Reduction Depth Dependent Structural Reversibility of Sn₃(PO₄)₂

Conversion reaction is an important method for lithium storage. Tin-based compounds have been regarded as promising anode materials for lithium ion batteries due to their high specific capacities. Herein, we report the structural reversibility of Sn₃(PO₄)₂ after conversion and Li–Sn alloying reactions. It is found that the reversibility of Sn₃(PO₄)₂ is highly dependent on the cutoff discharge potential. The conversion reaction of Sn₃(PO₄)₂ is partially reversible when it is discharged to 1.55 and then recharged to 3.00 V but is not between 0.00 and 3.00 V

Multicenter Intestinal Current Measurements in Rectal Biopsies from CF and Non-CF Subjects to Monitor CFTR Function

<div><p>Intestinal current measurements (ICM) from rectal biopsies are a sensitive means to detect cystic fibrosis transmembrane conductance regulator (CFTR) function, but have not been optimized for multicenter use. We piloted multicenter standard operating procedures (SOPs) to detect CFTR activity by ICM and examined key questions for use in clinical trials. SOPs for ICM using human rectal biopsies were developed across three centers and used to characterize ion transport from non-CF and CF subjects (two severe CFTR mutations). All data were centrally evaluated by a blinded interpreter. SOPs were then used across four centers to examine the effect of cold storage on CFTR currents and compare CFTR currents in biopsies from one subject studied simultaneously either at two sites (24 hours post-biopsy) or when biopsies were obtained by either forceps or suction. Rectal biopsies from 44 non-CF and 17 CF subjects were analyzed. Mean differences (µA/cm²; 95% confidence intervals) between CF and non-CF were forskolin/IBMX=102.6(128.0 to 81.1), carbachol=96.3(118.7 to 73.9), forskolin/IBMX+carbachol=200.9(243.1 to 158.6), and bumetanide=-44.6 (-33.7 to -55.6) (<i>P</i><0.005, CF vs non-CF for all parameters). Receiver Operating Characteristic curves indicated that each parameter discriminated CF from non-CF subjects (area under the curve of 0.94-0.98). CFTR dependent currents following 18-24 hours of cold storage for forskolin/IBMX, carbachol, and forskolin/IBMX+carbachol stimulation (n=17 non-CF subjects) were 44%, 47.5%, and 47.3%, respectively of those in fresh biopsies. CFTR-dependent currents from biopsies studied after cold storage at two sites simultaneously demonstrated moderate correlation (n=14 non-CF subjects, Pearson correlation coefficients 0.389, 0.484, and 0.533). Similar CFTR dependent currents were detected from fresh biopsies obtained by either forceps or suction (within-subject comparisons, n=22 biopsies from three non-CF subjects). Multicenter ICM is a feasible CFTR outcome measure that discriminates CF from non-CF ion transport, offers unique advantages over other CFTR bioassays, and warrants further development as a potential CFTR biomarker.</p> </div

ROC curve analysis.

<p>Note that CF participants are coded as one, and non-CF participants are coded as zero. Average true-positive rate is the sensitivity of the current to detect CF participants, whereas the average-false positive rate (one-specificity) marks the cutoff whereby non-CF participants are falsely determined as CF. AUC values varied from 0.946-0.978 for the three CFTR-specific measurements (forskolin/IBMX (cAMP), carbachol (CCh), cAMP + CCh).</p

Bland-Altman plots of ICM responses for biopsies from single subjects studied at two sites simultaneously after cold storage.

<p>Difference between <b>A</b>. forskolin/IBMX (cAMP), <b>B</b>. carbachol, or <b>C</b>. forskolin/IBMX (cAMP + carbachol) responses at site of biopsy origin and test site. Each dot is the mean ICM response for one subject (both sites). The X axis is the mean of the response (both sites), and the Y axis is the difference between the means at the two sites. The red line is the hypothetical zero difference, and the green line is the actual mean difference. Blue lines are ± 2 SDs.</p

Partial CFTR function detected in F508del/F508del CF subject.

<p>Representative tracing from an F508del/F508del subject with functional F508del CFTR. Adding forskolin/IBMX to raise cAMP increased the current > 30µA/cm² which was further augmented by carbachol.</p

Individual ICM responses across study sites.

<p>Boxplots of CFTR responses in non-CF subjects segregated by site (site identifiers S032, S076, S191). Whiskers are minimum and maximum values, boxes included data within 25^th-75^th percentiles, the horizontal line is the median, and the diamond is the mean. <b>A</b>. Change in I_sc following cAMP stimulation (10 µM forskolin/100 µM IBMX). <b>B</b>. Change in I_sc following carbachol (CCh) stimulation (100 µM, basolateral). <b>C</b>. Change in I_sc following cAMP + CCh stimulation (10 µM forskolin, 100 µM IBMX, 100 µM CCh).</p