Tuning Molecular Self‐Assembly on Bulk Insulator Surfaces by Anchoring of the Organic Building Blocks

Molecular self‐assembly constitutes a versatile strategy for creating functional structures on surfaces. Tuning the subtle balance between intermolecular and molecule‐surface interactions allows structure formation to be tailored at the single‐molecule level. While metal surfaces usually exhibit interaction strengths in an energy range that favors molecular self‐assembly, dielectric surfaces having low surface energies often lack sufficient interactions with adsorbed molecules. As a consequence, application‐relevant, bulk insulating materials pose significant challenges when considering them as supporting substrates for molecular self‐assembly. Here, the current status of molecular self‐assembly on surfaces of wide‐bandgap dielectric crystals, investigated under ultrahigh vacuum conditions at room temperature, is reviewed. To address the major issues currently limiting the applicability of molecular self‐assembly principles in the case of dielectric surfaces, a systematic discussion of general strategies is provided for anchoring organic molecules to bulk insulating materials.     

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.     

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.     

Aspects of high hydrostatic pressure food processing: Perspectives on technology and food safety

The last two decades saw a steady increase of high hydrostatic pressure (HHP) used for treatment of foods. Although the science of biomaterials exposed to high pressure started more than a century ago, there still seem to be a number of unanswered questions regarding safety of foods processed using HHP. This review gives an overview on historical development and fundamental aspects of HHP, as well as on potential risks associated with HHP food applications based on available literature. Beside the combination of pressure and temperature, as major factors impacting inactivation of vegetative bacterial cells, bacterial endospores, viruses, and parasites, factors, such as food matrix, water content, presence of dissolved substances, and pH value, also have significant influence on their inactivation by pressure. As a result, pressure treatment of foods should be considered for specific food groups and in accordance with their specific chemical and physical properties. The pressure necessary for inactivation of viruses is in many instances slightly lower than that for vegetative bacterial cells; however, data for food relevant human virus types are missing due to the lack of methods for determining their infectivity. Parasites can be inactivated by comparatively lower pressure than vegetative bacterial cells. The degrees to which chemical reactions progress under pressure treatments are different to those of conventional thermal processes, for example, HHP leads to lower amounts of acrylamide and furan. Additionally, the formation of new unknown or unexpected substances has not yet been observed. To date, no safety-relevant chemical changes have been described for foods treated by HHP. Based on existing sensitization to non-HHP-treated food, the allergenic potential of HHP-treated food is more likely to be equivalent to untreated food. Initial findings on changes in packaging materials under HHP have not yet been adequately supported by scientific data.     

A Potential Involvement of Anandamide in the Modulation of HO/NOS Systems: Women,Menopause, and “Medical Cannabinoids”

Endocannabinoids and their receptors are present in the cardiovascular system; however, their actions under different pathological conditions remain controversial. The aim of our study was to examine the effects of anandamide (AEA) on heme oxygenase (HO) and nitric oxide synthase (NOS) systems in an estrogen-depleted rat model. Sham-operated (SO) and surgically induced estrogen-deficient (OVX) female Wistar rats were used. During a two-week period, a group of OVX rats received 0.1 mg/kg estrogen (E₂) per os, while AEA-induced alterations were analyzed after two weeks of AEA treatment at the dose of 1.0 mg/kg. At the end of the experiment, cardiac activity and expression of HO and NOS enzymes, content of cannabinoid 1 receptor, as well as concentrations of transient potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) were measured. Our results show that estrogen withdrawal caused a significant decrease in both NOS and HO systems, and a similar tendency was observed regarding the TRPV1/CGRP pathway. Two weeks of either AEA or E₂ treatment restored the adverse changes; however, the combined administration of these two molecules did not result in a further improvement. In light of the potential relationship between AEA and HO/NOS systems, AEA-induced upregulation of HO/NOS enzymes may be a therapeutic strategy in estrogen-deficient conditions.     

Plant-Origin Stabilizer as an Alternative of Natural Additive to Polymers Used in Packaging Materials

Over the past 25 years, cannabis plants have gained major popularity in the research community. This study aimed to evaluate the antioxidant capacity and stabilization efficiency of cannabidiol (CBD) extract in two different polymers: polylactide (PLA) and ethylene–norbornene copolymer (Topas) that are used in packaging materials more often. The research technology included weathering in a special chamber, surface free energy and color change measurements, surface morphology and Fourier-transform infrared spectroscopy (FTIR) analysis, thermogravimetry, and determination of the oxidation induction time or temperature (OIT) values, based on which the effectiveness of the cannabidiol extract could be estimated. Obtained results showed that the addition of CBD to polymer mixtures significantly increased their resistance to oxidation, and it can be used as a natural stabilizer for polymeric products. Moreover, samples with cannabidiol changed their coloration as a result of weathering. Therefore, this natural additive can also be considered as a colorimetric indicator of aging that informs about the changes in polymeric materials during their lifetime. On the other hand, surface properties of samples with cannabidiol content did not alter much compared to pure Topas and PLA.     

Identification of Specific and Nonspecific Inhibitors of Bacillus anthracis Type III Pantothenate Kinase (PanK)

Antibiotics with novel mechanisms of action are desperately needed to combat the increasing rates of multidrug-resistant infections. Bacterial pantothenate kinase (PanK) has emerged as a target of interest to cut off the biosynthesis of coenzyme A. Herein we report the results of an in vitro high-throughput screen of over 10 000 small molecules against Bacillus anthracis PanK, as well as a follow-up screen of hits against PanK isolated from Pseudomonas aeruginosa and Burkholderia cenocepacia. Nine hits are structurally categorized and analyzed to set the stage for future drug development.     

Effects of triiodothyronine on morphology, growth behavior, and the actin cytoskeleton in mouse osteoblastic cells (MC3T3-E1)

We investigated the effects of thyroid hormone treatment on morphology, growth behaviour, and cytoskeletal structures of long-term cultured MC3T3-E1 cells. Morphological investigations were carried out on native cells by phase contrast microscopy and on epon-embedded semithin sections. The area covered by the cell and matrix layers (tissue-like area), percent extracellular matrix, average height of tissue-like area, and length and height of single cells were measured histomorphometrically on the cross sections. F-actin was analyzed histochemically and quantitated after fluorochrome-labeled phalloidin staining using confocal microscopy and fluorometry. Significant differences between control and T3-treated cells were found after confluency, but not in subconfluent cultures. Control cells continued to proliferate forming multilayers, and produced increasing amounts of extracellular matrix. In contrast, T3-treated cells stopped to proliferate forming two cell layers at the maximum. These cells were flattened, distinctly enlarged, and polygonal in shape. Histochemical staining for F-actin revealed three different staining patterns, depending on the position of the cell within the multilayer of control cultures. Basal cells contained a large number of thick stress fibers in parallel arrangement. Intermediate cells exhibited only a few thick actin filament bundles located at the outermost periphery. The superficial cells were characterized by a large number of thin, parallel-oriented microfilament bundles extending across the entire cytoplasm. The actin pattern of T3-treated cells resembled that of the basal cell layer of the control cells. The amount of F-actin increased with the prolonged T3 treatment. We conclude from these data that the known specific cellular responses to T3 treatment are accompanied by significant morphological alterations indicating pivotal effects of thyroid hormones on osteoblastic differentiation.     

Supermolecular structure of isotactic polypropylene

The crystalline structure, spherulitic crystallization and melting behaviour of isotactic polypropylene (iPP) is comprehensively reviewed, illustrated and discussed. It is demonstrated and summarized how the nucleation, development and growth of the different spherulites depend on the crystallization and melting conditions both in quiescent and sheared melt. Based on the results the microtexture development during real processing conditions is elucidated for selected examples. Several subjects of intense debate on the above topics are clarified using evidence from polarized optical micrography and differential scanning calorimetry.     

Comparative molecular field analysis of haptens docked to the multispecific antibody IgE(Lb4)

Using comparative molecular field analysis (CoMFA), three-dimensional quantitative structure-activity relationships were developed for 27 haptens which bind to the monoclonal antibody IgE(Lb4). In order to obtain an alignment for these structurally very diverse antigens, the compounds were docked to a previously modeled receptor structure using the automated docking program AUTODOCK (Goodsell, D.S.; Olson, A.J. Proteins: Struct., Funct., Genet. 1990, 8, 195-202). Remarkably, this alignment method yielded highly consistent QSAR models, as indicated by the corresponding cross-validated r2 values (0.809 for a model with carbon as probe atom, 0.773 for a model with hydrogen as probe atom). Conventional alignment failed in providing a basis for self-consistent CoMFAs. Amino acids Tyr H 50, Tyr H 52, and Trp H 95 of the receptor appeared to be of crucial importance for binding of various antigens. These findings are consistent with earlier considerations of aromatic residues being responsible for the multispecificity of certain immunoglobulins.