Acid/Base-Controllable FRET and Self-Assembling Systems Fabricated by Rhodamine B Functionalized Pillar[5]arene-Based Host–Guest Recognition Motifs

A novel supramolecular Föster resonance energy transfer (FRET) system was fabricated by utilizing rhodamine B (<b>RB</b>) functionalized pillar[5]­arene (<b>EtP5-RB</b>) and cyano-modified boron dipyrromethene (<b>BDP-CN</b>) based on their host–guest recognition at 5.0 × 10^–5 M, which could be turned “on” and “off” by adding trifluoroacetic acid (TFA) and triethylamine (TEA), respectively. At a higher concentration (1.0 × 10^–4 M) in acetone, <b>EtP5-RB</b> self-assembled into vesicles while <b>EtP5-RBH</b> self-assembled into nanoribbons. After the addition of <b>BDP-CN</b>, both <b>EtP5-RB</b>⊃<b>BDP-CN</b> and <b>EtP5-RBH</b>⊃<b>BDP-CN</b> self-assembled into nanoparticles, which caused the fluorescence of the host–guest complexes to be quenched

Pneumocystis Pneumonia in Patients with Autoimmune Diseases: A Retrospective Study Focused on Clinical Characteristics and Prognostic Factors Related to Death

<div><p>Background</p><p>With the increasing use of immunosuppressive agents, the number of opportunistic infections has risen in patients with autoimmune diseases. Pneumocystis pneumonia (PCP) is one of these opportunistic infections that have a high mortality rate. However, only a few studies have described PCP in these patients, and these studies are limited in scope. We conducted this retrospective study to describe the clinical characteristics and factors associated with outcomes of PCP in patients with autoimmune diseases.</p><p>Methods</p><p>A retrospective study was performed in laboratory diagnosed PCP patients with autoimmune diseases in an academic hospital over a 10-year period. Patients with human immunodeficiency virus (HIV) infection were not included. Clinical characteristics were collected and the factors related to death were analysed.</p><p>Results</p><p>A total of 69 patients with PCP during the study period were included. Common clinical features included fever (81%), cough (56%), and dyspnea (35%). Ground glass opacity (81%) and reticulation (52%) were the most common radiological findings. Concurrent pulmonary infections including bacterium, aspergillus and cytomegalovirus were found in 34% of the patients. The overall in-hospital mortality rate was 32%. High mortality was associated with lower PaO₂/FiO₂ ratios and albumin levels. The lymphocyte count, CD4+ T cell count, previous usage of immunosuppressive agents, the duration and dose of glucocorticoids did not affect the outcome.</p><p>Conclusions</p><p>The mortality rate in PCP patients with autoimmune diseases is high. Low PaO₂/FiO₂ ratios and albumin levels are independent prognostic factors of mortality.</p></div

Demographical details, underlying diseases, and diagnostic procedures of the patients.

<p>* Vasculitis: Behcet’s disease, microscopic polyangiitis, granulomatosis with polyangiitis</p><p>** Other CTDs: Sjogren syndrome (SS), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease, scleroderma</p><p># Immunosuppressive agents: cyclophosphamide, cyclosporin A, mycophenlatemofetil, and tripterygium glycosides</p><p>& Biological agents: ritaximab, and antitumor necrosis factor α(infliximab, entanercept)</p><p>Demographical details, underlying diseases, and diagnostic procedures of the patients.</p

Univariate analyses of risk factors among PCP patients determining survival rates.

<p>* Corticosteroids doses were expressed as the prednisolone equivalent dose</p><p>Univariate analyses of risk factors among PCP patients determining survival rates.</p

Clinical manifestations, Radiologic characters and laboratory findings of the patients.

<p>* Included <i>pseudomonas aeruginosa</i> in three specimens, <i>Acinetobacter baumannii</i> in one specimen, <i>Klebsiella pneumonia</i> in one specimen</p><p>Clinical manifestations, Radiologic characters and laboratory findings of the patients.</p

Kaplan-Meier survival curve for the patients with pneumocystis pneumonia.

<p>Kaplan-Meier survival curve for the patients with pneumocystis pneumonia.</p

Supramolecular Nanomedicine Constructed from Cucurbit[8]uril-Based Amphiphilic Brush Copolymer for Cancer Therapy

An amphiphilic supramolecular brush copolymer CB[8]⊃(PEG-Np·PTPE) was constructed on the basis of a novel host–guest molecular recognition model formed by cucurbit[8]­uril (CB[8]), 4,4′-bipyridinium derivative, and PEGylated naphthol (PEG-Np). In aqueous solution, the resultant supramolecular brush copolymer self-assembled into supramolecular nanoparticles (SNPs), by which the anticancer drug doxorubicin (DOX) was encapsulated in the hydrophobic core, establishing an artful Förster resonance energy transfer system with dual fluorescence quenched. With the help of intracellular reducing agents and low pH environment, the SNPs disassembled and the loaded drug molecules were released, realizing in situ visualization of the drug release via the location and magnitude of the energy transfer-dependent fluorescence variation. The cytotoxicity evaluation indicated DOX-loaded SNPs effectively inhibited cell proliferation against HeLa cells. Animal experiments demonstrated that these DOX-loaded SNPs highly accumulated in tumor tissues through the enhanced permeability and retention effect and also had a long blood circulation time. These multifunctional supramolecular nanoparticles possessing self-imaging and controllable drug release ability exhibited great potential in cancer therapy

Presentation_1_Decreased Bilateral FDG-PET Uptake and Inter-Hemispheric Connectivity in Multi-Domain Amnestic Mild Cognitive Impairment Patients: A Preliminary Study.PDF

<p>Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern.</p><p>Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (¹⁸F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18^F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers.</p><p>Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition.</p><p>Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.</p

Highly Emissive Self-Assembled BODIPY-Platinum Supramolecular Triangles

Light-emitting supramolecular coordination complexes (SCCs) have been widely studied for applications in the chemical and biological sciences. Herein, we report the coordination-driven self-assembly of two highly emissive platinum­(II) supramolecular triangles (<b>1</b> and <b>2</b>) containing BODIPY-based bridging ligands. The metallacycles exhibit favorable anticancer activities against HeLa cells (IC₅₀ of 6.41 and 2.11 μM). The characteristic ∼570 nm fluorescence of the boron dipyrromethene (BODIPY) moieties in the metallacycles permits their intracellular visualization using confocal microscopy. Additionally, the BODIPY fluorophore is an excellent photodynamic agent, making the metallacycles as ideal therapeutics for photodynamic therapy (PDT) and chemotherapy. In vitro studies demonstrate that the combination indexes against HeLa cells are 0.56 and 0.48 for <b>1</b> and <b>2</b>, respectively, confirming their synergistic anticancer effect. More importantly, these SCCs also exhibit superior anticancer efficacy toward cisplatin-resistant A2780cis cell line by combining PDT and chemotherapy, showing promise in overcoming drug resistance. This study exploits a multicomponent approach to self-assembled metallacages that enables design of effective theranostic agents wherein the platinum acceptors are toxic chemotherapeutics and the BODIPY donors are imaging probes and photosensitizers. Since each piece may be independently tuned, i.e., Pt­(II) polypyridyl fragment swapped for Pt­(II) phosphine, the activity may be optimized without a total redesign of the system

Highly Emissive Self-Assembled BODIPY-Platinum Supramolecular Triangles

Light-emitting supramolecular coordination complexes (SCCs) have been widely studied for applications in the chemical and biological sciences. Herein, we report the coordination-driven self-assembly of two highly emissive platinum­(II) supramolecular triangles (<b>1</b> and <b>2</b>) containing BODIPY-based bridging ligands. The metallacycles exhibit favorable anticancer activities against HeLa cells (IC₅₀ of 6.41 and 2.11 μM). The characteristic ∼570 nm fluorescence of the boron dipyrromethene (BODIPY) moieties in the metallacycles permits their intracellular visualization using confocal microscopy. Additionally, the BODIPY fluorophore is an excellent photodynamic agent, making the metallacycles as ideal therapeutics for photodynamic therapy (PDT) and chemotherapy. In vitro studies demonstrate that the combination indexes against HeLa cells are 0.56 and 0.48 for <b>1</b> and <b>2</b>, respectively, confirming their synergistic anticancer effect. More importantly, these SCCs also exhibit superior anticancer efficacy toward cisplatin-resistant A2780cis cell line by combining PDT and chemotherapy, showing promise in overcoming drug resistance. This study exploits a multicomponent approach to self-assembled metallacages that enables design of effective theranostic agents wherein the platinum acceptors are toxic chemotherapeutics and the BODIPY donors are imaging probes and photosensitizers. Since each piece may be independently tuned, i.e., Pt­(II) polypyridyl fragment swapped for Pt­(II) phosphine, the activity may be optimized without a total redesign of the system