Study on Local-Structure Symmetrization of K2XF6 Crystals Doped with Mn4+ Ions by First-Principles Calculations.

The crystals of Mn4+-activated fluorides, such as those of the hexafluorometallate family, are widely known for their luminescence properties. The most commonly reported red phosphors are A2XF6: Mn4+ and BXF6: Mn4+ fluorides, where A represents alkali metal ions such as Li, Na, K, Rb, Cs; X=Ti, Si, Ge, Zr, Sn, B = Ba and Zn; and X = Si, Ge, Zr, Sn, and Ti. Their performance is heavily influenced by the local structure around dopant ions. Many well-known research organizations have focused their attention on this area in recent years. However, there has been no report on the effect of local structural symmetrization on the luminescence properties of red phosphors. The purpose of this research was to investigate the effect of local structural symmetrization on the polytypes of K2XF6 crystals, namely Oh-K2MnF6, C3v-K2MnF6, Oh-K2SiF6, C3v-K2SiF6, D3d-K2GeF6, and C3v-K2GeF6. These crystal formations yielded seven-atom model clusters. Discrete Variational Xα (DV-Xα) and Discrete Variational Multi Electron (DVME) were the first principles methods used to compute the Molecular orbital energies, multiplet energy levels, and Coulomb integrals of these compounds. The multiplet energies of Mn4+ doped K2XF6 crystals were qualitatively reproduced by taking lattice relaxation, Configuration Dependent Correction (CDC), and Correlation Correction (CC) into account. The 4A2g→4T2g (4F) and 4A2g→4T1g (4F) energies increased when the Mn-F bond length decreased, but the 2Eg → 4A2g energy decreased. Because of the low symmetry, the magnitude of the Coulomb integral became smaller. As a result, the decreasing trend in the R-line energy could be attributed to a decreased electron-electron repulsion.

Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants

The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.

Efficacy and safety of ivermectin for COVID-19: A systematic review and meta-analysis

Objective: To critically evaluate the trials that have assessed the efficacy and safety of ivermectin COVID-19 and to validate the rationality of using this drug in the management of COVID-19 either as a prophylactic or therapeutic agent. Methods: The authors conducted a systematic search through various databases, i.e., Cochrane library, PubMed, clincialtrials.gov, and preprint servers, for publications from 2020 to May 2021. The keywords used for the search were: "COVID-19 and ivermectin"(with filter set for "trials"). All the trials assessing efficacy in prophylaxis and treatment of COVID-19 were included for analysis. The primary outcome was the proportion of patients showing disease progression. Secondary outcomes were mean duration of hospitalization and resolution of symptoms, the proportion of patients testing positive on day 5-7, the mortality rate in severe cases, incidence of serious adverse events, and contacts of COVID-19 positive patients who turned RT-PCR positive after prophylaxis treatment. Results: A total of 17 clinical trials were included for the evaluation. Ivermectin proved to be a beneficial add-on therapy, as it reduced the risk of disease progression (OR 0.47, 95% CI 0.30-0.74, P =0.001), led to early resolution of symptoms (MD -1.16, 95% CI-1.52 - 0.81, P <0.001), and had less duration of hospitalization (MD -2.21, 95% CI -3.23 - 1.19, P <0.001). In addition, ivermectin was better in providing effective prophylaxis (OR 0.13, 95% CI 0.05-0.30, P <0.001). The incidence of serious adverse events was low. Conclusions: As an adjunct to standard care, ivermectin has shown its efficacy and safety in treating and prophylaxis in COVID-19 disease. These results should be interpreted cautiously as these trials had significant shortcomings.

Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model

We have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.

Antibacterial and cellular response of piezoelectric Na0.5K0.5NbO3modified 1393 bioactive glass.

In the present study, the combined effect of addition of varying concentrations (10-30 vol%) of biocompatible piezoelectric Na0.5K0.5NbO3 (NKN) as well as electrostatic and dynamic pulsed electrical treatment on antibacterial and cellular response of 1393 bioactive glass (1393 BG) has been examined. The phase analyses of the sintered (at 800 °C for 30 min) samples revealed the formation of 1393 BG - NKN composites without any appearance of secondary phases. The addition of 10-30 vol% NKN significantly improved the mechanical behaviour of 1393 BG like, hardness (1.7 to 2 times), fracture toughness (1.3 to 2.6 times), compressive (2.3 to 8 times) and flexural strengths (2 to 3.5 times) than monolithic 1393 BG. The piezoelectric NKN is observed to induce the antibacterial activity in 1393 BG - (10- 30 vol%) NKN composites, while Staphylococcus aureus (S. aureus, gram positive) and Escherichia coli (E. coli, gram negative) bacterial cells were exposed to unpolarized and polarized (20 kV, 500°C for 30 min) sample surfaces. The antibacterial response was examined using disc diffusion, nitro blue tetrazolium (NBT) and MTT assays. The statistical analyses revealed the significant reduction in the viability of bacterial cells on polarized 1393 BG - (10- 30 vol%) NKN composite samples. In addition, the combined effect of electrostatic and dynamic pulsed electrical stimulation (1 V/cm, 500 µs pulses) on the cellular response of 1393 BG and 1393 BG - 30 vol% NKN composites has been analysed with MG-63 osteoblast-like cells. The cell proliferation was observed to increase significantly for the dynamic pulsed electric field treated negatively charged surfaces.

Electro-mechanical and Polarization-Induced Antibacterial Response of 45S5 Bioglass-Sodium Potassium Niobate Piezoelectric Ceramic Composites.

Besides the excellent osteoconductivity and biocompatibility of 45S5 bioglass (BG), poor mechanical and electrical properties as well as susceptibility toward bacterial adhesion limit its widespread clinical applications. In this context, the present study investigates the effect of addition of piezoelectric sodium potassium niobate (Na0.5K0.5NbO3; NKN) on mechanical, dielectric, and antibacterial response of BG. BG-xNKN (x = 0, 10, 20, and 30 vol%) composites were synthesized at 800 °C for 30 min. The phase analyses using spectral techniques revealed the formation of the composite without any reaction between BG and piezoelectric ceramic NKN. The dielectric and electrical measurements were performed over a wide range of temperature (30-500 °C) and frequency (1 Hz-1 MHz) which suggests that space charge and dipolar polarizations are the dominant polarization mechanisms. The complex impedance analyses suggest that the average activation energies for grain and grain boundary resistances for BG-xNKN (x = 10, 20, and 30 vol%) composites are 0.59, 0.87, 0.94 and 0.76, 0.93, 1.06 eV, respectively. The issue of bacterial infection has been addressed by electrical polarization of the developed composite samples, at 20 kV for 30 min. Statistical analyses reveal that the viability of Gram-positive (S. aureus) and Gram-negative (E. coli) bacterial cells has been reduced significantly on positively and negatively charged BG-NKN composite samples, respectively. The qualitative analyses using the Kirby-Bauer test supports the above findings. Nitro blue tetrazolium and lipid peroxide assays were performed to understand the mechanism of such antibacterial response, which suggested that the combined effect of NKN addition and polarization significantly enhances the superoxide production, which kills the bacterial cells. Overall, incorporation of NKN in BG enhances the mechanical, electrical, and dielectric properties as well as improves the antibacterial response of polarized BG-xNKN composites.

Multifunctional Response of Piezoelectric Sodium Potassium Niobate (NKN)-Toughened Hydroxyapatite-Based Biocomposites.

In this study, hydroxyapatite (HA)-sodium potassium niobate (NKN) composites with varying concentrations of NKN (10, 20, and 30 wt %) were optimally developed at 1075 °C for 2 h. Detailed microstructural analyses have been performed by means of scanning and transmission electron microscopy. The maximum fracture toughness, hardness, and compressive and flexural strengths were obtained to be ∼209, ∼93, ∼112, and ∼88%, respectively, for the HA-30 wt % NKN composite compared to monolithic HA. The antibacterial tests revealed the significant reduction in bacterial viability on poled (@ 20 kV for 30 min at 500 °C) HA-NKN composite samples while cultured with Staphylococcus aureus and Escherichia coli bacteria. The cytocompatibility tests revealed the significantly enhanced MG63 cell proliferation for electrical stimulation-treated negatively charged HA and H30N composite samples.

Synthesis and oral hypoglycemic effect of novel thiazine containing trisubstituted benzenesulfonylurea derivatives.

A new series of 3-(4-substituted phenyl)-1-(4-(4,6-dimethyl-6H-1,3-thiazin-2-yl)phenylsulfonyl)-1-substituted urea (5a-o) was synthesized by an effectual route via sulfonylcarbamates and explores the novel site for substitution in sulfonylurea as well as the way of thiazine can be prepared. The molecules were established by elemental analysis and spectroscopic viz. IR, (1)H NMR, (13)C NMR and MS techniques. All the fifteen derivatives were shown very prominent oral hypoglycemic effect at the dose of 40 mg/kg body weight (p.o.) in respect of standard drug glibenclamide and control. The hypoglycemic effect was studied using oral glucose tolerance test in normal and NIDDM in STZ-rat model. The compounds 5a, 5d, 5f, 5i, 5k and 5n were dominant out of fifteen derivatives for blood glucose lowering activity (more than 80%) when comparing with NIDDM control. These derivatives were either containing simply phenyl ring (5a, 5f and 5k) on to the second amine of sulfonylurea (R' = H) or nitro group at the para position in compound 5d, 5i and 5n (R' = NO2 ) to produce significant oral hypoglycemic effect. Other structural activity relationship is also observed regarding the heteroaromatic and substituted aromatic group at R and R' position respectively.

A review of neglected tropical diseases: filariasis.

Filariasis is result of parasitic infection caused by three specific kinds of round worm. Lymphatic filariasis is found in under developed region of South America, Central Africa, pacific and Caribbian. It has been found for centuries, with main symptoms as elephant like swelling of the arms, legs and genitals. It is estimate that 120 millions peoples in the world have lymphatic filariasis. The spread of diseases and the challenge encountered in its management are discussed along with a review on drugs against filariasis in this article. Detail on clinical effect of drugs on the infection, safety profile, status in clinical practices and drug resistances are also covered.

A review of neglected tropical diseases: filariasis

Filariasis is result of parasitic infection caused by three specific kinds of round worm. Lymphatic filariasis is found in under developed region of South America, Central Africa, pacific and Caribbian. It has been found for centuries, with main symptoms as elephant like swelling of the arms, legs and genitals. It is estimate that 120 millions peoples in the world have lymphatic filariasis. The spread of diseases and the challenge encountered in its management are discussed along with a review on drugs against filariasis in this article. Detail on clinical effect of drugs on the infection, safety profile, status in clinical practices and drug resistances are also covered.