Structural studies of calcium silicate hydrate modified with heavy metal cations.

This study investigates the immobilization mechanisms of heavy metal ions in the C-S-H phase. Synthetic C-S-H phases were prepared via the precipitation method, incorporating five different ions (Pb(II), Cd(II), Ni(II), Zn(II), and Cr(III)). Structural analysis of the obtained material was conducted using vibrational spectroscopy (both FT-IR and Raman), X-ray photoelectron spectroscopy, and X-ray diffraction. Spectroscopic methods were primarily employed to evaluate the structural effects and polymerization degree of the resulting C-S-H phase. Morphological changes were characterized using scanning and transmission electron microscopy (SEM and TEM, respectively). Our findings reveal several mechanisms for immobilizing heavy metal cations: precipitation of insoluble compounds (particularly notable for Ni(II) and Cr(III)), replacement of Ca(II) ions within the silicate structure (evident in the crystallization of Ca(OH)2 in samples containing Cd(II), Ni(II), and Zn(II) in minimal quantities), and strong bonding of certain metals (such as Pb(II)) with the C-S-H phase structure. These insights contribute to understanding the potential applications of C-S-H phases in heavy metal immobilization.

Effect of compaction on bisulfide diffusive transport through MX-80 bentonite.

Canada's deep geological repository (DGR) design includes an engineered barrier system where highly compacted bentonite (HCB) surrounds the copper-coated used fuel containers (UFCs). Microbial-influenced corrosion is a potential threat to long-term integrity of UFC as bisulfide (HS-) may be produced by microbial activities under anaerobic conditions and transported via diffusion through the HCB to reach the UFC surface, resulting in corrosion of copper. Therefore, understanding HS- transport mechanisms through HCB is critical for accurate prediction of copper corrosion allowance. This study investigated HS- transport behaviour through MX-80 bentonite at dry densities 1070-1615 kg m-3 by performing through-diffusion experiments. Following HS- diffusion, bromide (Br-) diffusion and Raman spectroscopy analyses were performed to explore possible physical or mineralogical alterations of bentonite caused by interacting with HS-. In addition, accessible porosity ε was estimated using extended Archie's law. Effective diffusion coefficient of HS- was found 2.5 × 10-12 m2 s-1 and 5.0× 10-12 m2 s-1 for dry densities 1330 and 1070 kg m-3, respectively. No HS- breakthrough was observed for highly compacted bentonite (1535-1615 kg m-3) over the experimental timeframe (170 days). Raman spectroscopy results revealed that HS- reacted with iron in bentonite and precipitated as mackinawite and, therefore, it was immobilized. Finally, results of this study imply that HS- transport towards UFC will be highly controlled by the available iron content and dry density of the buffer material.

Targeted therapies for glioblastoma treatment.

Glioblastoma, the most common and aggressive type of brain tumor in adults, poses significant challenges in terms of treatment. Conventional approaches including surgery, chemotherapy, and radiotherapy have yielded limited success, with a median survival of approximately 15 months. However, extensive research into the biology of glioblastoma has identified molecular targets that can be exploited by newly developed drugs, leading to the emergence of precise personalized therapies. Several innovative treatment strategies are currently under development, aiming to enhance effectiveness while minimizing side effects. Clinical trials are underway to evaluate the efficacy of monoclonal antibodies that target glioblastoma cells, either by blocking specific receptors or by modifying molecular interactions that impede cell proliferation. Another promising avenue involves the use of oncolytic viruses designed to selectively infect glioblastoma cells. Additionally, the review explores the utilization of nanocarriers capable of surmounting the formidable obstacle of the blood-brain barrier, enabling efficient drug delivery. Cell therapies represent another promising approach, with dendritic cells, chimeric antigen receptor-T cells, and macrophages emerging as potential treatment modalities. By summarizing recent advances in targeted therapies against glioblastoma, this review aims to provide a comprehensive overview of ongoing efforts to discover effective and safe methods for treating glioblastoma patients. The ultimate goal is to improve patient outcomes and transform the landscape of glioblastoma treatment.

Real-world treatment patterns in patients with nontuberculous mycobacterial lung disease in the Netherlands based on medication dispensing data.

PURPOSE: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data. METHODS: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment. RESULTS: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped. CONCLUSION: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers.

Spectroscopic studies of heavy metal cations influence on the structure of synthetic hydrated calcium aluminosilicates.

Calcium aluminosilicate hydrates (C-(A)-S-H) with two different C/S molar ratios of 1.0 and 1.7 were synthesized by precipitation with the use of the alkali-activation method. The samples were synthesized with solutions of heavy metals nitrates such as nickel (Ni), chromium (Cr), cobalt (Co), lead (Pb), and zinc (Zn). Metal cations were added in the amount of Ca:Me equal to 9:1, while Al/Si was 0.05. The influence of the addition of heavy metal cations on the structure of the C-(A-)S-H phase was investigated. For this purpose, XRD was used to examine the phase composition of the samples, FT-IR and Raman spectroscopy were used to determine the effect of heavy metal cations on the structure of the obtained C-(A)-S-H phase and their degree of polymerization. Using SEM and TEM, changes in the morphology of the obtained materials were determined. Possible mechanisms of immobilization of heavy metal cations have been determined. It was found that some heavy metals (Ni, Zn, and Cr) could be immobilized by precipitation of insoluble compounds. On the other hand, they could remove Ca2+ ions from the structure of aluminosilicate and take their place, as evidenced by the crystallization of Ca(OH)2 in samples with the addition of Cd, but also Ni and Zn in small amounts. A third possibility is the incorporation of heavy metal cations at the silicon and/or aluminum tetrahedral sites, as is the case with Zn.

Annihilation of exceptional points from different Dirac valleys in a 2D photonic system.

Topological physics relies on Hamiltonian's eigenstate singularities carrying topological charges, such as Dirac points, and - in non-Hermitian systems - exceptional points (EPs), lines or surfaces. So far, the reported non-Hermitian topological transitions were related to the creation of a pair of EPs connected by a Fermi arc out of a single Dirac point by increasing non-Hermiticity. Such EPs can annihilate by reducing non-Hermiticity. Here, we demonstrate experimentally that an increase of non-Hermiticity can lead to the annihilation of EPs issued from different Dirac points (valleys). The studied platform is a liquid crystal microcavity with voltage-controlled birefringence and TE-TM photonic spin-orbit-coupling. Non-Hermiticity is provided by polarization-dependent losses. By increasing the non-Hermiticity degree, we control the position of the EPs. After the intervalley annihilation, the system becomes free of any band singularity. Our results open the field of non-Hermitian valley-physics and illustrate connections between Hermitian topology and non-Hermitian phase transitions.

Treatment persistence in paediatric and adolescent patients with psoriasis followed into young adulthood. From topical to systemic treatment: a prospective, longitudinal, observational cohort study of 448 patients.

BACKGROUND: Although solely topical treatment often suffices, patients with psoriasis may require more intensive treatment (phototherapy and/or systemic treatments) to control their disease. However, in paediatric, adolescent and young adult patients, little is known about persistence of topical treatment and time until switch to systemic treatment. OBJECTIVES: To determine the median time from psoriasis onset until (i) discontinuation of solely topical agents and (ii) switch to systemic treatment, and to identify patient characteristics associated with switching to systemic treatments. METHODS: Data were extracted from the Child-CAPTURE registry, a prospective, observational cohort of patients with paediatric-onset psoriasis followed into young adulthood from 2008 to 2018. Data prior to inclusion in the registry were collected retrospectively. Median times were determined through Kaplan-Meier survival analyses. Cox regression analysis was used to identify patient characteristics associated with switch to systemic treatment. RESULTS: Of 448 patients, 62·3% stayed on solely topical treatment until data lock; 14·3% switched from topicals to phototherapy, but not to systemic treatment; and 23·4% switched to systemic treatment. The median time from psoriasis onset until discontinuation of solely topical treatment was 7·3 years, and until switch to systemics was 10·8 years. Higher Psoriasis Area and Severity Index and (Children's) Dermatology Life Quality Index > 5 were independently associated with switching to systemic treatment. CONCLUSIONS: In a population of paediatric and adolescent patients with mild-to-severe psoriasis, one-third needed more intensive treatment than solely topical therapy to control their disease. We consider the median time until switching to systemics to be long.

Quantification of nitrogen oxides emissions from build-up of pollution over Paris with TROPOMI.

Nitrogen dioxide (NO2) is a regulated air pollutant that is of particular concern in many cities, where concentrations are high. Emissions of nitrogen oxides to the atmosphere lead to the formation of ozone and particulate matter, with adverse impacts on human health and ecosystems. The effects of emissions are often assessed through modeling based on inventories relying on indirect information that is often outdated or incomplete. Here we show that NO2 measurements from the new, high-resolution TROPOMI satellite sensor can directly determine the strength and distribution of emissions from Paris. From the observed build-up of NO2 pollution, we find highest emissions on cold weekdays in February 2018, and lowest emissions on warm weekend days in spring 2018. The new measurements provide information on the spatio-temporal distribution of emissions within a large city, and suggest that Paris emissions in 2018 are only 5-15% below inventory estimates for 2011-2012, reflecting the difficulty of meeting NOx emission reduction targets.

Exploiting iron-binding proteins for drug delivery.

Currently, many therapies fail due to an insufficient drug dose reaching the target site and high systemic toxicity. Protein-based drug delivery systems that allow an increase in drug concentration at a specific location in the body or predominantly target malignant cells are promising technologies. Due to the high need for iron in many disorders including various types of cancer, iron-binding proteins: transferrin, ferritin and hemoglobin, are a promising tool as drug carriers. In this review we summarize the characteristics of human iron-binding proteins and present their use in targeted drug delivery strategies.

Influence of Clonal Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts on Progression and Survival in Multiple Myeloma Patients After Autologous Peripheral Blood Stem Cell Transplantation in Long-term Observation.

BACKGROUND: High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) remains the mainstay of treatment of eligible patients diagnosed multiple myeloma. The role of clonal plasma cell (CPC) contamination was found as a reason for relapse, but results in terms of survival, progression, and purging were ambiguous. Therefore, the aim of the study was to explore the influence of CPC contamination in the autograft on survival and progression after auto-PBSCT. STUDY DESIGN: The study included 59 patients diagnosed and treated for multiple myeloma in 1998-2004. Cells with coexpression of CD38+++CD138++CD56+ and lacking the expression of CD45, CD19, CD10, CD20, and CD23 were considered CPC in flow cytometry. RESULTS: The risk of death and progression after auto-PBSCT increased significantly by 10% (P < .021) and 8% (P < .034) per 1 × 106/kg of the CPC number, respectively. For CPC number above 2.96 × 106/kg overall survival achieved clinical significance. Two years after auto-PBSCT, the risk of death was independent of CPC number among the patients who survived (P = .70). Analogous conclusions concerned results of progression-free survival at 1 year after auto-PBSCT. CONCLUSIONS: High clonal plasma cell contamination (>2.96 ×1 06/kg; 90th percentile of CPC number) is associated with the worst progression-free survival and overall survival. Therefore purging in vitro might be considered for the patients with the highest CPC contamination. Negative consequences of CPC contamination on the risk of death are observed for only 2 years after auto-PBSCT. Thereafter only those patients who had lower CPC contamination survived.

Wnt signaling pathway in development and cancer.

Wnt signaling pathway is one of the most important signaling pathways. The complexity of Wnt signals and their functional role is crucial in development and growth. It is the most active during embryogenesis facilitating new organism formation by cell differentiation, polarization and migration. Its activation is also common during development of many tumors and others diseases. In this review we shortly describe a role of Wnt pathway in development in order to better understand its role in cancer progression. We also describe current anti-cancer therapies targeting Wnt pathway.

A retrospective analysis of medication prescription records for determining the levels of compliance and persistence to urate-lowering therapy for the treatment of gout and hyperuricemia in The Netherlands.

Urate-lowering therapy (ULT) is a recommended life-long treatment for gout patients. However, despite these recommendations, recurrent gout attacks are commonly observed in clinical practice. The purpose of this study was to assess the levels of compliance and persistence to ULT in The Netherlands, in order to reflect on the current gout care delivered by health professionals. Anonymous prescription records were obtained from IQVIA's Dutch retrospective longitudinal prescription database, containing ULT dispensing data for allopurinol, febuxostat, and benzbromarone from November 2013 to July 2017. Compliance to ULT was determined by calculating the proportion of days covered (PDC) over 12 months. Persistence over 12 months was evaluated by determining the time to discontinuation, without surpassing a refill gap of > 30 days. Association of PDC and persistence with age, gender, and first prescriber were examined using beta regression- and cox-regression models, respectively. There were 45,654 patients who met the inclusion criteria. Overall, 51.7% of the patients had a ULT coverage of ≥ 80% of the days in 1 year (PDC ≥ 0.80), and 42.7% of the patients were still persistent after 1 year. Men, older patients, and patients whose first prescriber was a rheumatologist were more persistent and had a higher PDC. Our results show that medication adherence to ULT after 1 year is suboptimal, considering that current guidelines recommend ULT as a life-long treatment. Future studies addressing the reasons for treatment cessation and improving treatment adherence seem warranted.

Influence of alkali metal cations/type of activator on the structure of alkali-activated fly ash - ATR-FTIR studies.

Coal fly ash as a secondary aluminosiliceous raw material that is commonly used in the so-called geopolymerization process has been activated with different alkali hydroxides solutions: LiOH, NaOH and KOH. Changes in the aluminosilicate structure of the material during alkali-activation have been analyzed in detail on the basis of ATR/FT-IR spectra. These changes mainly affect both the integral intensity and FWHM of bands in the range of 1200-950cm-1, however dehydration and carbonation process can be also analyzed based on obtaining results.

Structural and functional integrity of Sulla carnosa photosynthetic apparatus under iron deficiency conditions.

The abundance of calcareous soils makes bicarbonate-induced iron (Fe) deficiency a major problem for plant growth and crop yield. Therefore, Fe-efficient plants may constitute a solution for use on calcareous soils. We investigated the ability of the forage legume Sulla carnosa (Desf.) to maintain integrity of its photosynthetic apparatus under Fe deficiency conditions. Three treatments were applied: control, direct Fe deficiency and bicarbonate-induced Fe deficiency. At harvest, all organs of deficient plants showed severe growth inhibition, the effect being less pronounced under indirect Fe deficiency. Pigment analysis of fully expanded leaves revealed a reduction in concentrations of chlorophyll a, chlorophyll b and carotenoids under Fe deficiency. Electron transport rate, maximum and effective quantum yield of photosystem II (PSII), photochemical quenching (qP), non-photochemical quenching (qN) as well as P700 activity also decreased significantly in plants exposed to direct Fe deficiency, while qN was not affected. The effects of indirect Fe deficiency on the same parameters were less pronounced in bicarbonate-treated plants. The relative abundances of thylakoid proteins related to PSI (PsaA, Lhca1, Lhca2) and PSII (PsbA, Lhcb1) were also more affected under direct than indirect Fe deficiency. We conclude that S. carnosa can maintain the integrity of its photosynthetic apparatus under bicarbonate-induced Fe deficiency, preventing harmful effects to both photosystems under direct Fe deficiency. This suggests a high capacity of this species not only to take up Fe in the presence of bicarbonate (HCO3- ) but also to preferentially translocate absorbed Fe towards leaves and prevent its inactivation.

Interferon lambda 2 promotes mammary tumor metastasis via angiogenesis extension and stimulation of cancer cell migration.

Myeloid-derived suppressor cells (MDSCs) support tumor development by stimulation of angiogenesis and immune response inhibition. In our previous study, we showed that interferon lambda 2 (IFN-λ2), secreted by MDSCs, enhances production of pro-angiogenic factors by cancer cells via phosphorylation of STAT3 and therefore promotes blood vessels formation. In the present study IFN-λ2 level was evaluated by ELISA in serum of tumor-bearing mice, whereas its expression in MDSCs isolated from the lungs with metastatic tumors and normal lungs was assessed by qPCR. The effect of IFN-λ2 on mouse mammary cancer cells motility was tested in Boyden chamber migration assay. In order to evaluate its pro-angiogenic function we performed in vitro tubule formation assay and in ovo angiogenesis assay on chicken embryo chorioallantoic membrane (CAM). Moreover, in order to design small molecule inhibitors of IFN-λ2 and its receptor we performed molecular modeling followed by the identification of potential natural inhibitors. Then, we examined their ability to inhibit angiogenesis in vitro. Our results showed that IFN-λ2 predisposed mouse mammary cancer cells to migration in vitro. It also enhanced angiogenesis induced by mouse mammary cancer cells in vitro and in ovo. For the first time we selected potential IFN-λ2 inhibitors and we validated that they were capable to abolish pro-angiogenic effect of IFN-λ2, similarly to blocking antibodies. Therefore, IFN-λ2 and its receptor may become targets of anti-cancer therapy, but their mechanism of action requires further investigation.

Doubly Dressed Bosons: Exciton Polaritons in a Strong Terahertz Field.

We demonstrate the existence of a novel quasiparticle, an exciton in a semiconductor doubly dressed with two photons of different wavelengths: a near infrared cavity photon and terahertz (THz) photon, with the THz coupling strength approaching the ultrastrong coupling regime. This quasiparticle is composed of three different bosons, being a mixture of a matter-light quasiparticle. Our observations are confirmed by a detailed theoretical analysis, treating quantum mechanically all three bosonic fields. The doubly dressed quasiparticles retain the bosonic nature of their constituents, but their internal quantum structure strongly depends on the intensity of the applied terahertz field.

Drug delivery systems improving chemical and physical properties of anticancer drugs currently investigated for treatment of solid tumors.

Cancer is the second leading cause of death worldwide. Conventional cancer treatment like chemotherapy do not fulfil the expectations of both patients and physicians and there is a pressing need for a new kind of therapies that will increase drug delivery to the tumor mass. Standard chemotherapy does not show either specific tumor-targeting, or selective mode of action for cancer cells. Moreover, tumor microenvironments additionally disturb drug perfusion and diffusion. Currently approved anticancer drugs have many limitations and therefore special delivery systems improving their chemical and physical properties are beneficial. In the present review paper we discuss various drug delivery systems for solid tumors that are actually at various stages of pre-clinical tests or approved for therapy.

Tumour-associated macrophages influence canine mammary cancer stem-like cells enhancing their pro-angiogenic properties.

Cancer stem-like cells as cells with ability to self-renewal and potential to differentiate into various types of cells are known to be responsible for tumour initiation, recurrence and drug resistance. Hence a comprehensive research is concentrated on discovering cancer stem-like cells biology and interdependence between them and other cells. The aim of our study was to evaluate the impact of macrophages on cancer stem-like cells in canine mammary carcinomas. As recent studies indicated presence of macrophages in cancer environment stimulates cancer cells into more motile and invasive cells by acquisition of macrophage phenotypes. From two canine mammary tumour cell lines, CMT-U27 and P114 cancer stem-like cells were stained with Sca1, CD44 and EpCAM monoclonal antibodies and isolated. Those cells were next co-cultured with macrophages for 5 days and used for further experiments. Canine Gene Expression Microarray revealed 29 different expressed transcripts in cancer stem-like cells co-cultured with macrophages compared to those in mono-culture. Up-regulation of C-C motif chemokine 2 was considered as the most interesting for further investigation. Additionally, those cells showed overexpression of genes involved in non-canonical Wnt pathway. The results of 3D tubule formation in endothelial cells induced by cancer stem-like cells co-cultured with macrophages compared to cancer stem-like cells from mono-cultures and with addition of Recombinant Canine CCL2/MCP-1 revealed the same stimulating effect. Based on those results we can conclude that macrophages have an impact on cancer stem-like cells increasing secretion of pro-angiogenic factors.

Statistical clumped isotope signatures.

High precision measurements of molecules containing more than one heavy isotope may provide novel constraints on element cycles in nature. These so-called clumped isotope signatures are reported relative to the random (stochastic) distribution of heavy isotopes over all available isotopocules of a molecule, which is the conventional reference. When multiple indistinguishable atoms of the same element are present in a molecule, this reference is calculated from the bulk (≈average) isotopic composition of the involved atoms. We show here that this referencing convention leads to apparent negative clumped isotope anomalies (anti-clumping) when the indistinguishable atoms originate from isotopically different populations. Such statistical clumped isotope anomalies must occur in any system where two or more indistinguishable atoms of the same element, but with different isotopic composition, combine in a molecule. The size of the anti-clumping signal is closely related to the difference of the initial isotope ratios of the indistinguishable atoms that have combined. Therefore, a measured statistical clumped isotope anomaly, relative to an expected (e.g. thermodynamical) clumped isotope composition, may allow assessment of the heterogeneity of the isotopic pools of atoms that are the substrate for formation of molecules.