Dihydroxanthene-based monoamine oxidase A-activated photosensitizers for photodynamic/photothermal therapy of tumors.

Small molecule photosensitizers for combined in vivo tailored cancer diagnostics and photodynamic/photothermal therapy are desperately needed. Monoamine oxidase A (MAO-A)-activated therapeutic and diagnostic compounds provide great selectivity because MAO-A can be employed as a biomarker for associated Tumors. In order to screen photosensitizers with photodynamic therapeutic potential, we have created a range of near-infrared fluorescent molecules in this work by combining dihydroxanthene parent with various heterocyclic fluorescent dyes. The NIR fluorescent diagnostic probe, DHMQ, was created by combining the screened fluorescent dye matrices with the propylamino group, which is the recognition moiety of MAO-A, based on the oxidative deamination mechanism of the enzyme. This probe has a low toxicity level and can identify MAO-A precisely. It has the ability to use fluorescence imaging on mice and cells to track MAO-A activity in real-time. It has strong phototoxicity and can produce singlet oxygen when exposed to laser light. The temperature used in photothermal imaging can get up to 50 °C, which can harm tumor cells permanently and have a positive phototherapeutic impact on tumors grown from SH-SY5Y xenograft mice. The concept of using MAO-A effectively in diseases is expanded by the MAO-A-activated diagnostic-integrated photosensitizers, which offer a new platform for in vivo cancer diagnostics and targeted anticancer treatment.

Monoamine oxidase B activatable red fluorescence probe for bioimaging in cells and zebrafish.

A real-time and specific for the detection of Monoamine Oxidase B (MAO-B) to investigate the MAO-B-relevant disease development and treatment process is urgently desirable. Here, we utilized MAO-B to catalyze the conversion of propylamino groups to aldehyde groups, which was then quickly followed by a ß-elimination process to produce fluorescent probes (FNJP) that may be used to detect MAO-B in vitro and in vivo. The FNJP probe possesses unique properties, including favorable reactivity (Km = 10.8 µM), high cell permeability, and NIR characteristics (λem = 610 nm). Moreover, the FNJP probe showed high selectivity for MAO-B and was able to detect endogenous MAO-B levels from a mixed population of NIH-3 T3 and HepG2 cells. MAO-B expression was found to be increased in cells under lipopolysaccharide-stimulated cellular oxidative stress in neuronal-like SH-SY5Y cells. In addition, the visualization of FNJP for MAO-B activity in zebrafish can be an effective tool for exploring the biofunctions of MAO-B. Considering these excellent properties, the FNJP probe may be a powerful tool for detecting MAO-B levels in living organisms and can be used for accurate clinical diagnoses of related diseases.

A versatile cellulose nanocrystal­carbon dots architecture: Preparation and environmental/biological applications.

In this work, a versatile cellulose nanocrystal­carbon dots (CNC-CDs) architecture is prepared and applied in environmental remediation and biological sensing. The citric acid (CA) is employed to extract CNCs and in-situ synthesize blue-emissive CDs. The carboxyl-rich surface of CNC-CDs enables the chelation of Hg2+ and fluorescence quenching of CDs, realizing the detection and adsorption of Hg2+ with a film comprised of the architecture. The limit of detection (LOD) is measured as 12.8 nM with satisfying retention efficiency. The versatility of CNC-CDs is demonstrated by the fabrication of a fluorescence resonance energy transfer (FRET) sensor using m-tetrakis(4-sulfonatophenyl)porphine (TSPP) as FRET acceptor and Fe3+ receptor. Fluorescence of the sensor is responsive to Fe3+ in a ratiometric manner, which significantly contributes to the visualized and sensitive Fe3+ detection (6.9 nM). In combination with excellent biocompatibility, the FRET sensor is capable of imaging intracellular Fe3+.

A FRET sensor based on quantum dots-porphyrin assembly for Fe(III) detection with ultra-sensitivity and accuracy.

Exploring sensors based on Förster resonance energy transfer (FRET) systems enables the continuous development of biological sensing technologies. Herein, we report the construction of a FRET sensor with dual-emissive quantum dots (QDs) and meso-tetra(4-sulfonatophenyl) porphine (TSPP). The sensor is composed of mesial green-emissive QDs with a thick silica shell (gQD@SiO2) and circumjacent blue-emissive QDs coated with ultra-thin silica spacer, on which is linked TSPP (bQD@SiO2-TSPP). The gQD@SiO2 endows the sensor with a fluorescent background. Due to the ultra-thin silica spacing, coupled with the superior resonance effect of bQD fluorescence and the Soret-band absorption of TSPP, the FRET efficiency is highly sensitive to the chelation state of TSPP. Relying on the absorbance transition of TSPP complexed with Fe(III), the FRET sensor is applied for ultra-sensitive Fe(III) detection. In aqueous solution, the sensor is demonstrated to linearly detect Fe(III) in the range of 0-1 µM, with a limit of detection (LOD) of 40 nM. More importantly, reliable Fe(III) detection can be achieved via the specific complexation of Fe(III) by TSPP and the ratiometric fluorescent response. As such, the inter-/intra-day precisions in standard samples, as well as the recovery rate in biological matrices, are fully validated. The excellent analytical performance, in combination with the excellent biocompatibility of the FRET sensor, allows semi-quantitative Fe(III) imaging in living cells.

Outbreak of Mycoplasma pneumoniae at a military academy.

In 2019, an outbreak of Mycoplasma pneumoniae occurred at a military academy in China. The attack rate (10.08%,60/595) was significantly different among the units. High-intensity training and crowded environments to which cadets are exposed are the high risk factors for the outbreak of M. pneumoniae. In-time prevention and control measures effectively controlled the spread of the epidemic.

Folic Acid Supplementation Suppresses Sleep Deprivation-Induced Telomere Dysfunction and Senescence-Associated Secretory Phenotype (SASP).

Sleep deprivation is reported to cause oxidative stress and is hypothesized to induce subsequent aging-related diseases including chronic inflammation, Alzheimer's disease, and cardiovascular disease. However, how sleep deprivation contributes to the pathogenesis of sleep deficiency disorder remains incompletely defined. Accordingly, more effective treatment methods for sleep deficiency disorder are needed. Thus, to better understand the detailed mechanism of sleep deficiency disorder, a sleep deprivation mouse model was established by the multiple platform method in our study. The accumulation of free radicals and senescence-associated secretory phenotype (SASP) was observed in the sleep-deprived mice. Moreover, our mouse and human population-based study both demonstrated that telomere shortening and the formation of telomere-specific DNA damage are dramatically increased in individuals suffering from sleeplessness. To our surprise, the secretion of senescence-associated cytokines and telomere damage are greatly improved by folic acid supplementation in mice. Individuals with high serum baseline folic acid levels have increased resistance to telomere shortening, which is induced by insomnia. Thus, we conclude that folic acid supplementation could be used to effectively counteract sleep deprivation-induced telomere dysfunction and the associated aging phenotype, which may potentially improve the prognosis of sleeplessness disorder patients.

Pharmacologic Effect of Miao Medicine Illicium simonsii Maxim. on Collagen-Induced Arthritis in Rats.

OBJECTIVES: To study the pharmacologic effect and mechanism of action of Miao medicine Illicium simonsii Maxim. (ISM) in treating rheumatoid arthritis. METHODS: Sixty rats were randomly divided to six groups: normal control (normal), collagen-induced arthritis (CIA) model (model), CIA + tripterygium glycosides (TG), CIA + ISM high dose oral (ISM-H), CIA + ISM low-dose oral (ISM-L), and CIA + ISM topical application (ISM-T). The treatment doses were selected based on published reports and folk medicine practice. The outcome measurements included paw swelling, joint pathology, organ index, blood count, T helper 17 (Th17) cell count, and interleukin-6 (IL-6) level. RESULTS: Compared to the CIA model group, all treatment groups showed a significant reduction in paw swelling, blood vessel pathology, Th17 cell count, and IL-6 levels (p < 0.05 or p < 0.01). All treatment groups showed alleviated foot swelling and lower total number of white blood cells, and these effects were observed earlier with oral ISM than topical ISM. The effect of ISM was weaker than that of TG. In addition, less organ damage was observed with topical ISM than oral ISM but better than TG. CONCLUSIONS: These results suggest that, by downregulating Th17 cells, ISM inhibits the production of Il-6, thereby alleviating the proliferation of endothelial and rheumatoid-like cells and leukocytosis in CIA rats, ultimately eliminating foot swelling.

A quantum dot-labelled aptamer/graphene oxide system for the construction of a half-adder and half-subtractor with high resettability.

By a combination of quantum dot-labelled aptamers and graphene oxide, a hybrid molecular system was developed for the integration of multiple logic gates to implement half adder and half subtractor functions. On the merits of quantum dots, repetitious arithmetic operations and a reliable fluorescent switch were demonstrated.

Hybridization chain reactions on silica coated Qbeads for the colorimetric detection of multiplex microRNAs.

A robust Qbead platform that integrated with target-binding, hybridization chain reaction and staining was developed for the direct multiplexed detection of endogenous miRNAs by amplified Qbead-colour change.

Multicolor bioimaging with biosynthetic zinc nanoparticles and their application in tumor detection.

Because they generate excellent images, nanoparticles (NPs), especially biosynthesized NPs, provide a new solution for tumor imaging. In this research, we unveil a novel type of biosynthesized NPs featuring multicolor fluorescence. These NPs exhibit little cytotoxicity to cells. The explored NPs, designated Zn-ZFP-GST NPs (Zinc NPs in abbreviation), are generated from leukemia cells treated with a Zn2+ solution, while zinc-finger protein and glutathione S-transferase (GST) were also identified in the Zinc NPs. Under near-UV illumination, the Zinc NPs simultaneously emit green, yellow, and red fluorescence. In addition, the intensity of the fluorescence increases with the existence of sulfides. Besides, the NPs are encapsulated by microvesicles (MVs) shed from the plasma membrane. As observed in whole-body research of nude mice, the NP-MVs migrate via blood circulation and are distinguished by their fluorescent signals. Furthermore, the folic acid (FA) &AVR2 (human VEGF antibody)-coated NP-MVs are exploited to target the tumor location, and the feasibility of this approach has been confirmed empirically. The Zinc NPs shed light on an alternative solution to tumor detection.

Targeted imaging and induction of apoptosis of drug-resistant hepatoma cells by miR-122-loaded graphene-InP nanocompounds.

BACKGROUND: Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. RESULTS: In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. CONCLUSION: In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.

Apoptosis Induction and Imaging of Cadmium-Telluride Quantum Dots with Wogonin in Multidrug-Resistant Leukemia K562/A02 Cell.

Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids isolated from Scutellariae radix and possesses antitumor effect against leukemia. Cadmium-telluride quantum dots (CdTe-QDs) are a kind of nanoparticles with great potential in functioning as an efficient drug delivery vector in biomedical research. In this study, we investigated the synergistic effect of CdTe-QDs with Wogonin on the induction of apoptosis using drug-resistant human leukemia KA cells. Flow cytometry analysis, assay of morphology under electron microscope, quantitative analysis of tumor volume and micro-CT imaging demonstrated that compared with that by pure CdTe-QDs or wogonin, the apoptosis rate increased sharply when treated wirh CdTe-QDs together with wogonin on KA cells. These results proved that the nanocomposites readily overcame the barrier of drug-resistance and provoked cell apoptosis in vitro and in vivo by facilitating the interaction between wogonin and KA cells. As known to all, it is an inevitable tendency that new effective therapies will take the place of conventional chemotherapy and radiotherapy presenting significant disadvantages. According to this article, CdTe-QD combined with wogonin is a possible alternative for some cancer treatments.

Ratiometric Quantum Dot-Ligand System Made by Phase Transfer for Visual Detection of Double-Stranded DNA and Single-Nucleotide Polymorphism.

We have developed a proof-of-concept quantum dot-ligand (QD-L) system for visual selective detection of nucleic acids, in combination with a ratiometric fluorescence technique. This system comprises a dual-emission QDs nanohybrid formed by embedding a red-emission QD (rQD) in a silica nanoparticle and electrostatically assembling green-emission QDs (gQDs) onto the silica surface, as the signal displaying unit, and a hydrophobic compound, dipyrido[3,2-a:2',3'-c]phenazine (dppz), attached onto the gQDs surface via phase transfer, as the ligand as well as fluorescence quencher of gQDs. This system is successfully used for quantification of double-stranded DNA (dsDNA). Because of its avid binding with dppz, dsDNA can break up the QD-L system, displacing the dppz ligand from the gQDs surface and restoring the gQDs emission. Since the red emission of embedded rQDs stays constant, variations of the dual-emission intensity ratios display continuous color changes from orange to bright green, which can be clearly observed by the naked eye. More importantly, this system is advantageous in terms of specificity over a QD ionic conjugate, because the electrical neutrality of dppz excludes its nonspecific electrostatic association with dsDNA. The QD-L system also is capable of detecting single-nucleotide polymorphism, exhibiting sequence-specific ratiometric fluorescence as a QD-bioconjugate does, but possessing the obvious advantage in terms of low cost, with the avoidance of modification, labeling, and purification processes. Therefore, the QD-L system provides an extremely simple but general strategy for detecting nucleic acids in a facile, sensitive, and specific manner.

Ligand displacement-induced fluorescence switch of quantum dots for ultrasensitive detection of cadmium ions.

This paper reports the construction of a simple CdTe quantum dots (QDs)-based sensor with 1,10-phenanthroline (Phen) as ligand, and the demonstration of a novel ligand displacement-induced fluorescence switch strategy for sensitive and selective detection of Cd(2+) in aqueous phase. The complexation of Phen at the surface quenches the green photoluminescence (PL) of QDs dominated by a photoinduced hole transfer (PHT) mechanism. In the presence of Cd(2+), the Phen ligands are readily detached from the surface of CdTe QDs, forming [Cd(Phen)2(H2O)2](2+) in solution, and as a consequence the PL of CdTe QDs switches on. The detection limit for Cd(2+) is defined as ∼0.01 nM, which is far below the maximum Cd(2+) residue limit of drinking water allowed by the U.S. Environmental Protection Agency (EPA). Two consecutive linear ranges allow a wide determination of Cd(2+) from 0.02 nM to 0.6 µM. Importantly, this CdTe QDs-based sensor features to distinctly discriminate between Cd(2+) and Zn(2+), and succeeds in real water samples. This extremely simple strategy reported here represents an attempt for the development of fluorescent sensors for ultrasensitive chemo/biodetection.

Fluorescent recognition of deoxyribonucleic acids by a quantum dot/meso-tetrakis(N-methylpyridinium-4-yl)porphyrin complex based on a photo induced electron-transfer mechanism.

We have developed a new fluorescent probe of thioglycolic acid (TGA)-capped CdTe quantum dots (QDs) complexed with a model drug, meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP) for detecting deoxyribonucleic acids (DNAs). This probe operates with an "Off-On" mode: TMPyP quenches the photoluminescence (PL) of QDs via a photo induced electron-transfer (PIET) process; the presence of DNA can break the QD/TMPyP complexation, interrupting the PIET process, and switch on the PL of QDs. Sensitive detection of DNA with the detection limit of 0.16 nM and a linear detection range of 0.25-6.0 nM are achieved. Importantly, this probe can be used to distinguish the binding modes of DNA-TMPyP interactions, exhibiting the DNA sequence-dependent PL recovery behaviors. The obtained binding constant for poly(dA)·poly(dT) is ∼3.30×10(7) L mol(-1), which is approximately one order of magnitude larger than those for native DNAs and poly(dG)·poly(dC). Furthermore, the thymine bases preferential of the TMPyP-DNA interaction is proved by this probe.

Quantum dot-phenanthroline dyads: detection of double-stranded DNA using a photoinduced hole transfer mechanism.

We have developed a new fluorescent probe based on direct conjugation between 1,10-phenanthroline (Phen) and water-soluble thioglycolic acid (TGA) capped CdTe quantum dots (QDs) for the detection of double-stranded DNA (dsDNA). Phen could directly adsorb onto the QDs surface by metal-affinity driven coordination, quenching the photoluminescence (PL) of QDs via the photoinduced hole transfer process; addition of dsDNA would bring the restoration of QDs PL, as Phen could intercalate into dsDNA followed by its dissociation from the QDs surface. The dependence of QDs PL on the dsDNA amount as well as temperature was utilized to investigate the Phen-dsDNA interaction. The obtained binding constant of the QD-Phen dyad was 2-3 orders of magnitude higher than that of Phen-based metal complexes. Both the binding constant and the binding site of dsDNA with Phen increased with the elevated temperature, owing to an endothermic process. At 37 °C, sensitive detection of dsDNA with a detection limit of ~3 nmol L(-1) was achieved. Therefore, the QD-molecule direct conjugation based fluorescent probe could provide an effective alternative to those based on QD-bioconjugation and QD-ionic conjugation.