Table_1_Comparison of physiological uptake of normal tissues in patients with cancer using 18F-FAPI-04 and 18F-FAPI-42 PET/CT.xlsx

PurposeTo calculate the physiological uptake of various tissues in patients with cancer using 18F-AlF-NOTA-FAPI-04 (18F-FAPI-04) and 18F-AlF-NOTA-FAPI-42 (18F-FAPI-42) PET/CT and to compare the variation in standard uptake values between the two scans.Materials and methodsThis retrospective analysis included 40 patients with cancer who underwent 18F-FAPI; the first 20 patients received 18F-FAPI-04 PET/CT and the remaining 20 patients received 18F-FAPI-42 PET/CT. A total of 49 normal tissues, including the brain (cerebrum/cerebellum), parotid and submandibular glands, palatine tonsils, and thyroid, were identified on CT images. For these normal tissues, maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were calculated. We also compared the SUVmean of identical tissues to explore the difference in biodistribution between the two radiotracers.ResultsThe accumulation of 18F-FAPI-04 and 18F-FAPI-42 showed an analogous pattern. High uptake of both radiotracers in the gallbladder, uterus, submandibular gland, and renal pelvis was demonstrated (range: SUVmax, 4.01–5.75; SUVmean, 2.92–4.22). Furthermore, the uptake of bony tissues was slightly higher in 18F-FAPI-42 than in 18F-FAPI-04 (range: SUVmean, 0.4 ± 0.22–0.9 ± 0.34 and 0.3 ± 0.24–0.7 ± 0.18, respectively, p 18F-FAPI-04 than in 18F-FAPI-42 (range: SUVmean, 0.9 ± 0.24–1.5 ± 0.35 and 0.9 ± 0.26–1.2 ± 0.37, respectively, p ConclusionsBoth radioligands exhibited similar physiological uptake of normal tissues in patients with cancers. In addition, 18F-FAPI-42 demonstrated higher uptake of bone tissues than 18F-FAPI-04 while showing lower uptake of soft tissues than 18F-FAPI-04.</p

Effects of Zinc Supplementation on the Incidence of Mortality in Preschool Children: A Meta-Analysis of Randomized Controlled Trials

<div><p>Background</p><p>Previous trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality.</p> <p>Methodology and Principal Findings</p><p>We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56–1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53–1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11–2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77–1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67–1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.</p> <p>Conclusions/Significance</p><p>Zinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.</p> </div

Molecular Insights on the Cyclic Peptide Nanotube-Mediated Transportation of Antitumor Drug 5-Fluorouracil

Self-assembled cyclic peptide nanotubes (CPNs) show a potential use in drug delivery. In this study, the CPN composed of (Trp-d-Leu)₄-Gln-d-Leu was synthesized and tested for the transport of the antitumor drug 5-fluorouracil (5-FU). CPN-mediated release of 5-FU from liposomes experimentally tested the transportation function of the synthetic CPNs. To explore the transportation mechanism of CPNs, computational studies have been performed on the CPN models stacked by 8 subuints, including conventional molecular dynamics (CMD) simulations, and steered molecular dynamics (SMD) simulations in the environment of hydrated dimyristoylphosphatidylcholine (DMPC) lipid bilayer. Our CMD simulations demonstrated that the <i>ortho</i>-CPN is the most stable nanotube, in which the Gln residue is in the <i>ortho</i>-position relative to other residues. The calculated diffusion coefficient value for inner water molecules was 1.068 × 10⁻⁵ cm²·s⁻¹, almost half that of the bulky water and 24 times faster than that of the typical gramicidin A channel. The CPN conserved its hollow structure along the 10 ns CMD simulations, with a tile angle of 50° relative to the normal of DMPC membrane. Results from SMD simulations showed that the 5-FU molecule was transported by hopping through different potential energy minima distributed along subunits, and finally exited the nanotube by escaping from the kink region at the last two subunits. The hopping of 5-FU was driven by switching from hydrophobic interactions between 5-FU and the interior wall of the nanotube to hydrogen bonding interactions of 5-FU with the backbone carbonyl group and amide group of <i>ortho</i>-CPN. The calculated binding free energy profile of 5-FU interacting with the CPN indicated that there was an energy well near the outer end of the nanotube

Flow diagram of the literature search and trials selection process.

<p>Flow diagram of the literature search and trials selection process.</p

Effect of zinc supplementation on the risk of total mortality.

<p>Effect of zinc supplementation on the risk of total mortality.</p

Subgroup analysis for total mortality.

<p>Subgroup analysis for total mortality.</p

Image_1_Comparison of physiological uptake of normal tissues in patients with cancer using 18F-FAPI-04 and 18F-FAPI-42 PET/CT.tif

PurposeTo calculate the physiological uptake of various tissues in patients with cancer using 18F-AlF-NOTA-FAPI-04 (18F-FAPI-04) and 18F-AlF-NOTA-FAPI-42 (18F-FAPI-42) PET/CT and to compare the variation in standard uptake values between the two scans.Materials and methodsThis retrospective analysis included 40 patients with cancer who underwent 18F-FAPI; the first 20 patients received 18F-FAPI-04 PET/CT and the remaining 20 patients received 18F-FAPI-42 PET/CT. A total of 49 normal tissues, including the brain (cerebrum/cerebellum), parotid and submandibular glands, palatine tonsils, and thyroid, were identified on CT images. For these normal tissues, maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were calculated. We also compared the SUVmean of identical tissues to explore the difference in biodistribution between the two radiotracers.ResultsThe accumulation of 18F-FAPI-04 and 18F-FAPI-42 showed an analogous pattern. High uptake of both radiotracers in the gallbladder, uterus, submandibular gland, and renal pelvis was demonstrated (range: SUVmax, 4.01–5.75; SUVmean, 2.92–4.22). Furthermore, the uptake of bony tissues was slightly higher in 18F-FAPI-42 than in 18F-FAPI-04 (range: SUVmean, 0.4 ± 0.22–0.9 ± 0.34 and 0.3 ± 0.24–0.7 ± 0.18, respectively, p 18F-FAPI-04 than in 18F-FAPI-42 (range: SUVmean, 0.9 ± 0.24–1.5 ± 0.35 and 0.9 ± 0.26–1.2 ± 0.37, respectively, p ConclusionsBoth radioligands exhibited similar physiological uptake of normal tissues in patients with cancers. In addition, 18F-FAPI-42 demonstrated higher uptake of bone tissues than 18F-FAPI-04 while showing lower uptake of soft tissues than 18F-FAPI-04.</p

Summary of the relative risks of all outcomes assessed.

<p>Summary of the relative risks of all outcomes assessed.</p

Higher-Affinity Agonists of 5‑HT_1AR Discovered through Tuning the Binding-Site Flexibility

Discovery of high-affinity and high-selectivity agonists of 5-HT_1AR has become very attractive due to their potential therapeutic effects on multiple 5-HT_1AR-related psychological and neurological problems. On the basis of our previously designed lead compound <b>FW01</b> (<i>K</i>_i = 51.9 nM, denoted as <b>9a</b> in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT_1AR-<b>9a</b> binding. We found the flip-packing events for the headgroup of <b>9a</b>, and we also found that its tail group could bind flexibly at the agonist-binding site of 5-HT_1AR. By finely tuning the flip-packing phenomenon of the <b>9a</b> headgroup and tuning the binding flexibility of <b>9a</b> tail group, we virtually designed a series of new <b>9a</b> derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed <b>9a</b> derivatives should be higher-affinity agonists of 5-HT_1AR. The computational predictions on the new <b>9a</b> derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT_1AR, with ∼50-fold increase in receptor-binding affinity and ∼25-fold improvements in agonistic function. In addition, our newly designed 5-HT_1AR agonists showed very high selectivity of 5-HT_1AR over subtype 5-HT_2AR and also over three subtypes of dopamine receptors (D₁, D₂, and D₃)

Copper(I)-Catalyzed Synthesis of 2,5-Disubstituted Furans and Thiophenes from Haloalkynes or 1,3-Diynes

A regioselective synthesis of 2,5-disubstituted furans using copper­(I) catalyst from haloalkynes in a one-pot procedure has been reported. This chemistry proceeds through the hydration reaction of 1,3-diynes, which can be readily prepared from the coupling reaction of haloalkynes in the presence of CuI. The procedure also can be used for the facile synthesis of 2,5-disubstituted thiophenes