Valleytronics in bulk MoS2 with a topologic optical field.

The valley degree of freedom1-4 of electrons in materials promises routes towards energy-efficient information storage with enticing prospects for quantum information processing5-7. Current challenges in utilizing valley polarization are symmetry conditions that require monolayer structures8,9 or specific material engineering10-13, non-resonant optical control to avoid energy dissipation and the ability to switch valley polarization at optical speed. We demonstrate all-optical and non-resonant control over valley polarization using bulk MoS2, a centrosymmetric material without Berry curvature at the valleys. Our universal method utilizes spin angular momentum-shaped trefoil optical control pulses14,15 to switch the material's electronic topology and induce valley polarization by transiently breaking time and space inversion symmetry16 through a simple phase rotation. We confirm valley polarization through the transient generation of the second harmonic of a non-collinear optical probe pulse, depending on the trefoil phase rotation. The investigation shows that direct optical control over the valley degree of freedom is not limited to monolayer structures. Indeed, such control is possible for systems with an arbitrary number of layers and for bulk materials. Non-resonant valley control is universal and, at optical speeds, unlocks the possibility of engineering efficient multimaterial valleytronic devices operating on quantum coherent timescales.

Capturing electron-driven chiral dynamics in UV-excited molecules.

Chiral molecules, used in applications such as enantioselective photocatalysis1, circularly polarized light detection2 and emission3 and molecular switches4,5, exist in two geometrical configurations that are non-superimposable mirror images of each other. These so-called (R) and (S) enantiomers exhibit different physical and chemical properties when interacting with other chiral entities. Attosecond technology might enable influence over such interactions, given that it can probe and even direct electron motion within molecules on the intrinsic electronic timescale6 and thereby control reactivity7-9. Electron currents in photoexcited chiral molecules have indeed been predicted to enable enantiosensitive molecular orientation10, but electron-driven chiral dynamics in neutral molecules have not yet been demonstrated owing to the lack of ultrashort, non-ionizing and perturbative light pulses. Here we use time-resolved photoelectron circular dichroism (TR-PECD)11-15 with an unprecedented temporal resolution of 2.9 fs to map the coherent electronic motion initiated by ultraviolet (UV) excitation of neutral chiral molecules. We find that electronic beatings between Rydberg states lead to periodic modulations of the chiroptical response on the few-femtosecond timescale, showing a sign inversion in less than 10 fs. Calculations validate this and also confirm that the combination of the photoinduced chiral current with a circularly polarized probe pulse realizes an enantioselective filter of molecular orientations following photoionization. We anticipate that our approach will enable further investigations of ultrafast electron dynamics in chiral systems and reveal a route towards enantiosensitive charge-directed reactivity.

Observation of interband Berry phase in laser-driven crystals.

Ever since its discovery1, the notion of the Berry phase has permeated all branches of physics and plays an important part in a variety of quantum phenomena2. However, so far all its realizations have been based on a continuous evolution of the quantum state, following a cyclic path. Here we introduce and demonstrate a conceptually new manifestation of the Berry phase in light-driven crystals, in which the electronic wavefunction accumulates a geometric phase during a discrete evolution between different bands, while preserving the coherence of the process. We experimentally reveal this phase by using a strong laser field to engineer an internal interferometer, induced during less than one cycle of the driving field, which maps the phase onto the emission of higher-order harmonics. Our work provides an opportunity for the study of geometric phases, leading to a variety of observations in light-driven topological phenomena and attosecond solid-state physics.

Four sides to the story: A proteomic comparison of liquid-phase and matrix-bound extracellular vesicles in 2D and 3D cell cultures.

Multipotent mesenchymal stromal cells (MSCs)-derived extracellular vesicles (EVs) play important roles in cellular communication and are extensively studied as promising therapeutic agents. While there is a substantial pool of studies on liquid-phase EVs, data on EVs bound to the extracellular matrix (ECM) is lacking. There is also an emerging trend of accumulating and comparing data on characteristics of EVs obtained in different culturing conditions. Aiming to reveal proteomic signatures of EVs obtained from conditioned media and ECM of MSCs cultured in 2D and 3D conditions, we performed liquid chromatography with tandem mass spectrometry. Bioinformatic analysis revealed common patterns in proteomic composition of liquid-phase EVs and matrix-bound vesicles (MBVs), namely extracellular environment organization, immune, and transport pathways enrichment. However, extracellular environmental organization pathways are more enriched in liquid-phase EVs than in MBVs, while MBVs proteins noticeably enrich enzymatic pathways. Furthermore, each type of EVs from 2D and 3D cultures has a unique differential abundance profile. We have also performed comparative functional assays, namely scratch assay to assess EVs effect on cell migration and tubulogenesis assay to evaluate EVs angiogenic potential. We found that both liquid-phase EVs and MBVs enhance cell migration, while angiogenic potential is higher in MBVs. Results of the present study suggest that while both liquid-phase EVs and MBVs have therapeutic potential, some unique features of each subgroup may determine optimal areas of their application.

Charged Amino Acid Substitutions Affect Conformation of Neuroglobin and Cytochrome c Heme Groups.

Neuroglobin (Ngb) is a cytosolic heme protein that plays an important role in protecting cells from apoptosis through interaction with oxidized cytochrome c (Cyt c) released from mitochondria. The interaction of reduced Ngb and oxidized Cyt c is accompanied by electron transfer between them and the reduction in Cyt c. Despite the growing number of studies on Ngb, the mechanism of interaction between Ngb and Cyt c is still unclear. Using Raman spectroscopy, we studied the effect of charged amino acid substitutions in Ngb and Cyt c on the conformation of their hemes. It has been shown that Ngb mutants E60K, K67E, K95E and E60K/E87K demonstrate changed heme conformations with the lower probability of the heme planar conformation compared to wild-type Ngb. Moreover, oxidized Cyt c mutants K25E, K72E and K25E/K72E demonstrate the decrease in the probability of methyl-radicals vibrations, indicating the higher rigidity of the protein microenvironment. It is possible that these changes can affect electron transfer between Ngb and Cyt c.

Effects of Progesterone and Selective Ligands of Membrane Progesterone Receptors in HepG2 Cells of Human Hepatocellular Carcinoma.

Progesterone exerts multiple effects in different tissues through nuclear receptors (nPRs) and through membrane receptors (mPRs) of adiponectin and progestin receptor families. The effect of progesterone on the cells through different types of receptors can vary significantly. At the same time, it affects the processes of proliferation and apoptosis in normal and tumor tissues in a dual way, stimulating proliferation and carcinogenesis in some tissues, suppressing them and stimulating cell death in others. In this study, we have shown the presence of high level of mPRß mRNA and protein in the HepG2 cells of human hepatocellular carcinoma. Expression of other membrane and classical nuclear receptors was not detected. It could imply that mPRß has an important function in the HepG2 cells. The main goal of the work was to study functions of this protein and mechanisms of its action in human hepatocellular carcinoma cells. Previously, we have identified selective mPRs ligands, compounds LS-01 and LS-02, which do not interact with nuclear receptors. Their employment allows differentiating the effects of progestins mediated by different types of receptors. Effects of progesterone, LS-01, and LS-02 on proliferation and death of HepG2 cells were studied in this work, as well as activating phosphorylation of two kinases, p38 MAPK and JNK, under the action of three steroids. It was shown that all three progestins after 72 h of incubation with the cells suppressed their viability and stimulated appearance of phosphatidylserine on the outer surface of the membranes, which was detected by binding of annexin V, but they did not affect DNA fragmentation of the cell nuclei. Progesterone significantly reduced expression of the proliferation marker genes and stimulated expression of the p21 protein gene, but had a suppressive effect on the expression of some proapoptotic factor genes. All three steroids activated JNK in these cells, but had no effect on the p38 MAPK activity. The effects of progesterone and selective mPRs ligands in HepG2 cells were the same in terms of suppression of proliferation and stimulation of apoptotic changes in outer membranes, therefore, they were mediated through interaction with mPRß. JNK is a member of the signaling cascade activated in these cells by the studied steroids.

NOVAprep-miR-Cervix: New Method for Evaluation of Cervical Dysplasia Severity Based on Analysis of Six miRNAs.

Cervical cancer is one of the most common gynecological malignancies and it is preventable through the yearly diagnosis and management of pre-cancerous cervical disease. The profile of miRNA expression in cervical epithelium cells is altered with cervical dysplasia development and further progression. The NOVAprep-miR-CERVIX is a new approach for the assessment of cervical dysplasia through the analysis of six marker miRNAs. This study aims to evaluate theperformance and diagnostic potency of the new method. Cytological smears from 226 women (NILM, n.114; HSIL, n.112) were included in the study. A VPH test was performed with RealBest DNAHPV HR screen Kit, six marker miRNAs (miR-21, -29b, -145, -451a, -1246, -1290) were assayed using NOVAprep-miR-CERVIX kit. Obtained data were analyzed using the Delta Ct method and random forest machine learning algorithm. The results of the quantitative analysis of six microRNAs were expressed as a miR-CERVIX parameter, which ranged from 0 to 1, where "0" corresponded to the healthy cervical epithelium, while "1" corresponded to high-grade squamous intraepithelial dysplasia. The average value of miR-CERVIX differed in groups of NILM and HSIL samples (0.34 vs. 0.72; p < 0.000005). An estimation of miR-CERVIX allowed for the differentiation between healthy and pre-cancerous samples with sensitivity of 0.79 and specificity of 0.79, as well as to confirm HSIL with specificity of 0.98. Interestingly, the HSIL group included HPV(+) and HPV(-) samples, which were statistically significantly different in terms of miR-CERVIX value. Analysis of CC-associated miRNAs in material of cervical smear might serve as an additional method for the evaluation of cervical dysplasia severity.

Nucleoside Analogs That Inhibit SARS-CoV-2 Replication by Blocking Interaction of Virus Polymerase with RNA.

The SARS-CoV-2 betacoronavirus pandemic has claimed more than 6.5 million lives and, despite the development and use of COVID-19 vaccines, remains a major global public health problem. The development of specific drugs for the treatment of this disease remains a very urgent task. In the context of a repurposing strategy, we previously screened a library of nucleoside analogs showing different types of biological activity against the SARS-CoV-2 virus. The screening revealed compounds capable of inhibiting the reproduction of SARS-CoV-2 with EC50 values in the range of 20-50 µM. Here we present the design and synthesis of various analogs of the leader compounds, the evaluation of their cytotoxicity and antiviral activity against SARS-CoV-2 in cell cultures, as well as experimental data on RNA-dependent RNA polymerase inhibition. Several compounds have been shown to prevent the interaction between the SARS-CoV-2 RNA-dependent RNA polymerase and the RNA substrate, likely inhibiting virus replication. Three of the synthesized compounds have also been shown to inhibit influenza virus. The structures of these compounds can be used for further optimization in order to develop an antiviral drug.

Intramolecular Hydrogen Bonding in N6-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy.

Two forms were found in the NMR spectra of N6-substituted 2-chloroadenosines. The proportion of the mini-form was 11-32% of the main form. It was characterized by a separate set of signals in COSY, 15N-HMBC and other NMR spectra. We assumed that the mini-form arises due to the formation of an intramolecular hydrogen bond between the N7 atom of purine and the N6-CH proton of the substituent. The 1H,15N-HMBC spectrum confirmed the presence of a hydrogen bond in the mini-form of the nucleoside and its absence in the main form. Compounds incapable of forming such a hydrogen bond were synthesized. In these compounds, either the N7 atom of the purine or the N6-CH proton of the substituent was absent. The mini-form was not found in the NMR spectra of these nucleosides, confirming the importance of the intramolecular hydrogen bond in its formation.

Electrophoretically Co-Deposited Collagen-Lactoferrin Membranes with Enhanced Pro-Regenerative Properties for Oral Soft Tissue Regeneration.

The quality of soft tissue defect regeneration after dental surgeries largely determines their final success. Collagen membranes have been proposed for the healing of such defects, but in some cases, they do not guarantee a sufficient volume of the regenerated tissue and vascularization. For this purpose, lactoferrin, a protein with natural pro-regenerative, anti-inflammatory, and pro-angiogenic activity, can be added to collagen. In this article, we used a semipermeable barrier-assisted electrophoretic deposition (SBA-EPD) method for the production of collagen-lactoferrin membranes. The membrane structure was studied by SEM, and its mechanical properties were shown. The lactoferrin release kinetics were shown by ELISA within 75 h. When tested in vitro, we demonstrated that the collagen-lactoferrin membranes significantly increased the proliferation of keratinocytes (HaCaT) and fibroblasts (977hTERT) compared to blank collagen membranes. In vivo, on the vestibuloplasty and free gingival graft harvesting models, we showed that collagen-lactoferrin membranes decreased the wound inflammation and increased the healing rates and regeneration quality. In some parameters, collagen-lactoferrin membranes outperformed not only blank collagen membranes, but also the commercial membrane Mucograft®. Thus, we proved that collagen-lactoferrin membranes produced by the SBA-EPD method may be a valuable alternative to commercially used membranes for soft tissue regeneration in the oral cavity.

Strong chiral response in non-collinear high harmonic generation driven by purely electric-dipole interactions.

High harmonic generation (HHG) records the ultrafast electronic response of matter to light, encoding key properties of the interrogated quantum system, such as chirality. The first implementation of chiral HHG [Cireasa et al, Nat. Phys.11, 654 (2015)10.1038/nphys3369] relied on the weak electronic response of a medium of randomly oriented chiral molecules to the magnetic component of an elliptically polarized wave, yielding relatively weak chiro-optical signals. Here we apply state-of-the-art semi-analytical modelling to show that elliptically polarized light can drive a strong chiral response in chiral molecules via purely electric-dipole interactions - the magnetic component of the wave does not participate at all. This strong chiro-optical response, which remains hidden in standard HHG experiments, can be mapped into the macroscopic far-field signal using a non-collinear configuration, creating new opportunities for imaging chiral matter and chiral dynamics on ultrafast time scales.

Cross-polarized common-path temporal interferometry for high-sensitivity strong-field ionization measurements.

Absolute density measurements of low-ionization-degree or low-density plasmas ionized by lasers are very important for understanding strong-field physics, atmospheric propagation of intense laser pulses, Lidar etc. A cross-polarized common-path temporal interferometer using balanced detection was developed for measuring plasma density with a sensitivity of ∼0.6 mrad, equivalent to a plasma density-length product of ∼2.6 × 1013 cm-2 if using an 800 nm probe laser. By using this interferometer, we have investigated strong-field ionization yield versus intensity for various noble gases (Ar, Kr, and Xe) using 800 nm, 55 fs laser pulses with both linear (LP) and circular (CP) polarization. The experimental results were compared to the theoretical models of Ammosov-Delone-Krainov (ADK) and Perelomov-Popov-Terent'ev (PPT). We find that the measured phase change induced by plasma formation can be explained by the ADK theory in the adiabatic tunneling ionization regime, while PPT model can be applied to all different regimes. We have also measured the photoionization and fractional photodissociation of molecular (MO) hydrogen. By comparing our experimental results with PPT and MO-PPT models, we have determined the likely ionization pathways when using three different pump laser wavelengths of 800 nm, 400 nm, and 267 nm.

Imprinting Chirality on Atoms Using Synthetic Chiral Light Fields.

Atoms are usually thought of as achiral objects. However, one can construct superpositions of atomic states that are chiral [1]. Here, we show how to excite such superpositions with tailored light fields both in the weak-field and strong-field regimes, using realistic laser parameters. First, we use time-dependent Schrödinger equation simulations to demonstrate the creation of a time-dependent bound chiral wave packet in sodium atoms. Second, we show how the time-dependent handedness of this wave packet can be probed by photoelectron circular dichroism, in spite of the central symmetry of the core potential. Third, we use time-dependent Schrödinger equation simulations to show how chirality can be directly imprinted on a photoelectron wave packet created by strong-field ionization and introduce an unambiguous chiral measure that allows us to characterize its handedness.

Disentangling enantiosensitivity from dichroism using bichromatic fields.

We discuss how tensorial observables, available in photoelectron angular distributions resulting from interaction between isotropic chiral samples and cross polarized ω-2ω bichromatic fields, allow for chiral discrimination without chiral light and within the electric-dipole approximation. We extend the concept of chiral setup [A. F. Ordonez and O. Smirnova, Phys. Rev. A, 2018, 98, 063428], which explains how chiral discrimination can be achieved in the absence of chiral light, to the case of tensorial observables. We derive selection rules for the enantiosensitivity and dichroism of the bl,m coefficients describing the photoelectron angular distribution valid for both weak and strong fields and for arbitrary ω-2ω relative phase. Explicit expressions for simple perturbative cases are given. We find that, besides the known dichroic non-enantiosensitive [R. E. Goetz, C. P. Koch and L. Greenman, J. Chem. Phys., 2019, 151, 074106], and dichroic-and-enantiosensitive bl,m coefficients found recently [P. V. Demekhin, Phys. Rev. A, 2019, 99, 063406], there are also enantiosensitive non-dichroic bl,m coefficients. These reveal the molecular enantiomer independently of the relative phase between the two colors and are therefore observable even in the absence of stabilization of the ω-2ω relative phase.

A geometric approach to decoding molecular structure and dynamics from photoionization of isotropic samples.

We propose a geometric approach to the description and analysis of photoelectron angular distributions resulting from isotropic samples in the case of few-photon ionization by electric fields of arbitrary polarization. This approach formulates the standard photoionization observables - the bl,m expansion coefficients of the photoelectron angular distribution, in terms of geometrical properties of the vector field D⃑(k⃑) ≡ 〈k⃑|d⃑|0〉 describing the electronic transition from a bound state |0〉 into a scattering state |k⃑〉 - the photoionization transition dipole. Besides revealing selection rules for the enantio-sensitivity of bl,m coefficients in multiphoton ionization, our approach yields very compact expressions for both chiral and achiral molecules revealing how the molecular rotational invariants couple to the rotational invariants of the setup defined by the electric field polarization and the arrangement of photoelectron detectors. We apply this approach to one-photon ionization and find that the forward-backward asymmetry parameter b1,0, emerging exclusively in chiral molecules and encoded in the field B⃑(k⃑) ≡ iD⃑*(k⃑) × D⃑(k⃑), is sensitive only to the components of D⃑(k⃑) perpendicular to k⃑, while the regular asymmetry parameter b2,0 emerging in chiral and achiral molecules is sensitive only to the component of D⃑(k⃑) parallel to k⃑. Next, we analyze resonantly enhanced two-photon ionization and show that b0,0 and b1,0 can be written in terms of an effectively stretched D⃑(k⃑), and how b1,0 and b3,0 can be used to probe B⃑(k⃑).

Propensity rules for photoelectron circular dichroism in strong field ionization of chiral molecules.

Chiral molecules ionized by circularly polarized fields produce a photoelectron current orthogonal to the polarization plane. This current has opposite directions for opposite enantiomers and provides an extremely sensitive probe of molecular handedness. Recently, such photoelectron currents have been measured in the strong-field ionization regime, where they may serve as an ultrafast probe of molecular chirality. Here we provide a mechanism for the emergence of such strong-field photoelectron currents in terms of two propensity rules that link the properties of the initial electronic chiral state to the direction of the photoelectron current.

Ultrafast chirality: the road to efficient chiral measurements.

Today we are witnessing the electric-dipole revolution in chiral measurements. Here we reflect on its lessons and outcomes, such as the perspective on chiral measurements using the complementary principles of "chiral reagent" and "chiral observer", the hierarchy of scalar, vectorial and tensorial enantio-sensitive observables, the new properties of the chiro-optical response in the ultrafast and non-linear domains, and the geometrical magnetism associated with the chiral response in photoionization. The electric-dipole revolution is a landmark event. It has opened routes to extremely efficient enantio-discrimination with a family of new methods. These methods are governed by the same principles but work in vastly different regimes - from microwaves to optical light; they address all molecular degrees of freedom - electronic, vibrational and rotational, and use flexible detection schemes, i.e. detecting photons or electrons, making them applicable to different chiral phases, from gases to liquids to amorphous solids. The electric-dipole revolution has also enabled enantio-sensitive manipulation of chiral molecules with light. This manipulation includes exciting and controlling ultrafast helical currents in vibronic states of chiral molecules, enantio-sensitive control of populations in electronic, vibronic and rotational molecular states, and opens the way to efficient enantio-separation and enantio-sensitive trapping of chiral molecules. The word "perspective" has two meanings: an "outlook" and a "point of view". In this perspective article, we have tried to cover both meanings.

Expression of Opsin Genes in the Retina of Female and Male Three-Spined Sticklebacks Gasterosteus aculeatus L.: Effect of Freshwater Adaptation and Prolactin Administration.

Color vision sensitivity is crucial for fish adaptation during migration and reproduction. Prolactin and prolactin-like hormone are important regulators in both these processes. We hypothesized that prolactin influences the color vision sensitivity during freshwater migrations in fish. We studied the effects of prolactin and freshwater adaptation during the spawning period on the expression of opsin genes (SWS1, SWS2, RH2, LWS) in the retina of female and male three-spined sticklebacks Gasterosteus aculeatus L. Expression of the prolactin gene increased in the brain of females, but not males, while expression of the prolactin-like hormone decreased in the brain of both male and female sticklebacks during freshwater adaptation. Expression of the SWS2 gene decreased in the retina of females and males during freshwater adaptation and after prolactin administration. Expression of the SWS1 gene decreased in the retina of male sticklebacks after prolactin administration, but not during freshwater adaptation. Expression of the RH2 and LWS genes did not depend on prolactin administration in male and female sticklebacks. We conclude that expression of some opsin genes in the retina of sticklebacks is regulated by prolactin and depends on sex and freshwater adaptation. This expands our knowledge of the adaptive effects of prolactin on fish during freshwater migrations.

Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions.

The polyamines, spermine (Spm) and spermidine (Spd), are important for cell growth and function. Their homeostasis is strictly controlled, and a key downregulator of the polyamine pool is the polyamine-inducible protein, antizyme 1 (OAZ1). OAZ1 inhibits polyamine uptake and targets ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, for proteasomal degradation. Here we report, for the first time, that polyamines induce dimerization of mouse recombinant full-length OAZ1, forming an (OAZ1)2-Polyamine complex. Dimerization could be modulated by functionally active C-methylated spermidine mimetics (MeSpds) by changing the position of the methyl group along the Spd backbone-2-MeSpd was a poor inducer as opposed to 1-MeSpd, 3-MeSpd, and Spd, which were good inducers. Importantly, the ability of compounds to inhibit polyamine uptake correlated with the efficiency of the (OAZ1)2-Polyamine complex formation. Thus, the (OAZ1)2-Polyamine complex may be needed to inhibit polyamine uptake. The efficiency of polyamine-induced ribosomal +1 frameshifting of OAZ1 mRNA could also be differentially modulated by MeSpds-2-MeSpd was a poor inducer of OAZ1 biosynthesis and hence a poor downregulator of ODC activity unlike the other MeSpds. These findings offer new insight into the OAZ1-mediated regulation of polyamine homeostasis and provide the chemical tools to study it.