Rational design of large flat nitrogen-doped graphene oxide quantum dots with green-luminescence suitable for biomedical applications

Rational synthesis and simple methodology for the purification of large (35–45 nm in lateral size) and flat (1.0–1.5 nm of height) nitrogen-doped graphene oxide quantum dots (GOQDs) are presented. The methodology allows robust metal-free and acid-free preparation of N-GOQDs with a yield of about 100% and includes hydrothermal treatment of graphene oxide with hydrogen peroxide and ammonia. It was demonstrated that macroscopic impurities can be separated from N-GOQD suspension by their coagulation with 0.9% NaCl solution. Redispersible in water and saline solutions, particles of N-GOQDs were characterized using tip-enhanced Raman spectroscopy (TERS), photoluminescent, XPS, and UV-VIS spectroscopies. The size and morphology of N-GOQDs were studied by dynamic light scattering, AFM, SEM, and TEM. The procedure proposed allows nitrogen-doped GOQDs to be obtained, having 60–51% of carbon, 34–45% of oxygen, and up to 7.2% of nitrogen. The N-GOQD particles obtained in two hours of synthesis contain only pyrrolic defects of the graphene core. The fraction of pyridine moieties grows with the time of synthesis, while the fraction of quaternary nitrogen declines. Application of TERS allows demonstration that the N-GOQDs consist of a graphene core with an average crystallite size of 9 nm and an average distance between nearest defects smaller than 3 nm. The cytotoxicity tests reveal high viability of the monkey epithelial kidney cells Vero in the presence of N-GOQDs in a concentration below 60 mg L⁻¹. The N-GOQDs demonstrate green luminescence with an emission maximum at 505 nm and sedimentation stability in the cell culture medium.

This paper reveals the methodology for robust preparation of purified nitrogen-doped graphene oxide quantum dots with non-cytotoxic activity against monkey epithelial kidney cells (Vero ATCC® CCL-81™).     

The regulation of hemopoiesis in long-term bone marrow cultures. II. Stimulation and inhibition of stem cell proliferation

The isolation of a DNA synthesis inhibitor (NBME fraction IV) and stimulator (RBME fraction III) specific for the hemopoietic stem cell (CFU-s) from freshly isolated normal adult and regenerating murine bone marrow, respectively, has been well documented. We have utilized long- term liquid bone marrow cultures in a further analysis of the role of these factors in the regulation of CFU-s proliferation. Our results show that shortly after feeding, at a time when the cultured CFU-s are actively proliferating, high levels of the hemopoietic stem cell proliferation stimulator fraction III can be isolated from the culture medium. In contrast, the presence of essentially noncycling CFU-s found in cultures fed 8-10 days previously correlates with high levels of the hemopoietic stem cell inhibitor fraction IV. These results suggest that a certain balance between these factors determines CFU-s proliferation in the long-term cultures. In support of this, DNA synthesis in actively cycling CFU-s in the long-term cultures is inhibited for at least 3 days by the addition of excess NBME fraction IV (inhibitor). Furthermore, DNA synthesis in noncycling cultured CFU-s is stimulated for at least 5 days by the addition of RBME fraction III (stimulator).     

Graphene oxide quantum dots immobilized on mesoporous silica: preparation,characterization and electroanalytical application

Because of its high surface area and combination of various functional groups, graphene oxide (GO) is currently one of the most actively studied materials for electroanalytical applications. It is not practical to utilize self-supported GO on its own and thus it is commonly integrated with different supporting carriers. Having a large lateral size, GO can only wrap the particles of the support and thus can significantly reduce the surface area of porous materials. To achieve synergy from the high surface area and polyfunctional nature of GO, and the rigid structure of a porous support, the lateral size of GO must essentially be decreased. Recently reported graphene oxide quantum dots (GOQDs) can fulfil this task. Here we report the successful preparation of an SiO₂-GOQDs hybrid, where GOQDs have been incorporated into the mesoporous network of silica. The SiO₂-GOQDs emit a strong luminescence with a band maximum at 404 nm. The Raman spectrum of SiO₂-GOQDs shows two distinct peaks at 1585 cm⁻¹ (G-peak) and 1372 cm⁻¹ (D-peak), indicating the presence of a graphene ordered basal plane with aromatic sp²-domains and a disordered oxygen-containing structure. Covalent immobilization of GOQDs onto aminosilica via such randomly structured oxygen fragments was proven with the help of Fourier transform infrared spectroscopy, solid-state cross-polarization magic angle spinning ¹³C nuclear magnetic resonance, and X-ray photoelectron spectroscopy. SiO₂-GOQDs were used as a modifier of a carbon paste electrode for differential pulse voltammetry determination of two antibiotics (sulfamethoxazole and trimethoprim) and two endocrine disruptors (diethylstilbestrol (DES) and estriol (EST)). The modified electrodes demonstrated a significant signal enhancement for EST (370%) and DES (760%), which was explained by a π–π stacking interaction between GOQDs and the aromatic system of the analytes.

Graphene oxide quantum dots incorporated into a mesoporous silica network have been used as a modifier of a carbon paste electrode for the determination of antibiotics and hormones.     

Motion artifacts in MRI: A complex problem with many partial solutions

Subject motion during magnetic resonance imaging (MRI) has been problematic since its introduction as a clinical imaging modality. While sensitivity to particle motion or blood flow can be used to provide useful image contrast, bulk motion presents a considerable problem in the majority of clinical applications. It is one of the most frequent sources of artifacts. Over 30 years of research have produced numerous methods to mitigate or correct for motion artifacts, but no single method can be applied in all imaging situations. Instead, a “toolbox” of methods exists, where each tool is suitable for some tasks, but not for others. This article reviews the origins of motion artifacts and presents current mitigation and correction methods. In some imaging situations, the currently available motion correction tools are highly effective; in other cases, appropriate tools still need to be developed. It seems likely that this multifaceted approach will be what eventually solves the motion sensitivity problem in MRI, rather than a single solution that is effective in all situations. This review places a strong emphasis on explaining the physics behind the occurrence of such artifacts, with the aim of aiding artifact detection and mitigation in particular clinical situations. J. Magn. Reson. Imaging 2015;42:887–901.     

Chronic biopsy proven post‐COVID myoendocarditis with SARS‐Cov‐2 persistence and high level of antiheart antibodies

PurposeTo study the clinical signs and mechanisms (viral and autoimmune) of myoendocarditis in the long‐term period after COronaVIrus Disease 2019 (COVID‐19).MethodsFourteen patients (nine male, 50.1 ± 10.2 y.o.) with biopsy proven post‐COVID myocarditis were observed. The diagnosis of COVID‐19 was confirmed by IgG seroconversion. The average time of admission after COVID‐19 was 5.5 [2; 10] months. An endomyocardial biopsy (EMB) of the right ventricle was obtained. The biopsy analysis included polymerase chain reaction diagnosis of viral infection, morphological, immunohistochemical (IHC) examination with antibodies to CD3, CD45, CD68, CD20, SARS‐Cov‐2 spike, and nucleocapsid antigens. Coronary atherosclerosis was ruled out in all patients over 40 years.ResultsThe new cardiac symptoms (congestive heart failure 3–4 New York Heart Association class with severe right ventricular involvement, various rhythm, and conduction disturbances) appeared 1–5 months following COVID‐19. Magnetic resonance imaging showed disseminated or focal subepicardial and intramyocardial late gadolinium enhancement, hyperemia, edema, and increased myocardial native T1 relaxation time. Antiheart antibodies levels were increased 3–4 times in 92.9% of patients. The mean left ventricular (LV) ejection fraction (EF) was 28% (24.5; 37.8). Active lymphocytic myocarditis was diagnosed in 12 patients, eosinophilic myocarditis in two patients. SARS‐Cov‐2 RNA was detected in 12 cases (85.7%), in association with parvovirus B19 DNA—in one. Three patients had also endocarditis (infective and nonbacterial, with parietal thrombosis). As a result of steroid and chronic heart failure therapy, the EF increased to 47% (37.5; 52.5).ConclusionsCOVID‐19 can lead to long‐term severe post‐COVID myoendocarditis, that is characterized by prolonged persistence of coronavirus in cardiomyocytes, endothelium, and macrophages (up to 18 months) in combination with high immune activity. Corticosteroids and anticoagulants should be considered as a treatment option of post‐COVID myoendocarditis.     

Lactobacillus rhamnosus CNCM I-3690 and the commensal bacterium Faecalibacterium prausnitzii A2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice

Impaired gut barrier function has been reported in a wide range of diseases and syndromes and in some functional gastrointestinal disorders. In addition, there is increasing evidence that suggests the gut microbiota tightly regulates gut barrier function and recent studies demonstrate that probiotic bacteria can enhance barrier integrity. Here, we aimed to investigate the effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal barrier function. In vitro results using a Caco-2 monolayer cells stimulated with TNF-α confirmed the anti-inflammatory nature of the strain CNCM I-3690 and pointed out a putative role for the protection of the epithelial function. Next, we tested the protective effects of L. rhamnosus CNCM I-3690 in a mouse model of increased colonic permeability. Most importantly, we compared its performance to that of the well-known beneficial human commensal bacterium Faecalibacterium prauznitzii A2-165. Increased colonic permeability was normalized by both strains to a similar degree. Modulation of apical tight junction proteins expression was then analyzed to decipher the mechanism underlying this effect. We showed that CNCM I-3690 partially restored the function of the intestinal barrier and increased the levels of tight junction proteins Occludin and E-cadherin. The results indicate L. rhamnosus CNCM I-3690 is as effective as the commensal anti-inflammatory bacterium F. prausnitzii to treat functional barrier abnormalities.