA is highly efficient, precise, and sensitive, and it is suitable for the rapid detection of patients with acute kidney injury

Label-Free Colorimetric Protein Assay and Logic Gates Design Based on the Self-assembly of Hemin-Graphene Hybrid Nanosheet

Here we report a label-free colorimetric method for protein assay based on the intrinsic peroxidase-like catalytic activity of DNA-hemin-graphene (DNA-GH) composite. By using aptamers as protein recognition elements, protein-mediated aggregation of the DNA-GH composite leads to the decrease or increase of the colorimetric signal depending on the sandwich or competitive design strategy. Thrombin and PDGF-BB were chosen as model analytes and the detection limits (LOD) by this method were estimated to be 0.5 nM and 5 nM, respectively. Compared to traditional ELISA method for protein detection, this method possesses the advantages of high sensitivity, simplicity, and low cost. In addition, by designing different DNA-modified hemin-graphene (GH) constructs, using proteins as inputs, the “OR” and “INHIBIT” logic gates were built. This procedure does not require chemical modification on the aptamer probes or analytes and circumvents the limitation associated with the number of target binding sites. Given the attractive analytical characteristics and distinct advantages of DNA-GH composite, the universal approach can be widely applied for the detection of diverse proteins and for the design of versatile logic gates

Constructing Chromium Multioxide Hole-Selective Heterojunction for High-Performance Perovskite Solar Cells

Perovskite solar cells (PSCs) suffer from significant nonradiative recombination at perovskite/charge transport layer heterojunction, seriously limiting their power conversion efficiencies. Herein, solution-processed chromium multioxide (CrOx) is judiciously selected to construct a MAPbI(3)/CrOx/Spiro-OMeTAD hole-selective heterojunction. It is demonstrated that the inserted CrOx not only effectively reduces defect sites via redox shuttle at perovskite contact, but also decreases valence band maximum (VBM)-HOMO offset between perovskite and Spiro-OMeTAD. This will diminish thermionic losses for collecting holes and thus promote charge transport across the heterojunction, suppressing both defect-assisted recombination and interface carrier recombination. As a result, a remarkable improvement of 21.21% efficiency with excellent device stability is achieved compared to 18.46% of the control device, which is among the highest efficiencies for polycrystalline MAPbI(3) based n-i-p planar PSCs reported to date. These findings of this work provide new insights into novel charge-selective heterojunctions for further enhancing efficiency and stability of PSCs.Funding Agencies|National Science Foundation of China [21875067]; Shanghai Science and Technology Innovation Action Plan [22ZR1418900]; Fundamental Research Funds for the Central Universities; Shanghai Rising-Star [19QA1403100]; East China Normal University (ECNU) Multifunctional Platform for Innovation; open research fund of Songshan Lake Materials Laboratory [2021SLABFK02]; National Key Research and Development Program of China [2017YFA0206600]; National Natural Science Foundation of China [51922032, 21961160720]</p

Alcohol-Tolerant Platinum Electrocatalyst for Oxygen Reduction by Encapsulating Platinum Nanoparticles inside Nitrogen-Doped Carbon Nanocages

Pt-based electrocatalysts are the most popular for direct alcohol fuel cells, but their performances easily deteriorate for the oxygen reduction reaction (ORR) at the cathode because of the alcohol crossover effect. Herein, we report the novel Pt electrocatalyst encapsulated inside nitrogen-doped carbon nanocages (Pt@NCNC), which presents excellent alcohol-tolerant ORR activity and durability in acidic media, far superior to the Pt counterpart immobilized outside the nanocages (Pt/NCNC). The superb performance is correlated with the molecule-sieving effect of the micropores penetrating through the shells of the nanocages, which admit the small-sized oxygen and ions but block the large-sized alcohols into the nanocages. This mechanism is confirmed by examining the size dependence of ORR and alcohol oxidation activities by regulating the micropores sizes. This study provides a promising strategy to develop the superior alcohol-tolerant Pt-based ORR electrocatalyst in acidic media