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The optimization of the quantum efficiency of single-molecule light-driven rotary motors typically relies on chemical modifications. While, in isolated conditions, computational methods have been frequently used to design more efficient motors, the role played by the solvent environment has not been satisfactorily investigated. In this study, we used multiscale nonadiabatic molecular dynamics simulations of the working cycle of a 2-stroke photon-only molecular rotary motor. The results, which display dynamics consistent with the available transient spectroscopy measurements, predict a considerable decrease in the isomerisation quantum efficiency in methanol solution with respect to the gas phase. The origin of such a decrease is traced back to the ability of the motor to establish hydrogen bonds with solvent molecules. The analysis suggests that a modified motor with a reduced ability to form hydrogen bonds will display increased quantum efficiency, therefore extending the set of engineering rules available for designing light-driven rotary motors. Increasing the rotational efficiency of single-molecule light-driven rotary motors often relies on chemical modifications aimed at eliminating the factors that hinder rotation. Using multiscale nonadiabatic simulations, the authors investigate the transient conformations assumed by the motor molecule during its operation in a solvent and examine possibilities for enhancing the motor's efficiency by blocking certain solvent-solute interactions that restrain successful completion of the rotational movement. [ABSTRACT FROM AUTHOR]

It is estimated that 72% of the worldwide primary energy consumption is lost as waste heat. Thermoelectric Generators (TEGs) are a possible solution to convert a part of this energy into electricity and heat for space heating. However, for their deployment a proven long-term operation is required. Therefore, this research investigates the long-term stability of TEGs on system level in air and argon atmosphere under thermal cycling up to 543 K. The layout of the examined test objects resembles a TEG in stack design. The results show that the maximal output power of the test object in air reaches a plateau at 57% of the initial power after 50 cycles caused by an increased electrical resistance of the system. Whereas the test object in argon atmosphere shows no significant degradation of electrical power or resistance. The findings represent a step towards the understanding of the long-term stability of TEGs and can be used as a guideline for design decisions. [ABSTRACT FROM AUTHOR]

The rational engineering of photoresponsive materials, e.g., light-driven molecular motors, is a challenging task. Here, we use structure-related design rules to prepare a prototype molecular rotary motor capable of completing an entire revolution using, exclusively, the sequential absorption of two photons; i.e., a photon-only two-stroke motor. The mechanism of rotation is then characterised using a combination of non-adiabatic dynamics simulations and transient absorption spectroscopy measurements. The results show that the rotor moiety rotates axially relative to the stator and produces, within a few picoseconds at ambient T, an intermediate with the same helicity as the starting structure. We discuss how such properties, that include a 0.25 quantum efficiency, can help overcome the operational limitations of the classical overcrowded alkene designs. Improving the efficiency of light-driven molecular rotary motors is a challenging task. Here, the authors combine theoretical modeling, synthesis and spectroscopy to prepare a prototype molecular motor capable of avoiding inefficient thermally activated motion; thus offering prospects to implement a 2-stroke photon-only molecular motor. [ABSTRACT FROM AUTHOR]

Malignant transformation is associated with loss of cell differentiation, anaplasia. Transcription factors gli, required for embryonic development, may be involved in this process. We studied the activity of transcription factors gli in high-grade gliomas and their role in maintenance of stem cell state and glioma cell survival. 20 glioma cell lines and a sample of a normal adult brain tissue were used in the present study. We found the expression of gli target genes, including GLI1 and FOXM1, in all tested glioma cell lines, but not in the normal tissue. Interestingly, the expression of gli target genes in some glioma cell lines was observed together with a high level of their transcriptional repressor, Gli3R. Knockdown of GLI3 in one of these lines resulted in decrease of gli target gene expression. These data suggest that Gli3R does not prevent the gli target genes transcription, and gli3 acts in glioma cells more as an activator, than a repressor of transcription. We observed that gli regulated the expression of such genes, as SOX2 or OCT4 that maintain stem cell state, and TET1, involving in DNA demethylation. Treatment with GANT61 or siRNA against GLI1, GLI2, or GLI3 could result in complete glioma cell death, while cyclopamine had a weaker and line-specific effect on glioma cell survival. Thus, the gli transcription factors are abnormally active in high-grade gliomas, regulate expression of genes, maintaining the stem cell state, and contribute to glioma cell survival. [ABSTRACT FROM AUTHOR]

P53 protein is more frequently mutated in human tumours compared with the other proteins. While the majority of the p53 mutations, especially within its DNA-binding domain, lead to the loss of the wild-type function, there are accumulating data demonstrating that the p53 mutants gain tumour promoting activities; the latter triggers a revitalised interest in functional analysis of the p53 mutants. A systematic screening for p53 mutations in surgical materials from patients with glioma revealed a 378C>G mutation that creates a stop codon at the position of amino acid residue 126. The mutation eliminates the recognition site for the restriction endonuclease Sca I that allowed us to carry out RFLP analysis of DNA extracted from the clinical samples and suggests that this mutation is more frequent than is documented in the p53 databases. Both the ECV-304 and EJ cell lines, that probably originate from the bladder carcinoma T24 cell line, were confirmed to contain the homozygous 378C>G mutation but were shown to produce the p53 protein of expected full-length size detected by Western blotting. We provide evidence that the 378C>G mutation generates an alternative 3’ splice site (ss) which is more often used instead of the authentic upstream 3’ ss, driving the production of mRNA encoding the protein with the single amino acid deletion (p53ΔY126). Using endogenous expression, we demonstrated that the p53ΔY126 protein is nearly as active as the wild type protein in inducing the p21/Waf1 expression and apoptosis. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1038/s41467-022-33695-x. Chem. i 37, 506-541 (2016)" was incorrectly given as [81], reference [81] "Ponder, J. W. & Richards, F. M. Tinker molecularmodeling package. Correction to: I Nature Communications i https://doi.org/10.1038/s41467-022-33695-x, published online 28 October 2022 The original version of this Article contained errors in the reference list, in which reference [80] "Aquilante, F. et al. [Extracted from the article]

The non-adiabatic dynamics of furan excited in the ππ* state (S2 in the Franck–Condon geometry) was studied using non-adiabatic molecular dynamics simulations in connection with an ensemble density functional method. The time-resolved photoelectron spectra were theoretically simulated in a wide range of electron binding energies that covered the valence as well as the core electrons. The dynamics of the decay (rise) of the photoelectron signal were compared with the excited-state population dynamics. It was observed that the photoelectron signal decay parameters at certain electron binding energies displayed a good correlation with the events occurring during the excited-state dynamics. Thus, the time profile of the photoelectron intensity of the K-shell electrons of oxygen (decay constant of 34 ± 3 fs) showed a reasonable correlation with the time of passage through conical intersections with the ground state (47 ± 2 fs). The ground-state recovery constant of the photoelectron signal (121 ± 30 fs) was in good agreement with the theoretically obtained excited-state lifetime (93 ± 9 fs), as well as with the experimentally estimated recovery time constant (ca. 110 fs). Hence, it is proposed to complement the traditional TRPES observations with the trXPS (or trNEXAFS) measurements to obtain more reliable estimates of the most mechanistically important events during the excited-state dynamics. [ABSTRACT FROM AUTHOR]

Simple Summary: Exosomes are nanoscale membrane extracellular vesicles that are involved in intercellular communication and signaling, and are a promising tool in biomedicine for drug delivery. Despite the progress in practical application and morphological characterization, information about their biomechanical properties is still scarce. The presence of non-membrane particles called exomeres with similar functions has recently been reported. We applied the atomic force microscopy technique to study the biomechanical properties of both types of particles in air and in liquid. We found a correlation between the biomechanical properties of the vesicles, their size, structure, and function. Our data provide useful information for a better understanding of the biomechanical characteristics of extracellular vesicles and non-membrane extracellular particles and their AFM detection. While extracellular vesicles (EVs) are extensively studied by various practical applications in biomedicine, there is still little information on their biomechanical properties due to their nanoscale size. We identified isolated blood plasma vesicles that carried on biomarkers associated with exosomes and exomeres and applied atomic force microscopy (AFM) to study them at single particle level in air and in liquid. Air measurements of exosomes revealed a mechanically indented internal cavity in which highly adhesive sites were located. In contrast, the highly adhesive sites of exomeres were located at the periphery and the observed diameter of the particles was ~35 nm. In liquid, the reversible deformation of the internal cavity of exosomes was observed and a slightly deformed lipid bi-layer was identified. In contrast, exomeres were not deformed and their observed diameter was ~16 nm. The difference in diameters might be associated with a higher sorption of water film in air. The parameters we revealed correlated with the well-known structure and function for exosomes and were observed for exomeres for the first time. Our data provide a new insight into the biomechanical properties of nanoparticles and positioned AFM as an exclusive source of in situ information about their biophysical characteristics. [ABSTRACT FROM AUTHOR]

The OCT4 transcription factor is necessary to maintain cell stemness in the early stages of embryogenesis and is involved in the formation of induced pluripotent stem cells, but its role in oncogenesis is not yet entirely clear. In this work, OCT4 expression was investigated in malignant gliomas. Twenty glioma cell lines and a sample of normal adult brain tissue were used. OCT4 expression was found in all studied glioma cell lines but was not detected in normal adult brain tissue. For one of these lines, OCT4 knockdown caused tumor cell death. By varying the culture conditions of these cells, we unexpectedly found that OCT4 expression increased when cells were incubated in serum-free medium, and this effect was significantly enhanced in serum-free and L-glutamine-free medium. L-glutamine and the Krebs cycle, which is slowed down in serum-free medium according to our NMR data, are sources of α-KG. Thus, our data indicate that OCT4 expression in gliomas may be regulated by the α-KG-dependent metabolic reprogramming of cells.

A new adaptive algorithm for penalty function optimization for minimum-energy three-states conical intersections (ME3CI) is suggested. The new algorithm differs from the original penalty function algorithm by (a) removing the redundancy in the target function, (b) using an adaptive increment for the penalty function weighting factor, and (c) using tighter convergence criteria for the energy gap. The latter was introduced to guarantee convergence to a true conical intersection rather than to a narrowly avoided crossing geometry. The new algorithm was tested in the optimization of the ME3CI geometries in butadiene and malonaldehyde, where all of the previously found true ME3CI geometries were recovered. The previously found butadiene's CI 3/2/1 turned out to be a narrowly avoided crossing. For butadiene, seven new ME3CI geometries have been located. Because of the removal of the redundancy and the use of the adaptive weighting factor, the convergence rate of the new algorithm is noticeably improved as compared to that of the previously proposed penalty function algorithm. The application to malonaldehyde and butadiene demonstrates that the three-state conical intersections may be more abundant and hence more involved in the photochemistry than previously thought. The recently developed mixed-reference spin flip (MRSF)-TDDFT method yields ME3CI geometries and relative energies quantitatively consistent with the previously reported calculations at a much reduced computational cost.

While extracellular vesicles (EVs) are extensively studied by various practical applications in biomedicine, there is still little information on their biomechanical properties due to their nanoscale size. We identified isolated blood plasma vesicles that carried on biomarkers associated with exosomes and exomeres and applied atomic force microscopy (AFM) to study them at single particle level in air and in liquid. Air measurements of exosomes revealed a mechanically indented internal cavity in which highly adhesive sites were located. In contrast, the highly adhesive sites of exomeres were located at the periphery and the observed diameter of the particles was ~35 nm. In liquid, the reversible deformation of the internal cavity of exosomes was observed and a slightly deformed lipid bi-layer was identified. In contrast, exomeres were not deformed and their observed diameter was ~16 nm. The difference in diameters might be associated with a higher sorption of water film in air. The parameters we revealed correlated with the well-known structure and function for exosomes and were observed for exomeres for the first time. Our data provide a new insight into the biomechanical properties of nanoparticles and positioned AFM as an exclusive source of in situ information about their biophysical characteristics.

The computation of electron attachment energies (electron affinities) was implemented in connection with an ensemble density functional theory method, the state-interaction state-averaged spin-restricted ensemble-referenced Kohn-Sham (SI-SA-REKS or SSR) method. With the use of the extended Koopmans' theorem, the electron affinities and the respective Dyson orbitals are obtained directly for the neutral molecule, thus avoiding the necessity to compute the ionized system. Together with the EKT-SSR (extended Koopmans' theorem-SSR) method for ionization potentials, which was developed earlier, EKT-SSR for electron affinities completes the implementation of the EKT-SSR formalism, which can now be used for obtaining electron detachment as well as the electron attachment energies of molecules in the ground and excited electronic states. The extended EKT-SSR method was tested in the calculation of several closed-shell molecules. For the molecules in the ground states, the EKT-SSR energies of Dyson's orbitals are virtually identical to the energies of the unoccupied orbitals in the usual single-reference spin-restricted Kohn-Sham calculations. For the molecules in the excited states, EKT-SSR predicts an increase of the most positive electron affinity by approximately the amount of the vertical excitation energy. The electron affinities of a number of diradicals were calculated with EKT-SSR and compared with the available experimental data. With the use of a standard density functional (BH&HLYP), the EKT-SSR electron affinities deviate on average by ca. 0.2 eV from the experimental data. It is expected that the agreement with the experiment can be improved by designing density functionals parametrized for ionization energies.

The mixed-reference spin-flip (MRSF) time-dependent density functional theory (TDDFT) method eliminates the notorious spin contamination of SF-TDDFT, thus enabling identification of states of proper spin-symmetry for automatic geometry optimization and molecular dynamics simulations. Here, we analyze and optimize the MRSF-TDDFT in the calculations of the vertical excitation energies (VEEs) and the singlet-triplet (ST) gaps. The dependence of the obtained VEEs and ST gaps on the intrinsic parameters of the MRSF-TDDFT method is investigated, and prescriptions for the proper use of the method are formulated. For VEEs, MRSF-TDDFT displays similar or better accuracy than SF-TDDFT (ca. 0.5 eV), while considerably outperforming the LR-TDDFT for the ST gaps. As a result, a new functional of STG1X (dubbed here), especially for ST gaps is suggested on the basis of splitting between the components of the atomic multiplets.

Background: Large protein aggregates, known as circulating immune complexes (CICs), are formed in biological fluids as a result of the development of the body's immune response to various provoking factors. The kinetic characteristics of the formation and removal of immune complexes (ICs), their physical parameters, the isotypic composition of immunoglobulins (Igs) and the antigenic component of the CICs may reflect certain aspects of certain pathological and metabolic processes taking place in humans and animals. The aim of this study is to assess the kinetic characteristics of the formation and removal of the CICs that form in blood after eating. We also analyze the changes in the isotypic composition of Igs of ICs that accompany this biological process in rodents and humans. Methods: We identified the CICs, which differed in size and class of Igs, using dynamic light scattering. To remove ICs from the plasma, we used immune-affinity sedimentation. Monoclonal antibodies for the Igs of different isotypes were added to the plasma samples to determine the isotypic composition of the ICs. Results: A large number of ICs were formed in the blood of rats and humans after eating (food CICs). In rats, food ICs are almost immediately filtered in the liver, without circulating in the bloodstream through the body. In humans, the level of food ICs in the blood increases for 3.5 h after ingestion, then within 7-8 h their gradual removal takes place. It was found that in the process of digestion in humans, the isotypic composition of Igs in the CICs changes and becomes more diverse. Conclusions: The molecular-cellular mechanisms of the formation and utilization of food CICs in humans and rodents do not match completely., Competing Interests: No competing interests were disclosed.

A quantum theory of atoms in molecules (QTAIM) and stress tensor analysis was applied to analyze intramolecular interactions influencing the photoisomerization dynamics of a light-driven rotary molecular motor. For selected nonadiabatic molecular dynamics trajectories characterized by markedly different S 1 state lifetimes, the electron densities were obtained using the ensemble density functional theory method. The analysis revealed that torsional motion of the molecular motor blades from the Franck-Condon point to the S 1 energy minimum and the S 1 /S 0 conical intersection is controlled by two factors: greater numbers of intramolecular bonds before the hop-time and unusually strongly coupled bonds between the atoms of the rotor and the stator blades. This results in the effective stalling of the progress along the torsional path for an extended period of time. This finding suggests a possibility of chemical tuning of the speed of photoisomerization of molecular motors and related molecular switches by reshaping their molecular backbones to decrease or increase the degree of coupling and numbers of intramolecular bond critical points as revealed by the QTAIM/stress tensor analysis of the electron density. Additionally, the stress tensor scalar and vector analysis was found to provide new methods to follow the trajectories, and from this, new insight was gained into the behavior of the S 1 state in the vicinity of the conical intersection.

Various types of interactions between halogen (X) and π moiety (X-π interaction) including halogen bonding play important roles in forming the structures of biological, supramolecular, and nanomaterial systems containing halogens and aromatic rings. Furthermore, halogen molecules such as X 2 and CX 4 (X = Cl/Br) can be intercalated in graphite and bilayer graphene for doping and graphene functionalization/modification. Due to the X-π interactions, though recently highly studied, their structures are still hardly predictable. Here, using the coupled-cluster with single, double, and noniterative triple excitations (CCSD(T)), the Møller-Plesset second-order perturbation theory (MP2), and various flavors of density functional theory (DFT) methods, we study complexes of benzene (Bz) with halogen-containing molecules X 2 and CX 4 (X = Cl/Br) and analyze various components of the interaction energy using symmetry adapted perturbation theory (SAPT). As for the lowest energy conformers (S1), X 2 -Bz is found to have the T-shaped structure where the electropositive X atom-end of X 2 is pointing to the electronegative midpoint of CC bond of the Bz ring, and CX 4 -Bz has the stacked structure. In addition to this CX 4 -Bz (S1), other low energy conformers of X 2 -Bz (S2/S3) and CX 4 -Bz (S2) are stabilized primarily by the dispersion interaction, whereas the electrostatic interaction is substantial. Most of the density functionals show noticeable deviations from the CCSD(T) complete basis set (CBS) limit binding energies, especially in the case of strongly halogen-bonded conformers of X 2 -Bz (S1), whereas the deviations are relatively small for CX 4 -Bz where the dispersion is more important. The halogen bond shows highly anisotropic electron density around halogen atoms and the DFT results are very sensitive to basis set. The unsatisfactory performance of many density functionals could be mainly due to less accurate exchange. This is evidenced from the good performance by the dispersion corrected hybrid and double hybrid functionals. B2GP-PLYP-D3 and PBE0-TS(Tkatchenko-Scheffler)/D3 are well suited to describe the X-π interactions adequately, close to the CCSD(T)/CBS binding energies (within ∼1 kJ/mol). This understanding would be useful to study diverse X-π interaction driven structures such as halogen containing compounds intercalated between 2-dimensional layers.