Strong angular and spectral narrowing of electroluminescence in an integrated Tamm-plasmon-driven halide perovskite LED.

Next-generation light-emitting applications such as displays and optical communications require judicious control over emitted light, including intensity and angular dispersion. To date, this remains a challenge as conventional methods require cumbersome optics. Here, we report highly directional and enhanced electroluminescence from a solution-processed quasi-2-dimensional halide perovskite light-emitting diode by building a device architecture to exploit hybrid plasmonic-photonic Tamm plasmon modes. By exploiting the processing and bandgap tunability of the halide perovskite device layers, we construct the device stack to optimise both optical and charge-injection properties, leading to narrow forward electroluminescence with an angular full-width half-maximum of 36.6° compared with the conventional isotropic control device of 143.9°, and narrow electroluminescence spectral full-width half-maximum of 12.1 nm. The device design is versatile and tunable to work with emission lines covering the visible spectrum with desired directionality, thus providing a promising route to modular, inexpensive, and directional operating light-emitting devices.

Biochar mitigates the postponed bioavailability and toxicity of phthalic acid esters in the soil.

Observed nowadays wide pollution of the environment with microplastic and phthalic acid esters (PAEs) (such as dimethyl phthalate, DMP; diethyl phthalate, DEP; dibutyl phthalate, DBP; benzyl butyl phthalate, BBP; di-(2-ethylhexyl) phthalate, DEHP and di-n-octyl phthalate, DNOP) is a result of their increased production and usage. Weak bonding with polymer matrix enables their easier mobilization in the environment and increased bioavailability. The aim of the presented studies was the estimation of the fate of six priority PAEs in the soil-vegetable system and the application of biochar to immobilize PAEs in the soil preventing their bioavailability to lettuce. Both the acute (one full lettuce development period) and prolongated effect (lettuce cultivated after 10 weeks from the first PAEs contamination) were estimated to examine the long-time exposure under crop rotation. The addition of 1 % of corn-derived biochar immobilized PAEs in the soil efficiently (up to 4 times increased concentration) with the following order: DBP < DEP < DMP < DEHP < DNOP < BBP. Bioavailable PAEs were determined in lettuce roots (DMP, BBP, DEHP), and lettuce leaves (DEP, DBP, DNOP) but the presence of biochar lowered their content. PAEs, although not available for lettuce, were available for other organisms, confirming that the bioavailability or lack of nutrients is of great importance in PAEs-polluted soil. In long-time experiments, without biochar amendment, all PAEs were 3-12 times more bioavailable and were mainly accumulated in lettuce roots. The biochar addition significantly reduces (1.5-11 times) PAEs bioavailability over time. However, the PAEs content in roots remained significantly higher in samples with crop rotation compared to samples where only lettuce was grown. The results confirmed that biochar addition to the soil reduces their bioavailability and mobility inside the plant, limiting their transport from roots to leaves and reducing the exposure risk but confirming that lettuce leaves may be a safe food when cultivated in PAEs-polluted soil.

Immunohistochemical evaluation of osteopontin expression in triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is associated with lack of expression of estrogen and progesterone receptors and HER2 and is the subgroup of breast cancers with the worst prognosis. Osteopontin is a phosphorylated glycoprotein whose overexpression may occur in pathological states such as cancers. The main purpose of our study was to evaluate the immunohistochemical expression of osteopontin in connection with the analysis of recognized clinical and pathological prognostic factors in primary sites of TNBC with and without lymph node metastases. Material and methods: The immunohistochemical evaluation of osteopontin expression in 35 women with TNBC, chosen from a group of 726 patients, was performed. The material came from the excisional biopsies of primary breast cancers and total mastectomies. Results: All patients showed expression of osteopontin, in most cases the expression of osteopontin rated at [+] (57.1%) and [++] (42.9%). Our study analyzed the relationship between the expression of osteopontin and traditional prognostic markers, such as the tumor grade, size, and lymph node involvement. We found a strong relationship only between the expression of osteopontin and the presence of lymph node metastases (p ≤ 0.0001). 93% of patients for whom the expression of osteopontin was determined at [++] had metastasis to lymph nodes and, for comparison, only 15% of women for whom the expression of osteopontin was rated at [+] showed the presence of metastases in the lymphatic nodes. Conclusions: There is a correlation between osteopontin expression and the presence of lymph node metastases in TNBC, suggesting that osteopontin plays an important role in the invasiveness of TNBC.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n-dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumours, and WRN inhibitors are in development. Here, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth In vitro and In vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair (MMR) alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft (PDX) models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic-lethal targeting of WRN in MSI cancer and tools to dissect WRN biology.

Utilization of High-Throughput Experimentation (HTE) and ChemBeads Toward the Development of an Aryl Bromide and Benzyl Bromide Photoredox Cross-Electrophile Coupling.

The discussion herein describes a metallaphotoredox reaction that allows for efficient exploration of benzyl structure-activity relationships in medicinal chemistry. The use of HTE (high-throughput experimentation) and ChemBeads allows for rapid reaction optimization. The formation of di(hetero)arylmethanes via cross-electrophile coupling between aryl bromides and benzyl bromides provides access to diverse chemical space. The breadth of the substrate scope will be discussed, along with the utilization of batch photochemistry for the preparation of this di(hetero)arylmethane motif on a larger scale.

Prescaling Relaxation to Nonthermal Attractors.

We study how isotropic and homogeneous far-from-equilibrium quantum systems relax to nonthermal attractors, which are of interest for cold atoms and nuclear collisions. We demonstrate that a first-order ordinary differential equation governs the self-similar approach to nonthermal attractors, i.e., the prescaling. We also show that certain natural scaling-breaking terms induce logarithmically slow corrections that prevent the scaling exponents from reaching the constant values during the system's lifetime. We propose that, analogously to hydrodynamic attractors, the appropriate mathematical structure to describe such dynamics is the transseries. We verify our analytic predictions with state-of-the-art 2PI simulations of the large-N vector model and QCD kinetic theory.

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma-Today and Tomorrow.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease represent major risk factors of HCC. Multiple different treatment options are available, depending on the Barcelona Clinic Liver Cancer (BCLC) algorithm. Systemic treatment is reserved for certain patients in stages B and C, who will not benefit from regional treatment methods. In the last fifteen years, the arsenal of available therapeutics has largely expanded, which improved treatment outcomes. Nevertheless, not all patients respond to these agents and novel combinations and drugs are needed. In this review, we aim to summarize the pathway of trials investigating the safety and efficacy of targeted therapeutics and immunotherapies since the introduction of sorafenib. Furthermore, we discuss the current evidence regarding resistance mechanisms and potential novel targets in the treatment of advanced HCC.

Surface Modification of ZnO Nanotubes by Ag and Au Coatings of Variable Thickness: Systematic Analysis of the Factors Leading to UV Light Emission Enhancement.

Surface modification by plasmonic metals is one of the most promising ways to increase the band-to-band excitonic recombination in zinc oxide (ZnO) nanostructures. However, the metal-induced modulation of the UV light emission depends strongly on the production method, making it difficult to recognize the mechanism responsible for charge/energy transfer between the semiconductor and a metal. Therefore, in this study, the ZnO/Ag and Au hybrids were produced by the same, fully controlled experimental approach. ZnO nanotubes (NTs), fabricated by a template-assisted ALD synthesis, were coated by metals of variable mass thickness (1-6.5 nm thick) using the electron beam PVD technique. The deposited Ag and Au metals grew in the form of island films made of metallic nanoparticles (NPs). The size of the NPs and their size distribution decreased, while the spacing between the NPs increased as the mass of the deposited Ag and Au metals decreased. Systematic optical analysis allowed us to unravel a specific role of surface defects in ZnO NTs in the processes occurring at the ZnO/metal interface. The enhancement of the UV emission was observed only in the ZnO/Ag system. The phenomena were tentatively ascribed to the coupling between the defect-related (DL) excitonic recombination in ZnO and the localized surface plasmon resonance (LSPR) at the Ag NPs. However, the enhancement of UV light was observed only for a narrow range of Ag NP dimensions, indicating the great importance of the size and internanoparticle spacing in the plasmonic coupling. Moreover, the enhancement factors were much stronger in ZnO NTs characterized by robust DL-related emission before metal deposition. In contrast to Ag, Au coatings caused quenching of the UV emission from ZnO NTs, which was attributed to the uncoupling between the DL and LSP energies in this system and a possible formation of the ohmic contact between the Au metal and the ZnO.

Increased concentration of PAH derivatives in biochar-amended soil observed in a long-term experiment.

During biochar preparation or application some toxic substances may be formed. The established limitations of the content of polycyclic aromatic hydrocarbons (PAHs) aim to monitor the fate of PAHs in the life cycle of biochar. The latest studies have revealed that besides PAHs, some of their derivatives with confirmed toxicity are formed. There has been no policy regards PAH derivatives in biochar yet. The aim of the presented studies was the estimation the changes in the content of PAHs and their derivatives during the agricultural application of biochar. A pot experiment with grass revealed that in a short time, both the content of PAHs and their derivatives was reduced. Similarly, when biochar was added to soil in a long-term experiment, the content of determined derivatives was below the limit of detection, whereas interestingly, the content of pristine PAHs increased with time. Co-addition of biochar and sewage sludge increased the content of PAHs and their derivatives indicating potential environmental hazard due to their presence. However, the key point is the estimation of the bioavailability of PAHs and their derivatives as only the bioavailable fraction is revealing the environmental hazard.

Cannabigerol (CBG) signal enhancement in its analysis by gas chromatography coupled with tandem mass spectrometry.

PURPOSE: According to recent reports, cannabigerol (CBG) concentration level in blood and body fluids may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking. While the analytical sensitivity of cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabichromene (CBC) or cannabinol (CBN) estimation by gas chromatography-mass spectrometry (GC-MS) is similar and sufficiently high, it is exceptionally low in the case of CBG (ca. 25 times lower than for the other mentioned cannabinoids). The purpose of this study is to explain the reasons for the extremely low analytical sensitivity of GC-MS in estimating CBG and to present possible ways of its improvement. METHODS: Nuclear magnetic resonance (NMR) data and GC-MS responses to CBG and its various derivatization and transformation products were studied. RESULTS: The validation data of individual derivatives of CBG and its transformation products were established. CBG silylation/acylation or hydration allows to decrease LOD about 3 times, whereas the formation of pyranic CBG derivative leads to 10-times decrease of LOD. The paper enriches the literature of the subject by providing MS and NMR spectra, not published so far, for derivatives of CBG and its transformation products. The most likely cause of low GC-MS response to CBG is also presented. CONCLUSIONS: The presented results shows that although the signal increase of CBG can be obtained through its derivatization by silylation and/or acylation, the greatest increase is observed in the case of its cyclization to the pyranic CBG form during the sample preparation process. The CBG cyclization procedure is very simple and workable in estimating this cannabinoid in blood/plasma samples.

Determination of 3- and 4-chloromethcathinone interactions with plasma proteins: study involving analytical and theoretical methods.

PURPOSE: The purpose of this paper was to determine 3- and 4-chloromethcathinone (3- and 4-CMC) binding degree and possible binding interaction modes with human serum albumin (HSA) using analytical and theoretical methods. METHODS: Experimental determination of 3- and 4-CMC binding degree with HSA was performed using gas chromatography-tandem mass spectrometry preceded by the equilibrium dialysis (ED) and ultrafiltration (UF). Nuclear magnetic resonance (NMR) spectroscopy was used to determine 3- and 4-CMC epitope-binding maps and possible binding sites in HSA. The molecular docking and molecular dynamics were employed to obtain detailed information about binding modes of 3- and 4-CMC enantiomers in HSA. RESULTS: As follows from the presented data, the degree of binding of 3- and 4-CMC is at a similar level of approx. 80%. This indicates a relatively strong binding of CMC to plasma proteins. The model studies employing the NMR spectroscopy and molecular simulations indicate that both CMCs bind to HSA. The whole 3- and 4-CMC molecules are embedded in the binding sites, with aromatic moieties being in the closest contact with the HSA residues. Moreover, conducted experiments show that  Sudlow site II is the main binding center for 3- and 4-CMC and  Sudlow site I acts as the secondary binding site. CONCLUSIONS: Although many studies describe pharmacological and toxicological properties of synthetic cathinones (SC), the data taking SCs binding in plasma into consideration are scarce. To our knowledge, this is the first report presenting comprehensive experimental and theoretical characterization of 3- and 4-CMC binding with plasma proteins.

Fast and reliable determination of phthalic acid esters in soil and lettuce samples based on QuEChERS GC-MS/MS.

Phthalates are commonly used as plasticizers, and solvents in industry and households. We propose an application of the QuEChERS method for the determination of six PAEs in the soil and lettuce (roots and leaves) by GC-MS/MS. The QuEChERS method validation procedure was performed and good linearity (>0.997), recovery (97.2-99.1 %), very low detection limits (0.09-0.43 ng/g), and satisfactory inter- and intraday precision (∼4%) were obtained confirming that QuEChERS GC-MS/MS applied for PAEs determination in the environmental samples is a cheap and environmentally friendly method. In general, the higher the number of carbon atoms in PAEs, the higher the percentage noted in the lettuce roots. At higher PAEs concentration (60 ng/g) the main bis(2-ethylhexyl) phthalate (DEHP) sink were roots whereas at lower concentrations (30 ng/g) most of DEHP was noted in lettuce leaves implying that the fate of PAEs was governed not by the chemical structure of PAEs but rather partitioning (logKow).

Fabrication and characterization of new levan@CBD biocomposite sponges as potential materials in natural, non-toxic wound dressing applications.

Wound healing is a complex process; therefore, new dressings are frequently required to facilitate it. In this study, porous bacterial levan-based sponges containing cannabis oil (Lev@CBDs) were prepared and fully characterized. The sponges exhibited a suitable swelling ratio, proper water vapor transmission rate, sufficient thermal stability, desired mechanical properties, and good antioxidant and anti-inflammatory properties. The obtained Lev@CBD materials were evaluated in terms of their interaction with proteins, human serum albumin and fibrinogen, of which fibrinogen revealed the highest binding effect. Moreover, the obtained biomaterials exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, as well as being non-hemolytic material as indicated by hemolysis tests. Furthermore, the sponges were non-toxic and compatible with L929 mouse fibroblasts and HDF cells. Most significantly, the levan sponge with the highest content of cannabis oil, in comparison to others, retained its non-hemolytic, anti-inflammatory, and antimicrobial properties after prolonged storage in a climate chamber at a constant temperature and relative humidity. The designed sponges have conclusively proven their beneficial physicochemical properties and, at the preliminary stage, biocompatibility as well, and therefore can be considered a promising material for wound dressings in future in vivo applications.

Possible Therapies for Hepatocellular Carcinoma-Preparing for the Modern War with the Insidious Enemy.

Hepatocellular carcinoma (HCC) accounts for 7% of all malignancies and about 90% of all primary liver malignancies, making it the most common type of malignant liver neoplasm [...].

Successful Use of Methylene Blue in Catecholamine-Resistant Septic Shock: A Case Report and Short Literature Review.

Despite efforts to improve treatment outcomes, mortality in septic shock remains high. In some patients, despite the use of several adrenergic drugs, features of refractory vasoplegic shock with progressive multiorgan failure are observed. We present a case report of the successful reversal of vasoplegic shock following the use of methylene blue, a selective inhibitor of the inducible form of nitric oxide synthase, which prevents vasodilation in response to inflammatory cytokines. We also briefly review the literature.

GC vs. HPLC in quantitation of CBD, CBG, ∆9-THC and CBN in plasma using different sample preparation methods.

The sensitivity of complex analytical procedures depends not only on the sensitivity of the analytical instrument used, but also on the recovery degree of the examined analyte by the employed sample preparation method. The recovery degrees of individual cannabinoids reported in literature, estimated using the same sample preparation method, are unexpectedly divergent. Therefore, the aim of this study was a thorough assessment of the most commonly used sample preparation methods, such as protein precipitation, LLE, QuEChERS and SPE, in the context of the reliability of the obtained results. The presented report shows that the highest sensitivity, precision and reliability of the chromatographic analysis of CBG, CBD, ∆9-THC and CBN in human plasma can be obtained using SPE. The recovery degrees of these cannabinoids by SPE are highly repeatable and exceed 95 %, while they are significantly lower for such sample preparation methods as protein precipitation, LLE and QuEChERS (ca. 80, 65 and 87, respectively). Moreover, the supernatants obtained by the latter methods contain interferents evoking matrix-effect, which makes reliable quantification of the listed cannabinoids by GC difficult. To our knowledge, the paper is the first such extensive comparison of sample preparation procedures used for the determination of cannabinoids in plasma by GC-MS and HPLC-MS. The presented results and the discussion allow to understand why different recovery degrees for the same xenobiotic can be find in literature despite they have been estimated using the same or different sample preparation method or different chromatography types.

Rigorous Bounds on Transport from Causality.

We use causality to derive a number of simple and universal constraints on dispersion relations, which describe the location of singularities of retarded two-point functions in relativistic quantum field theories. We prove that all causal dissipative dispersion relations have a finite radius of convergence in cases where stochastic fluctuations are negligible. We then give two-sided bounds on all transport coefficients in units of this radius, including an upper bound on diffusivity.

Synthesis, Electrochemical and Photochemical Properties of Sulfanyl Porphyrazine with Ferrocenyl Substituents.

Ferrocene is useful in modern organometallic chemistry due to its versatile applications in material sciences, catalysis, medicinal chemistry, and diagnostic applications. The ferrocene moiety can potentially serve many purposes in therapeutics and diagnostics. In the course of this study, (6-bromo-1-oxohexyl)ferrocene was combined with dimercaptomaleonitrile sodium salt to yield a novel maleonitrile derivative. Subsequently, this compound was subjected to an autocyclotetramerization reaction using the Linstead conditions in order to obtain an octaferrocenyl-substituted magnesium(II) sulfanyl porphyrazine. Following that, both compounds-the maleonitrile derivative and the porphyrazine derivative-were subjected to physicochemical characterization using UV-Vis, ES-TOF, MALDI-TOF, and one-dimensional and two-dimensional NMR spectroscopy. Moreover, the sulfanyl porphyrazine was subjected to various photophysical studies, including optical absorption and emission measurements, as well as the evaluation of its photochemical properties. Values of singlet oxygen generation quantum yields were obtained in different organic solvents. The electrochemical properties of the synthesized compounds were studied using cyclic voltammetry. According to the electrochemical results, the presence of electron-withdrawing oxohexyl groups attached to ferrocene afforded significantly more positive oxidation potentials of the ferrocene-based redox process up to 0.34 V vs. Fc+/Fc.

Sublingual Microcirculation in Temporary Mechanical Circulatory Support: A Current State of Knowledge.

Cardiogenic shock causes hypoperfusion within the microcirculation, leading to impaired oxygen delivery, cell death, and progression of multiple organ failure. Mechanical circulatory support (MCS) is the last line of treatment for cardiac failure. The goal of MCS is to ensure end-organ perfusion by maintaining perfusion pressure and total blood flow. However, machine-blood interactions and the nonobvious translation of global macrohemodynamics into the microcirculation suggest that the use of MCS may not necessarily be associated with improved capillary flow. With the use of hand-held vital microscopes, it is possible to assess the microcirculation at the bedside. The paucity of literature on the use of microcirculatory assessment suggests the need for an in-depth look into microcirculatory assessment within the context of MCS. The purpose of this review is to discuss the possible interactions between MCS and microcirculation, as well as to describe the research conducted in this area. Regarding sublingual microcirculation, 3 types of MCS will be discussed: venoarterial extracorporeal membrane oxygenation, intra-aortic balloon counterpulsation, and microaxial flow pumps (Impella).

The Anti-Acne Potential and Chemical Composition of Knautia drymeia Heuff. and Knautia macedonica Griseb Extracts.

The treatment of acne and other seborrheic diseases has arisen as a significant clinical challenge due to the increasing appearance of multi-drug resistant pathogens and a high frequency of recurrent lesions. Taking into consideration the fact that some Knautia species are valuable curatives in skin diseases in traditional medicine, we assumed that the thus far unstudied species K. drymeia and K. macedonica may be a source of active substances used in skin diseases. The purpose of this study was to evaluate the antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities of their extracts and fractions. An LC-MS analysis revealed the presence of 47 compounds belonging to flavonoids and phenolic acids in both species while the GC-MS procedure allowed for the identification mainly sugar derivatives, phytosterols, and fatty acids and their esters. The ethanol as well as methanol-acetone-water (3:1:1) extracts of K. drymeia (KDE and KDM) exhibited great ability to scavenge free radicals and good capacity to inhibit cyclooxygenase-1, cyclooxygenase-2, and lipoxygenase. Moreover, they had the most favorable low minimal inhibitory concentration values against acne strains, and importantly, they were non-toxic toward normal skin fibroblasts. In conclusion, K. drymeia extracts seem to be promising and safe agents for further biomedical applications.