Research on the Mechanism of Aggregation-Induced Emission through Supramolecular Metal–Organic Frameworks with Mechanoluminescent Properties and Application in Press-Jet Printing

This study investigates the mechanism of AIE in the solid state through supramolecular metal–organic frameworks and mechanoluminescent materials for the first time. Herein, four novel differently substituted Schiff base building blocks, <b>SB1</b>–<b>SB4</b>, exhibit typical AIE properties with various fluorescence emissions from yellow to green. <b>SB1</b>–<b>SB4</b> are linked through C–H···O hydrogen bonding interactions to construct supramolecular metal–organic frameworks (SMOFs): namely, <b>SMOFSB1</b>–<b>SMOFSB4</b>. Particularly, among these SMOFs, <b>SMOFSB3</b> is observed to have micropores in the 3D supramolecular structure and exhibits mechanoluminescent properties (grinding). An emission turn-on mechanism occurs with destruction of micropores by grinding and blockage of intramolecular rotations of the methyl and acetonitrile in the micropores, resulting in emission turn-on in <b>SMOFSB3</b>. Single-crystal X-ray structures, powder X-ray diffraction, emission spectra at room temperature, temperature-dependent emission spectra, DFT calculations, and a charge separation hypothesis well demonstrate the emission turn-on mechanism, which is consistent with the mechanism of AIE. More importantly, the molecules demonstrated potential application for press-jet printing

Quantitative Mass Spectrometry Imaging of Prostaglandins as Silver Ion Adducts with Nanospray Desorption Electrospray Ionization

Prostaglandins (PG) are an important class of lipid biomolecules that are essential in many biological processes, including inflammation and successful pregnancy. Despite a high bioactivity, physiological concentrations are typically low, which makes direct mass spectrometric analysis of endogenous PG species challenging. Consequently, there have not been any studies investigating PG localization to specific morphological regions in tissue sections using mass spectrometry imaging (MSI) techniques. Herein, we show that silver ions, added to the solvent used for nanospray desorption electrospray ionization (nano-DESI) MSI, enhances the ionization of PGs and enables nano-DESI MSI of several species in uterine tissue from day 4 pregnant mice. It was found that detection of [PG + Ag]⁺ ions increased the sensitivity by ∼30 times, when compared to [PG – H]⁻ ions. Further, the addition of isotopically labeled internal standards enabled generation of quantitative ion images for the detected PG species. Increased sensitivity and quantitative MSI enabled the first proof-of-principle results detailing PG localization in mouse uterus tissue sections. These results show that PG species primarily localized to cellular regions of the luminal epithelium and glandular epithelium in uterine tissue. Further, this study provides a unique scaffold for future studies investigating the PG distribution within biological tissue samples

Effects of miltefosine on glucose metabolism in HFD mice.

<p>Mice were fed with a HFD or CD for 16 weeks. Miltefosine (2.5 or 5 mg/kg/d) was intraperitoneally administrated for additional 4 weeks plus HFD treatment (B-D). Body weights of the mice (A) were calculated every week. After sacrifice, liver tissues were removed to measure the weight (B). Blood levels of glucose (C) and insulin (D) were measured in fasted CD mice and HFD mice. (E-F) Glucose tolerance tests were performed by pretreatment with miltefosine or vehicle 2 hours before challenged with an administration of glucose (1g/kg) in mice (E). mRNA expression of IRS2 in the liver was measured by RT-PCR (F). n = 8. Data are expressed as the mean ± SEM. † P < 0.05, †† P < 0.01, HFD vs HFD MT 2.5 mg/kg/d; <b>#</b> P < 0.05, <b>##</b> P < 0.01, HFD vs HFD MT 5 mg/kg/d; * P < 0.05, **P < 0.01, ***P < 0.001.</p

Effects of miltefosine administration on lipid accumulation and morphology of the liver in mice.

<p>(A-B) Serum triglycerides (A) and cholesterol levels (B) were measured in fasted mice. n = 8. (C-D) Liver triglycerides (C) and cholesterol (D) levels. n = 8. (E-F) Representative hematoxylin-eosin (HE) staining (E) and oil red staining (F) of the mouse liver. (G-H) Effects of compound C on intracellular triglycerides (G) and cholesterol (H) levels. n = 5. Data are expressed as the mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001.</p

Effects of compound C on lipid metabolism and AMPK signal pathway in the mouse liver.

<p>(A-D) Levels of triglycerides (A, C) and cholesterol (B, D) in the mouse serum and liver were determined. n = 7. (E-F) Liver lipid accumulation was assessed by HE staining (E) and oil red staining (F). (G) Representative western blots of AMPK signal pathway in the mouse liver. n = 5. (H-J) RT-PCR measurements for mRNA levels of CPT1A (H), SREBP1C (I), FAS (J) and GAPDH (K) in the liver. n = 7. Data are expressed as the mean ± SEM. * P < 0.05, ** P < 0.01.</p

Effects of miltefosine on inflammation and NF-κb signaling in cultured cells.

<p>(A-D) Cultured mouse peritoneal macrophages were stimulated with LPS (100 ng/ml) and co-supplemented with indicated concentration of miltefosine. mRNA levels of IL-1 (A), IL-6 (B), INOS (C), and CD86 (D) in cells were measured by RT-PCR. n = 5. (E) Western blot of NF-κb signaling. n = 5. (F-I) Cultured primary hepatocytes were co-cultured with macrophages stimulated by LPS (100 ng/ml) and co-supplemented with the indicated concentration of miltefosine. mRNA levels of CPT1A (F), IRS2 (G), SREBP1C (H), and FAS (I) in cells were measured by RT-PCR after stimulation. n = 5. Data are expressed as the mean ± SEM. * P < 0.05, ** P < 0.01.</p

Miltefosine decreases macrophage infiltration and attenuates HFD-induced inflammation in the mouse liver tissue.

<p>(A-D) RT-PCR measurements for mRNA levels of CD68 (A), EMR1 (B), IL-1 (C), and IL-6 (D). n = 10. (E and F) Levels of CRP in mouse serum (E) and liver (F) were determined. n = 8. Data are expressed as the mean ± SEM. * P < 0.05.</p

Effects of miltefosine on fatty acid metabolism-related signal molecules in mouse liver.

<p>(A) Western blot analysis of AMPK signal pathway in mouse liver lysates. n = 5. (B-E) Measurements of mRNA levels of AMPK signal pathway in the mouse liver by RT-PCR. n = 10. Data are expressed as the mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001.</p

Effect of miltefosine on AMPK signal pathway in cultured primary mouse hepatocytes.

<p>Primary hepatocytes were cultured in serum-free medium overnight and treated with miltefosine for the indicated times. (A) Representative western blots of AMPKα, ACC, IRS2, and SREBP1C. (B) Effect of miltefosine on CPT1A and LKB1 expression. Cells were treated with miltefosine for 24 hours and cell lysates were quantified by western blot. (C) Nuclear and cytosolic levels of LKB1 were determined by western blot. (D) High glucose on AMPK activity in liver cells. (E) High glucose on AMPK signal pathway in liver cells. (F) High glucose on expression levels of CPT1A and LKB1 in liver cells. Data are expressed as the mean ± SEM. n = 5. * P < 0.05, *** P < 0.001.</p