Notes

Brand-new titanocene offshoot using increased stability along with binding power to albumin displays large anticancer activity.
The worldwide COVID-19 vaccination program is already underway, raising hopes and aspirations to contain the spread of the COVID-19 pandemic that halted economic and social activities. However, the issue of vaccine effectiveness and its side-effects is influencing the potential acceptance of vaccines. In this uncertain situation, we used data from a nationwide survey in Japan during February 2021, following the Japanese government's initial phase of COVID-19 vaccination. Our results show that 47% of the respondents are willing to take a vaccine once it is available, while 22% are not willing and another 31% remain indecisive. Our ordered probit regression results show that demographic, socioeconomic, and behavioral variables such as gender, age, subjective health status, children, household income, household assets, financial literacy, future anxiety, and myopic view of the future are associated with willingness to take a COVID-19 vaccine. Our findings suggest that Japan's government should not adopt a one-size-fits-all policy to promote the vaccination program, but rather target people with specific socioeconomic backgrounds who are less willing and more hesitant to take a vaccine.Rheumatoid arthritis (RA) can be initiated and driven by immune responses to multiple antigenic epitopes including those in cartilage proteoglycan (PG, aggrecan) and type II collagen. RA is driven by T helper 1 (Th1) or Th17 pro-inflammatory T cell responses. LEAPS (Ligand Epitope Antigen Presentation System) DerG peptide conjugate vaccines were prepared using epitopes from PG that elicit immune responses in RA patients epitope PG70 (DerG-PG70, also designated CEL-4000) and the citrullinated form of another epitope (PG275Cit). The LEAPS peptides were administered alone or together in Seppic ISA51vg adjuvant to mice with PG G1 domain-induced arthritis (GIA), a mouse model of RA. Each of these LEAPS peptides and the combination modulated the inflammatory response and stopped the progression of arthritis in the GIA mouse model. Despite having a therapeutic effect, the DerG-PG275Cit vaccine did not elicit significant antibody responses, whereas DerG-PG70 (alone or with DerG-PG275Cit) induced both therapy and antibodies. Spleen T cells from GIA mice, vaccinated with the DerG LEAPS peptides, preferentially produced anti-inflammatory (IL-4 and IL-10) rather than pro-inflammatory (IFN-γ or IL-17) cytokines in culture. Similarly, cytokines secreted by CD4+ cells of unvaccinated GIA mice, differentiated in vitro to Th2 cells and treated with either or both DerG vaccine peptides, exhibited an anti-inflammatory (IL-4, IL-10) profile. These results suggest that the two peptides elicit different therapeutic immune responses by the immunomodulation of disease-promoting pro-inflammatory responses and that the combination of the two LEAPS conjugates may provide broader epitope coverage and, in some cases, greater efficacy than either conjugate alone.
Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it provides a novel perspective on the pathomechanism of cutaneous RDD. We aim to investigate the genomic mutations in MAPK/ERK pathway in cutaneous RDD.

We retrospectively recruited all cases of cutaneous RDD from two hospitals in Taiwan from January 2010 to March 2020 with the clinicopathologic features, immunohistochemistry, and treatment. Mutations of neuroblastoma RAS viral oncogene homolog (
)
Kirsten rat sarcoma 2 viral oncogene homolog (
), and v-raf murine sarcoma viral oncogene homolog B1 (
) in MAPK/ERK pathway were investigated by the highly sensitive polymerase chain reaction with Sanger sequencing.

Seven patients with cutaneous RDD were recruited with nvolve the pathogenesis of cutaneous RDD.Combining drugs, a phenomenon often referred to as polypharmacy, can induce additional adverse effects. The identification of adverse combinations is a key task in pharmacovigilance. In this context, in silico approaches based on machine learning are promising as they can learn from a limited number of combinations to predict for all. In this work, we identify various subtasks in predicting effects caused by drug-drug interaction. Predicting drug-drug interaction effects for drugs that already exist is very different from predicting outcomes for newly developed drugs, commonly called a cold-start problem. We propose suitable validation schemes for the different subtasks that emerge. These validation schemes are critical to correctly assess the performance. We develop a new model that obtains AUC-ROC =0.843 for the hardest cold-start task up to AUC-ROC =0.957 for the easiest one on the benchmark dataset of Zitnik et al. Finally, we illustrate how our predictions can be used to improve post-market surveillance systems or detect drug-drug interaction effects earlier during drug development.In this work, the application of quantum dots is evaluated in order to sensitize the commercially popular Si detectors in the UV range. The wavelength-shifting properties of two types of all-inorganic halide perovskite quantum dots as well as ZnCuInS/ZnS quantum dots are determined in order to assess their potential in the effective enhancement of the sensors' detection range. In a further part of the study, the wavelength-shifting layers are formed by embedding the quantum dots in two kinds of polymers PMMA or Cyclic Olefin Polymer. The performance of the layers is evaluated by transmission and PLE measurement. Incorporating the nanoparticles seemingly increases the transmittance in the UV range by several percent. The observed phenomenon is proportional to the quantum dots to polymer concentration, which indicates the successful conversion action of the luminescent agents.Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control p less then 0.01) and hypertension (mean of Psys 200 ± 2 vs. BI-1347 nmr control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.In Europe, protecting the genetic diversity of Apis mellifera is usually perceived in the context of limiting the spread of the evolutionary C-lineage within the original range of the M-lineage. However, due to climate change and large-scale ongoing movement of breeding individuals, the expansion of bees from the African A-lineage could represent another threat. This issue has not yet been investigated in detail, although A-mitotypes occur in South-West and South Europe due to natural gene flow. Here, we determine the diversity of mtDNA in honey bees from East-Central Europe. We sequenced the COI-COII region in 427 bees sampled along two 900 km transects (17.5° N and 23° E). We found that 1.64% of bees (95% CI 0.66-3.35 %) had A-mitotypes. It is unlikely that their presence in the area resulted from natural migration but instead human driven introductions of hybrids of African ancestry. This expansion deserves more attention, as it may contribute to the dissemination of undesirable traits, parasites and diseases.The extracellular matrix (ECM) plays an important role in the evolution of early metazoans, as it provides structural and biochemical support to the surrounding cells through the cell-cell and cell-matrix interactions. In multi-cellular organisms, ECM plays a pivotal role in the differentiation of tissues and in the development of organs. Fibulins are ECM glycoproteins, found in a variety of tissues associated with basement membranes, elastic fibers, proteoglycan aggregates, and fibronectin microfibrils. The expression profile of fibulins reveals their role in various developmental processes such as elastogenesis, development of organs during the embryonic stage, tissue remodeling, maintenance of the structural integrity of basement membrane, and elastic fibers, as well as other cellular processes. Apart from this, fibulins are also involved in the progression of human diseases such as cancer, cardiac diseases, congenital disorders, and chronic fibrotic disorders. Different isoforms of fibulins show a dual role of tumor-suppressive and tumor-promoting activities, depending on the cell type and cellular microenvironment in the body. Knockout animal models have provided deep insight into their role in development and diseases. The present review covers details of the structural and expression patterns, along with the role of fibulins in embryonic development and disease progression, with more emphasis on their involvement in the modulation of cancer diseases.When operating under lean fuel-air conditions, flame flashback is an operational safety issue in stationary gas turbines. In particular, with the increased use of hydrogen, the propagation of the flame through the boundary layers into the mixing section becomes feasible. Typically, these mixing regions are not designed to hold a high-temperature flame and can lead to catastrophic failure of the gas turbine. Flame flashback along the boundary layers is a competition between chemical reactions in a turbulent flow, where fuel and air are incompletely mixed, and heat loss to the wall that promotes flame quenching. The focus of this work is to develop a comprehensive simulation approach to model boundary layer flashback, accounting for fuel-air stratification and wall heat loss. A large eddy simulation (LES) based framework is used, along with a tabulation-based combustion model. Different approaches to tabulation and the effect of wall heat loss are studied. An experimental flashback configuration is used to understand the predictive accuracy of the models. It is shown that diffusion-flame-based tabulation methods are better suited due to the flashback occurring in relatively low-strain and lean fuel-air mixtures. Further, the flashback is promoted by the formation of features such as flame tongues, which induce negative velocity separated boundary layer flow that promotes upstream flame motion. The wall heat loss alters the strength of these separated flows, which in turn affects the flashback propensity. Comparisons with experimental data for both non-reacting cases that quantify fuel-air mixing and reacting flashback cases are used to demonstrate predictive accuracy.
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