Metal–Organic Framework Nanoparticles Induce Pyroptosis in Cells Controlled by the Extracellular pH

Ion homeostasis is essential for cellular survival, and elevated concentrations of specific ions are used to start distinct forms of programmed cell death. However, investigating the influence of certain ions on cells in a controlled way has been hampered due to the tight regulation of ion import by cells. Here, it is shown that lipid-coated iron-based metal–organic framework nanoparticles are able to deliver and release high amounts of iron ions into cells. While high concentrations of iron often trigger ferroptosis, here, the released iron induces pyroptosis, a form of cell death involving the immune system. The iron release occurs only in slightly acidic extracellular environments restricting cell death to cells in acidic microenvironments and allowing for external control. The release mechanism is based on endocytosis facilitated by the lipid-coating followed by degradation of the nanoparticle in the lysosome via cysteine-mediated reduction, which is enhanced in slightly acidic extracellular environment. Thus, a new functionality of hybrid nanoparticles is demonstrated, which uses their nanoarchitecture to facilitate controlled ion delivery into cells. Based on the selectivity for acidic microenvironments, the described nanoparticles may also be used for immunotherapy: the nanoparticles may directly affect the primary tumor and the induced pyroptosis activates the immune system.     

Simple colorimetric method for quantification of surface carboxy groups on polymer particles

We present a novel, simple, and fast colorimetric method to quantify the total number of carboxy groups on polymer microparticle and nanoparticle surfaces. This method exploits that small divalent transition metal cations (M(2+) = Ni(2+), Co(2+), Cd(2+)) are efficiently bound to these surface functional groups, which allows their extraction by a single centrifugation step. Remaining M(2+) in the supernatant is subsequently quantified spectrophotometrically after addition of the metal ion indicator pyrocatechol violet, for which Ni(2+) was identified to be the most suitable transition metal cation. We demonstrate that the difference between added and detected M(2+) is nicely correlated to the number of surface carboxy groups as determined by conductometry, thereby affording a validated measure for the trueness of this procedure. The variation coefficient of ~5% found in reproducibility studies underlines the potential of this novel method that can find conceivable applications for the characterization of different types of poly(carboxylic acid)-functionalized materials, e.g., for quality control by manufacturers of such materials.     

Note on the connectivity of line graphs

Let G be a connected graph with vertex set V(G), edge set E(G), vertex-connectivity κ(G) and edge-connectivity λ(G).A subset S of E(G) is called a restricted edge-cut if G−S is disconnected and each component contains at least two vertices. The restricted edge-connectivity λ₂(G) is the minimum cardinality over all restricted edge-cuts. Clearly λ₂(G)?λ(G)?κ(G).In 1969, Chartrand and Stewart have shown that

     

Vicious and virtuous circles of offshoring attitudes and relational behaviours. A configurational study of German IT developers

Prior research has shown that the success of offshoring is affected by relational behaviours of the employees involved in an offshoring collaboration. However, hardly anything is known about the attitudes that onshore colleagues hold towards offshoring, and how such offshoring attitudes affect relational behaviours towards offshore colleagues. We therefore present an interpretivist, qualitative case study that explores the offshoring attitudes of German information technology developers. We found that offshoring attitudes affected relational behaviours towards Indian offshore colleagues, in terms of (1) treating Indian colleagues as fellow team members as opposed to suppliers; (2) spending more or less effort in communication and knowledge transfer; and (3) supporting vs. avoiding the task transfer. These relational behaviours fed back into participants' offshoring attitudes, leading to vicious and virtuous circles. The circles created two contrasting configurations of offshoring attitudes and relational behaviours, driven by opposing forces within the departmental context. Our findings highlight the value of taking a configurational perspective for understanding offshoring success and for identifying drivers that need to be managed in order to achieve favourable configurations. We suggest that future research should further expand the typology of attitude‐behaviour configurations and could apply theories of efficacy, self‐reinforcing spirals and planned behaviour.     

Looking on Heterogeneous Catalytic Systems from Different Perspectives: Multitechnique Approaches as a New Challenge for In Situ Studies

Adapting physico-chemical characterization techniques for in situ studies of real heterogeneous catalysts during conditioning, reaction, and deactivation processes is a research topic of growing importance. Up to now, in most studies only one single in situ technique is applied. However, new trends are focused on using a portfolio of several in situ methods to obtain comprehensive information on structure-reactivity relationships. This review discusses such application examples with the aim to point out the particular benefits that arise from multitechnique approaches for understanding processes like formation of active sites, interaction of those sites with reactant molecules, and catalyst deactivation. Except for Fourier-transform infrared spectroscopy and quasi-in situ X-ray photoelectron spectroscopy, the examples deal mainly with the combined use of bulk techniques such as electron paramagnetic resonance, ultraviolet/visible diffuse reflection spectroscopy, laser-Raman spectroscopy, temperature-programmed spectroscopy, X-ray diffraction, and X-ray absorption spectroscopy. However, although not being surface-sensitive per se, these techniques provide results relevant for the catalyzed reaction. Illustrative case studies comprise the investigation of (i) vanadia-based catalysts during selective oxidation and ammoxidation of toluene and during methanol synthesis, (ii) supported chromium oxides during octane aromatization, (iii) zeolite crystallization and catalysis, and (iv) a Cu/ZnO catalyst during methanol synthesis.     

Morphology and properties of foamed high crystallinity PEEK prepared by high temperature thermally induced phase separation

Polyetheretherketone (PEEK) is a high-performance semi-crystalline thermoplastic polymer with outstanding mechanical properties, high thermal stability, resistance to most common solvents, and good biocompatibility. A high temperature thermally induced phase separation technique was used to produce PEEK foams with controlled foam density from PEEK in 4-phenylphenol (4PPH) solutions. Physical and mechanical properties, foam and bulk density, surface area, and pore morphology of foamed PEEK were characterized and the role of PEEK concentration and cooling rate was investigated. Porous PEEK with densities ranging from 110 to 360 kg/m³ with elastic moduli and crush strength ranging from 13 to 125 MPa and 0.8 to 7 MPa, respectively, was produced.     

Gastric Serotonin Biosynthesis and Its Functional Role in L-Arginine-Induced Gastric Proton Secretion

Among mammals, serotonin is predominantly found in the gastrointestinal tract, where it has been shown to participate in pathway-regulating satiation. For the stomach, vascular serotonin release induced by gastric distension is thought to chiefly contribute to satiation after food intake. However, little information is available on the capability of gastric cells to synthesize, release and respond to serotonin by functional changes of mechanisms regulating gastric acid secretion. We investigated whether human gastric cells are capable of serotonin synthesis and release. First, HGT-1 cells, derived from a human adenocarcinoma of the stomach, and human stomach specimens were immunostained positive for serotonin. In HGT-1 cells, incubation with the tryptophan hydroxylase inhibitor p-chlorophenylalanine reduced the mean serotonin-induced fluorescence signal intensity by 27%. Serotonin release of 147 ± 18%, compared to control HGT-1 cells (set to 100%) was demonstrated after treatment with 30 mM of the satiating amino acid L-Arg. Granisetron, a 5-HT3 receptor antagonist, reduced this L-Arg-induced serotonin release, as well as L-Arg-induced proton secretion. Similarly to the in vitro experiment, human antrum samples released serotonin upon incubation with 10 mM L-Arg. Overall, our data suggest that human parietal cells in culture, as well as from the gastric antrum, synthesize serotonin and release it after treatment with L-Arg via an HTR3-related mechanism. Moreover, we suggest not only gastric distension but also gastric acid secretion to result in peripheral serotonin release.     

Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.     

Novel Azocoumarin Derivatives—Synthesis and Characterization

The paper presents synthesis and characterization of nine new thiazolyl-(phenyldiazenyl)-2H-chromen-2-one dyes. The impact of substituent structure in thiazole ring in the synthesized azocoumarin derivatives on electrochemical properties, photoisomerization process and photovoltaic response was examined. The dyes were electrochemically active and undergo reduction and oxidation processes. They showed low electrochemically estimated energy band gap in the range of 1.71–2.13 eV. Photoisomerization process of the synthesized molecules was studied in various solvents such as ethanol, chloroform and N,N-dimethylformamide (DMF) upon the UV illumination. It was found that novel azodyes showed reversible trans-cis-trans isomerization and exhibited long thermal back to the trans form, that was even 7 days in DMF. Selected azocoumarin were molecularly dispersed in polystyrene for preparation of guest-host azopolymer systems to study the cis-trans thermal isomerization of obtained dyes in solid state. The photovoltaic activity of the azochromophores was tested in bulk-heterojunction solar cells. They acting as weak donors in device with structure ITO/PEDOT:PSS/dye:PC70BM/Al. No photovoltaic response of cells with azocoumarin derivatives bearing 4-fluorobenzene, 3,4-dichlorobenzene, or 4-(1-adamantyl) unit was found. Additionally, dye which showed the best activity was examined in three-component solar cells ITO/PEDOT:PSS/PTB7:PC70BM:dye/PFN/Al.