Mitoxantrone and Mitoxantrone-Loaded Iron Oxide Nanoparticles Induce Cell Death in Human Pancreatic Ductal Adenocarcinoma Cell Spheroids.

Pancreatic ductal adenocarcinoma is a hard-to-treat, deadly malignancy. Traditional treatments, such as surgery, radiation and chemotherapy, unfortunately are still not able to significantly improve long-term survival. Three-dimensional (3D) cell cultures might be a platform to study new drug types in a highly reproducible, resource-saving model within a relevant pathophysiological cellular microenvironment. We used a 3D culture of human pancreatic ductal adenocarcinoma cell lines to investigate a potential new treatment approach using superparamagnetic iron oxide nanoparticles (SPIONs) as a drug delivery system for mitoxantrone (MTO), a chemotherapeutic agent. We established a PaCa DD183 cell line and generated PANC-1SMAD4 (-/-) cells by using the CRISPR-Cas9 system, differing in a prognostically relevant mutation in the TGF-ß pathway. Afterwards, we formed spheroids using PaCa DD183, PANC-1 and PANC-1SMAD4 (-/-) cells, and analyzed the uptake and cytotoxic effect of free MTO and MTO-loaded SPIONs by microscopy and flow cytometry. MTO and SPION-MTO-induced cell death in all tumor spheroids in a dose-dependent manner. Interestingly, spheroids with a SMAD4 mutation showed an increased uptake of MTO and SPION-MTO, while at the same time being more resistant to the cytotoxic effects of the chemotherapeutic agents. MTO-loaded SPIONs, with their ability for magnetic drug targeting, could be a future approach for treating pancreatic ductal adenocarcinomas.

[Sports cardiology : Which sport can be recommended for heart diseases?] / Sportkardiologie : Welcher Sport kann bei Herzerkrankungen empfohlen werden?

Within cardiology the field of sports cardiology has gradually increased in importance over the past 10 years. This is mainly due to the fact that the spectrum of issues relating to physical training in prevention and secondary prevention has expanded beyond classical cardiovascular rehabilitation. This spectrum affects above all adolescents and young adults with a manifest cardiac disease who want to continue being physically active and, in some cases strive for leisure and competitive sports. In addition, the group of patients with cardiac diseases who are still striving for top athletic performance even in old age and are looking for advice is continuously growing. In these cases, it is a matter of recommending physical training as a therapy strategy but also to protect the cardiovascular system. Dedicated recommendations for physical training must therefore also take individual aspects into consideration. In addition, the recommendation for the clearance for competitive sports is addressed in ambitious leisure and competitive sports. Patients ask about sport and training recommendations with cardiovascular risk factors, such as arterial hypertension, pathologies of the coronary arteries in the sense of a malformed outlet of coronary arteries, muscle bridges or coronary heart disease, cardiomyopathies and myocarditis as well as arrhythmia and cardiac valvular defects. This article discusses these diseases with the corresponding sport cardiological specific aspects and recommendations for physical training and competitive sports are given for each case.

Long-Term Stable, High-Capacity Anode Material for Sodium-Ion Batteries: Taking a Closer Look at CrPS4 from an Electrochemical and Mechanistic Point of View.

Electrochemical performance of the layered compound CrPS4 for the usage as anode material in sodium-ion batteries (SIBs) was examined and exceptional reversible long-term capacity and capacity retention were found. After 300 cycles, an extraordinary reversible capacity of 687 mAh g-1 at a current rate of 1 A g-1 was achieved, while rate capability tests showed an excellent capacity retention of 100%. Detailed evaluation of the data evidence a change of the electrochemical reaction upon cycling leading to the striking long-term performance. Further investigations targeted the reaction mechanism of the first cycle by applying complementary techniques, i.e., powder X-ray diffraction (XRD), pair distribution function (PDF) analysis, X-ray absorption spectroscopy (XAS), and 23Na/31P magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. The results indicated an unexpectedly complex reaction pathway including formation of several intercalation compounds, depending on the amount of Na inserted at the early discharge states and subsequent conversion to Na2S and strongly disordered metallic Cr at the completely discharged state. While XAS measurements suggest no further presence of intermediates after formation of Na intercalation compounds, several different phases are detected via MAS NMR upon continued discharging. Especially the data obtained from the MAS NMR investigations therefore point toward a very complex reaction pathway. Furthermore, solid electrolyte interphase (SEI) formation, resulting in the presence of NaF, was observed. After recharging the anode material, no structural long-range order occurred, but short-range order indeed resembled the local environment of the starting material, to a certain extent.

Aqueous Flow Reactor and Vapour-Assisted Synthesis of Aluminium Dicarboxylate Metal-Organic Frameworks with Tuneable Water Sorption Properties.

Energy-efficient indoors temperature and humidity control can be realised by using the reversible adsorption and desorption of water in porous materials. Stable microporous aluminium-based metal-organic frameworks (MOFs) present promising water sorption properties for this goal. The development of synthesis routes that make use of available and affordable building blocks and avoid the use of organic solvents is crucial to advance this field. In this work, two scalable synthesis routes under mild reaction conditions were developed for aluminium-based MOFs: (1) in aqueous solutions using a continuous-flow reactor and (2) through the vapour-assisted conversion of solid precursors. Fumaric acid, its methylated analogue mesaconic acid, as well as mixtures of the two were used as linkers to obtain polymorph materials with tuneable water sorption properties. The synthesis conditions determine the crystal structure and either the MIL-53 or MIL-68 type structure with square-grid or kagome-grid topology, respectively, is formed. Fine-tuning resulted in new MOF materials thus far inaccessible through conventional synthesis routes. Furthermore, by varying the linker ratio, the water sorption properties can be continuously adjusted while retaining the sigmoidal isotherm shape advantageous for heat transformation and room climatisation applications.

Unveiling the Reaction Mechanism during Li Uptake and Release of Nanosized "NiFeMnO4": Operando X-ray Absorption, X-ray Diffraction, and Pair Distribution Function Investigations.

Here, we report that the trimetallic nanosized oxide NiFeMnO4 consists of a mixture of NiO and a strained cubic spinel phase, which is clearly demonstrated by analysis of the pair distribution function (PDF) and synchrotron X-ray data. Such a finding can easily be overlooked by using only inhouse X-ray powder diffraction, leading to inaccurate assumption of the stoichiometry and oxidation states. Such advanced characterization is essential because a homogeneous distribution of the elements is observed in energy-dispersive X-ray spectroscopy maps, giving no hints for a phase separation. Cycling of the sample against Li delivers a high reversible capacity of ≈840 mAh/g in the 50th cycle. Operando X-ray absorption spectroscopy (XAS) experiments indicate that ≈0.8 Li/fu is consumed without detectable changes of the electronic structure. Increasing amounts of Li, Mn3+, and Fe3+ are simultaneously reduced. The disappearance of the pre-edge features in X-ray absorption near-edge spectroscopy indicates movement of these cations from tetrahedral sites to octahedral sites. PDF analysis of the pattern after an uptake of 2 Li/fu evidences that the principal structure can be sufficiently well modeled assuming coexisting NiO, a mixed monoxide, and a small amount of residual spinel phase. Thus, the majority of cations is located on octahedral sites. Furthermore, an improvement of the PDF model is achieved taking into account small amounts of LiOH. The 7Li MAS NMR spectrum of this sample clearly shows the signal of Li in a diamagnetic environment, excluding Li-O-TM bonds. A further increase of the Li content leads to a successive conversion of the cations to nanosized metal particles embedded in a LiOH/Li2O matrix. Ex situ XAS results indicate that Fe can be reversibly reoxidized to Fe3+ during charge whereas Mn does not reach the oxidation state observed in the pristine material. After excessive cycling, reoxidation of metallic Ni is suppressed and contributes to a capacity loss compared with the early discharge/charge cycles.