High-Energy Metallic Lithium Batteries Enabled by Polymer-in-Salt Electrolytes of Cyclic Carbonate Substituted Polyethers

A class of polymer-in-salt electrolytes (PISEs) based on cross-linkable polyethers bearing pendant cyclic carbonate groups has been developed. This type of cyclic carbonate substituted polyether has a low glass transition temperature and shows good chemical and electrochemical stability. We have revealed the effects of the spacer length and the backbone on the ion conduction in detail. The PISE with a moderate interaction between polymer segments and lithium ions exhibits a higher ionic conductivity, and a nearly 3-fold increase in lithium ion transference number compared to that of conventional salt-in-polymer electrolytes. With a high concentration of salt, the growth of dendrites from the lithium–metal anode can be effectively suppressed and a uniform lithium deposition has been observed, which has been related to the formation of the inorganic-rich solid electrolyte interphase. Moreover, the in situ cross-linking of the PISE gives rise to a flexible yet mechanically robust elastomeric thin film with a fast lithium ion conduction, which eventually enables the good-performance all-solid-state Li/LiFePO4 batteries with high cycling stability and Coulombic efficiency at ambient conditions. This work is anticipated to advance the research of PISEs for potential applications in high-energy lithium metal batteries

Schematic diagram of the most relevant metabolic differences between diabetic rats and their age-matched control rats during the evolution of diabetes.

<p>Schematic diagram of the most relevant metabolic differences between diabetic rats and their age-matched control rats during the evolution of diabetes.</p

Additional file 3 of Post-translational modification of CDK1–STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties

Additional file 3: Table S2. Protein kinase like domain associated genes

Metabolic alterations obtained from ¹H NMR spectra of urine samples collected from control group (shaded markers, n = 13–16) and diabetic group (open markers, n = 15–18) rats of 1 wk, 5 wks, 10 wks, and 15 wks after STZ injection.

<p>The results are expressed as means ± standard deviations. ^*p<0.05 and ^**p<0.01 compared to age-matched control rats by independent samples t-test.</p

Additional file 2 of Post-translational modification of CDK1–STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties

Additional file 2: Table S1. Proteins identified by proteomic

Additional file 1 of Post-translational modification of CDK1–STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties

Additional file 1: Figure S1. a Representative flow cytometry plots for CD44 and CD24 expression in human pancreatic cancer HPC-Y5 cells with DMSO or fisetin treatment. Cells were treated with fisetin (100 µM) for 48 h. b Statistical plot of ratio of CD44 + /CD24 + positive and CD44-/CD24- negative cells in control or fisetin treatment HPC-Y5 cells. Data are presented as mean ± SD (n = 3); *P  1.5). d Heat map of Biological Process in GO enrichment analysis of differentially expressed proteins in each Q subset according to P value of Fisher's exact test. Figure S2. Heat map of Cellular Component in GO enrichment analysis of differentially expressed proteins in each Q subset according to P value of Fisher's exact test. Figure S3. Heat map of Molecular Function in GO enrichment analysis of differentially expressed proteins in each Q subset according to P value of Fisher's exact test. Figure S4. a Heat map of KEGG pathway enrichment analysis of differentially expressed proteins in each Q subset according to P value of Fisher's exact test. Enrichment pathways of Q1 and Q2 indicated proteins in important pathways including PI3K–Akt signaling, pathways in cancer, metabolism pathways and ECM-receptor interaction were declined in PANC-1 cells with fisetin treatment. b Heat map of protein domain enrichment analysis of differentially expressed proteins in each Q subset. Enrichment protein domain of Q1 and Q2 indicated proteins with EGF-like domain and Laminin EGF domain were reduced by fisetin treatment. c Protein domain enrichment analysis of whole differentially expressed proteins quantified by proteomics analysis. Figure S5. a Summary of acetylated sites and proteins quantified by acetyl-proteomics analysis. b Summary of differentially expressed acetylated sites and proteins quantified by acetyl-proteomics analysis. 368 sites were changed over 1.2-folds (P < 0.05) including 307 up-regulated and 61 down-regulated in 264 proteins. c Go enrichment analysis of differentially expressed acetylated proteins. d Immunoprecipitation and western blot determined that EP300 was acetyl-transferase of CDK1. Figure S6. Protein motif analysis was performed by statistical analysis of the patterns of amino acid sequences before and after all acetylated sites in samples. 19 types of conserved motifs were identified by motif analysis. Figure S7. a Western blot analysis was used to determine expression of CDK1, STAT3, CD44 and Sox2 in adherent PANC-1 cells or spheres generated from PANC-1 cells. Adhe, adherent cells. b Inhibition of CD44 and Sox2 by CDK1 silencing can be rescued by over-expressing STAT3. Expression of CD44, Sox2, CDK1, STAT3, p-CDK1 and p-STAT3 were examined by western blot analysis. c Inhibition of CDK1-STAT3 signaling by fisetin in purified pancreatic cancer stem cell spheres. Expression of CD44, Sox2, CDK1, STAT3, p-CDK1 and p-STAT3 were performed by western blot analysis. d-e Direct suppression of purified pancreatic oncospheres by fisetin. Second generation of PANC-1 and HPC-Y5 cells from oncospheres were subjected to the tumor sphere-formation assay in ultra-low cluster plates. After the cultivation process to initial point, these tumor spheres were treated with or without fisetin (100 μM) for 48 h. Scale bars, 100 μm. Data are presented as mean ± SD (n = 3),*P < 0.05; ns, no significance. Figure S8. a HDAC3 silencing reduced levels of p-CDK1, p-STAT3, CD44 and Sox2. Western blot analysis was used to determine expression of CDK1, STAT3, CD44 and Sox2 in HDAC3 silencing PANC-1 cells. b-c Lack of HDAC3 weakened tumor sphere formatting capacity in PDAC cells. Scale bars, 100 μm. Data are presented as mean ± SD (n = 4); *P < 0.05. d HDAC3 over-expression increased levels of p-CDK1, p-STAT3, CD44 and Sox2. Western blot analysis was used to determine expression of CDK1, STAT3, CD44 and Sox2 in HDAC3 over-expression PANC-1 cells. e–f Over-expressing HDAC3 enhanced the sphere formatting capacity both in PANC-1 and HPC-Y5 cells. Scale bars, 100 μm. Data are presented as mean ± SD (n = 4); *P < 0.05, **P < 0.01. g Fisetin reduced expression of HDAC3 both in PANC-1 and HPC-Y5 cells. Figure S9. a Fraction-affected (Fa) and CI are explored after 48-h incubation with fisetin and gemcitabine combination, CI < 1 represents synergy. b Representative section of magnetic resonance imaging (MRI) for spontaneous pancreatic ductal adenocarcinoma in KPC mice. Figure S10. a Western blot analysis was used to determine expression of CDK1 in stable CDK1 knockout PANC-1 cells. CDK1-KO: CDK1-knockout. b Quantification of relative phosphorylation of CDK1 was performed by analyzing western blot results with image J software. The relative phosphorylation of CDK1 was significant reduced in PANC-1 and HPC-Y5 cells with fisetin (100 μM) treatment. Fis, fisetin; *P < 0.05; ns, no significance. c qRT-PCR showed that mRNA expression of CDK1 was not influenced by fisetin treatment in pancreatic cancer cells. Data are presented as mean ± SD (n = 3). ns, no significance. d Proteasome inhibitor MG132 restore the expression of CDK1 in PDAC cells with fisetin treatment. PANC-1 and HPC-Y5 ells were cultured with or without fisetin (100 μM) treatment for 48 h. Before the collection of cells, MG132 (10 μM) were added to culture medium for 0, 6 and 12 h. h, hours. e Immunoprecipitation and western blot determined that fisetin induced prominent ubiquitination of CDK1 in pancreatic cancer cells. IP, immunoprecipitation. Ub, ubiquitin. Figure S11. a Western blot analysis was used to determine phosphorylation of CDK1 at Thr14 and Thr161 residues in pancreatic cancer PANC-1 and HPC-Y5 cells. p-CDK1(T161): phosphorylation of CDK1 at Thr161; p-CDK1(T14): phosphorylation of CDK1 at Thr14

(A) PLS trajectory based on the mean ¹H NMR spectra of urine samples collected from animals treated with STZ (▪) at various time points (1-wk, 5-wk, 10-wk, and 15-wk), and the age-matched control rats (▴).

<p>(C) OPLS-DA scores plot based on ¹H NMR spectra of urine samples from diabetic 1-wk (▴, n = 15), 5-wk (•, n = 17), 10-wk (♦, n = 18), and 15-wk (<b>□</b>, n = 18) rats. (B) and (D) are the loading plots revealing the metabolites with large intensities responsible for the discrimination of the corresponding score plot shown in (A) and (C), respectively.</p

Additional file 4 of Post-translational modification of CDK1–STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties

Additional file 4: Table S3. Levels of transcriptome and protein phosphorylation of genes in HIF-1 signaling

PLS-DA score plots based on ¹H NMR spectra of urine samples from rats of (A) diabetic 1-wk (□, n = 15) and its control (▪, n = 13), (C) diabetic 15-wk (Δ, n = 18) and its control (▴, n = 16) rats, and (E) diabetic 1-wk, 15-wk, and their control rats, respectively.

<p>(B), (D) and (F) are the loading plots revealing the metabolites with large intensities responsible for the discrimination of the corresponding score plots (A), (C) and (E), respectively.</p

Effect of STZ treatment on various urine parameters at different time points after induction.

<p>Values are expressed as mean ± SD (n = 6 for each group). UA, uric acid; UN, urea nitrogen; CRE, creatinine.</p>*<p><i>p<</i>0.05,</p>**<p><i>p<</i>0.01 compared with the control group.</p