Intriguing Low-Temperature Phase in the Antiferromagnetic Kagome Metal FeGe.

The properties of kagome metals are governed by the interdependence of band topology and electronic correlations resulting in remarkably rich phase diagrams. Here, we study the temperature evolution of the bulk electronic structure of the antiferromagnetic kagome metal FeGe using infrared spectroscopy. We uncover drastic changes in the low-energy interband absorption at the 100 K structural phase transition that has been linked to a charge-density-wave (CDW) instability. We explain this effect by the minuscule Fe displacement in the kagome plane, which results in parallel bands in the vicinity of the Fermi level. In contrast to conventional CDW materials, however, the spectral weight shifts to low energies, ruling out the opening of a CDW gap in FeGe.

Higher Infectivity of the Human Immunodeficiency Virus in Sensitive Cells with a Modification of the CCR5 Gene.

As a natural mutation of the human ccr5 gene has been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, a new avenue has opened in the development of alternative treatment approaches through genome editing. One of the two chemokine co-receptors of the plasma membrane is utilized by HIV-1 to infect CD4+ cells. HIV-1 strains that utilize CCR5 circulate in early infection, and strains that utilize CXCR4 circulate at advanced stages. A complex relationship may exist in the expression regulation of the receptors and may affect virus replication in cells that normally do not express CCR5 on the membrane, such as the MT-4 cell line. MT-4 cells were used to study the effect of ccr5 modification HIV-1 replication in vitro. Genetic modification of ccr5 in MT-4 cells was shown to increase the activities of HIV-1 strains, especially in homozygote. The results indicate that genome editing should be performed with caution in human cells and that the issue needs comprehensive investigation.

Magneto-Optics of a Weyl Semimetal beyond the Conical Band Approximation: Case Study of TaP.

Landau-level spectroscopy, the optical analysis of electrons in materials subject to a strong magnetic field, is a versatile probe of the electronic band structure and has been successfully used in the identification of novel states of matter such as Dirac electrons, topological materials or Weyl semimetals. The latter arise from a complex interplay between crystal symmetry, spin-orbit interaction, and inverse ordering of electronic bands. Here, we report on unusual Landau-level transitions in the monopnictide TaP that decrease in energy with increasing magnetic field. We show that these transitions arise naturally at intermediate energies in time-reversal-invariant Weyl semimetals where the Weyl nodes are formed by a partially gapped nodal-loop in the band structure. We propose a simple theoretical model for electronic bands in these Weyl materials that captures the collected magneto-optical data to great extent.

Protective Properties of Lanthanum Nitrate against Pathogens with Various Morphological and Functional Properties.

Dose-dependent protective effects of lanthanum nitrate solution and gel were shown on the model of experimental infection caused by a virulent strain of Shigella flexneri 2a or opportunistic bacteria Klebsiella pneumoniae in outbred and DBA mice.

Linear-in-Frequency Optical Conductivity in GdPtBi due to Transitions near the Triple Points.

The complex optical conductivity of the half-Heusler compound GdPtBi is measured in a frequency range from 20 to 22 000 cm^{-1} (2.5 meV-2.73 eV) at temperatures down to 10 K in zero magnetic field. We find the real part of the conductivity, σ_{1}(ω), to be almost perfectly linear in frequency over a broad range from 50 to 800 cm^{-1} (∼6-100 meV) for T≤50 K. This linearity strongly suggests the presence of three-dimensional linear electronic bands with band crossings (nodes) near the chemical potential. Band-structure calculations show the presence of triple points, where one doubly degenerate and one nondegenerate band cross each other in close vicinity of the chemical potential. From a comparison of our data with the optical conductivity computed from the band structure, we conclude that the observed nearly linear σ_{1}(ω) originates as a cumulative effect from all the transitions near the triple points.

Polyprenyl Phosphates Induce a High Humoral and Cellular Response to Immunization with Recombinant Proteins of the Replicative Complex of the Hepatitis C Virus.

The search for new adjuvants remains the critical task for the creation of hepatitis C vaccines due to the weak immunogenicity of biotechnological products. When immunizing mice with the recombinant proteins NS3 and NS5B of the hepatitis C virus (HCV), the adjuvant activity of three immunomodulators was compared. Phosprenyl® on the basis of polyprenyl phosphate (PPP), chemically synthesized analogue of the bacterial cell wall glucosaminyl muramyl dipeptide (GMDP), and IFN-α recombinant protein were tested. GMDP increased the activity of IgG1 antibodies 4-6 times but did not stimulate the production of IFN-γ; IFN-α has not shown any adjuvant properties. The introduction of recombinant HCV proteins together with PPP in low doses increased the activity of IgG2a isotype antibodies 4-7 times and increased IFN-γ secretion 3 times. Thus, it was first shown that PPP polarizes the immune response to Th1-type and is a promising adjuvant for the development of a vaccine against hepatitis C.

Flat Optical Conductivity in ZrSiS due to Two-Dimensional Dirac Bands.

ZrSiS exhibits a frequency-independent interband conductivity σ(ω)=const(ω)≡σ_{flat} in a broad range from 250 to 2500 cm^{-1} (30-300 meV). This makes ZrSiS similar to (quasi-)two-dimensional Dirac electron systems, such as graphite and graphene. We assign the flat optical conductivity to the transitions between quasi-two-dimensional Dirac bands near the Fermi level. In contrast to graphene, σ_{flat} is not universal but related to the length of the nodal line in the reciprocal space, k_{0}. Because of spin-orbit coupling, the discussed Dirac bands in ZrSiS possess a small gap Δ, for which we determine an upper bound max(Δ)=30 meV from our optical measurements. At low temperatures the momentum-relaxation rate collapses, and the characteristic length scale of momentum relaxation is of the order of microns below 50 K.

Effects of Miramistin and Phosprenil on Microbial Biofilms.

Effects of Miramistin and Phosprenil on biofilms of S. pyogenes, S. aureus, E. coli, L. acidophilus, and L. plantarum were studied. Significant differences in the effects of these substances on mature biofilms of microorganisms and the process of their formation were observed. Miramistin had significant inhibiting effects on the forming of biofilms and on the formed biofilms of all studied microorganisms. Treatment with Miramistin inhibited biofilm formation by 2-3 times compared to the control. This effect was found already after using of Miramistin in the low doses (3.12 µg/ml). Inhibition of the growth of a formed biofilm was observed only after treatment with Miramistin in the high doses (25-50 µg/ml). Phosprenil in the high doses (15-30 mg/ml) inhibited the forming of biofilms, especially the biofilms of S. pyogenes and L. plantarum (by 3-4.5 times). Treatment of formed biofilms with the agent in doses of 6.0 and 0.6 mg/ml was associated with pronounced stimulation of its growth in S. pyogenes, S. aureus, and L. acidophilus.

[Antiviral activity of phosprenyl and gamapren against infection caused by influenza a (H5N1) virus in cell culture].

The antiviral activity of Phosprenyl and Gamapren in vitro against highly pathogenic strain of avian influenza H5N1 virus was studied. Inoculation of the virus to the susceptible cell culture led to development of the cytopathogenic effect. Preliminary introduction of Phosprenyl and Gamapren an hour prior to infecting the cells with virus 10.0 TCID50 dose completely inhibited the cytopathogenic activity of the virus. At higher doses of virus (100.0 TCID50) significant inhibition of the infectious activity of the virus was observed: 70% of infected cells survived under the action of Phosprenyl, and 90% under the action of Gamapren. With the introduction of the preparations simultaneously with the infection of cells with virus at a dose of 10.0 TCID50 virtually 100% of infected cells survived, while in control cultures death of 100% of the cells occurred. After infection with the virus at a dose of 100.0 TCID50 Phosprenyl and Gamapren caused 50% protection of the cells. The antiviral effect of the drugs Phosprenyl and Gamapren may be associated not only with their virulicidal, but with anti-viral activity as well.

[Efficacy of polyprenyl phosphates in the experimental genital herpes model].

An experimental model of the primary genital herpes (herpes simplex type 2, HSV-2) in the female guinea pigs was suggested to study the infectious process activity of polyprenyl phosphates (PPP) and PPP+acyclovir (AC) complex treatment. The morphofunctional features of the guinea pig ovaries were studied in the control and experimental groups (the latter were inoculated with PPP and/or AC as a primary infection treatment) at the stage of the recurrent genital herpes aggravation. It was shown that in the case of combined PPP +AC use significant changes in the disease symptoms were observed, as well as a decrease in the infectious process activity and duration, and positive remote effect on the ovarian morphophysiology.

[IMMUNOLOGIC MONITORING OF HELICOBACTER PYLORI PERSISTENCE IN THE ORGANISM].

Generalized results of 15-year prospective studies of frequency of occurrence and dynamics of circulation of pathogenetically significant LPS/O-antigens, high molecular weight proteins, including CagA, and VacA of Helicobacter pylori in biological media of organism in patients with gastrointestinal diseases and asymptomatic volunteers due to effects of external and internal factors are presented. Features of antigen circulation and reciprocal immune reaction of the organism are established, that reflect their interaction in the parasite-host tandem, risk and prognosis of possible complications in the process of long-term persistence of Helicobacter pylori in the organism.

[TREATMENT OF PATIENTS WITH CHRONIC RECURRENT HERPES VIRUS INFECTION OF GENITAL LOCALIZATION: A CLINICAL STUDY OF FORTEPREN PREPARATION].

AIM: Selection of optimal dosage regimen, length of treatment course (frequency of administration), safety, tolerance and clinical effectiveness evaluation of the medical preparation fortepren in patients with chronical recurrent herpes virus infection of genital localization. MATERIALS AND METHODS: The medical product of antiviral and immune modulating effect--fortepren (sodium polyprenyl phosphate) as a 4 mg/ml solution for injections combined with the base course of acyclic nucleoside acyclovir, 400 mg tablets, held studies. 40 male and female patients participated in the study. After a 10-day acyclovir course (400 mg x 3 times a day) for removing the acute phase, 4 groups of 10 individuals were formed: 1--5 ml (20 mg) of fortepren i/m once at day 13 ± 2 after the start of the study after the completion of the treatment of the acute phase of the disease; 2--5 ml (20 mg) fortepren i/m 3 times at an interval of 21 days; 3--2 ml (8 mg) fortepren i/m 3 times at an interval of 21 days; 4 (control)--5 ml of placebo i/m at remission stage 3 times at an interval of 21 days. Increase of the duration of inter-recurrence period, decrease of the severity of the recurrences, state of skin and mucous damage elements, improvements of immunologic parameters were considered during effectiveness evaluation. RESULTS: Significant differences in the frequency of recurrences of genital herpes were shown for 3 months of observation in experimental and control groups. A significant reduction of genital herpes recurrence frequency from 3.52 ± 0.09 (before treatment) to 2.89 ± 0.08 (after treatment) was noted in patients of group 3 (p < 0.001). The frequency of recurrences in the control group was 3.84 ± 0.10, that was higher than the parameters in all the experimental groups. A significant reduction of the rash area was noted in group 3, moreover, a redution of frequency of detection of clinical manifestations of genital herpes in the form of vesicle elements after treatment in groups 2 (p = 0.02) and 3 (p = 0.005) was found. Evaluation of local symptoms has established that burning have caused minimal discomfort for patients of groups 3 and 4 and itch and soreness--of groups 1 and 3. The least pronounced exacerbations were noted in patients of group 3. Intramuscular administration of fortepren preparation was established to result in the increase of titers of leukocyte virus-induced interferon for the whole duration of treatment. CONCLUSION: An intramuscular dose of 2 ml (8 mg) at recurrence stage 3 times at an interval of 21 days after the completion of the 10-day base course of treatment of the acute phase of chronical recurrent herpes virus infection of genital localization using acyclovir was accepted as an optimal dosage regimen. Analysis of the obtained results has shown an acceptable safety profile and a good level of tolerance for fortepren preparation.

[Electrical properties of water: a new insight].

New insight into the electrical properties of liquid water, from a standpoint of the physics of electrolytes, is proposed. The dielectric spectrum of water at frequencies 10(4)-10(11) Hz is described by a simple diffusional model taking into account the electrophoretic and relaxation effects inherent in electrolytes. The static dielectric permittivity and microwave absorption are derived from diffusion of Coulomb interacting H3O+ and OH- ions instead of orientational motion of H2O molecules. The drift component of diffusion provides the proton dc-conductivity. Ion concentration is found to be 7 orders of magnitude higher than commonly accepted.(- 1% of the total concentration of H2O molecules). The findings refer to the basic properties of water and therefore can be the key to solving the water-related problems.

[Antiviral activity and possible mechanisms of action of moraprenil phosphates during experimental infection caused by herpes simplex type 1 virus].

AIM: Study of antiviral activity of moraprenil phosphates (MPP) against herpes simplex type 1 virus (HSV1) in vitro and during experimental infection caused by HSV1 in mice. MATERIALS AND METHODS: Activity of MPP in vitro was tested by the ability to suppress formation of symplasts in VERO cells infected with HSV1, strain VR-3. A series of MPP that suppress virus-induced symplast-formation by 30 times was selected for in vivo experiments. Anti-viral activity of MPP in vivo was studied in HSV-1 infected mice after administration of either prophylaxis or therapy regimens. RESULTS: MPP at the dose of 20 microg/mice during s/c administration exhibited a pronounced prophylactic-therapeutic effect. Effectiveness of MPP during clinically evident herpes against the background of developing neurologic symptoms was demonstrated for the first time. Visual observation of the mice, that had received MPP as the first clinical symptoms of the disease appeared, has shown that against the background of preparation injection the clinical signs have ceased after 2 - 3 days and did not registered at least for the whole duration of the observation period (14 days). CONCLUSION: Active herpes infection is accompanied by the increase of FoxP3 expression in-thymus was shown. Possible mechanisms of anti-viral effect of MPP are discussed.

[Adjuvant effect of dispersed fullerene C60 on the immune response to constructs harboring amino acid and nucleotide sequences of hepatitis C virus nonstructural NS5B protein].

INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.

In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 µM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

[Antiviral activity of polyprenylphosphates in experimental infection caused by hepatitis C virus in vitro].

AIM: Study antiviral effect of sodium polyprenylphosphate (PPP) in experimental infection model caused by hepatitis C virus (HCV) in cell culture. MATERIALS AND METHODS: Cytopathogenic variant of HCV isolated from blood serum of a chronically infected patient was used. HCV infectious dose was 10.0 TCD50. Highly sensitive to cytopathogenic effect of HCV continuous swine embryo kidney cells (SPEV) as 1 day monolayer grown in 24 well plastic plates on 199 medium with 10% calf serum with addition of L-glutamine and antibiotics (100 U/ml) were used. PPP was used in concentrations that do not have cytotoxic effect (from 60 to 7.5 microg in 50 microl); introduced into SPEV cell cultures immediately after infection, 24 hours before or 24 hours after the infection of cells with HCV. Infectious activity of HCV was evaluated by using Reed-Muench formula based on results of medium samples titration obtained 3 days after the infection of cells. RESULTS: PPP was shown to have antiviral properties when added into the cell cultures immediately after the infection with HCV. Under the effect of PPP HCV titers were established to decrease by 3.0 lg (PPV dose of 60 microg) and by 1.9 lg (PPV dose of 30 microg). Positive effect was also obtained for prophylactic use of PPP. When PPP at a dose of 60 microg was introduced 24 hours before the infection of SPEV with HCV, the titer of the virus decreased by 3.5 lg. Prophylactic administration of low doses of the preparation (7.5 and 15.0 microg) also showed evident antiviral effect (decrease of infectious activity of HCV by 3.2 - 2.3 lg, respectively). CONCLUSION: PPP at the doses tested has an ability to reduce concentration of HCV in SPEV cell cultures when added immediately after infection or 24 hours before.

[A systematic analysis of neurobiological roles of lithium]. / Neirobiologicheskaya rol' solei litiya.

Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since the FDA approved the treatment in 1970. Molecular mechanisms of lithium's action include inhibition of glycogen synthase kinase 3 beta and inositol monophosphatase, resulting in induction of brain-derived neurotrophic factor, antiapoptotic proteins, deprivation of calcium-induced apoptosis. Recent findings suggest autophagy regulation as a possible mechanism of lithium neuroprotective action. Moreover, lithium treatment has been reported to decrease accumulation of various pathological proteins including phosphorylated tau and amyloid-B. Also, telomeres length and telomerase activity are suggested to be upregulated by lithium. Clinical applications of lithium treatment include various neurodegenerative diseases, primarily Alzheimer disease, with increasing importance given to the use of lithium microdoses. Chemoreactome screening is used to find more safe and effective lithium compounds.

Mouse splenocyte blast transformation in the presence of plasma γ-globulin fraction proteins and their complexes with copper and zinc.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by these cations and human serum γ-globulin induce blast transformation of splenocytes from BALB/c mice at a level comparable to that induced by concanavalin A. Zinc bound to γ-globulin reduces by 25% and copper in complex with this protein stimulates by 1.6 times its capacity to induce blast transformation. Combinations with concanavalin A reproduce the effects of γ-globulin-metal complex under conditions of mitogen induction. Incorporation of(3)H-thymidine in splenocytes incubated with combinations of γ-globulin-copper metalcomplex, copper cations, and control protein with concanavalin A was by 1.4, 1.3 (p<0.1), and 1.25 times higher (p<0.05), respectively, than after incubation with concanavalin A alone.

["Non-immune" interactions of gamma-globulin in regulation of immune reactions].

It was shown using the model of L2-dependent proliferation of T-cells that IL2 forms complexes with gamma-globulin inhibiting IL2 activity. In this interaction IL2 acts as lectin binding with two-antenna terminals of 5 or 6 mannose residues in one and the same region of immunoglobulin. Similar effect is observed in vivo in case of induction of DTH to listerial antigens. This phenomenon accounts for suppression of the immune response after passive injection of autoantibodies and for the inverse relationship between humoral and cellular immunity. Reduction of IL2 activity after its interaction with IgG or immune complexes may be regarded as a universal feedback immunoregulatory mechanism. External and internal factors showing affinity to mannose, e.g. sodium polyprenyl phosphate or lactobacillus, can interfere with this process and exert immunomodulating effect.