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1 macrophages. Our results indicate a viable and interesting approach in planning new chemical entities that act as transmission-blocking drugs for treating malaria caused by P. falciparum and P. vivax and the anti-inflammatory process related to this disease.T-cell engaging bispecific antibodies (T-biAbs) mediate potent and selective cytotoxicity by combining specificities for target and effector cells in one molecule. Chemically programmed T-biAbs (cp-T-biAbs) are precisely assembled compositions of (i) small molecules that govern cancer cell surface targeting with high affinity and specificity and (ii) antibodies that recruit and activate T cells and equip the small molecule with confined biodistribution and longer circulatory half-life. Conceptually similar to cp-T-biAbs, switchable chimeric antigen receptor T cells (sCAR-Ts) can also be put under the control of small molecules by using a chemically programmed antibody as a bispecific adaptor molecule. As such, cp-T-biAbs and cp-sCAR-Ts can endow small molecules with the power of cancer immunotherapy. We here review the concept of chemically programmed antibodies for recruiting and activating T cells as a promising strategy for broadening the utility of small molecules in cancer therapy.Pim-1 kinase targeted recently has proved an essential goal of breast cancer therapy. We report the design, synthesis with full characterization analysis of pyrazolo[3,4-b]pyridine scaffold-based derivatives targeting Pim-1 kinase as anti-breast cancer agents. All the newly synthesized compounds were screened for their in vitro cytotoxic activity against two breast cancer cell lines MCF-7 and MDA-MB-231, and non-cancerous MCF-10A cells. Four derivatives notably, 17 and 19 exhibited a remarkable cytotoxic activity with IC50 values 5.98 and 5.61 µM against MCF-7 (ERα-dependent) cells in a selective way, as they weren't active against MDA-MB-231 (non-ERα-dependent) and safe against MCF-10A. The most active compounds through in vitro screening were subjected to PIM-1 kinase to elucidate the Pim-1 kinase inhibitory activity as the mechanistic mode of action. Among the tested derivatives, Compounds 17 and 19 showed the highest inhibitory activity with IC50 values 43 and 26 nM, respectively, compared to the 5-FU with IC50 value 17 nM. Moreover, apoptotic investigation through flow cytometry and gene expression analysis of the apoptosis-related genes for the most active compound 19 against MCF-7. It was found that compound 19 induced apoptotic MCF-7 cell death by cell cycle arrest at G2/M phase and by elevation the expression of pro-apoptotic genes and inhibition of anti-apoptotic genes expression. Finally, the PIM-1 inhibition activities for compounds 17 and 19 were in accordance with the molecular docking study that revealed good interaction with the Pim-1 kinase active site.
Cancer nurses across Europe are being tasked with delivery of an increasing number of complex treatments and supportive care interventions as a result of ongoing advances in cancer research, and a rise in cancer incidence due to demographic changes. However, all health systems delivering cancer treatment innovations require access to an educated and motivated nursing workforce to meet demand. This study by the European Oncology Nursing Society examines comparative features of cancer nursing in Estonia, Germany, the Netherlands (NL) and the United Kingdom (UK).
Descriptive qualitative study using focus groups and individual interviews drawing on the views of cancer nurses, managers and stakeholders from four European countries (n=97). Data collection was designed around national cancer nursing conferences held in Berlin (Germany), Ede (NL), Harrogate (UK) and Tallinn and Tartu (Estonia) between May 2017 and April 2018. Participants included a mix of nursing grades and specialisms.
According to the partice appropriate education and career structure to support patients. This study provides insights from four countries and suggests the need for better recognition as well as working conditions, education and career structures that advance the potential of the cancer nursing role in Europe.Calcification of anaerobic granular sludge causing the decrease of microbial activity has been focused for several decades, but the mechanism of calcification and deactivation of calcified granule are still lacking. In this study, the calcification process of anaerobic granular sludge was analyzed in the UASB reactor with long-term exposure to a high calcium level of 2 gCa2+L-1. Greyish-white calcified granules with larger size and density first appeared at the bottom of sludge bed. Characterization of granular surface demonstrated that calcified granules had smaller specific surface area and pore volume with the disappearing channels in granules visualized over calcification. The coverage of calcite on granular surface with a thickness of 500-600 µm was observed by a microscope, which is responsible for the blockage of channels for substrate diffusion and transport. The evaluation of mass transfer showed that the 'effectiveness factor' η of calcified granules was higher than 1.23, proving the existence of mass transfer resistance. Furthermore, the interactions between calcium and extracellular polymeric substances (EPS) revealed the possible mechanism of calcite location at the outer layer of anaerobic granular sludge The bulk calcite directly binds the EPS such as humic acids via charging functional groups, and bulk CO32- could react easily with Ca2+ bound to EPS according to thermodynamic analysis.Electroactive biofilms (EABs) can be integrated with conductive nanomaterials to boost extracellular electron transfer (EET) for achieving efficient waste treatment and energy conversion in bioelectrochemical systems. However, the in situ nanomaterial-modified EABs of mixed-culture, and their response under environmental stress are rarely revealed. VIT-2763 Here, two nanocatalyst-decorated EABs were established by self-assembled Au nanoparticles-reduced graphene oxide (Au-NPs/rGO) in mixed-biofilms with different maturities, then their multi-property were analyzed under long-term phenolic shock. Results showed that the power density of Au-NPs/rGO decorated EABs was significantly enhanced by 28.66-42.82% due to the intensified EET pathways inside biofilms. Meanwhile, the electrochemical and catalytic performance of EABs were controllably regulated by 0.3-3.0 g/L phenolic compounds, which, however, resulted in differential alterations in their architecture, composition, and viability. EABs originated with higher maturity displayed more compact structure, lower thickness (110 μm), higher biomass (8.