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We develop a multiscale coarse-grain model of the NIST Monoclonal Antibody Reference Material 8671 (NISTmAb) to enable systematic computational investigations of high-concentration physical instabilities such as phase separation, clustering, and aggregation. Our multiscale coarse-graining strategy captures atomic-resolution interactions with a computational approach that is orders of magnitude more efficient than atomistic models, assuming the biomolecule can be decomposed into one or more rigid bodies with known, fixed structures. This method reduces interactions between tens of thousands of atoms to a single anisotropic interaction site. The anisotropic interaction between unique pairs of rigid bodies is precomputed over a discrete set of relative orientations and stored, allowing interactions between arbitrarily oriented rigid bodies to be interpolated from the precomputed table during coarse-grained Monte Carlo simulations. We present this approach for lysozyme and lactoferrin as a single rigid body and for the NISTmAb as three rigid bodies bound by a flexible hinge with an implicit solvent model. This coarse-graining strategy predicts experimentally measured radius of gyration and second osmotic virial coefficient data, enabling routine Monte Carlo simulation of medically relevant concentrations of interacting proteins while retaining atomistic detail. All methodologies used in this work are available in the open-source software Free Energy and Advanced Sampling Simulation Toolkit. [ABSTRACT FROM AUTHOR]

Through an expansive international effort that involved data collection on 12 small-angle X-ray scattering (SAXS) and four small-angle neutron scattering (SANS) instruments, 171 SAXS and 76 SANS measurements for five proteins (ribonuclease A, lysozyme, xylanase, urate oxidase and xylose isomerase) were acquired. From these data, the solvent-subtracted protein scattering profiles were shown to be reproducible, with the caveat that an additive constant adjustment was required to account for small errors in solvent subtraction. Further, the major features of the obtained consensus SAXS data over the q measurement range 0-1 Å-1 are consistent with theoretical prediction. The inherently lower statistical precision for SANS limited the reliably measured q-range to 2.2 Å-1 showed good mutual agreement, affirming that this region has interpretable features for structural modelling. SAS measurements with inline size-exclusion chromatography (SEC) proved to be generally superior for eliminating sample heterogeneity, but with unavoidable sample dilution during column elution, while batch SAS data collected at higher concentrations and for longer times provided superior statistical precision. Careful merging of data measured using inline SEC and batch modes, or low- and high-concentration data from batch measurements, was successful in eliminating small amounts of aggregate or interparticle interference from the scattering while providing improved statistical precision overall for the benchmarking data set.

Background. he dependences of the light intensity on time and the photocurrent flowing in the resistor are generally described by various functions. Methods have been studied for obtaining the time dependence of the intensity of light pulses of arbitrary shape, following with a frequency ω, from the time dependence of the photocurrent in the presence of recombination of charge carriers on the surface of the semiconductor. Materials and methods. The results were obtained based on a study of the kinetics of photoconductivity of a resistor for linear and quadratic recombination laws in the bulk of a semiconductor. The diffusion of nonequilibrium charge carriers to the surfaces of the photoresistor with their subsequent surface recombination is taken into account. The first method is based on the use of the photocurrent differentiation operation. The second method allows you to restore the intensity of an optical pulse of an arbitrary shape from the amplitudes of the harmonics of the expansion of the function that specifies the dependence of the current on time in a Fourier series. Results and conclusions. Nonlinear, frequency and phase distortions in the region of high frequencies are small. The proposed methods are valid when the inequality ωτ≥1 (τ is the effective lifetime of the main charge carriers) is fulfilled.

The review summarizes and analyzes the available literature to provide information to clinicians about the best treatment strategies for type 2 diabetes in stable coronary artery disease. This data should help health care professionals make decisions in routine practice. 2023 European and Russian guidelines on type 2 diabetes suggest giving preference to glucose-lowering agents with proven benefits for the cardiovascular system, followed by drugs with proven safety for the cardiovascular system.

Folded proteins show a high degree of structural order and undergo (fairly constrained) collective motions related to their functions. On the other hand, intrinsically disordered proteins (IDPs), while lacking a well-defined three-dimensional structure, do exhibit some structural and dynamical ordering, but are less constrained in their motions than folded proteins. The larger structural plasticity of IDPs emphasizes the importance of entropically driven motions. Many IDPs undergo function-related disorder-to-order transitions driven by their interaction with specific binding partners. As experimental techniques become more sensitive and become better integrated with computational simulations, we are beginning to see how the modest structural ordering and large amplitude collective motions of IDPs endow them with an ability to mediate multiple interactions with different partners in the cell. To illustrate these points, here, we use Prostate-associated gene 4 (PAGE4), an IDP implicated in prostate cancer (PCa) as an example. We first review our previous efforts using molecular dynamics simulations based on atomistic AWSEM to study the conformational dynamics of PAGE4 and how its motions change in its different physiologically relevant phosphorylated forms. Our simulations quantitatively reproduced experimental observations and revealed how structural and dynamical ordering are encoded in the sequence of PAGE4 and can be modulated by different extents of phosphorylation by the kinases HIPK1 and CLK2. This ordering is reflected in changing populations of certain secondary structural elements as well as in the regularity of its collective motions. These ordered features are directly correlated with the functional interactions of WT-PAGE4, HIPK1-PAGE4 and CLK2-PAGE4 with the AP-1 signaling axis. These interactions give rise to repeated transitions between (high HIPK1-PAGE4, low CLK2-PAGE4) and (low HIPK1-PAGE4, high CLK2-PAGE4) cell phenotypes, which possess differing sensitivities to the standard PCa therapies, such as androgen deprivation therapy (ADT). We argue that, although the structural plasticity of an IDP is important in promoting promiscuous interactions, the modulation of the structural ordering is important for sculpting its interactions so as to rewire with agility biomolecular interaction networks with significant functional consequences.

The synthesis of the title compounds was performed from (-)-cis-myrtanic and (-)-myrtenic acids. The compounds obtained were characterized using 1H- and 13C-NMR, IR, and high-resolution mass spectrometry. Despite the presence of quaternary ammonium moiety, both compounds had moderate antimicrobial activity with a MIC of 128 µg/mL on S. aureus and 512 µg/mL on E. coli. The antifungal activity was low on Candida isolates, while also comparable with conventional antimycotic (Fluconazole) on filamentous fungi. These data suggest that two bulky bicyclic terpene fragments apparently both increase lipophilicity and close the quaternary ammonium moiety located in the center of molecules and thus drastically decrease the antimicrobial potential of bipharmacophore.

A first cadmium copper selenite–bromide Cd7Cu2(SeO3)8Br2 (1) was obtained via chemical vapor transport reactions. The new compound is triclinic, P 1 ‾ , a = 5.3280(5) Å, b = 10.6190(12) Å, c = 11.4380(13) Å, α = 100.856(4)°, β = 93.321(4)°, γ = 91.021(4)°, V = 634.22(12) Å3, R1 = 0.027. 1 has no structural analogs and belongs to a new structure type. The structure of 1 can be described as a host-guest architecture. The host is the [Cd7(SeO3)8]2− interrupted framework, which consists of zigzag layers with a large aperture. The guests are copper bromide species. Thus, the formula can be written as [Cd7(SeO3)8]{Cu2Br2}. [ABSTRACT FROM AUTHOR]

A first cadmium copper selenite–bromide Cd7Cu2(SeO3)8Br2 (1) was obtained via chemical vapor transport reactions. The new compound is triclinic, P 1 ‾ , a = 5.3280(5) Å, b = 10.6190(12) Å, c = 11.4380(13) Å, α = 100.856(4)°, β = 93.321(4)°, γ = 91.021(4)°, V = 634.22(12) Å3, R1 = 0.027. 1 has no structural analogs and belongs to a new structure type. The structure of 1 can be described as a host-guest architecture. The host is the [Cd7(SeO3)8]2− interrupted framework, which consists of zigzag layers with a large aperture. The guests are copper bromide species. Thus, the formula can be written as [Cd7(SeO3)8]{Cu2Br2}. [ABSTRACT FROM AUTHOR]

Systematic studies of crystalline compounds formed in aqueous systems containing aliphatic diamines, divalent transition metal halides, and selenious acid resulted in the discovery of a large family of new complex species corresponding to several new structure types. With ethylenediamine (en), layered (enH2)[M(HSeO3)2X2] compounds are the most commonly formed species which constitute a significant contribution to the family of layered hydrogen selenites containing neutral [M(HSeO3)2] (M = Mg, Mn, Co, Ni, Cu, Zn, Cd) 2D building blocks. In contrast to some previous suggestions, piperazine (pip), as well as its homologue N-methylpiperazine, mostly give rise to quite different, sometimes more complex, structures of varied dimensionality while the (pipH2)[M(HSeO3)2X2] compounds are formed only with M = Cu and Cd. In addition, metal-, halide-, or selenium-free by-product species are observed. The SeIV can be present in a multitude of forms, including H2SeO3, HSeO3−, SeO32−, and Se2O52−, reflecting amazing adaptability to the shape of the templating cations.

1,1-Dimethylhydrazine (Heptil, rocket fuel (UDMH)) is characterized by extremely high toxicity, teratogenicity and the ability to constantly absorb water from the atmosphere, losing its energy characteristics. In this regard, as well as due to the alternative fuel (“Angara”) transition, there is a need for UDMH utilization in huge amounts. A more benign approach involves its immediate reaction with a formalin solution to form 1,1–dimethyl-2-methylene hydrazone (MDH), which is significantly less toxic by an order of magnitude. MDH can then be polymerized under acidic conditions, and the resulting product can be burned, yielding a substantial amount of nitrogen oxides. We propose an alternative to incineration by involving MDH in organic synthesis. We studied the reactions of MDH and its analog N,N-dimethyl-2-(methylenamino)ethane-1-amine (MDEA) with available CH-acids: tetracyanoethylated ketones (TCEKs) based on cyclohexanone, 4-propylcyclohexanone, 2-methylcyclohexanone, cyclododecanone and tetracyanoethane. The structures synthesized were confirmed by IR, 1H, 13C NMR and mass spectroscopy methods. MDH-based adducts were also identified by X-ray structural analysis. TCEKs and MDH, as well as TCEK based on cyclohexanone and MDEA, form bi- and tricyclic structures: pyrrolo [3,4c]-quinolines (using TCEKs based on cyclohexanone and 4-propylcyclohexanone), epiminomethanoquinoline-3,4-dicarbonitrile (using TCEK based on 2-methylcyclohexanone) and cyclododec[b]pyran-3,4-dicarbonitrile (using TCEK based on cyclododecanone). MDH and TCNEH2 formed a pyrrole derivative. Thus, we synthesized the structures that are of interest for molecular design and pharmaceutical chemistry.

Carrasco et al. report a method that can predict the lipid nanoparticles (LNP) pKa from the structure of the ionizable lipid. They investigate the delivery efficiency for intramuscular and intravascular administration and propose design principles to limit off-target systemic distribution and expression for mRNA LNP vaccines.

The isolation of small extracellular vesicles (sEVs), including those secreted by pathological cells, with high efficiency and purity is highly demanded for research studies and practical applications. Conventional sEV isolation methods suffer from low yield, presence of contaminants, long-term operation and high costs. Bead-assisted platforms are considered to be effective for trapping sEVs with high recovery yield and sufficient purity for further molecular profiling. In this study, magnetically responsive beads made of calcium carbonate (CaCO3) particles impregnated with iron oxide (Fe3O4) nanoparticles are fabricated using a freezing-induced loading (FIL) method. The developed magnetic beads demonstrate sufficient magnetization and can be collected by a permanent magnet, ensuring their rapid and gentle capture from an aqueous solution. The tannic acid on the surface of magnetic beads is formed by a layer-by-layer (LbL) method and is used to induce coupling of sEVs with the surface of magnetic beads. These tannic acid coated magnetic beads (TAMB) were applied to capture sEVs derived from MCF7 and HCT116 cell lines. Quantitative data derived from nanoparticle tracking analysis (NTA) and BCA methods revealed the capture efficiency and recovery yield of about 60%. High-resolution transmission electron microscopy (HRTEM) imaging of sEVs on the surface of TAMBs indicated their structural integrity. Compared with the size exclusion chromatography (SEC) method, the proposed approach demonstrated comparable efficiency in terms of recovery yield and purity, while offering a relatively short operation time. These results highlight the high potential of the TAMB approach for the enrichment of sEVs from biological fluids, such as cell culture media. [ABSTRACT FROM AUTHOR]

The synthesis and crystal structure of new hydrated lead selenite nitrate Pb4(SeO3)3(NO3)2·2H2O (1) are reported. The crystal structure of 1 ( , a = 7.2590(2) Å, b = 7.6454(2) Å, c = 14.7293(4) Å, α = 84.386(2)°, β = 78.311(2)°, γ = 83.643(2)°, V = 793.18(4) Å3, R1 = 3.1%) belongs to a new structure type. It is based on a porous framework composed of [Pb4(SeO3)3]2+ layers strongly bound via nitrate anions. Water molecules are located in the channels. Stereochemically active electron pairs of SeO3E groups are directed toward each other. The structure of 1 is compared with similar architectures involving Pb2+ and Se4+ cations. [ABSTRACT FROM AUTHOR]