Lymphocytes and monocytes undergo swift suppression of IL-10R, IL-6R, and IL-2Rβγ signaling under high concentrations of different cytokines.

The JAK-STAT signaling pathway is fundamental for immune system regulation. It involves phosphorylation of several types of STAT proteins in response to binding of cytokines to immune cell receptors. Traditionally, the immune signaling studies focus on measuring the levels of phosphorylated STATs (pSTATs) following individual cytokine application.

Antiproliferative Water-Soluble Mono- and Binuclear Ruthenium Complexes with Pyridone-Imidazole Ligands.

In this study, we synthesized and characterized new imidazole ligands containing pyridone groups, as well as mononuclear and binuclear ruthenium complexes, which are a new class of water-soluble metallacycles. We studied the antiproliferative activity of these compounds in vitro using the MTT assay on a panel of human cancer cell lines and on primary rat fibroblasts, where we observed a complete absence of cytotoxicity up to a concentration of 1000 µM. For the binuclear metallocycle compounds, we investigated their solubility in water, resistance to hydrolysis, and ability to induce apoptosis in tumor cells.

Ligand Discrimination in Immune Cells: Signal Processing Insights into Immune Dysfunction in ER+ Breast Cancer.

Prior studies have shown that approximately 40% of estrogen receptor positive (ER+) breast cancer (BC) patients harbor immune signaling defects in their blood at diagnosis, and the presence of these defects predicts overall survival. Therefore, it is of interest to quantitatively characterize and measure signaling errors in immune signaling systems in these patients. Here we propose a novel approach combining communication theory and signal processing concepts to model ligand discrimination in immune cells in the peripheral blood.

QuickVol: A lightweight browser tool for immersive visualizations of volumetric data.

Volumetric layouts of data are becoming increasingly common in a number of fields. Visualizing these data often requires downloading a large suite of dedicated tools with a significant learning curve. This process can be overwhelming for students or new researchers looking to quickly visualize and showcase a volumetric dataset.

Tandem Deacetalization-Knoevenagel Condensation Reactions for the Synthesis of Benzylidene Malononitrile Using Ruthenium(II) Cymene Complexes.

In this study, we report the synthesis and full characterization of five novel ruthenium(II) cymene complexes with the general formula [Ru(cym)(L')Cl], featuring N,O- and N,N-coordinating pyrazolone-based hydrazone ligands. We have characterized these complexes using single X-ray crystallography, Fourier-transform infrared spectroscopy (FT-IR), Nuclear magnetic resonance (NMR), elemental analysis, and Electrospray Ionization Mass Spectroscopy (ESI-MS). Crystallographic analysis confirmed that all of the complexes have a similar type of half-sandwich, pseudo-octahedral "three-legged piano-stool" geometry where the cymene moiety displays the typical η-coordination mode and the hydrazone ligands coordinate to the Ru(II) center in a bidentate fashion.

Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers.

Mathematical modeling yields general principles for optimization of TRT in mouse models of multiple myeloma that can be extrapolated to other cancer models and clinical settings.

Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers.

Targeted radionuclide therapy is based on injections of cancer-specific molecules conjugated with radioactive nuclides. Despite the specificity of this treatment, it is not devoid of side-effects limiting its use and is especially harmful for rapidly proliferating organs well perfused by blood, like bone marrow. Optimization of radioconjugates administration accounting for toxicity constraints can increase treatment efficacy.

Designing combination therapies for cancer treatment: application of a mathematical framework combining CAR T-cell immunotherapy and targeted radionuclide therapy.

Introduction: Cancer combination treatments involving immunotherapies with targeted radiation therapy are at the forefront of treating cancers. However, dosing and scheduling of these therapies pose a challenge. Mathematical models provide a unique way of optimizing these therapies.

Optimization of Size of Nanosensitizers for Antitumor Radiotherapy Using Mathematical Modeling.

The efficacy of antitumor radiotherapy can be enhanced by utilizing nonradioactive nanoparticles that emit secondary radiation when activated by a primary beam. They consist of small volumes of a radiosensitizing substance embedded within a polymer layer, which is coated with tumor-specific antibodies. The efficiency of nanosensitizers relies on their successful delivery to the tumor, which depends on their size.

Why a simple vanadate is inefficient as a catalyst in the oxidation of alkanes with HO - the long-standing puzzle is solved.

In contrast to V(V) complexes with various organic ligands, a simple vanadate without any additive is inactive in neutral medium toward the oxidation of alkanes with HO. In this work, we discovered that the insufficient activation of HO upon coordination to the simple vanadate - the commonly accepted reason for the low catalytic activity of the vanadate - cannot explain this phenomenon. Two main findings are reported here on the basis of DFT calculations.

Optimization of antitumor radiotherapy fractionation via mathematical modeling with account of 4 R's of radiobiology.

A spatially-distributed continuous mathematical model of solid tumor growth and treatment by fractionated radiotherapy is presented. The model explicitly accounts for the factors, widely referred to as 4 R's of radiobiology, which influence the efficacy of radiotherapy fractionation protocols: tumor cell repopulation, their redistribution in cell cycle, reoxygenation and repair of sublethal damage of both tumor and normal tissues. With the use of special algorithm the fractionation protocols that provide increased tumor control probability, compared to standard clinical protocol, are found for various physiologically-based values of model parameters under the constraints of fixed overall normal tissue damage and maximum admissible fractional dose.

Bayesian Aggregation Improves Traditional Single-Image Crop Classification Approaches.

Accurate information about growing crops allows for regulating the internal stocks of agricultural products and drawing strategies for negotiating agricultural commodities on financial markets. Machine learning methods are widely implemented for crop type recognition and classification based on satellite images. However, field classification is complicated by class imbalance and aggregation of pixel-wise into field-wise forecasting.

Efficacy and safety of Actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO).

Background: This study aimed to assess the efficacy and safety of Actovegin for the treatment of patients with Fontaine stage IIB peripheral arterial disease (PAD).

Methods: The study included 366 patients with Fontaine stage IIB PAD from 19 centers (Russia, Georgia, Kazakhstan). Placebo or Actovegin (1200 mg daily [QD]) were administered intravenously for two weeks, followed by a 10-week course of oral administration (placebo or Actovegin 1200 mg QD).

Recognition and mechanistic investigation of anion sensing by ruthenium(II) arene complexes and bio-imaging application.

In this work, four new ruthenium complexes [Ru(η--cymene)(L1)Cl] 1, [Ru(η--cymene)(L2)Cl] 2, [Ru(η--cymene)(L3)Cl] 3 and [Ru(η--cymene)(L4)Cl] 4 [HL1 = (2-cyanophenyl)glycine; HL2 = (5-chloro-2-cyanophenyl)glycine; HL3 = (2-cyano-3-fluorophenyl)glycine; HL4 = (4-cyanophenyl)glycine] were synthesized and well characterized by several spectroscopic and analytical techniques. Complexes 1 and 3 were found to be fluorescent in most of the solvents; however, 2 and 4 were found to be fluorescent mostly in EtOAc, DMF and ethanol. Amongst these four complexes, 3 has shown selective sensing against CO and SO anions by quenching of fluorescence.

Photo- and Electroluminescent Neutral Iridium(III) Complexes Bearing Imidoylamidinate Ligands.

Imidoylamidinate-based heteroleptic bis(2-phenylbenzothiazole)iridium(III) and -rhodium(III) complexes [()M(NN)] ( = 2-phenylbenzothiazole, NN = '-(benzo[]thiazol-2-yl)acetimidamidyl ( and ), '-(6-fluorobenzo[]thiazol-2-yl)acetimidamidyl (), '-(benzo[]oxazol-2-yl)acetimidamidyl (), '-(1-methyl-1-benzo[]imidazol-2-yl)acetimidamidyl (); yields 70-84%) were obtained by the reaction of the in situ-generated solvento-complex [()M(NCMe)]NO and benzo[]thia/oxa/-methylimidozol-2-amines in the presence of NaOMe. Complexes - exhibited intense orange photoluminescence, reaching 37% at room temperature quantum yields, being immobilized in a poly(methyl methacrylate) matrix. A photophysical study of these species in a CHCl solution, neat powder, and frozen (77 K) MeOCHOH-EtOH glass matrix─along with density-functional theory (DFT), ab initio methods, and spin-orbit coupling time-dependent DFT calculations─verified the effects of substitution in the imidoylamidinate ligands on the excited-state properties.

Density Functional Theory Approach to the Vibrational Properties and Magnetic Specific Heat of the Covalent Chain Antiferromagnet KFeS.

Ternary potassium-iron sulfide, KFeS, belongs to the family of highly anisotropic quasi-one-dimensional antiferromagnets with unusual "anti-Curie-Weiss" susceptibility, quasi-linearly growing with a rising temperature up to 700 K, an almost vanishing magnetic contribution to the specific heat, drastically reduced magnetic moment, etc. While some of the measurements can be satisfactorily described, the deficiency of the entropy changes upon the magnetic transition and the spin state of the iron ion remains a challenge for the further understanding of magnetism. In this work, high-quality single-crystalline samples of KFeS were grown by the Bridgman method, and their stoichiometry, crystal structure, and absence of alien magnetic phases were checked, utilizing wave-length dispersive X-ray electron-probe microanalysis, powder X-ray diffraction, and Fe Mössbauer spectroscopy, respectively.

Robust controlled formation of Turing patterns in three-component systems.

Over the past few decades, formation of Turing patterns in reaction-diffusion systems has been shown to be the underlying process in several examples of biological morphogenesis, confirming Alan Turing's hypothesis, put forward in 1952. However, theoretical studies suggest that Turing patterns formation via classical "short-range activation and long-range inhibition" concept in general can happen within only narrow parameter ranges. This feature seemingly contradicts the accuracy and reproducibility of biological morphogenesis given the stochasticity of biochemical processes and the influence of environmental perturbations.

Halogen bonding in cadmium(II) MOFs: its influence on the structure and on the nitroaldol reaction in aqueous medium.

A solvothermal reaction of Cd(II) with the dicarboxyl-functionalized arylhydrazone pro-ligands, 5-(2-(2,4,6-trioxotetrahydro-pyrimidin-5(2)-ylidene)hydrazineyl)isophthalic acid (HL) and 5-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)isophthalic acid (HL), or their halogen bond donor centre(s) decorated analogs 2,4,6-triiodo-5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2)-ylidene)hydrazineyl)isophthalic acid (HL) and 5-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)-2,4,6-triiodoisophthalic acid (HL), leads to the formation of known [Cd(HL)(HO)] (1) and new {[Cd(HL)(HO)(DMF)]·HO} (2), [Cd(HL)] (3) and {[Cd(μ-HO)(μ-HL)(HL)]·2HO} (4) coordination compounds, respectively. The aggregation of mononuclear units Cd-OC and Cd-OH coordination and C-I⋯I types of intramolecular halogen bonds lead to a dinuclear tecton 4. Both C-I⋯O and C-I⋯I types of intermolecular halogen bonds play a fundamental role in the supramolecular architectures of the obtained metal-organic frameworks 3 and 4.

Proof of concept for the sapphire scalpel combining tissue dissection and optical diagnosis.

Objectives: The development of compact diagnostic probes and instruments with an ability to direct access to organs and tissues and integration of these instruments into surgical workflows is an important task of modern physics and medicine. The need for such tools is essential for surgical oncology, where intraoperative visualization and demarcation of tumor margins define further prognosis and survival of patients. In this paper, the possible solution for this intraoperative imaging problem is proposed and its feasibility to detect tumorous tissue is studied experimentally.

Copper(II)-Mediated Iodination of 1-Nitroso-2-naphthol.

The 3-Iodo-1-nitrosonaphthalene-2-ol (I-NON) was obtained by the copper(II)-mediated iodination of 1-nitroso-2-naphthol (NON). The suitable reactants and optimized reaction conditions, providing 94% NMR yield of I-NON, included the usage of Cu(OAc)·HO and 1:2:8 Cu/NON/I molar ratio between the reactants. The obtained I-NON was characterized by elemental analyses (C, H, N), high-resolution ESI-MS, H and C{H} NMR, FTIR, UV-vis spectroscopy, TGA, and X-ray crystallography (XRD).

Metal-Involving Chalcogen Bond. The Case of Platinum(II) Interaction with Se/Te-Based σ-Hole Donors.

Platinum(II) complexes exhibiting an expressed -nucleophilicity of the positively charged metal centers, namely, [Pt(ppy)(acac)] (; acacH is acetylacetone; ppyH is 2-Ph-pyridine) and [Pt(ppy)(tmhd)] (; tmhdH is 2,2,6,6-tetramethylheptanedione-3,5), were cocrystallized with the chalcogen bond donors (4-NCF)Ch (Ch = Se, Te) to form two isostructural cocrystals ·/(4-NCF)Ch, and ·/(4-NCF)Se and ·(4-NCF)Te. The X-ray data for these cocrystals and appropriate theoretical DFT calculations (PBE0-D3BJ) allowed the recognition of the metal-involving chalcogen bond, namely, Ch···-Pt (its energy spans from -7 to -12 kcal/mol). In ·/(4-NCF)Ch, Ch···-Pt bonding is accompanied by the C···-Pt interaction, representing a three-center bifurcate, whereas in ·(4-NCF)Te the chalcogen bond Te···-Pt is purely two-centered and is stronger than that in ·/(4-NCF)Ch because of more efficient orbital overlap.

Strength of the [Z-I···Hal] and [Z-Hal···I] Halogen Bonds: Electron Density Properties and Halogen Bond Length as Estimators of Interaction Energy.

Bond energy is the main characteristic of chemical bonds in general and of non-covalent interactions in particular. Simple methods of express estimates of the interaction energy, E, using relationships between E and a property which is easily accessible from experiment is of great importance for the characterization of non-covalent interactions. In this work, practically important relationships between E and electron density, its Laplacian, curvature, potential, kinetic, and total energy densities at the bond critical point as well as bond length were derived for the structures of the [Z-I···Hal] and [Z-Hal···I] types bearing halogen bonds and involving iodine as interacting atom(s) (totally 412 structures).

Combination of epidural electrical stimulation with triple gene therapy for spinal cord injury: a proof of principle study.

Despite emerging contemporary biotechnological methods such as gene- and stem cell-based therapy, there are no clinically established therapeutic strategies for neural regeneration after spinal cord injury. Our previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules, including vascular endothelial growth factor (VEGF), glial cell-line derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) can improve morpho-functional recovery of injured spinal cord in rats and mini-pigs. To investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury, in this study, rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165, GDNF, NCAM1 at 4 hours after spinal cord injury.

Resonance Assisted Chalcogen Bonding as a New Synthon in the Design of Dyes.

Intramolecular chalcogen bonding in arylhydrazones of sulfamethizole is strengthened by conjugation in the π-system of a noncovalent five-membered ring. The S⋅⋅⋅O distance in the sulfamethizole moiety of these compounds ranges from 2.698(3) to 2.