Sunlight exposure might account for the relatively low COVID-19 morbidity and mortality in tropical countries.

The present study aimed at exploring whether sunlight exposure might account for the relative difference in COVID-19-related morbidity and mortality between tropical and non-tropical countries. A retrospective observational study was designed and data from the World Health Organization weekly COVID-19 epidemiological update was compiled. We examined the total number of confirmed COVID-19 cases per 100 000 population, as well as the total number of COVID-19-related mortalities per 100 000 population. Solar variables data were obtained from the Global Solar Atlas website (https://globalsolaratlas.info/). These data were analyzed to determine the association of sunlight exposure to COVID-19-related morbidity and mortality in tropical and non-tropical countries. Results revealed a statistically significant decrease in the number of confirmed COVID-19 cases per 100 000 population (P<0.001), as well as the number of COVID-19-related mortalities per 100 000 population (P<0.001) between tropical and non-tropical countries. Analyses of sunlight exposure data found that specific photovoltaic power output, global horizontal irradiation, diffuse horizontal irradiation and global tilted irradiation at optimum angle were significantly inversely correlated to COVID-19-related morbidity and mortality. This suggests that stronger sunlight exposure potentially leads to lower COVID-19-related morbidity and mortality. Findings from this study suggest that the relatively low COVID-19-related morbidity and mortality in tropical countries were possibly due to better sunlight exposure that translates into adequate vitamin D status.

CDK9 inhibition as an effective therapy for small cell lung cancer.

Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance to first-line therapy and alternative therapies are urgently required to overcome this resistance. In this study, we tested the efficacy of dinaciclib, an FDA-orphan drug and inhibitor of the cyclin-dependent kinase (CDK) 9, among other CDKs, in SCLC. Furthermore, we report on a newly developed, highly specific CDK9 inhibitor, VC-1, with tumour-killing activity in SCLC. CDK9 inhibition displayed high killing potential in a panel of mouse and human SCLC cell lines. Mechanistically, CDK9 inhibition led to a reduction in MCL-1 and cFLIP anti-apoptotic proteins and killed cells, almost exclusively, by intrinsic apoptosis. While CDK9 inhibition did not synergise with chemotherapy, it displayed high efficacy in chemotherapy-resistant cells. In vivo, CDK9 inhibition effectively reduced tumour growth and improved survival in both autochthonous and syngeneic SCLC models. Together, this study shows that CDK9 inhibition is a promising therapeutic agent against SCLC and could be applied to chemo-refractory or resistant SCLC.

Evaluation of Charge and Energy Storage in Molecular Nanocapacitors.

A model is presented herein for the evaluation of stored charge and energy in molecular-scale capacitors composed of parallel nanosheets. In this model, the nanocapacitor is exposed to an external electric field, and the charging process is considered as a three-stage mechanism, including isolated, exposed, and frozen stages, where each stage possesses its own Hamiltonian and wavefunction. In this way, the third stage's Hamiltonian is the same as that of the first stage, while its wavefunction is frozen to that of the second stage, and consequently, stored energy can be calculated as the expectation value of second stage's wavefunction with respect to the first stage's Hamiltonian. Electron density is then integrated over half-space, i.e., the space separated by a virtual plane located at the middle and parallel to electrodes, to reveal stored charge on nanosheets. The formalism is applied to two parallel hexagonal graphene flakes as nanocapacitor's electrodes, and results are compared with experimental values of similar systems.

Density functional theory computation of the intermolecular interactions of Al2@C24 and Al2@Mg12O12 semiconducting quantum dots conjugated with the glycine tripeptide.

The nature of intermolecular forces within semiconductor quantum dot systems can determine various physicochemical properties, as well as their functions, in nanomedical applications. The purpose of this study has been to investigate the nature of the intermolecular forces operating between Al2@C24 and Al2@Mg12O12 semiconducting quantum dots and the glycine tripeptide (GlyGlyGly), and also consider whether permanent electric dipole-dipole interactions play a significant role vis-à-vis these molecular systems. The energy computations, including the Keesom and the total electronic interactions and the energy decomposition, together with the quantum topology analyses were performed. Our results demonstrate that no significant correlation is found between the magnitude and orientation of the electrical dipole moments, and the interaction energy of the Al2@C24 and Al2@Mg12O12 with GlyGlyGly tripeptide. The Pearson correlation coefficient test revealed a very weak correlation between the quantum and the Keesom interaction energies. Apart from the quantum topology analyses, the energy decomposition consideration confirmed that the dominant share of the interaction energies was associated with the electrostatic interactions, yet both the steric and the quantum effects also made appreciable contributions. We conclude that, beside the electrical dipole-dipole interactions, other prominent intermolecular forces, such as the polarization attraction, the hydrogen bond, and the van der Waals interactions can also influence the interaction energy of the system. The findings of this study can be utilized in several areas in the field of nanobiomedicine, including the rational design of cell-penetrating and intracellular drug delivery systems using semiconducting quantum dots functionalized with a peptide.

The role of a redox-active non-innocent ligand in additive-free C-C Glaser-Hay and Suzuki coupling reactions by an o-aminophenol palladium(ii) complex.

A novel mononuclear palladium complex with 2-(3,5-di-tert-butyl-2-hydroxyphenyl amino) benzonitrile as a non-innocent ligand (abbreviated as PdIIL2 NIS) was synthesized, and characterized by IR, UV-Vis, 1H and 13C NMR spectroscopies and elemental analysis. The crystal structure clearly showed that the metal center was in a square planar environment. The bond lengths obtained from X-ray structure analysis revealed that both ligands are in the o-iminobenzosemiquinone radical form. The neutral complex showed strong absorptions in the NIR region, corresponding to the ILCT (intra-ligand charge transfer). Catalytic tests performed for the coupling reaction of terminal alkynes showed that the palladium PdIIL2 NIS complex acts as a highly effective catalyst for the base-free C-C coupling reactions, leading to diyne derivatives with excellent yields. The PdIIL2 NIS complex in ethanol, as a green solvent, is demonstrated to be an exceptionally active phosphine-free catalyst for the Suzuki reaction of aryl iodides and bromides. The reaction can be carried out under mild conditions (room temperature) with high yields without using a microwave or phosphine ligands. This catalyst exhibits an interesting application of redox non-innocent ligands, the electron reservoir behavior, which makes it needless to use additional reagents. The theoretical calculation provides more details about the complex structure, molecular orbitals, and electronic state.

Strong intramolecular hydrogen bonding in confined amino acids.

Intramolecular hydrogen bonding is evaluated in three different amino acids encapsulated in C60 fullerene in the context of electron density analysis. While conventional intramolecular hydrogen bonding in isolated amino acids are dominated by electrostatic character, it is shown that strong intramolecular hydrogen bonding can be formed in confined amino acids so that in two cases covalent intramolecular hydrogen bonding is appeared in the confined species. Also, results show that zwitterionic amino acids are stable in confined state, where no implicit or explicit solvation is applied. Covalent character for intramolecular hydrogen bonding in amino acids have not yet been reported.

Molecular Detection of Anaplasma Phagocytophilum as a Zoonotic Agent in Owned and Stray Dogs in Tehran, Iran.

The genus Anaplasma is an obligated intracellular Rickettsia and among its species, Anaplasma phagocytophilum (A. phagocytophilum) is a zoonotic agent that infects host neutrophils. The aim of this study was molecular detection of A. phagocytophilum infection based on MSP4 gene in owned and stray dogs in Tehran, capital of Iran. One hundred and fifty blood samples were collected from dogs in Tehran and suburbs of Tehran, Iran. Firstly, the thin blood smears were prepared and Giemsa staining method was conducted. Then, the samples were examined under oil immersion objective and 0.67% of them were observed infected with A. phagocytophilum. The DNA was extracted from blood samples using a DNA isolation kit (MBST, Iran), and MSP4 gene extraction was performed by Polymerase chain reaction (PCR) and nested-PCR. Finally, 2% of the samples were positive for A. phagocytophilum. The data were analyzed using SPSS software (version 19.0) and Chi-square test was performed. There was no significant relation between infection and age, as well as sex and ectoparasitic infestation (P&gt;0.05). This article was a report of A. phagocytophilum infection in dogs and their potentials as host carriers of this important microorganism in Tehran, Iran.

Electron Density Analysis of Hyperconjugation.

Hyperconjugation is analyzed through the electron density of orbitals responsible for hyperconjugative interactions, which cannot be detected by means of conventional electron-density-based calculations. This interaction is detected through the π electron density topology, by excluding σ electron density from the total. As the presence of the hyperconjugation phenomenon in carbocation systems is well understood, several carbocations are benchmarked, and the results show that the positive carbon atom establishes a hyperconjugative critical point with the adjacent methyl group(s). Also, π localization and delocalization indices are employed to support the conclusions made by the topological analysis.

Rapid Detection of Toxoplasma gondii Antigen in Experimentally Infected Mice by Dot- ELISA.

BACKGROUND: Toxoplasmosis is a worldwide endemic disease. In congenitally infected infants and AIDS patients, toxoplasmosis causes high rates of morbidity and mortality. In these cases antibody detection is difficult; so detection of parasite or its components could be useful tool for early detection and following treatment of the infection. METHODS: Sixty-three BALB/c mice were injected intra-peritoneal with 5×10(3) tachyzoites of Toxoplasma gondii RH strain, nine mice were sacrificed daily for 7 days. Fourteen mice were injected with phosphate buffer saline as control group. Dot-ELISA was performed for detection of T.gondii antigen in mice sera and capture - ELISA was done as golden standard assay too. RESULTS: Toxoplasma gondii antigen was detected from day 2 in mice sera; 22% of mice sera on day 2, 33% on day 3,77% on day 4 and 100% on day 5 till their death on day 7 had shown antigenemia by dot - ELISA, no positive result was detected in control mice by dot- ELISA. CONCLUSION: Dot-ELISA is a sensitive method for diagnosis of T. gondii infection in the animal model; also, this technique is more rapid and easy to perform method in comparison with capture-ELISA.

Electron density based characterization of π bonds in planar molecules.

A new method has been developed to detect and analyze molecular π systems. The concept of bonding critical point is generalized to electronic π systems, and it is shown how a π bond can be characterized via the corresponding bond critical point (BCP) in planar molecules. In this context, charge density and its Laplacian at the BCP(π) of a strongly delocalized π system can be distinguished from that of a localized one. The presented formalism is applied to three types of nanoconductors as conjugated polyenes, which revealed the alternative pattern of the double bonds. Also, several cyclic conjugated molecules are considered to explore their π electronic structure and aromaticity.

Orbital representation of kinetic energy pressure.

The kinetic energy pressure (KEP) is quantified in terms of displaced charges and their orbital representations. Two deformation density matrices are introduced to separate reorganization of the electron density due to Pauli antisymmetrization from that of orbital relaxation. The formalism is applied to interaction of carbon nanotubes with hydrogen molecule and the results confirmed that KEP has the main contribution to such interaction. Also, it was found that the contribution of KEP can be easily traced in the complex formation.

Essential role for Bclaf1 in lung development and immune system function.

Bcl-2 associated factor 1 (Bclaf1) is a nuclear protein that was originally identified in a screen of proteins that interact with the adenoviral bcl-2 homolog E1B19K. Overexpression of Bclaf1 was shown to result in apoptosis and transcriptional repression that was reversible in the presence of Bcl-2 or Bcl-x(L). Furthermore, antiapoptotic members, but not proapoptotic members of the Bcl-2 protein family, were shown to interact with Bclaf1 and prevent its localization to the nucleus. Bclaf1 has also recently been identified as a binding partner for Emerin, a nuclear membrane protein that is mutated in X-linked recessive Emery-Dreifuss muscular dystrophy. To ascertain the in vivo function of Bclaf1, we have generated mice that carry a targeted mutation of the bclaf1 locus. In this study, we show that Bclaf1 is required for proper spatial and temporal organization of smooth muscle lineage during the saccular stage of lung development. We also show that Bclaf1 is dispensable for thymocyte development but is essential for peripheral T-cell homeostasis. Despite its postulated role as a proapoptotic protein, Bclaf1-deficient cells did not show any defect in cell death linked to development or after exposure to various apoptotic stimuli. Our findings show a critical role for Bclaf1 in developmental processes independent of apoptosis.

Effect of protein intake on mineral (calcium, magnesium, and phosphorus) balance in Japanese males.

A 26-day balance study was conducted to examine the effect of a high protein diet on calcium, magnesium, and phosphorus utilization in six healthy males (age 20-22 years, body weight 54.0-64.4 kg, body height 165-173 cm). In addition, the effect of physical exercise on calcium, magnesium, and phosphorus balance was also examined. After a 2-day stabilization period, two levels of protein--control (1.0 g/kg of body weight) and high (2.0 g/kg of body weight) protein--diets were given for three 4-day periods at each protein level. During the last 4-day period of each protein level, subjects exercised on a bicycle ergometer for two 1-h periods daily at a load of 1.5 kp., 50 cyc./min. The high protein diet increased urinary calcium and caused a significant negative calcium balance. Magnesium balance tended to be negative in the control diet. There were no significant changes in urinary calcium, magnesium, and phosphorus and also in the calcium, magnesium, and phosphorus balance during physical exercise.