Adaptive Cation Pillar Effects Achieving High Capacity in Li-Rich Layered Oxide, Li₂MnO₃-LiMeO₂ (Me = Ni, Co, Mn)

リチウムイオン電池正極の低結晶層状構造を支える2種類の支柱. 京都大学プレスリリース. 2022-09-05.Intensive research is underway to further enhance the performance of lithium-ion batteries (LIBs). To increase the capacity of positive electrode materials, Li-rich layered oxides (LLO) are attracting attention but have not yet been put to practical use. The structural mechanisms through which LLO materials exhibit higher capacity than conventional materials remain unclear because their disordered phases make it difficult to obtain structural information by conventional analysis. The X-ray total scattering analysis reveals a disordered structure consisting of metal ions in octahedral and tetrahedral sites of Li layers as a result of cation mixing after the extraction of Li ions. Metal ions in octahedral sites act as rigid pillars. The metal ions move to the tetrahedral site of the Li layer, which functions as a Li-layer pillar during Li extraction, and returns to the metal site during Li insertion, facilitating Li diffusion as an adaptive pillar. Adaptive pillars are the specific structural features that differ from those of the conventional layered materials, and their effects are responsible for the high capacity of LLO materials. An essential understanding of the pillar effects will contribute to design guidelines for intercalation-type positive electrodes for next-generation LIBs

Disordered Cubic Spinel Structure in the Delithiated Li2MnO3 Revealed by Difference Pair Distribution Function Analysis

An archetypical Li-rich layered oxide, Li2MnO3, shows a large initial charge capacity of ~350 mAh g-1 with little oxidation of the constituent Mn ions, yet, the crystal structure of delithiated Li2MnO3 is still unclarified because the structural disorder induced by the considerable Li extraction makes the analysis challenging. X-ray pair distribution function (PDF) analysis is a powerful tool to experimentally elucidate the structure of the disordered phase. Here, we conducted a comprehensive analysis with a focus on PDF analysis in combination with the X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), and X-ray absorption spectroscopy (XAS) to reveal the disordered crystalline structure of the electrochemically delithiated Li2MnO3. The XRPD and TEM analyses clarified the formation of a low-crystallinity phase in the light of the average structure. The XAS and PDF analyses further revealed that the MnO6–based framework was rearranged with maintaining the MnO6 octahedral coordination after the initial charge. The difference pair distribution function (d-PDF) technique was therefore employed to extract the structural information of the low-crystallinity disordered phase. The delithiated phase was found to have a structure similar to the cubic spinel, LiMn2O4, rather than that of delithiated LiMn2O4 (λ-MnO2). In addition, the middle-range order of the delithiated phase deteriorated after the charge, indicating a decrease of coherent domain size to a single nm order. The composite structure formed after the first charge, therefore, consists of the disordered cubic spinel structure and unreacted Li2MnO3. The formation of the composite structure “activates” the electrode material structurally and eventually induces characteristic large capacity of this material

Adaptive Cation Pillar Effects Achieving High Capacity in Li-Rich Layered Oxide, Li2MnO3-LiMeO2 (Me = Ni, Co, Mn)

Intensive research is underway to further enhance the performance of lithium-ion batteries (LIBs). To increase the capacity of positive electrode materials, Li-rich layered oxides (LLO) are attracting attention but have not yet been put to practical use. The structural mechanisms through which LLO materials exhibit higher capacity than conventional materials remain unclear because their disordered phases make it difficult to obtain structural information by conventional analysis. The X-ray total scattering analysis reveals a disordered structure consisting of metal ions in octahedral and tetrahedral sites of Li layers as a result of cation mixing after the extraction of Li ions. Metal ions in octahedral sites act as rigid pillars. The metal ions move to the tetrahedral site of the Li layer, which functions as a Li-layer pillar during Li extraction, and returns to the metal site during Li insertion, facilitating Li diffusion as an adaptive pillar. Adaptive pillars are the specific structural features that differ from those of the conventional layered materials, and their effects are responsible for the high capacity of LLO materials. An essential understanding of the pillar effects will contribute to design guidelines for intercalation-type positive electrodes for next-generation LIBs

Structural modification by adding Li cations into Mg/Cs-TFSA molten salt facilitating Mg electrodeposition

Free volume around Mg ions in Li/Mg/Cs-TFSA by adding Li cations would facilitate the Mg electrodeposition, which has been studied by Raman spectroscopy, high-energy X-ray diffraction, and reverse Monte Carlo structural refinement using molecular mechanics.</p

Coexistence of muscle atrophy and high subcutaneous adipose tissue radiodensity predicts poor prognosis in hepatocellular carcinoma

IntroductionWe aimed to assess the prognostic implications of muscle atrophy and high subcutaneous adipose tissue (SAT) radiodensity in patients with hepatocellular carcinoma (HCC).MethodsIn this retrospective study, muscle atrophy was assessed using the psoas muscle index (PMI) obtained from computed tomography. SAT radiodensity was evaluated based on radiodensity measurements. Survival and multivariate analyses were performed to identify factors associated with prognosis. The impact of muscle atrophy and high SAT radiodensity on prognosis was determined through survival analysis.ResultsA total of 201 patients (median age: 71 years; 76.6% male) with HCC were included. Liver cirrhosis was observed in 72.6% of patients, and the predominant Child–Pugh grade was A (77.1%). A total of 33.3% of patients exhibited muscle atrophy based on PMI values, whereas 12.9% had high SAT radiodensity. Kaplan–Meier survival analysis demonstrated that patients with muscle atrophy had significantly poorer prognosis than those without muscle atrophy. Patients with high SAT radiodensity had a significantly worse prognosis than those without it. Muscle atrophy, high SAT radiodensity, the Barcelona Clinic Liver Cancer class B, C, or D, and Child–Pugh score ≥ 6 were significantly associated with overall survival. Further classification of patients into four groups based on the presence or absence of muscle atrophy and high SAT radiodensity revealed that patients with both muscle atrophy and high SAT radiodensity had the poorest prognosis.ConclusionMuscle atrophy and high SAT radiodensity are significantly associated with poor prognosis in patients with HCC. Identifying this high-risk subgroup may facilitate the implementation of targeted interventions, including nutritional therapy and exercise, to potentially improve clinical outcomes

Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats

Background: Liver fibrosis is a complex inflammatory and fibrogenic process, and the progression of fibrosis leads to cirrhosis. The only therapeutic approaches are the removal of injurious stimuli and liver transplantation. Therefore, the development of anti-fibrotic therapies is desired. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide belonging to the N-acylethanolamines family and contained in foods such as egg yolks and peanuts. PEA has therapeutic anti-inflammatory, analgesic, and neuroprotective effects. However, the effects and roles of PEA in liver fibrosis remain unknown. Here we investigated the therapeutic effects of PEA in rats with liver fibrosis. Methods: We conducted in vitro experiments to investigate the effects of PEA on the activation of hepatic stellate cells (HSCs, LX-2). Liver fibrosis was induced by an intraperitoneal injection of 1.5 mL/kg of 50% carbon tetrachloride twice a week for 4 weeks. Beginning at 3 weeks, PEA (20 mg/kg) was intraperitoneally injected thrice a week for 2 weeks. Then rats were sacrificed and we performed histological and quantitative reverse-transcription polymerase chain reaction analyses. Results: The expression of α-smooth muscle actin (SMA) induced by transforming growth factor (TGF)-β1 in HSCs was significantly downregulated by PEA. PEA treatment inhibited the TGF-β1-induced phosphorylation of SMAD2 in a dose-dependent manner, and upregulated the expression of SMAD7. The reporter gene assay demonstrated that PEA downregulated the transcriptional activity of the SMAD complex upregulated by TGF-β1. Administration of PEA significantly reduced the fibrotic area, deposition of type I collagen, and activation of HSCs and Kupffer cells in rats with liver fibrosis. Conclusion: Activation of HSCs was significantly decreased by PEA through suppression of the TGF-β1/SMAD signaling pathway. Administration of PEA produced significant improvement in a rat model of liver fibrosis, possibly by inhibiting the activation of HSCs and Kupffer cells. PEA may be a potential new treatment for liver fibrosis

Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats

Background. There are no approved drug treatments for liver fibrosis and nonalcoholic steatohepatitis (NASH), an advanced stage of fibrosis which has rapidly become a major cause of cirrhosis. Therefore, development of anti-inflammatory and antifibrotic therapies is desired. Mesenchymal stem cell- (MSC-) based therapy, which has been extensively investigated in regenerative medicine for various organs, can reportedly achieve therapeutic effect in NASH via paracrine action. Extracellular vesicles (EVs) encompass a variety of vesicles released by cells that fulfill functions similar to those of MSCs. We herein investigated the therapeutic effects of EVs from amnion-derived MSCs (AMSCs) in rats with NASH and liver fibrosis. Methods. NASH was induced by a 4-week high-fat diet (HFD), and liver fibrosis was induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) twice a week for six weeks. AMSC-EVs were intravenously injected at weeks 3 and 4 in rats with NASH (15 μg/kg) and at week 3 in rats with liver fibrosis (20 μg/kg). The extent of inflammation and fibrosis was evaluated with quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The effect of AMSC-EVs on inflammatory and fibrogenic response was investigated in vitro. Results. AMSC-EVs significantly decreased the number of Kupffer cells (KCs) in the liver of rats with NASH and the mRNA expression levels of inflammatory cytokines such as tumor necrosis factor- (Tnf-) α, interleukin- (Il-) 1β and Il-6, and transforming growth factor- (Tgf-) β. Furthermore, AMSC-EVs significantly decreased fiber accumulation, KC number, and hepatic stellate cell (HSC) activation in rats with liver fibrosis. In vitro, AMSC-EVs significantly inhibited KC and HSC activation and suppressed the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway. Conclusions. AMSC-EVs ameliorated inflammation and fibrogenesis in a rat model of NASH and liver fibrosis, potentially by attenuating HSC and KC activation. AMSC-EV administration should be considered as a new therapeutic strategy for chronic liver disease

Effects of human amnion-derived mesenchymal stem cells and conditioned medium in rats with sclerosing cholangitis

Mesenchymal stem cells (MSCs) represent a valuable cell source in regenerative medicine, and large numbers of MSCs can be isolated from the amnion noninvasively. Sclerosing cholangitis is a chronic cholestatic disease and characterized by progressive biliary destruction leading to cirrhosis. Many factors are involved in the development of sclerosing cholangitis; however, effective medical therapy is not established. We investigated the effects of human amnion-derived MSCs (hAMSCs) and conditioned medium (CM) obtained from hAMSC cultures in rats with sclerosing cholangitis. Sclerosing cholangitis was induced via the intragastric administration of 100 mg/kg alpha-naphthylisothiocyanate (ANIT) twice weekly for 4 weeks. One million hAMSCs or 200 mu L of CM were intravenously administered on days 15 and 22. Rats were sacrificed on day 29 and evaluated via histological, immunohistochemical, and mRNA expression analyses. hAMSC transplantation and CM administration significantly improved the histological score. In addition, these two interventions significantly improved biliary hyperplasia, peribiliary fibrosis, and inflammation in Glisson's sheath. Accordingly, CK19, MMP-9, and TNF-alpha, and MCP-1 expression in the liver was also decreased by hAMSC and CM administration. In conclusion, hAMSC and CM administration ameliorated biliary hyperplasia, peribiliary fibrosis, and inflammation in a rat model of sclerosing cholangitis. hAMSCs and CM may represent new modalities for treating sclerosing cholangitis