Endoplasmic reticulum stress is closely associated with the onset and progression of inflammatory bowel disease. ERdj5 is an endoplasmic reticulum-resident protein disulfide reductase that mediates ...the cleavage and degradation of misfolded proteins. Although ERdj5 expression is significantly higher in the colonic tissues of patients with inflammatory bowel disease than in healthy controls, its role in inflammatory bowel disease has not yet been reported. In the current study, we used ERdj5-knockout mice to investigate the potential roles of ERdj5 in inflammatory bowel disease. ERdj5 deficiency causes severe inflammation in mouse colitis models and weakens gut barrier function by increasing NF-κB-mediated inflammation. ERdj5 may not be indispensable for goblet cell function under steady-state conditions, but its deficiency induces goblet cell apoptosis under inflammatory conditions. Treatment of ERdj5-knockout mice with the chemical chaperone ursodeoxycholic acid ameliorated severe colitis by reducing endoplasmic reticulum stress. These findings highlight the important role of ERdj5 in preserving goblet cell viability and function by resolving endoplasmic reticulum stress.
Continuous glucose monitoring (CGM) technology has evolved over the past decade with the integration of various devices including insulin pumps, connected insulin pens (CIPs), automated insulin ...delivery (AID) systems, and virtual platforms. CGM has shown consistent benefits in glycemic outcomes in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) treated with insulin. Moreover, the combined effect of CGM and education have been shown to improve glycemic outcomes more than CGM alone. Now a CIP is the expected future technology that does not need to be worn all day like insulin pumps and helps to calculate insulin doses with a built-in bolus calculator. Although only a few clinical trials have assessed the effectiveness of CIPs, they consistently show benefits in glycemic outcomes by reducing missed doses of insulin and improving problematic adherence. AID systems and virtual platforms made it possible to achieve target glycosylated hemoglobin in diabetes while minimizing hypoglycemia, which has always been challenging in T1DM. Now fully automatic AID systems and tools for diabetes decisions based on artificial intelligence are in development. These advances in technology could reduce the burden associated with insulin treatment for diabetes.
We investigated the effects of derhamnosylmaysin (DM) on adipogenesis and lipid accumulation in 3T3-L1 adipocytes. Our data showed that DM inhibited lipid accumulation and adipocyte differentiation ...in 3T3-L1 cells. Treatment of 3T3-L1 adipocytes with DM decreased the expression of major transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), the CCAAT-enhancer-binding protein (CEBP) family, and peroxisome proliferator-activated receptor gamma (PPARγ), in the regulation of adipocyte differentiation. Moreover, the expression of their downstream target genes related to adipogenesis and lipogenesis, including adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), stearyl-CoA-desaturase-1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), was also decreased by treatment with DM during adipogenesis. Additionally, DM attenuated insulin-stimulated phosphorylation of Akt. These results first demonstrated that DM inhibited adipogenesis and lipogenesis through downregulation of the key adipogenic transcription factors SREBP-1c, the CEBP family, and PPARγ and inactivation of the major adipogenesis signaling factor Akt, which is intermediated in insulin. These studies demonstrated that DM is a new bioactive compound for antiadipogenic reagents for controlling overweight and obesity.
Herein, Ti4+ in P′2‐Na0.67(Mn0.78Fe0.22)0.9Ti0.1O2 is proposed as a new strategy for optimization of Mn‐based cathode materials for sodium‐ion batteries, which enables a single phase reaction during ...de‐/sodiation. The approach is to utilize the stronger Ti–O bond in the transition metal layers that can suppress the movements of Mn–O and Fe–O by sharing the oxygen with Ti by the sequence of Mn–O–Ti–O–Fe. It delivers a discharge capacity of ≈180 mAh g−1 over 200 cycles (86% retention), with S‐shaped smooth charge–discharge curves associated with a small volume change during cycling. The single phase reaction with a small volume change is further confirmed by operando synchrotron X‐ray diffraction. The low activation barrier energy of ≈541 meV for Na+ diffusion is predicted using first‐principles calculations. As a result, Na0.67(Mn0.78Fe0.22)0.9Ti0.1O2 can deliver a high reversible capacity of ≈153 mAh g−1 even at 5C (1.3 A g−1), which corresponds to ≈85% of the capacity at 0.1C (26 mA g−1). The nature of the sodium storage mechanism governing the ultrahigh electrode performance in a full cell with a hard carbon anode is elucidated, revealing the excellent cyclability and good retention (≈80%) for 500 cycles (111 mAh g−1) at 5C (1.3 A g−1).
The substitution of Mn with Fe3+ and Ti4+ in P′2‐type Na0.67(Mn0.78Fe0.22)0.9Ti0.1O2 leads to the suppression of phase transitions with an increased average Mn oxidation state. Therefore, it delivers high reversible capacity during cycling with a small volume change. Above all, it shows excellent high rate capability, accompanied by low activation barrier energy of ≈541 meV for Na+ diffusion.
In this work, rhombohedral KTi2(PO4)3 is introduced to investigate the related theoretical, structural, and electrochemical properties in K cells. The suggested KTi2(PO4)3 modified by ...electro‐conducting carbon brings about a flat voltage profile at ≈1.6 V, providing a large capacity of 126 mAh (g‐phosphate)−1, corresponding to 98.5% of the theoretical capacity, with 89% capacity retention for 500 cycles. Structural analyses using electrochemical performance measurements, first‐principles calculations, ex situ X‐ray absorption spectroscopy, and operando X‐ray diffraction provide new insights into the reaction mechanism controlling the (de)intercalation of potassium ions into the host KTi2(PO4)3 structure. It is observed that a biphasic redox process by Ti4+/3+ occurs upon discharge, whereas a single‐phase reaction followed by a biphasic process occurs upon charge. Along with the structural refinement of the electrochemically reduced K3Ti2(PO4)3 phase, these new findings provide insight into the reaction mechanism in Na superionic conductor (NASICON)‐type KTi2(PO4)3. The present approach can also be extended to the investigation of other NASICON‐type materials for potassium‐ion batteries.
The mechanism that guides the insertion/extraction of K+ into/from KTi2(PO4)3 structure is clarified by operando X‐ray diffraction, X‐ray absorption near‐edge structure, and first‐principles calculations. A two‐phase reaction activated by Ti4+/Ti3+ is responsible for high cycling stability over the 500 cycles with capacity retention of 89%.
Background and Aim
Nuclear factor kappa B (NF‐κB) activation and endoplasmic reticulum (ER) stress signaling play significant roles in the pathogenesis of inflammatory bowel disease (IBD). Thus, we ...evaluated whether new therapeutic probiotics have anti‐colitic effects, and we investigated their mechanisms related to NF‐κB and ER‐stress pathways.
Methods
Luciferase, nitric oxide, and cytokine assays using HT‐29 or RAW264.7 cells were conducted. Mouse colitis was induced using dextran sulfate sodium and confirmed by disease activity index and histology. Macrophages and T‐cell subsets in isolated peritoneal cavity cells and splenocytes were analyzed by flow cytometry. Gene and cytokine expression profiles were determined using reverse‐transcription polymerase chain reaction.
Results
Lactobacillus acidophilus (LA1) and Pediococcus pentosaceus inhibited nitric oxide production in RAW264.7 cells, but only LA1 inhibited Tnfa and induced Il10 expression. LA1 increased the lifespan of dextran sulfate sodium‐treated mice and attenuated the severity of colitis by inducing M2 macrophages in peritoneal cavity cells and Th2 and Treg cells in splenocytes. The restoration of goblet cells in the colon was accompanied by the induction of Il10 expression and the suppression of pro‐inflammatory cytokines. Additionally, we found that LA1 exerts an anti‐colitic effect by improving ER stress in HT‐29 cells as well as in vivo.
Conclusions
We showed that LA1 significantly interferes with ER stress and suppresses NF‐κB activation. Our findings suggest that LA1 can be used as a potent immunomodulator in IBD treatment, and the regulation of ER stress may have significant implications in treating IBD.
We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes ...with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP
mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.
A high‐rate of oxygen redox assisted by cobalt in layered sodium‐based compounds is achieved. The rationally designed Na0.6Mg0.2Mn0.6Co0.2O2 exhibits outstanding electrode performance, delivering a ...discharge capacity of 214 mAh g−1 (26 mA g−1) with capacity retention of 87% after 100 cycles. High rate performance is also achieved at 7C (1.82 A g−1) with a capacity of 107 mAh g−1. Surprisingly, the Na0.6Mg0.2Mn0.6Co0.2O2 compound is able to deliver capacity for 1000 cycles at 5C (at 1.3 A g−1), retaining 72% of its initial capacity of 108 mAh g−1. X‐ray absorption spectroscopy analysis of the O K‐edge indicates the oxygen‐redox species (O2−/1−) is active during cycling. First‐principles calculations show that the addition of Co reduces the bandgap energy from ≈2.65 to ≈0.61 eV and that overlapping of the Co 3d and O 2p orbitals facilitates facile electron transfer, enabling the long‐term reversibility of the oxygen redox, even at high rates. To the best of the authors' knowledge, this is the first report on high‐rate oxygen redox in sodium‐based cathode materials, and it is believed that the findings will open a new pathway for the use of oxygen‐redox‐based materials for sodium‐ion batteries.
A new compound, P2‐Na0.6Mg0.2Mn0.8Co0.2O2, exhibits outstanding electrochemical performance assisted by high‐rate oxygen redox as well as structural stability for prolonged cycles. The electrode delivers high capacity because of the overlapping of Co 3d and O 2p orbitals. Moreover, the electrode displays excellent long‐term cycling performance, retaining 72% of its initial capacity after 1000 cycles at 5C.
Recently, the tribological properties of graphene have been intensively examined for potential applications in micro- and nano-mechanical graphene-based devices. Here, we report that the tribological ...properties can be easily altered via simple chemical modifications of the graphene surface. Friction force microscopy measurements show that hydrogenated, fluorinated, and oxidized graphenes exhibit, 2-, 6-, and 7-fold enhanced nanoscale friction on their surfaces, respectively, compared to pristine graphene. The measured nanoscale friction should be associated with the adhesive and elastic properties of the chemically modified graphenes. Density-functional theory calculations suggest that, while the adhesive properties of chemically modified graphenes are marginally reduced down to ~30 %, the out-of-plane elastic properties are drastically increased up to 800 %. Based on these findings, we propose that nanoscale friction on graphene surfaces is characteristically different from that on conventional solid surfaces; stiffer graphene exhibits higher friction, whereas a stiffer three-dimensional solid generally exhibits lower friction. The unusual friction mechanics of graphene is attributed to the intrinsic mechanical anisotropy of graphene, which is inherently stiff in plane, but remarkably flexible out of plane. The out-of-plane flexibility can be modulated up to an order of magnitude by chemical treatment of the graphene surface. The correlation between the measured nanoscale friction and the calculated out-of-plane flexibility suggests that the frictional energy in graphene is mainly dissipated through the out-of-plane vibrations, or the flexural phonons of graphene.
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