Notes

Systematic strategies in essential fatty acid examination for bacterial applications: the current developments.
Chronic active Epstein Barr virus (CAEBV) typically presents as persistent infectious mononucleosis-like disease and/or haemophagocytic lymphohistocytosis, reflecting ectopic EBV infection and lymphoproliferation of T and/or NK-cells. Clinical behaviour ranges from indolent, stable disease through to rapidly progressive, life-threatening disease. Whilst it is thought the chronicity and/or progression reflect an escape from immune control, very little is known about the phenotype and function of the infected cells versus co-resident non-infected population, nor about the mechanisms that could underpin their evasion of host immune surveillance. To investigate these questions, we developed a multicolour flow cytometry technique combining phenotypic and functional marker staining with in-situ hybridisation for the EBER RNAs expressed in every infected cell. This allows the identification, phenotyping and functional comparison of infected (EBERPOS) and non-infected (EBERNEG) lymphocyte subset(s) in patients' blood samples ex vivo. We have characterised CAEBV and HLH cases with monoclonal populations of discrete EBV-activated T-cell subsets, in some cases accompanied by EBV-activated NK-cell subsets, with longitudinal data on the infected cells' progression despite standard steroid-based therapy. Given that cytotoxic CD8+ T-cells with relevant EBV antigen specificity were detectable in the blood of the best studied patient, we searched for means whereby host surveillance might be impaired. This revealed a unique feature in almost every CAEBV patient studied the presence of large numbers of myeloid derived suppressor cells which exhibited robust inhibition of T-cell growth. We suggest that their influence is likely to explain the host's failure to contain EBV-positive T/NK-cell proliferation.Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) stem cell niche, which provides a vital source of HSC regulatory signals. Radiation and chemotherapy disrupt the HSC niche, including its sinusoidal vessels and perivascular cells, contributing to delayed hematopoietic recovery. Thus, identification of factors that can protect the HSC niche during an injury could offer a significant therapeutic opportunity to improve hematopoietic regeneration. In this study, we identified a critical function for vascular endothelial growth factor-C (VEGF-C), that of maintaining the integrity of the BM perivascular niche and improving BM niche recovery after irradiation-induced injury. Both global and conditional deletion of Vegfc in endothelial or leptin receptor-positive (LepR+) cells led to a disruption of the BM perivascular niche. Furthermore, deletion of Vegfc from the microenvironment delayed hematopoietic recovery after transplantation by decreasing endothelial proliferation and LepR+ cell regeneration. Exogenous administration of VEGF-C via an adenoassociated viral vector improved hematopoietic recovery after irradiation by accelerating endothelial and LepR+ cell regeneration and by increasing the expression of hematopoietic regenerative factors. Our results suggest that preservation of the integrity of the perivascular niche via VEGF-C signaling could be exploited therapeutically to enhance hematopoietic regeneration.The oncogenic transcription factor c-Maf has been proposed as an ideal therapeutic target for multiple myeloma (MM) but how to achieve it is still elusive. see more In the present study we found the Otub1/c-Maf axis could be a potential target. Otub1, an OTU family deubiquitinase, was found to interact with c-Maf by mass spectrometry. Otub1 abrogates c-Maf K48-linked polyubiquitination thus preventing its degradation and enhancing its transcriptional activity. Specifically, this deubiquitinating activity depends on its Lys71 and the N-terminus but independent UBE2O, a known E2 of c-Maf. Otub1 promotes MM cell survival and MM tumor growth. In contrast, silence of Otub1 leads to c-Maf degradation and c-Maf-expressing MM cell apoptosis. Therefore, the Otub1/c-Maf axis could be a therapeutic target of MM. In order to explore this concept, we performed a c-Maf-recognition element-driven luciferase-based screen against FDA-approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf. Consequently, LanC inhibits c-Maf transcriptional activity, induces c-Maf-expressing MM cell apoptosis, and suppresses MM growth and prolongs overall survival of model mice but without apparent toxicity. Therefore, the present study identifies Otub1 as a novel deubiquitinase of c-Maf and establishes that the Otub1/c-Maf axis is a potential therapeutic target for MM.Because of their photothermal properties, gold nanoparticles (AuNPs) have gained attention regarding their use in drug delivery and therapeutic applications. In this sense, it is interesting to consider their interactions with biologically available proteins, such as serum albumin, as well as the effects of irradiation and photothermal conversion on the protein structure that can lead to a loss of function or generate an immune response. Gold nanoprisms (AuNPrs) have gained interest due to their low toxicity, ease of synthesis, and excellent stability, promoting their use in bioapplications such as surface-enhanced Raman spectroscopy (SERS), drug delivery, and photothermal therapy. The interaction between AuNPrs, with plasmon bands centred in the near-infrared region (NIR), and bovine serum albumin (BSA) has not been explored yet. UV-Vis spectroscopy, dynamic light scattering (DLS) and fluorescence spectroscopy were used to study the interaction between AuNPrs and BSA in addition to estimation of the adsorptindary structure level, no relevant changes were observed. This provides possibilities for the use of NPs-BSA for bioapplications based on the photothermal effect promoted by laser irradiation, since the biological identity of the protein is preserved after NIR irradiation.Organic room temperature phosphorescence (RTP) liquid composites exhibit the potential to make innovative changes in large area flexible lighting applications, and it is extremely challenging to achieve high-efficiency RTP in pure organic solvent-free liquid systems. The excited state properties and inner lighting mechanisms of these composites are unclear; therefore, a theoretical perspective to design high efficiency RTP liquids with tunable lifetime is highly desired. Herein, we systematically investigate the photophysical properties of a series of long swallow-tailed bromonaphthalimide (BT unit) molecules by the newly proposed optimally tuned range-separated (RS) functional method, and a state-of-the-art RTP molecule with an absolute quantum yield (ΦRTP) of 57.1% and a lifetime (τ) of 160 ms in solvent-free liquid is obtained. Moreover, theoretical results show that the energy gap between the lowest singlet excited state (S1) and triplet excited state (T1) can be reduced and the non-radiative energy consumption process can be restricted by modulating the length and number of alkyl chains in organic RTP molecules.
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