Focus: Preventive Medicine: The Impact of the Social Distancing Policy on COVID-19 Incidence Cases and Deaths in Iran from February 2020 to January 2021: Insights from an Interrupted Time Series Analysis

Background: In December 2019, a viral outbreak occurred in China, and rapidly spread out worldwide. Due to the lack of immediately available vaccines and effective drugs, many policy- and decision-makers have focused on non-pharmacological methods, including social distancing. This study was aimed at assessing the effects of the implementation of this policy in Iran, one of the countries most affected by COVID-19. We conducted a quasi-experimental study, utilizing the interrupted time series analysis (ITSA) approach. Methods: We collected daily data between February 20, 2020 and January 29, 2021, through governmental websites from 954 public hospitals and healthcare settings. The Iranian government launched the social distancing policy on March 27, 2020. Statistical analyses, including ITSA, were carried out with R software Version 3.6.1 (London, UK). Results: During the study period, 1,398,835 confirmed incidence cases and 57,734 deaths occurred. We found a decrease of -179.93 (95% CI: -380.11 to -20.25, P-value=0.078) confirmed incidence cases following the implementation of the social distancing policy, corresponding to a daily decrease in the trend of -31.17 (95% CI: -46.95 to -15.40, P-value=0.08). Moreover, we found a decrease of -28.28 (95% CI: -43.55 to -13.01, P-value=0.05) deaths, corresponding to a daily decrease in the trend of -4.52 (95% CI: -5.25 to -3.78, P-value=0.003). Conclusion: The growth rate of confirmed incidence cases and deaths from COVID-19 in Iran has decreased from March 27, 2020 to January 29, 2021, after the implementation of social distancing. By implementing this policy in all countries, the burden of COVID-19 may be mitigated.     

Hamsters running on time: is the lateral habenula a part of the clock?

Previous anatomical and physiological studies have implicated the lateral habenula, and especially its medial division (LHbM), as a candidate component of the circadian timing system in rodents. We assayed lateral habenula rhythmicity in rodents using c-FOS immunohistochemistry and found a robust rhythm in immunoreactive cell counts in the LHbM, with higher counts during the dark phase of a light-dark (LD) cycle and during subjective night in constant darkness. We have also observed an obvious asymmetry of c-FOS expression in the LHbM of behaviorally "split" hamsters in constant light, but only during their active phase (when they were running in wheels). Locomotor activity rhythms appear to be regulated by the suprachiasmatic nucleus (SCN) via multiple output pathways, one of which might be diffusible while the other might be neural, involving the lateral habenula.     

Slavery in plants: how the facultative hemi‐parasitic plant Rhamphicarpa fistulosa can completely dominate its host

The rain‐fed lowland rice weed Rhamphicarpa fistulosa (Rice Vampireweed) is a facultative root parasitic plant. Growth and reproduction of R. fistulosa benefit considerably from parasitism, but how this affects the host plant is not well established. We determined accumulation and partitioning of rice–parasite biomass in two pot experiments. First, rice (cv. IR64) was grown under eight R. fistulosa densities (15–1000 seeds per pot) with two sampling times. Next, 2 parasite densities (6 and 13 plants per pot) were combined with 9 destructive samplings. Infection increased host root: shoot ratios and decreased host plant height, leaf area and tiller number. Reductions in light interception were followed by reductions in light use efficiency, causing 22–71% losses in host plant biomass and 78–100% losses in host kernel production. Parasitism eventually caused a complete standstill of host plant growth, while the parasite managed to gradually increase its share in total host plant–parasite biomass up to 50–82%. This implies that ultimately the host plant was producing solely for the sake of the parasite. Due to its facultative nature, R. fistulosa may incorrectly be perceived as relatively harmless. Upon infection this Rice Vampireweed, however, turns into a genuine slave master, whereby it completely dominates its host.     

Antiproliferative activity of morpholine-based compounds on MCF-7 breast cancer,colon carcinoma C26, and normal fibroblast NIH-3T3 cell lines and study of their binding affinity to calf thymus-DNA and bovine serum albumin

Abstract

This report describes the results of a study on the antiproliferative activity of the morpholine-based ligand 1,3-bis(1-morpholinothiocarbonyl)benzene (HL) and its nickel(II) complex (NiL) against human breast cancer cells (MCF-7), colon carcinoma cells (C26), and normal fibroblast NIH-3T3 cells. NiL showed better cytotoxicity on both cancerous cells relative to normal cells in vitro with the highest selective index of 2.22 in MCF-7 cells. The interaction of both compounds with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was studied using various spectroscopic techniques and analytical methods such as UV???vis titrations, thermal denaturation, circular dichroism, competitive fluorescent intercalator displacement assays, as well as molecular modeling. The fluorescence intensity of the probe molecule increases clearly when HL and NiL are added to the methylene blue (MB)–DNA system. Furthermore, the binding of HL and NiL quenches the BSA fluorescence, revealing a 1:1 interaction with a binding constant of about 10⁵?M^?1.

Communicated by Ramaswamy H. Sarma     

Exploring the binding mechanism of saccharin and sodium saccharin to promoter of human p53 gene by theoretical and experimental methods

Abstract

In the past few decades, extensive discussions have been on the impact of artificial sweeteners on the risk of cancer. The present study aimed to evaluate the interaction of saccharin (SA) and sodium saccharin (SSA) with the promoter of the human p53 gene. The binding ability was assessed using the spectroscopic technique, molecular docking and molecular dynamics (MD) simulation methods. Free energy of binding has been calculated using Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Fluorescence spectra of mentioned gene with concentration profiles of SA and SSA were obtained in a physiological condition. A gradual increase without any significant spectral shift in the fluorescence intensity of around 350?nm was evident, indicating the presence of an interaction between both compounds and gene. The docking results showed that both compounds were susceptible to bind to 5′-DG56DG57-3′ nucleotide sequence of gene. Furthermore, the MD simulation demonstrated that the binding positions for SA and SSA were 5′-A1T3T4-3′ and 5′-G44T45-3′ sequences of gene, respectively. The binding of these sweeteners to gene made significant conformational changes to the DNA structure. Hydrogen and hydrophobic interactions are the major forces in complexes stability. Through the groove binding mode, the non-interactive DNA-binding nature of SSA and SA has been demonstrated by the results of spectrofluorometric and molecular modeling. This study could provide valuable insight into the binding mechanism of SA and its salt with p53 gene promoter as macromolecule at the molecular level in atomistic details. This work can contribute to the possibility of the potential hazard of carcinogenicity of this sweetener and to design and apply new and safer artificial sweeteners. Abbreviations SA Saccharin

SSA Sodium Saccharin

Pp53g promoter of human p53 gene

MD Molecular dynamics

RMSD Root-mean-square deviation

RMSF Root-mean-square fluctuation

Rg Radius of Gyration

SASA Solvent-Accessible Surface Area

ADI Acceptable daily intake

MM/PBSA Molecular Mechanics/Poisson–Boltzmann Surface Area

Communicated by Ramaswamy H. Sarma     

Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo

Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. Our screen enriched for regions of the genome not previously connected with Ras phenotypic modification. We mapped the underlying gene from one modifier to the ribosomal gene RpS21. In multiple contexts, we show that RpS21 preferentially influences weak Ras/MAPK signaling outputs. These data show that codon usage manipulation can identify new, output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator.     

Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid

In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations. PPI G5-Alkyl 30% indicated a decreased drug release may be due to alkyl chains on the surface of PPI, which serve as an additional hindrance for drug diffusion. In vitro cytotoxicity experiments demonstrated that co-delivery system induced apoptosis of tumor cells more efficiently than each of delivery system alone. Furthermore, these results revealed that our combined delivery platform of pTRAIL and DOX using Alkyl-modified PPI G5 can significantly improve the anti-tumor activity and this strategy might develop a new therapeutic window for cancer treatment.