Revisiting the activity of two poly(vinyl chloride)- and polyethylene-degrading enzymes.

Biocatalytic degradation of non-hydrolyzable plastics is a rapidly growing field of research, driven by the global accumulation of waste. Enzymes capable of cleaving the carbon-carbon bonds in synthetic polymers are highly sought-after as they may provide tools for environmentally friendly plastic recycling. Despite some reports of oxidative enzymes acting on non-hydrolyzable plastics, including polyethylene or poly(vinyl chloride), the notion that these materials are susceptible to efficient enzymatic degradation remains controversial, partly driven by a general lack of studies independently reproducing previous observations. Here, we attempt to replicate two recent studies reporting that deconstruction of polyethylene and poly(vinyl chloride) can be achieved using an insect hexamerin from Galleria mellonella (so-called "Ceres") or a bacterial catalase-peroxidase from Klebsiella sp., respectively. Reproducing previously described experiments, we do not observe any activity on plastics using multiple reaction conditions and multiple substrate types. Digging deeper into the discrepancies between the previous data and our observations, we show how and why the original experimental results may have been misinterpreted.

Neoadjuvant letrozole and palbociclib in patients with HR-positive/HER2-negative early breast cancer and Oncotype DX Recurrence Score ≥18: DxCARTES study.

BACKGROUND: The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18. PATIENTS AND METHODS: Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR). RESULTS: A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified. CONCLUSIONS: The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.

Ab Initio Study of the Influence of Spin and Orbital Magnetic Moments on the Stability of Magnetic and Charge Distribution in Co:ZnO Monolayer.

The development of ultrathin magnets with tunable magnetic properties is essential for advancing quantum computing technologies. In this study, density functional theory (DFT) calculations were employed to investigate the atomic and electronic structures of a ZnO monolayer embedded with cobalt atoms. The impact of spin dynamics on charge transfer within the Co:ZnO system was thoroughly examined. Results revealed that the orbital magnetic moment of the cobalt atoms plays a crucial role in stabilizing the magnetic and charge distributions across the system. These findings offer valuable insights for the design and fabrication of quantum devices, thereby highlighting the potential of Co-doped ZnO monolayers in quantum computing applications.

Synthesis and antiproliferative activity of cisplatin-3-chloropiperidine conjugates.

We report the synthesis and characterization of two novel cisplatin- alkylating agents conjugates. Combining a platinum based cytostatic agent with a sterically demanding alkylating agent could potentially induce further DNA damage, block cell repair mechanisms and keep the substrate active against resistant tumor cell lines. The 3-chloropiperidines utilized as ligands in this work are cyclic representatives of the N-mustard family and were not able to coordinate platinum on their own. The introduction of a second coordination site, in form of a pyridine moiety, led to the isolation of the desired conjugates. They were characterized with HRMS, CHN-analyses and XRD. We concluded this work by examining the cytotoxicity of the ligands and the obtained complexes with MTT assays in human cancer cell lines. While the ligands showed hardly any activity, the novel conjugates both displayed a high antiproliferative and cytotoxic potency in a panel of three cell lines. Moreover, both complexes were able to largely circumvent the acquired cisplatin resistance of A2780cisR ovarian cancer cells, both in the MTT assay and a flow-cytometric apoptosis assay.

The Effect of Cryotherapy on Buccal Blood Vessels Evaluated by Optical Coherence Tomography Angiography: A Pilot Study.

While cryotherapy is one of the traditional ways to reduce postoperative complications in maxillofacial surgery, the cooling degree is not regulated in most cases and the achieved effect is not properly controlled. Therefore, to develop optimal cooling modes, we propose to study the buccal vascular response to cooling, which has not been previously shown. To evaluate the effect of cooling, we analyzed vessel networks using optical coherence tomography angiography (OCT-A). The cheek vessels were OCT-A monitored using cooling by an ice bag/cooling mask. We found the advantages of using a cooling mask over an ice bag consist of a statistically significant decrease in the perfused vessel density (PVD) of the papillary layer at the oral mucosa. The absence of the reticular layer vessel reaction to any type of cooling was noted. We argue for the necessity to develop optimal modes of cryotherapy, which will contribute to blood perfusion reduction and reduction of PVD recovery.

Unraveling the Liver-Brain Axis: Resveratrol's Modulation of Key Enzymes in Stress-Related Anxiety.

Stress-related anxiety disorders and anxiety-like behavior in post-traumatic stress disorder (PTSD) are associated with altered neurocircuitry pathways, neurotransmitter systems, and the activities of monoamine and glucocorticoid-metabolizing enzymes. Resveratrol, a natural polyphenol, is recognized for its antioxidant, anti-inflammatory, and antipsychiatric properties. Previous studies suggest that resveratrol reduces anxiety-like behavior in animal PTSD models by downregulating key enzymes such as 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) and monoamine oxidases (MAOs). However, the underlying mechanisms remain unclear. In this study, we explored the efficacy of resveratrol in treating stress-induced anxiety using a chronic predator stress model in rats. Resveratrol was administered intraperitoneally at 100 mg/kg following a 10-day stress exposure, and anxiety behavior was assessed with an elevated plus maze. Our results indicated that stress-related anxiety correlated with increased activities of brain MAO-A, MAO-B, and hepatic 11ß-HSD-1, alongside elevated oxidative stress markers in the brain and liver. Resveratrol treatment improved anxiety behavior and decreased enzyme activities, oxidative stress, and hepatic damage. We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol's potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.

Circulating microRNAs in Carotid Atherosclerosis: Complex Interplay and Possible Associations with Atherothrombotic Stroke.

Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate-severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, p = 0.047), miR-106b-3p (31.01 vs. 30.25, p = 0.004), and miR-494-5p (39 vs. 33, p < 0.001), while others (miR183-3p [25.5 vs. 28.6, p < 0.001], miR-126-5p [35.6 vs. 37.1, p = 0.03], and miR-216-3p [12.34 vs. 16.2, p < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke.

Octahedral molybdenum iodide clusters with pyrazole or pyrazolate ligands.

Due to the combination of useful physicochemical properties (luminescence, X-ray contrast, etc.), octahedral molybdenum halide cluster complexes [Mo6X8L6]n have been the subject of active investigation during the last decades. The most common methods for synthesizing new compounds with organic ligands involve the use of silver salts of organic acids or the substitution of terminal methylate ligands. However, these methods often necessitate the use of special conditions, such as an inert atmosphere, absolute solvents, and silver salts, which can be costly. In contrast, aqua-hydroxo complexes formed by hydrolysis of many complexes are considered final unreactive products, despite the tendency for them to form. This work proposes a simple and affordable method for the preparation of hexaaqua and hexahydroxo iodide clusters of molybdenum from [Mo6I14]2- in a single step. Furthermore, the possibility of using such compounds as starting complexes for the synthesis of clusters with organic ligands such as pyrazole is discussed. The paper presents synthetic approaches, detailed characterization both in solid and in solution, and a study of the reactivity and luminescence properties of the obtained compounds.

The nature of structural defects in ZIF-8 revealed with 1H and 31P MAS NMR and X-ray absorption spectroscopy.

The metal-organic frameworks (MOFs) attract interest as potential catalysts whose catalytic properties are driven by defects. Several methods have been proposed for the defects-inducing synthesis of MOFs. However, the active species formed on the defective sites remain elusive and uncharacterized, as the spectroscopic fingerprints of these species are hidden by the regular structure signals. In this work, we have performed the synthesis of ZIF-8 MOF with defect-inducing procedures using fully deuterated 2-methylimidazolate ligands to enhance the defective sites' visibility. By combining 1H and 31P MAS NMR spectroscopy and X-ray absorption spectroscopy, we have found evidence for the presence of different structural hydroxyl Zn-OH groups in the ZIF-8 materials. It is demonstrated that the ZIF-8 defect sites are represented by Zn-OH hydroxyl groups with the signals at 0.3 and -0.7 ppm in 1H MAS NMR spectrum. These species are of basic nature and may be responsible for the catalytic activity of the ZIF-8 material.

Pore-Fiber Transport Dynamics of Aqueous Cosolvent Solutions in Paper.

After inkjet printing onto uncoated and unsized paper, the ink is first imbibed into the interfiber pores and subsequently absorbed by the cellulose fibers. The achievable print quality depends on the rate of this pore-fiber transport. The latter is accompanied by mechanical expansion of the fibers and the paper sheet. Therefore, we systematically monitored the swelling dynamics of several paper types as a function of ink composition by means of four different measurement techniques. Using aqueous cosolvent solutions as model inks, we found an approximately exponential relation of the time scales of pore-fiber transport with the cosolvent concentration and an approximately linear relation with its molecular weight. Addition of surfactants can substantially speed-up pore-fiber transport.

Winding Back the Clock on Advanced Therapies: It's Time to Get Smart.

Our language affects patients' perceptions of therapies. In Parkinson's disease, emergent response fluctuations and dyskinesias typically trigger conversations around commencing an "Advanced Therapy" which carries notions of Advanced Disease. The patient, resolute in their commitment to fighting the disease, is misled. Chasing reassurance that their disease has not yet progressed considerably; they may therefore resist a potentially life-changing therapy. Instead, we should offer a "Smart Therapy". This term more accurately and positively describes therapies on offer that stabilize response fluctuations and improve quality of life, without a focus on the negative connotations of progression to more advanced disease.

The language we use with our patients affects their perception of a therapy on offer and their willingness to take it up. In Parkinson's disease when motor response fluctuations and dyskinesias become extremely challenging and disabling for patients despite medication optimization, it might prompt conversations with the patient in appropriate circumstances about offering an "Advanced Therapy" such as deep brain stimulation surgery or continuous infusion pumps. However, from the patient's perspective, putting up a steadfast fight against their disease, this label carries unwanted and misleading connotations of Advanced Disease. This can lead to hesitation from taking up these potentially life-changing therapies. Therefore, in this Commentary we propose a rebranding in line with other modern technology like smart phones and smart homes, emphasizing the positive and personalized features of these therapies, and focusing on the goal of stabilizing symptoms and improving quality of life. We should offer patients "Smart Therapies". It's time to Get Smart!

Mouse embryo CoCoPUTs: novel murine transcriptomic-weighted usage website featuring multiple strains, tissues, and stages.

Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue's codon and codon pair usage landscape, we have established a novel resource-Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

Altering the structures of 3D supramolecular assemblies from melamine and cyanuric acid derivatives in water.

Herein, we obtained two supramolecular assemblies with layered structures from melamine, N-methylmelamine, and hexynyl-cyanuric acid in water. By combination of X-ray diffraction, electron microscopy, and molecular dynamics studies, we found that introducing one methyl group in melamine alters the arrangement of the layers in these structures.

Observation of a chemical reaction in a levitating microdroplet cluster and droplet-generated music.

Ordered clusters of water droplets levitating over a heated water surface can be used as chemical microreactors and computational devices. Here we show that a chemical reaction between melamine and cyanuric acid can occur during coalescence of pairs of droplets containing these reagents and lead to the sedimentation of the product, crystals of melamine cyanurate. In rotating droplets, the crystals flash with frequencies dependent mostly on the rotational velocity of the droplets defined by the rotor of the velocity field of the air-vapor flow above the heated water surface. With the Machine Learning (ML) approach, we trace the brightness and frequencies of individual crystals and convert the frequencies into musical notes thus making a "micro-orchestra" of the levitation cluster.

Giant ultrafast dichroism and birefringence with active nonlocal metasurfaces.

Switching of light polarization on the sub-picosecond timescale is a crucial functionality for applications in a variety of contexts, including telecommunications, biology and chemistry. The ability to control polarization at ultrafast speed would pave the way for the development of unprecedented free-space optical links and of novel techniques for probing dynamical processes in complex systems, as chiral molecules. Such high switching speeds can only be reached with an all-optical paradigm, i.e., engineering active platforms capable of controlling light polarization via ultrashort laser pulses. Here we demonstrate giant modulation of dichroism and birefringence in an all-dielectric metasurface, achieved at low fluences of the optical control beam. This performance, which leverages the many degrees of freedom offered by all-dielectric active metasurfaces, is obtained by combining a high-quality factor nonlocal resonance with the giant third-order optical nonlinearity dictated by photogenerated hot carriers at the semiconductor band edge.

Introduction of Niobium in the Chemistry of Octahedral Chalcogenide Clusters: Synthesis and Detailed Study of Compounds Based on Condensed and Discrete {Re5NbQ8} (Q = S or Se) Cores.

It is known that niobium practically does not form cluster chalcogenide compounds of the {M6(µ3-Q8)} type, which are widespread in the chemistry of group 6 and 7 metals. This work reports the preparation of a series of polymeric and discrete niobium-containing heterometallic clusters based on the {Re5Nb(µ3-S8)} and {Re5Nb(µ3-Se8)} cores. The compounds were prepared by the high-temperature reaction between rhenium and niobium dichalcogenides in a KCN melt. The 1D polymers K5[Re5NbQ8(CN)5] (Q = S or Se), which were formed as a result of the reaction, crystallize in the structural type of K6[Mo6Se8(CN)5], similar to the previously reported heterometallic clusters K6[Re6-xMoxQ8(CN)5] (x = 2-3). The polymers were solubilized to form discrete anionic clusters [Re5NbQ8(CN)6]4-. The structure and properties of the new clusters were investigated using a combination of X-ray diffraction analysis, UV/vis spectroscopy, high-resolution electrospray mass spectrometry, cyclic voltammetry, and DFT calculations. Among other features, the compounds showed high electrochemical activity, being able to form three redox states in solution with reversible transitions. It was found that redox potentials of the isoelectronic octahedral clusters demonstrate a strong cathodic shift in the sequence [Re5OsSe8(CN)6]3- > [Re6Se8(CN)6]4- > [Re5MoSe8(CN)6]5- > [Re5NbSe8(CN)6]6-, illustrating the effect of systematic changes in the composition of octahedral cluster cores on their properties.

Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization.

Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes.

Exploring the Frontiers of Heterometallic Systems: the {FeW5} Octahedral Cluster Complex.

This research presents the first examples of heterometallic octahedral cluster complexes incorporating both 5d and 3d metals, specifically, tungsten and iron. The key compound, (TBA)2[FeW5Br14] (TBA = tetrabutylammonium), exhibits selective ligand substitution reactions at the iron site when exposed to various solvents. Several {FeW5}-type anions, namely, [FeW5Br14]2-, [FeW5Br13(L)]- (L = H2O, DMSO, CH3CN), and [(FeW5Br13)2O]4-, were revealed and characterized by single-crystal X-ray diffraction analysis. The redox properties of [FeW5Br14]2- were studied and compared with those of [W6Br14]2-. Density functional theory calculations demonstrated that the bonding between Fe and W atoms is fundamentally different from the bonding between 4d (Mo-Mo) or 5d (W-W) metals in isotypic {M6} clusters.

Electrical properties determine the liquid flow direction in plasma-liquid interactions.

During atmospheric pressure plasma impingement, plasma induced liquid flow will influence the transport and distribution of plasma generated charged and reactive species in liquids. We use particle image velocimetry and supplementary pH, conductivity and temperature measurements to investigate electrical properties of an AC kHz plasma jet interacting with water and electrolytes. We observe that the dominant driving mechanism in low conductive solutions are surface forces such as shear stresses and stagnation-pressure induced dimpling. These give upwards flows beneath the plasma-liquid interaction point. In highly conductive solutions, such as water with dissolved salts, the dominant driving mechanism is electro-hydrodynamic forces, with flows directed downwards underneath the plasma jet in our system. We therefore demonstrate that the direction of initial plasma induced liquid flows can be controlled through the addition of salt ions. In electrically grounded salt solutions, we also observe time resolved flow direction switching, possibly due to modification of salt solutions via electrolytic and plasma induced reactions changing the dominant flow mechanism over time.