High-Pressure Reverse Osmosis for Industrial Water Recycling: Permeate-Sided Pressure Drop as Performance-Limiting Factor

In the chemical industry large amounts of saline wastewater occur. Its disposal into rivers is a considerable burden to the ecosystem. To strive for a circular economy and enable a viable raw material recycling, energy-efficient concentration processes are requisite. High-pressure reverse osmosis meets this criterion, but its industrial application demands suitable membrane elements that withstand the exceptional operation conditions and provide sufficient performance. Hence, new requirements regarding the design of spiral-wound elements arise. To identify those, specific performance-limiting effects need a better understanding.     

Genetic and Epigenomic Modifiers of Diabetic Neuropathy

Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.     

Water-repellent films from corn protein and tomato cutin

Flexible and hydrophobic biobased films were obtained using zein esterified with methanol and para-toluene (p-toluene) sulfonic acid, cutin from tomato peels and ethanol. Esterification was confirmed by proton nuclear magnetic resonance and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR). Non-modified zein films were brittle and hydrophilic. ATR-FTIR demonstrated that zein esterification increased zein hydrophobicity. Without cutin, esterified zein films were hydrophobic but brittle. Addition of cutin yielded films that were flexible and hydrophobic, as demonstrated by contact angle measurements. Principal component analysis (PCA) of ATR-FTIR data showed that intensities at 3195 cm⁻¹ and 3490 cm⁻¹ were correlated to the relative hydrophobicity of zein films. PCA also showed that films of esterified zein and cutin were more hydrophobic than their counterparts (non-modified zein without cutin). Optical and scanning electron microscopy demonstrated that esterified zein was compatible with cutin and yielded cohesive films, which did not fracture upon bending.     

Influence of the stoichiometry,microstructure, and metallization method on the dielectric properties of 0.94 Na0.5Bi0.5TiO3-0.06 BaTiO3

The morphotropic composition of the lead-free solid solution between Na_0.5Bi_0.5TiO₃ and BaTiO₃ (0.94 Na_0.5Bi_0.5TiO₃-0.06 BaTiO₃ or NBT-6BT) is of particular interest for the next generation of high-temperature capacitors but remains plagued by the diversity of dielectric properties reported in the literature. In order to explain the apparent inconsistencies among the reported dielectric properties of NBT-6BT, we examine the influence of stoichiometry, phase separation, and metallization method. We show that the nominal stoichiometry has a crucial effect, since increasing the nominal Na/Bi ratio increases conductivity and dielectric losses (tan δ). It also increases the real part of the permittivity (ε’) and the frequency dispersion of both ε’ and tan δ, thereby altering the shape of the evolution with temperature of the dielectric properties. Moreover it increases the depolarization temperature (T_d) and decreases the temperature of maximum permittivity (T_m). Phase separation also occurs during the synthesis of NBT-6BT as Na evaporation leads to the formation of secondary Ba-containing phases. We report that these phases can have a positive impact on the dielectric properties: a moderate volume fraction (2.5 to 3.0%) and average grain surface (0.9 to 3.0 µm²) of these secondary Ba-containing phases increase the relative permittivity, decrease the dielectric losses, and increase the insulation resistance. We also show that the metallization method impacts the dielectric properties and therefore may contribute to the differences between various reports. The dielectric properties of NBT-6BT samples are measured during successive heating/cooling cycles and reveal that the permittivity value is lower during the first heating when silver paste, even cured, is used. These three components contribute to explaining the diversity of the reported dielectric properties of NBT-6BT.     

Single Cell Bioprinting with Ultrashort Laser Pulses

Tissue engineering requires the precise positioning of mammalian cells and biomaterials on substrate surfaces or in preprocessed scaffolds. Although the development of 2D and 3D bioprinting technologies has made substantial progress in recent years, precise, cell-friendly, easy to use, and fast technologies for selecting and positioning mammalian cells with single cell precision are still in need. A new laser-based bioprinting approach is therefore presented, which allows the selection of individual cells from complex cell mixtures based on morphology or fluorescence and their transfer onto a 2D target substrate or a preprocessed 3D scaffold with single cell precision and high cell viability (93–99% cell survival, depending on cell type and substrate). In addition to precise cell positioning, this approach can also be used for the generation of 3D structures by transferring and depositing multiple hydrogel droplets. By further automating and combining this approach with other 3D printing technologies, such as two-photon stereolithography, it has a high potential of becoming a fast and versatile technology for the 2D and 3D bioprinting of mammalian cells with single cell resolution.     

Antithrombin and Its Role in Host Defense and Inflammation

Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects: depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.     

The Emerging Clinical Role of Spermine in Prostate Cancer

Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management.     

Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range. Insights into the structure–activity relationships are given, along with determination of the thioredoxin reductase inhibition potential, two-photon imaging of the fluorescent derivatives, and evaluation of gold uptake.     

Small-Molecule Inhibitors of the Proteasome's Regulatory Particle

Cells need to synthesize and degrade proteins consistently. Maintaining a balanced level of protein in the cell requires a carefully controlled system and significant energy. Degradation of unwanted or damaged proteins into smaller peptide units can be accomplished by the proteasome. The proteasome is composed of two main subunits. The first is the core particle (20S CP), and within this core particle are three types of threonine proteases. The second is the regulatory complex (19S RP), which has a myriad of activities including recognizing proteins marked for degradation and shuttling the protein into the 20S CP to be degraded. Small-molecule inhibitors of the 20S CP have been developed and are exceptional treatments for multiple myeloma (MM). 20S CP inhibitors disrupt the protein balance, leading to cellular stress and eventually to cell death. Unfortunately, the 20S CP inhibitors currently available have dose-limiting off-target effects and resistance can be acquired rapidly. Herein, we discuss small molecules that have been discovered to interact with the 19S RP subunit or with a protein closely associated with 19S RP activity. These molecules still elicit their toxicity by preventing the proteasome from degrading proteins, but do so through different mechanisms of action.     

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.