Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M - 59, F - 22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water and sodium manipulation were the most commonly utilized peak week strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2 % of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.

The seeds of red clover are heteromorphic and two color morphs can be visually recognized, light purple and yellow, resulting from heterozygosity and recessive homozygosity at two loci. Here, we report the responses of seed imbibition, seed germination, and early seedling growth of the two morphs to distilled water, sodium chloride, and complete nutrient solution. The sensitivity of red clover seeds to treatments increased with the stage of development in what seems to be a cumulative process. No differences were found in seed imbibition between morphs or between treatments. In seedling growth, on the contrary, treatments were always effective, but differences between morphs were only observed in seeds that were treated with nutrient solution, whereas in the intermediate stage of seed germination, the effects by treatments were observed together with the appearance of differences between morphs in distilled water and in the treatment by sodium chloride solution. Simultaneously, the superior performance of the yellow morph that was found in germination, which appears to be a trait stable across cultivars of red clover seeds, turned into a superior performance of the light purple morph in seedling growth.

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.

Acellular bacterial ghosts (BGs) are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs) were generated by chemically induced lysis and the method is based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH), acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, < 50.0, 25.0, 6.25, 1.56 and 0.781 mg/ml. Except boric acid, the lysis efficiency was reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs showed completely DNA-free that was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS) extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS), anti-inflammatory cytokine (IL-10) and dual activities (IL-6) in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning electron microscopy showed the formation of trans-membrane lysis tunnel structures in the NaOH-induced VPGs. SDS-PAGE and agarose gel electrophoresis also confirmed that cytoplasmic proteins and genomic DNA released from the VPGs to culture medium through the lysis tunnel structures. Taken together, all these results indicated that the NaOH-induced VPGs show the potency of safe, economical and effective inactivated bacterial vaccine candidate.

In this paper, we examine the mathematical and physical consistencies of the three primary couple stress theories: original Mindlin-Tiersten-Koiter couple stress theory (MTK-CST), modified couple stress theory (M-CST) and consistent couple stress theory (C-CST). As has been known for many years, MTK-CST suffers from some fundamental inconsistencies, such as the indeterminacy of the couple-stress tensor. Therefore, despite the fact that MTK-CST has a fundamental position in the evolution of size-dependent continuum mechanics, it is not a reliable theory within continuum mechanics, for example, in developing new size-dependent multi-physics formulations. We also observe that M-CST not only inherits all inconsistences from the original MTK-CST, but also suffers from new additional inconsistencies, such as the introduction of a new non-physical governing equation. These inconsistencies refute the claim of those who state that the couple-stress tensor may be chosen symmetric. Therefore, the apparent success of MTK-CST and M-CST in describing a size-effect for some problems, such as two-dimensional plate and beam bending, is not enough to justify these theories as suitable for general cases. In fact, the symmetric couple-stresses in M-CST create torsional or anticlastic deformation, not bending. On the other hand, C-CST, with a skew-symmetric couple-stress tensor, is the consistent continuum mechanics suitable for solving different size-dependent solid, fluid and multi-physics problems.

The pharmacokinetics of salicylic acid (SA) in sheep was evaluated following intravenous (IV) and oral administration of sodium salicylate (sodium salt of salicylic acid) at different doses. Six healthy sheep were administered sodium salicylate (SS) IV at doses of 10, 50, 100 and 200 mg/kg body weight and another six sheep were drenched with 100 and 200 mg/kg of SS orally. Both studies were randomised crossover trials. A one-week washout period between each treatment was allowed in both studies. Blood samples were collected at 0, 15, 30 minutes and 1, 2, 4 and 6 hours after IV and oral SS administrations. Plasma SA concentrations were determined using high performance liquid chromatography with diode array detection method. Pharmacokinetic variables were calculated in a non-compartmental model. The elimination half-life (T_{1/2 el}) of SA after IV administration of 200 mg/kg SS was 1.16 ± 0.32 hours. Mean bioavailability of SA was 64%, and mean T_{1/2 el} was 1.90 ± 0.35 hours, after 200 mg/kg of oral SS. The minimum plasma SA concentration (16.8 µg/mL) required to produce analgesia in humans was achieved after IV administration of 100 and 200 mg/kg SS in sheep for about 0.17 hour in this study. Experiments on pharmacokinetic-pharmacodynamics modelling are required to determine the actual effective plasma concentration range of SA in sheep.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

As the natural resources are getting exhausted, the concept of sustainable development of region has received increasing attentions, especially for resource-dependent cities. In this paper an innovative method that emergy analysis and IPAT (Human Impact Population Affluence Technology) model were combined in order to analyze the quantitative relationship of economic growth and energy consumption and further to evaluate its overall sustainability level. Taiyuan, a traditional, resource-dependent city in China, is selected as the case study region. The main results show that total emergy of Taiyuan increased from 9.023× 1023 sej in 2007 to 9.116× 1023sej in 2014, with 38% reduction on non-renewable emergy and 125% growth on imported emergy. Regional emergy money ratio (RMB) was reduced by 48% from 5.31× 1013sej/$ in 2007 to 2.74× 1013sej/$ in 2014, indicating that the increasing speed of consuming resources and energy was faster than the increase of GDP, and that Taiyuan’s money purchasing power declined. The lower emergy sustainability index (ESI) indicates that Taiyuan was explored and produced large quantities of mineral resources, which puts more stress on the environment as a consequence, and that this is not sustainable in the long run. The IPAT analysis demonstrates that Taiyuan sticks to the efforts of energy conservation and environmental protection, in order to promote regional sustainable development, it is necessary to take an integrated effort. Policy insights suggest that resourceful regions should improve include energy and resource efficiency, optimizing energy and resourceful structure.

In this paper, we study the problem of controllability of impulsive neutral evolution integrodifferential equations with state dependent delay in Banach spaces. The main results are completely new and are obtained by using Sadovskii's fixed point theorem, theory of resolvent operators, and an abstract phase space. An example is given to illustrate the theory.

Titanium dioxide (TiO₂) micro and nano architectures have been intensively studied in the past years because of many varied applications in environmental, energy conversion, and storage fields, such as heterogeneous catalysis, dye-sensitized solar cells, lithium/sodium ion batteries, lithium-sulfur (Li-S) batteries, and bio-nanotechnology, etc. Especially the surface and interface structures in the TiO₂ structures play important roles in those applications. This mini review article focuses on TiO₂ micro and nano architectures with the prevalent crystal structures (anatase, rutile, brookite, and TiO₂(B)), and summarizes major advances in the surface and interface engineering and applications in environmental and electrochemical applications. We present the principles and growth mechanisms of TiO₂ nanostructures via different strategies, with an emphasis on rational control of the surface and interface structures. We further discuss the applications of TiO₂ micro and nano architectures in photocatalysis, lithium/sodium ion batteries, and Li-S batteries. Throughout the discussion, the relationship between the device performance and the surface structures of TiO₂ micro/nano structures will be highlighted. Then we discuss the phase transitions of TiO₂ nanostructures and possible strategies of improving the phase stability. The review concludes with a perspective on the current challenges and future research directions.

Considering the important demand of fresh water and its scarce availability, water desalination is an interesting technology, producing about 44 Mm³/year worldwide, but, in general the most common desalination techniques are highly energy demanding. Freezing-Melting (F/M) desalination uses just up to 70% less thermal energy, but is the least used process mainly, due to the difficulty of the salt separation. This study proposes a model able to analyses the thermodynamic potential that allows the salt diffusion during the F/M process, using an aqueous solution of sodium chloride. This should allow to obtain a sensitive analysis of the process to promote the separation between the high concentration brine and the ice with liquid separation by physical process. The unidimensional model is based on the evolution of both processes: thermal and mass diffusions, depending on temperature and saline gradients, predicting whether the salt will remain inside the ice or not. Thus, the thermal potential is adjusted to frozen only when the salt has been "pushed" towards the brine. Mostly models have base their results on the assumption of a “certain value of saline concentration of the liquid fraction”, value in which there is great disagreement. In this paper the calculations are based on the concentration in the solid-liquid interface, which has been extensively studied and there is a coincidence in those results, being the main advantage of the proposed model.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Brine-dependent recovery process has seen much global research efforts in the past two decades because of their benefits over other oil recovery methods. The process involves the tweaking of the ionic composition and strength of the injected water to improve oil production. In recent years, several studies ranging from laboratory coreflood experiments by many researchers to field trials by several companies admit to the potential of recovering additional oil in sandstone and carbonate reservoirs. Sandstone and carbonate rocks are composed of completely different minerals, with varying degree of complexity and heterogeneity, but wettability alteration has been widely considered as the consequence rather than the cause of brine-dependent recovery. However, there is no consensus on the cause as several mechanisms have been proposed to relate the wettability changes to the improved recovery. This review paper aims to provide a state-of-the-art development in published research and various efforts of the industry. This review outlines an overview of laboratory and field observations, descriptions of underlying mechanisms and their validity, the complexity of the oil-brine-rock interactions, modelling works, and comparison between sandstone and carbonate rocks. The provided information is intended to provide the reader with up-to-date information, point to relevant studies for those who are new and those implementing either laboratory- or field-scale projects to speed up the process of further investigations in this research area. Overall, the outcome of this review would potentially be of immense benefit to the oil industry.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

New antibacterial agents are needed to overcome the increasing number of infectious diseases caused by pathogenic microorganisms due to the emergence of multi-drug resistant strains. In this context, halogens, especially Iodine is known since ages for its antimicrobial activity. Therefore, especially triiodides encapsulated in organometallic complexes can be helpful as new agents against microorganisms. The aims of this work was to study the biological activity of [Na(12-Crown-4)₂]I₃ against gram positive Streptococcus pyogenes, Streptococcus faecalis, the spore forming bacteria Bacillus subtilis and gram negative bacteria Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as the yeast Candida albicans. The antimicrobial and antifungal activities of the triiodide were determined by zone of inhibition plate studies. [Na(12-Crown-4)₂]I₃ exhibited potent antimicrobial activity on gram positive Streptochocci and the yeast C. albicans. Furthermore, the gram negative bacteria P. aeruginosa and K. pneumoniae were less effectively inhibited, while E. coli and P. mirabilis proved to be even resistant.

Abstract The global concern about the leather industries is increasing as the leather industries grow bigger each year. These industries face a very challenging task with an increase in stringent pollution control regulation enforced by various bodies due to environmental concern and human risks. The chromium salts are the most widely used chemical for the tanning process in leather industries, about 35% of chromium used for the tanning process remain as metal and discharge to wastewater stream. The removal and recovery of this quantity of wasted chromium are necessary for environmental pollution control and economic reason. This paper sheds light on the chromium recovery and reuse system of Chromium salts in tanning wastewater by using NaOH as an effective chemical precipitation method to regenerate chromium solution, adapted chrome recovery plant, and evaluated the system technically and economically.

Increasing salt intake has substantial negative impacts on health and well-being. This review article focusses on the effect of salinity intrusion (SI) on the water quality and community health of coastal Bangladesh and to find out the effectiveness of interventions for reducing the negative effects of salinity. Saline water is a noteworthy reason for hypertension or high blood pressure in the coastal areas. Health status of women especially the pregnant women are vulnerable because of drinking water sodium (DWS) prompting to pre-eclampsia, high blood pressure and hypertension as well as infant mortality. Several interventions such as rainwater harvesting and Pond sand filter (PSF) system as well as managed aquifer recharge (MAR) usage and the integration of mixed sources were reviewed on the content of drinking water sodium (DWS). Although rainwater has the positive impact of low or no sodium intake on human health, it still possesses negative impacts from not having vital minerals. Despite what might be expected, in MAR a steady increment in sodium concentration through the span of the dry season was observed. It is, subsequently, important to increase awareness about drinking water sodium (DWS) intake by providing and adopting correct technological interventions.

A reduction in population sodium (as salt) consumption is one of the most cost-effective strategies to reduce the burden of cardiovascular disease and it is a global health priority. High potassium intake is also recommended to reduce cardiovascular disease. To establish effective policies for setting targets and monitoring effectiveness within each country, the current level of consumption should be known. Greece lacks data on actual sodium and potassium intakes. The aim of the present study was therefore to assess dietary salt (using sodium as biomarker) and potassium intakes in a sample of healthy adults in northern Greece and to determine whether adherence to a Mediterranean diet is related to different sodium intakes or sodium-to-potassium ratio. A cross-sectional survey was carried out in Thessaloniki greater metropolitan area (northern Greece) (n=252, aged 18-75 years, 45.2% males). Participants’ dietary sodium and potassium intakes were determined by 24h urinary sodium and potassium excretions. In addition, we estimated their adherence to Mediterranean diet by the use of an 11-item MedDietScore (range 0-55). The mean sodium excretion was 175 (SD 72) mmol/day, equivalent to 4,220 (1,745) mg of sodium or 10.7 (4.4) g of salt per day and potassium excretion was 65 (25) mmol/day, equivalent to 3,303 (1,247) mg/day. Men had higher sodium and potassium excretions compared to women. Only 5.6% of the sample had salt intake <5g/d, which is the target intake recommended by the WHO. Mean sodium-to-potassium excretion ratio was 2.82 (1.07). There was no significant difference in salt or potassium intake or their ratio across MedDietScore quartiles. No significant relationships were found between salt intake and adherence to Mediterranean diet, suggesting that the perception of the health benefits of the Mediterranean diet does not hold when referring to salt consumption. These results suggest the need for a larger nation-wide survey on salt intake in Greece and underline the importance of continuation of salt reduction initiatives in Greece.

The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of aminoacids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µ-O CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperxcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions.

A simple model has been used to investigate the nature of chemical order in Na-Pb and Na-Hg liquid binary alloy at 700K and 673K respectively. The energy parameter obtained from the model was used to calculate the concentration dependent mixing properties such as Gibb’s free energy of mixing, Concentration fluctuations in the long wavelength limit and the Warren-Cowley chemical short range order parameter. Results obtained showed that both alloys are hetero-coordinated throughout the entire concentration and there is tendency for segregation and demixing to take place in the liquid alloys. We observed that Na-Hg liquid alloy is more strongly interacting binary alloy and chemically ordered than Na-Pb liquid alloy.

Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH　(LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.

External quantum efficiency of industrial-grade green InGaN light-emitting diodes (LEDs) has been measured in a wide range of operating currents at various temperatures from 13 K to 300 K. Unlike blue LEDs, the efficiency as a function of current is found to have a multi-peak character, which could not be fitted by a simple ABC-model. This observation correlated with splitting of LED emission spectra into two peaks at certain currents. The characterization data are interpreted in terms of non-uniformity of the LED active region, which is tentatively attributed to extended defects like V-pits. We suggest a new approach to evaluation of temperature-dependent light extraction and internal quantum efficiencies taking into account the active region non-uniformity. As a result, the temperature dependence of light extraction and internal quantum efficiencies have been evaluated in the temperature range mentioned above and compared with those of blue LEDs.

The transmission characteristic of COVID-19 is of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. The virus is now in more than 100 countries and on nearly all continents. The World Health Organization (WHO) declared the COVID-19 outbreak a pandemic. There is no current evidence from random clinical trials (RCTs) to recommend any specific anti-COVID-19 treatment for patients with suspected or confirmed COVID-19 infection. In order to mitigate the impact of the COVID-19 outbreak, here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated viruses might interact in co-infected patients. During SIT, the patient benefit from superinfection with an apathogenic dsRNA virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). Importantly, the epidemiological efficacy of a similar strategy to SIT had already been successfully tested in large controlled trials. Standard live orally administered enterovirus vaccines that stimulate the production of endogenous interferon of the host mitigated the seasonal outbreaks of influenza and other associated acute respiratory infections in 152,042 individuals without adverse reactions.

Magneto-electrochemistry (MEC) is a unique paradigm in science, where electrochemical experiments are carried out as a function of an applied magnetic field, creating a new horizon of potential scientific and technological applications. Over the time, detailed understanding of this research domain was developed to identify and rationalize the possible effects exerted by a magnetic field on the various microscopic processes occurring in an electrochemical system, such as: electrolyte properties governed by charge-transfer process (electric conductivity, viscosity, and diffusivity), mass transfer, electrochemical kinetics and on the structure/quality of products formed either at the working electrode or in the electrochemical cell. Particularly, magnetic field controlled chiral architecture obtained from deposited metal, alloys and catalyst and their excellent enantio-recognition in experimental frame is highly appealing. Interestingly, Hall effect was also demonstrated in electrolytic medium via an impressive experimental technique which is being employed for further theoretical understanding in the field of magneto-electrochemical science. Later, a highly reproducible local temperature variation was observed in electrochemical electrolytes exposed to perpendicular magnetic and electric fields. However, until recent studies, none of the above mentioned reports considered the possibility of a spin-dependent related charge-transfer process. Recent experimental and theoretical studies reveal that electron’s transmission through chiral molecules is spin-selective and this effect has been referred to as chiral-induced spin-selectivity (CISS) effect. The CISS effect pave the way for the building up of a system characterized by a net magnetic moment exploiting the spin-filtering ability of chiral molecules. This interplay between chirality and magnetism may shed light on fundamental scientific aspects underlying the enantio-recognition and highly efficient electron-transfer that occurs in biological process.

Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

The synthesis of additives for thinning mineral suspensions based on sodium polyacrylate was carried out. The effect of molecular weight regulators on the molecular weight characteristics of the polymer and the effect of such polymers on the rheological properties of suspensions was studied. Sodium acrylate polymers are synthesized by free radical polymerization in aqueous solution using molecular weight regulators. The molecular weight characteristics of the polymeric samples were estimated by viscometry using Mark-Houwink-Kuhn-Sakurada (MHKS) equation. Synthesized polymers were used as thinners ceramic slurries, prepared according to the recipe of the enterprises producing ceramic products. The thinning ability of polymer samples with different molecular weights was estimated using an Engler viscometer from the time of the ceramic slurry flow. The influence of the type and amount molecular weight regulator on polyacryates was revealed. It was found that molecular weight synthesized samples was in the range of 21000 - 91000. It was determined that samples with a molecular weight of 28000 - 35000 synthesized using mercaptoethanol (at a dosage of 0.5-1.5% by weight of the monomer) provide optimal fluidity to the ceramic slurry.

INTRODUCTION The goal of root canal treatment is to shape and clean the endodontic space, reducing the bacterial load and removing the pulp tissue. Obviously, the action of the endodontic instruments is limited to the main canals, regardless of the complexity of the endodontic space. Consequently, finding the best possible cleaning technique, which can be obtained chemically using irrigation solutions, is a fundamental aid in the endodontic therapy. One of the most commonly used root canal irrigant is sodium hypochlorite (NaOCl), available in various commercial formulations. The effectiveness of NaOCl is undeniable. However, the action of dissolution of the pulp tissue is merely dependent on the concentration and the characteristics of the irrigant itself. AIM The aim of this study is to evaluate the effective concentration of different commercial formulas of sodium hypochlorite, by evaluating the percentage of total chlorine in each product. The dissolution capacity of the pulp tissue of each of the tested products was then analyzed by measuring the required time. MATERIALS AND METHODS Three commercial types of sodium hypochlorite were selected for this study: 5% NaOCl (ACE, Procter & Gamble), 5% NaOCl (N5, Simit Dental) and 6% NaOCl (CanalPro, Coltene). For each product, 10 packages were used, from which samples of the product were taken and 30 x 5 ml tubes were filled. All samples were divided into 3 groups and were analyzed using the DIN EN ISO 7393-2 method and the percentage of total chlorine (expressed as a percentage) was calculated. 40 samples of vital pulp were obtained from teeth freshly extracted for periodontal reasons and stored in physiological solution. In order to unify the size and weight of the samples (0.0001 mg), a microtome and a precision balance (Pro Explorer Ohaus) were used. Each sample, carefully examined by stereomicroscope (40x), was placed in artificial plastic containers and submerged in 0.1 ml of irrigating solution at room temperature (26 ° C). A fourth control group used saline solution as irrigant. Simultaneously with the insertion of the irrigating solution, a digital stopwatch was activated and the time necessary for the complete dissolution of the pulp sample was measured. The data obtained were subjected to statistical analysis. RESULTS The average percentages of chlorine detected for each group were: 4.26% (ACE), 5.16% (N5) and 5.97% (CanalPro). The Kruskal-Wallis test showed statistically significant differences between the different commercial formulations of hypochlorite (P <0.05). CanalPro showed the lowest values, while ACE showed the highest values of dissolution time of the pulp. DISCUSSION The analysis of the total chlorine percentage found that the actual concentration of the sodium hypochlorite in the samples is close to the values declared by the manufacturers both in the case of N5 and CanalPro. On the contrary, the concentration detected in the samples of common bench bleach (ACE) is significantly lower, which has average values less than 5%. This explains the longer time taken for the complete dissolution of the pulp tissue. The average dissolution time of the pulp samples was in fact inversely proportional to the concentration detected in the tested irrigants, so that a lower time corresponds to a higher concentration.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

Information taken from David A. Scott’s book “Copper and Bronze in Art” was crucial for research on copper corrosion products in Stuttgart. Examples discussed are the nature and variability of ‘Black Spots’ (aka ‘Brown Fuzzies’); cupric hydroxide by cleaning, patination, and pigment synthesis; the wondrous phenomenon of curly malachite; chalconatronite formed by contact to soda glass; the formation of copper formates by glass-induced metal corrosion; and synthesis and X-ray diffraction of basic copper acetates (‘verdigris’).

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained-release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4 by 5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~ 39 m) across 5 groups with different alginate:NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loaded efficiency. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate:NaHCO3 = 1 exhibited rough and porous surfaces, high Young’s modulus and hardness. In each group with the same alginate:NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relative high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relative high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relative high NaHCO3 concentrations improved the cytotoxicity effects in vitro.

Measurements of copper and zinc in transfusion-dependent thalassemia (TDT) show contradictory results.Aim of the study: To examine serum levels of these minerals in TDT in relation to iron overload indices and erythron variables. Methods: This study recruited 60 children with TDT and 30 healthy children aged 3-12 years old.Results: Zinc was significantly higher in TDT children than in control children, whilst copper and the copper to zinc ratio were significantly lowered in TDT. Serum zinc was significantly associated with the number of blood transfusions and iron overload variables (including serum iron and TS%) and negatively with erythron variables (including hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin). Serum copper was significantly and negatively associated with the same iron overload and erythron variables. The copper to zinc ratio was significantly correlated with iron, TS%, ferritin, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. Albumin levels were significantly higher in TDT children than in control children. Conclusion: Our results suggest that the increase in zinc in children with TDT may be explained by iron loading anemia and hemolysis and the consequent shedding of high amounts of intracellular zinc into the plasma. Increased albumin levels and treatment with Desferral may further contribute towards higher zinc levels in TDT. We suggest that the elevations in zinc in TDT are a compensatory mechanism protecting against infection, inflammation, and oxidative stress. Previous proposals for prophylactic use of zinc supplements in TDT may not be warranted.

Depletion of ore deposits, increasing demand for raw materials, the need to process low-grade, complex and finely disseminated ores and the reprocessing of tailings are challenges, especially for froth flotation separation technologies. Even though capable of handling relatively fine grain sizes the flotation separation of very fine and ultrafine particles faces many problems still. Further, the flotation of low-contrast semi-soluble salt-type minerals with very similar surface properties, many complex interactions between minerals, reagents and dissolved species often result in poor selectivity. This study investigates the flotation beneficiation of ultrafine magnesite rich in dolomite from de-sliming, currently reported to the tailings. The paper especially focuses on the impact of the depressant sodium hexametaphosphate (SHMP) on: (i) the froth properties using dynamic froth analysis (DFA), (ii) the separation between magnesite and dolomite/calcite and (iii) its effect on the entrainment. Furthermore, the application of 1-hydroxyethylene-1,1-diphosphonic acid (HEDP) is a more environmentally friendly and low-cost alternative to SHMP is presented and discussed. The paper contributes to understanding on the complexity of depressant responses in froth flotation.

Aqueous dispersions of magnetic nanocomposites have been proposed as draw electrolytes in forward osmosis. One possible approach for the production nanocomposites based on magnetite nanoparticles and sodium polyacrylate, is the synthesis of the magnetic iron oxide by coprecipitation or oxidative precipitation in presence of an excess of the polymer. In this work we explored the effect of the polymer proportion on the nanomaterials produced by these procedures. The materials obtained were compared s with the obtained by the coating of magnetite nanocrystals produced beforehand with the same polymer. The samples were characterized by chemical analysis, photon correlation spectroscopy, thermogravimetry, X-ray diffraction, infrared spectroscopy, transmission electron microscopy and magnetometry. The general trend observed is that part of the polymer is incorporated to the magnetic material during the synthesis heavily modifying its texture, with a drastic reduction of the particle size and magnetic response. The aqueous dispersions of the nanocomposites were highly stable with hydrodynamic size roughly independent on the polymer proportion. Their osmotic pressure proportional to the concentration of the polyelectrolyte, was similar than the generated by the equivalent amount of free polymer in the case of samples generated by oxidative precipitation and smaller in the case of samples generated by coprecipitation. Finally the possibilities of using these materials as draw electrolytes in forward osmosis will be briefly discussed.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

Myocardium transcriptomes of mouse left and right atria and ventricles were profiled separately to identify the differences that might be responsible for the distinct functional roles of the four heart chambers. In total, 16,886 distinct unigenes have been quantified in all 16 samples collected from four adult male mice from the same litter. 15.76% of the quantified genes on the left and 16.5% on the right exhibited differential expression between the corresponding atrium and ventricle of the same side, while 5.8% in atria and 1.2% in ventricles were differently expressed between the left and the right. Beyond the differentially expressed genes, the study revealed distinct expression control and coordination of ion channels and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/glucogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 (encoding ankyrin-B) oscillates in phase with all its binding partners in the left ventricle, the percentage of synergistically expressed partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis revealed also the high interventricular synchrony of the expression of ion channels.

The possibilities of manufacturing batteries with Nafion 117 membranes in the Na⁺-form intercalated by mixtures of non-aqueous organic solvents used both as electrolyte, separator and binder were investigated. Electrochemical stability of various organic solvent mixtures based on N,N-dimethylacetamide, ethylene carbonate, propylene carbonate, tetrahydrofuran was characterized. It was shown that sodium battery based on Nafion-Na membrane intercalated by mixture of ethylene carbonate ‑ propylene carbonate with Na₃V_1.9Fe_0.1(PO₄)₃/C positive electrode is characterized by a discharge capacity of ca. 110 mAh g^-1 (C/10) at room temperature and shows the ability to cycle for a long time. Batteries with Nafion membrane electrolytes, containing N,N-dimethylacetamide were characterized by capacity fading during cycling, which is due to the interaction of N,N-dimethylacetamide and a negative sodium electrode.

Background and Research Highlights: Despite all the concerns and initiatives, natural resources like forests, as well as biodiversity are decreasing at an alarming rate worldwide. Conservation is considered as one of the major tools to prevent such loss and rapid degradation. Evidence around the world shows the adverse effects of conservation laws and policies on indigenous peoples and other local communities. Objectives: This study was conducted in one of the forest-dependent communities situated in Sundarban (world’s largest mangrove forest) to understand the impact of conservation laws and policies on their livelihood. Materials and Methods: A qualitative methodology was designed to collect data, using focus group discussions and case study with community people, and individual interviews with the personnel from NGOs and relevant government departments. Findings: Strict conservation policies and restrictions in accessing forest resources made lives and livelihoods of the local community insecure and unstable, thus putting the community in a vulnerable situation. The had to leave their traditional mode of income and look for alternative livelihood options. Almost no evidence was found in relation to upkeeping their rights in conservation activities. Prohibited movement, provision of punishment for entering into the forest without proper permission and struggles in everyday life were some of the highlighted issues. They had no participation in conservation activities, management of alternative livelihood options, and even they were not sensitized before putting restrictions. Although they had a history of emotional and physical attachment with the forest, existing activities did not consider these issues. In addition, corruption and abuse of power by law enforcement agencies towards the local community intensified the sufferings. Conclusion: This study argues that the realization of human rights in conservation activities and the sensitization of the implementing stakeholders are prerequisites for ensuring the sustainability of both biodiversity and the affected people.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

In recent years, the dominant cementitious materials have been industrial by products such as fly ash. This present paper describes some of the cementitious products that are attracting attention in the global research community and the properties and characteristics of these materials that affect their performance such durability, mechanically properties and reduction of carbon dioxid (CO2). The present investigation deals with the chemical synthesis of cementitious material using fly ash of eggs shell rich in calcium(Ca) and sand dune(southern of Algeria) rich in silica(SiO2).The composition is the most compressive resistant with a maximum stress of 49.71 MPa, the most flexible (E = 2.63 GPa) and the most ductile (εr = 65.42 %).The characteristic properties of the chemically synthesized cementitious materials were analyzed by the chemical composition analysis XRF, XRD and SEM analyses.

Obesity has been identified as an emerging health concern for Chinese American children; however, very little is known about diets in Asian American children. The objective of our paper was to describe the dietary intakes of urban Chinese American schoolchildren using a state-of-the-art approach for dietary assessment. Data for this analysis come from the Food Journal Project 2017, a pilot and feasibility study conducted by a multi-sector collaboration. Children aged 8-12 (n=83) completed two dietary assessments using a food diary from January-June 2017. Children were then interviewed using the food diary as a guide and dietary data were entered into the online ASA24 system by study staff. Chinese American children were identified using surname, and were compared to non-Chinese peers with respect to nutrient intake and the Healthy Eating Index 2010 (HEI-2010). Chinese American children consumed more sodium dense diets, more protein, and less sugar compared to non-Chinese children. With regards to the HEI-2010, Chinese American children had less favorable whole grains and sodium scores; and more favorable seafood protein and empty calories scores compared to non-Chinese children. Sodium reduction and increasing whole grain intakes may be warranted in this group, but should be verified with additional studies.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

Red mud is a hazardous waste of alumina industry that contains high amounts of iron, aluminum, titanium and REEs. One of the promising methods for the extraction of iron from red mud is car-bothermic reduction with the addition of sodium salts. This research focuses on the process of hy-drochloric high-pressure acid leaching using 10–20% HCl of two samples of non-magnetic tailings obtained by 60-minute carbothermic roasting of red mud at 1300 °C and the mixture of 84.6 wt. % of red mud and 15.4 wt. % Na2SO4 at 1150 °C, respectively, with subsequent magnetic separation of metallic iron. An influence of temperature, leaching duration, solid-to-liquid-ratio and acid con-centration on dissolution behavior of Al, Ti, Mg, Ca, Si, Fe, Na, La, Ce, Pr, Nd, Sc, Zr were studied. Based on the investigation of the obtained residues, mechanism of passing of valuable elements into the solution was proposed. It has shown that 90% Al, 91% Sc and above 80% of other REEs can be dissolved under optimal conditions; Ti can be extracted into the solution or the residue depending on the leaching temperature and acid concentration. Based on the research results, novel flowsheets for red mud treatment were developed.

The multidrug resistance transporter NorM is an important drug resistance pump and plays a critical role in multidrug resistance in bacteria and mammals. In this study we carried out molecular dynamics simulation to study the mechanism of Na+ binding and dynamical structures of two long loops in the substrate-releasing process in substrate binding NorM. Our simulation study identified several key residues (D41, E261 D377) along the Na+ binding pathway and a multi-state ion-binding mechanism is proposed based on the simulation study. In this proposed model, the transport of Na+ is a multi-stage process with D41 being the first station for binding to Na+, followed by Na+ binding to the second station E262 and finally to the cation-binding site of E262 and D377. During the transport of Na+, the transmembrane components TM1, TM7 and TM2 are rearranged to facilitate the ion transport as well conformational changes of NorM to a closed state. Further, substrate-bound simulation revealed that Loop3-4 and Loop9-10 control the substrate-releasing process.

1) Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. 2) Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. 3) Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. 4) Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

The purpose of this study was to investigate the effect of chitosan (CS) and Alginate (Alg) polymers concentrations and CaCl2 concentration on metronidazole (MET) drug loading (LE), size particles and zeta potential. Nanocomposites were prepared by ionotropic pregelation method. A (21 *31 *21) *3= 36 full factorial design (FFD) was used to predict statistical equation and responses. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, scanning electron microscope and in vitro drug release studies. All data indicated the presence of drug into MET-CS-AlgNPs nanocomposites. The release profile of MET-CS-AlgNPs nanocomposites was found to be sustained

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

Ceftiofur (CEF) sodium is a third-generation broad-spectrum cephalosporin commonly used in an extra-label manner in dogs for the treatment of respiratory and urinary system infections. To contribute to the literature supporting CEF use in companion animals, we have developed a compartmental, nonlinear mixed-effects (NLME) model of CEF pharmacokinetics in dogs (PK). We then used the mathematical model to predict (via Monte Carlo simulation) the duration of time for which plasma concentrations of CEF and its pharmacologically active metabolites remained above minimum inhibitory concentrations (respiratory tractEscherichia coli spp). Twelve healthy beagle dogs were administered either 2.2 mg/kg ceftiofur-sodium (CEF-Na) intravenously (I.V) or 2.2 mg/kg CEF-Na subcutaneously (S.C). Plasma samples were collected over a period of 72 hours post-administration. To produce a measurement of total CEF, both CEF and CEF metabolites were derivatized into desfuroylceftiofur acetamide (DCA) before analysis by UPLC-MS/MS. No adverse effects were reported after I.V or S.C dosing. The NLME PK models were parameterized using the stochastic approximation expectation maximization algorithm as implemented in Monolix 2018R2. A two-compartment mamillary model with first-order elimination and first-order S.C absorption best described the available kinetic data. Final parameter estimates indicate that CEF has a low systemic clearance (0.25 L/h/kg) associated with a low global extraction ratio E = 0.02) and a moderate volume of distribution (2.97 L/kg) in dogs. The absolute bioavailability after S.C administration was high (93.7%). Gender was determined to be a significant covariate in explaining the variability of S.C absorption. Our simulations predicted that a dose of 2.2 mg/kg CEF-Na S.C would produce median plasma concentrations of CEF of at least 0.5 µg/mL (MIC₅₀) for approximately 30 hours.

The potential of sodium alginate (ALG) and gum arabic (GA) as wall polymers for L-ascorbic acid (AA) encapsulation as a tool for their preservation against the thermo-oxidative degradation was investigated. The influence of such polymers used as wall material on the AA-content, size, encapsulation efficiency, encapsulation yield and thermo-oxidative stability were evaluated. The AA-microparticles were obtained using the spray-drying technique. An experimental Taguchi design was employed to assess the influence of the variables in the encapsulation process. The microparticles morphology and size distribution were characterized by scanning electron microscopy and laser diffraction. The thermal stability of AA microparticles was studied by differential scanning calorimetry and thermogravimetry analysis. This work points out the viability to encapsulate AA using GA and ALG through a spray-drying process. In general, a product yield ranging from 35.1% to 83.2% and an encapsulation efficiency above 90% was reached. Spherical microparticles with a smooth surface were obtained with a mean diameter around 6 μm and 9 μm for the those prepared with GA and ALG, respectively. The thermo-oxidative analysis showed that both polymers allow maintaining AA stable up to 188 °C, which is higher than the traditional processing temperature used in the fish feed industry.

Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and micro-neutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA) which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain specific. This led to the emphasis on stalk targeting antibodies which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE targeting antibodies and compare them with head and stalk class antibodies.

The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the “Central Dogma of Molecular Biology”, has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesisfound to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundanceof a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer’s disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a Two-Tier Paradox and RNA Dark Matter. RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.

Transfusion dependent thalassemia (TDT) patients are treated with continued blood transfusions and show a higher prevalence of depression. TDT with consequent iron overload and inflammation is associated with increased severity of depressive symptoms in TDT children.Aim of the study: To construct a pathway-phenotype which combines iron overload and neuro-immune biomarkers with depressive symptom subdomains in TDT children.Methods: We measured iron status parameters (iron, ferritin, transferrin saturation percentage) and inflammatory (interleukin-1β and tumour necrosis factor-α) biomarkers in TDT (n=111) and healthy (n=53) children and analyzed the results using machine learning.Results: Cluster analysis separated TDT children with depression from those without depression and revealed two depressive subgroups one with low self-esteem and another with increased social-irritability scores. Exploratory factor analysis validated four depressive symptom dimensions as reliable constructs, namely key depressive, physiosomatic, lowered self-esteem and social-irritability dimensions. Partial Least Squares showed that 73.0% of the variance in a latent vector extracted from those four clinical subdomains, immune-inflammatory and iron overload biomarkers was explained by exposure variables including the number of blood transfusions and hospitalizations and use of deferoxamine. The exposure data, iron and immune biomarkers, and symptom subdomains are reflective manifestations of a single latent trait, which shows internal consistency reliability and predictive relevance.Conclusions: The nomological network combining exposure, pathways and behavioral phenome manifestations provides an index of overall severity and disease risk and, therefore, constitutes a new drug target, indicating that iron overload and immune activation should be targeted to treat depression due to TDT.

To compare The effects of organic and inorganic impregnation on the properties of unmodified, phenol formaldehyde oligomer-modified (PFOMCF), and sodium silicate-modified Chinese fir wood (SSMCF) were compared using samples prepared using the respiratory impregnation method. Impregnation and reinforcement effects and water resistance of PFOMCF and SSMCF were compared and the results was showed that the weight percentage gain, density increase rate, bending strength, and compressive strength of SSMCF were clearly higher than those of PFOMCF and had a lower water absorption rate within 60 h. The impregnation and reinforcement effects and dimensional stability of SSMCF were better than those of PFOMCF. FT-IR, XRD, CONE, and TGA examinations were used to test and analyze the chemical structure, crystalline structure, flame retardancy, and heat resistance of these modified woods. The results indicated that SSMCF possessed more hydrogen bonds than PFOMCF and that Si–O–Si chemical bonding with high bond energy was formed. Meanwhile, the weakened degree of the diffraction peak of SSMCF was much less than that of PFOMCF. These results explained that the mechanical properties and water resistance of SSMCF were better than PFOMCF. Compared with PFOMCF, SSMCF had a lower heat release rate (HRR), peak-HRR, mean-HRR, total heat release, smoke production rate, and total smoke production as well as higher thermal decomposition temperature and residual rate. Inorganic sodium silicate was shown to be a better flame retardant, while SSMCF had good smoke suppression effects, thermal stability, and safety performance in the case of fire.

Sodium substitution Li1-xNaxMn2O4 cathodes were synthesized by a solid-state reaction method. The morphologies and crystal structures of Li1-xNaxMn2O4 were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. All Li1-xNaxMn2O4 samples exhibited a single phase LiMn2O4 spinel structure with good crystallinity. The effect of Na+ ions on the electrochemical performance of Li1-xNaxMn2O4 was investigated by galvanostatic charge-discharge test. The results showed that lithium substituted by sodium deteriorated its capacity retention but enhance its discharge capacity when it worked at large current densities. The initial discharge capacity was 114.2 mAh/g for Li0.94Na0.06Mn2O4, and 93.1 mAh/g remained after 300 cycles at a current density of 2220 mA/g in the voltage range 3.0–4.3 V at room temperature.

Chronic kidney diseases (CKD) and end stage renal disease (ESRD) are growing threats worldwide. Tissue engineering is a new hope to surpass the current limitations such as the shortage of donor. To do so, the first step would be fabrication of an intact decellularized kidney scaffold. In the current study, an automatic decellularization device was developed to perfuse and decellularize male rats' kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their efficacy in kidney decellularization and post-transplantation angiogenesis. After anesthesia, kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Masson’s trichrome, and alcian blue to determine cell removal and glycogen, collagen and glycosaminoglycans (GAGs) contents, respectively. Moreover, scanning electron microscopy (SEM) was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quantification assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility and bioactivity of the decellularized scaffolds, allotransplantation was performed in back muscle and angiogenesis was evaluated. Complete cell removal in both SLES and SDS groups was observed in SEM and DNA quantification assays. Moreover, the extracellular matrix (ECM) architecture of rat kidney in the SLES group was significantly preservation better than the SDS group was shown. The formation of blood capillaries and vessels were observed in the kidney allotransplantations in both SLES and SDS decellularized kidneys. In conclusion, we demonstrated that both SLES and SDS could be promising tools in kidney tissue engineering. The better preservation of ECM than SDS, introduces SLES as the solvent of choice for kidney decellularization. ¬¬

Around the world, every year, about 17 million people death cause happen due to CardioVascular Diseases (CVD). As per clinical records, primarily sufferers exhibit myocardial infarctions and Heart Failures (HF). Creatinine is a Musculo - skeletal waste product. The kidneys filter creatinine from the blood and excrete it through the urine in a healthy body. High creatinine levels can suggest renal problems. Elevated Serum Creatinine (SC) has been well established in the HF. Patients’ electronic medical records can be used to quantify symptoms and other related clinical laboratory test values, which would then be utilized to direct biostatistics exploration to uncover patterns and associations that doctors would otherwise miss. The latest American Heart Association guidelines for 1500 mg/d sodium tend to be sufficiently relevant for patients with stage A and B with HF. In this article, we used a dataset of the year 2015 of heart patients records of 299 patients. The present paper used the data analytic and statistical tools to verify the significant differences between alive and dead patients’ SC and Serum Sodium (SS). It also demonstrates the impact of significant features on abnormal SC and SS on the Survival-Status levels. The Age-Group feature, which is derived from age attribute and, Ejection Fraction (EF), anemia, platelets, Creatinine Phosphokinase (CPK), Blood-Pressure (BP), gender, diabetes, and smoking-status were utilized to determine the potential contributing features to mortality with Cox regression model. The Kaplan Meier plot was used to investigate the overall pattern of survival concerning age-group. During pre-processing of the dataset, Age and SS were removed due to multicollinear features during performing machine learning algorithms experiments. This paper also predicted patients’ survival, age group, and gender using supervised machine learning classifiers. Detection of significant features would help in making informed decisions to balance the lifestyle of heart patients. The author revealed that the patient’s follow-up months, as well as SC, EF, CPK, and platelets, are sufficient key features to predict heart patient survival using Random Forest (RF) stratified 10-fold CV method with accuracy (96%) with 5% Standard Deviation (SD) from medical records dataset. We identified the age-group and gender of the patient, and the RF model outperformed others with the best accuracy 96% and 94% in both cases having 11% SD. Also, prominent features such as CPK, SC, follow-up month, platelets, and ejection were found to be significant factors in predicting the patient’s age-group. Smoking habits, CPK, platelets, follow-up month, and SC of each patient were discovered to be significant predictors of patient gender. The hypothetical study proved that SC and SS making substantial differences in the survival of patients (p &lt; 0.05) and failed to reject that anemia, diabetes, and BP making a significant impact on the creatinine and sodium of each patient (p &gt; 0.05). With χ2(1) = 8.565, the Kaplan Meier plot revealed that mortality was high in the extremely elder age-group. The finding has possible effects on clinical practice and becomes a new medical support system when predicting whether a patient can survive a heart attack or not. The doctor should primarily concentrate on follow-up month, SC and EF, CPK, and platelet count since the aim is to understand whether a patient survives after HF.

We have evaluated the antihypertensive effect of several flavonoid extracts in the spontaneous hypertensive rat model (SHR). Treatments were carried out for 6 and 12 weeks in two groups of SHR rats which received Apigenin, Lemon Extract, Grapefruit + Bitter Orange (GBO) extracts and Cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts significantly reduced the elevated blood pressure of the SHR6 animals, but none of the extracts was effective in the SHR12 group. Apigenin, LE, GBO and captopril also ameliorated nitric oxide-dependent and independent aortic vascular relaxation and elevated plasma and urinary excretion of nitrites, only in the SHR6 group. Kidney and urinary TBARS were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary TBARS excretion and proteinuria. Vascular abnormalities such as lumen/wall ratio in coronary arteries and thoracic aorta were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoids included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in BP. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.

Lettuce is a salt-sensitive crop and has a threshold electrical conductivity of 1.3–2.0 mS cm-1 and above that is considered detrimental. As there has been very little information on the physio-logical response of different critical stages of lettuce under different salt stress (SS), the current study is focused on investigating the effects of SS on the critical physiological traits influencing the carbon assimilation in different growth stages of lettuce. The experiment was conducted in deep-water culture hydroponic system in a greenhouse condition. Four levels of sodium chloride salt treatments (EC: 20, 16, 8, and 1.8 mS cm-1) were applied. During both growth stages (day 11 (GS1) and day 19 (GS2) after salt treatment), the leaf transpiration rate, stomatal conductance, and intercellular CO2 were severely decreased. However, the carbon assimilation rate remained unchanged under SS. Similarly, the water use efficiency increased under the SS. It is concluded that the increasing SS increased stomatal and non-stomatal limiting factors during GS1 suggesting the enhanced limitation in photosynthetic activity while no such trend was observed during GS2. The decreased gm with increased SS at GS1 and GS2 suggested that SS induced the irreversible decrease of gm, which in turn can be responsible for the transient reduction in the Vcmax and Jmax during GS2. Taken together, the evidence from this research recommends that varying the SS levels can significantly affect the physiological performance of lettuce at both growth stages.

A theoretical nonlocal thermoelastic model for studying the effects of the thermal conductivity variability on a rotating nanobeam has been described in the present article. The theory of thermal stress is employed using the Euler–Bernoulli beam model and generalized heat conduction with phase lags. It is believed that the thermal conductivity of the current model varies linearly according to temperature. Due to variable harmonic heat, the considered nanobeam excited and was subjected to a time-varying exponential decay load. Using the Laplace transform process, the analytical solutions for displacement, deflection, thermodynamic temperature and bending moment of rotating nanobeams are provided in final forms and a numerical example has been taken to address the problem. A comparison of the stated results was displayed and additionally, the influences of non-local parameters and varying load were analyzed and examined. We also investigate how the linear changes in the temperature of physical properties can influence both the static and dynamic responses to the rotating nanobeam.

Polydopamine (PDA) deposition, obtained from the oxidation of dopamine and other catecholamines is an universal way to coat all known materials with a conformal coating which can subsequently be functionalyzed at will. The structural analogies between polydopamine and eumelanin, the black-brown pigment of the skin, incited to produce stable polydopamine nanoparticles in solution instead of amorphous precipitates obtained from the oxidation of dopamine. Herein, we demonstrate that size controlled and colloidally stable PDA based nanoparticles can be obtained in acidic conditions, where spontaneous auto-oxidation of dopamine is suppressed, using sodium periodate as the oxidant and a protein like alkaline phosphatase as a templating agent. The size of the PDA@Alp nanoparticles depends on the dopamine/enzyme ratio and the obtained particles display the enzymatic activity of alkaline phosphatase with an activity extending up to two weeks after particle synthesis. The PDA@ alkaline phosphatase (Alp) nanoparticles can be engineered in polyelectrolyte multilayered films to potentially design model biosensors.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

Ion channels contribute fundamental properties to all cell membranes. The ion channels are highly diverse in conductivity, structure, location and function. However, many of them can be regulated by common mechanisms, such as voltage or (de-)phosphorylation. Considering primarily pain-related ion channels, this review covers more novel and less known features of ion channel function, also with the aim to transfer knowledge between fields, which get inevitably more separate due to their size.

Excess salt and inadequate potassium intakes are associated with high cardiovascular disease (CVD). In Montenegro, CVD is the leading cause of death and disability. There is no survey that has directly measured salt and potassium consumption in Montenegro. The aim is to estimate population salt and potassium intakes and explore knowledge, attitudes and behaviour (KAB), amongst the adult population of Podgorica. Random samples of adults were obtained from primary care centres. Participants attended a screening including demographic, anthropometric and physical measurements. Dietary salt and potassium intakes were assessed by 24h urinary sodium (UNa) and potassium (UK) excretions. Creatinine was measured. KAB was collected by questionnaire. Six hundred and thirty-nine (285 men, 25-65 years) were included in the analysis (response rate 63%). Mean UNa was 186.5 (SD 90.3) mmol/day, equivalent to 11.6g of salt/day, and potassium excretion 62.5 (26.2) mmol/day, equivalent to 3.2g/day. Only 7% of them had a salt intake below the WHO recommended target of 5g/day, and 13% ate enough potassium (>90 mmol/day). The majority (86%) knew that high salt causes ill-health. However, only 44% thought it would be useful to reduce consumption. Salt consumption is high, and potassium consumption is low, in men and women living in Podgorica.

Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

Seed germination is the most sensitive stage to abiotic stress, including salt stress (SS). SS affects plant growth and performance through ion toxicity, decreases seed germination percentage, and increases the germination time. Several priming treatments were used to enhance germination under SS. The objectives of this study are to 1) identify priming treatments to shorten the emergence period; 2) evaluate priming treatments against the SS; 3) induce synchronized seed germination. Salt-sensitive “Burpee bibb’ lettuce seeds were treated with 0.05% Potassium nitrate, 3 mM Gibberellic acid, and distilled water (HP). All the primed and non-primed seeds were subjected to 100 mM NaCl or 0 mM NaCl. The 7-day experiment arranged in a complete randomized block design with four replications was conducted in a growth chamber maintained with 16/8 h photoperiod (light/dark), 60% relative humidity, and day/night temperature of 22/18 °C. The result indicated that HP seeds were better synchronized under SS. Similarly, FM and DM of cotyledon, hypocotyl, and radicle were highest in HP lettuce regardless of SS. Electrolyte leakage was the lowest in the HP lettuce, while other priming methods under SS increased membrane permeability leading to osmotic stress and tissue damage. Overall, the HP can be a suitable priming method to synchronize germination and increase FM and DM by creating the least osmotic stress and ion toxicity in lettuce under SS.

Based on the Expected Utility Theory and Regret Theory, the Extended Regret Theory (ERT) is proposed in this paper to study the optimal pricing strategy of retailers in e-commerce environment. Taking the diversity of sales channels and the uncertainty of consumers in e-commerce environment into consideration, author of the paper designs an extended regret utility function which comprehensively considers both pessimistic and optimistic attitudes of decision makers in retailing industry to describe their regret-avoidance behavior. According to the sensitivity analysis, it is found that the optimal retail price decreases as the consumer price sensitivity coefficient increases, yet does not show variation with changes of the consumers pessimism degree. Moreover, the optimal retail price(s) obtained under EUT, ERT and combination of EUT and ERT represent the same.

The open communication is an exigent need for future power system where the time delay is unavoidable. In order to secure the stability of the grid, the frequency must remain within its limited range which is achieved through the load frequency control. The load frequency control signals are transmitted through communication networks which induces time delay that could destabilize the power systems. So, in order to guarantee the stability the delay margin should be computed. In this paper, we present a new method for calculating the delay margin in load frequency control systems. The transcendental time delay characteristics equation is transformed to frequency dependant equation. The spectral radius is used to find the frequencies at which the roots crosses the imaginary axis. The crossing frequencies are determined through the sweeping test and the binary iteration algorithm. A one-area load frequency control system is chosen as case study. The effectiveness of the proposed method has been proved through comparing with the most recent published methods. The method shows its merit with less conservativeness and less computations. The PI controller gains are preferable to be chosen large to reduce the damping, however, the delay margin decreases with increasing the PI controller gains.

High sodium intake increases blood pressure and consequently increases the risk of cardiovascular diseases. In Australia, the best estimate of sodium intake is 3840 mg sodium/day, almost double the World Health Organization guideline (2000 mg/day), and processed meats contribute approximately 10% of daily sodium intake to the diet. This study assessed the median sodium levels of 2510 processed meat products, including bacon and sausages, available in major Australian supermarkets in 2010, 2013, 2015 and 2017, and assessed changes over time. The median sodium content of processed meats in 2017 was 775 mg/100 g (IQR 483–1080). There was an 11% reduction in the median sodium level of processed meats for which targets were set under the government’s Food and Health Dialogue (p < 0.001). This includes bacon, ham/cured meat products, sliced luncheon meat and meat with pastry categories. There was no change in processed meats without a target (median difference 6%, p = 0.093). The new targets proposed by the current government’s Healthy Food Partnership, capture a larger proportion of products than the Food and Health Dialogue (66% compared to 36%) and a lower proportion of products are at or below the target (35% compared to 54%). These results demonstrate that voluntary government targets can drive nutrient reformulation. Future efforts will require strong government leadership and robust monitoring and evaluation systems.

(1) Background: After the discovery and application of Chlamydomonas reinhardtii channelrhodopsins, the optogenetic toolbox has been greatly expanded with engineered and newly discovered natural channelrhodopsins. However, channelrhodopsins of higher Ca2+ conductance or more specific ion permeability are still in demand. (2) Methods: In this study, we mutated the conserved aspartate of the transmembrane helix 4 (TM4) within Chronos (Stigeoclonium helveticum channelrhodopsin = ShChR) and PsChR (Platymonas subcordiformis channelrhodopsin) and compared them with published ChR2 (C. reinhardtii channelrhodopsin-2) aspartate mutants. (3) Results: We found that the ChR2 D156H mutant (XXM) showed enhanced Na+ and Ca2+ conductance, which was not noticed before, while the D156C mutation (XXL) influenced the Na+ and Ca2+ conductance only slightly. Furthermore, the D173H mutant of PsChR showed a much improved photocurrent, compared to wildtype, and even higher Na+ selectivity to H+ than XXM. PsChR D173H also showed a strongly enhanced Ca2+ conductance, more than 2-fold that of the calcium translocating L132C of ChR2 (CatCh). (4) Conclusions: We found that mutating the aspartate of the TM4 to histidine influences the ion selectivity of channelrhodopsins. With the large photocurrent and enhanced Na+ selectivity and Ca2+ conductance, XXM and PsChR D139H are promising powerful optogenetic tools, especially for Ca2+ manipulation.

Protein immobilization for the functionalization of particles is used in various applications, including biosensors, lateral-flow immunoassays (LFIA), bead-based assays, and others. Common methods for the quantification of bound protein are measuring protein in the supernatant before and after coating and calculating the difference. This popular approach has the potential for a significant overestimation of the amount of immobilized protein since layers not directly bound to the surface (soft protein corona) are usually lost during washing and handling. Only the layer directly bound to the surface (hard corona) can be used in subsequent assays. A simplified amino acid analysis method based on acidic hydrolysis and RP-HPLC-FLD of tyrosine and phenylalanine (aromatic amino acid analysis, AAAA) is proposed to directly quantify protein bound to the surface of gold nano- and latex microparticles. The results are compared with indirect methods such as colorimetric protein assays, such as Bradford, bicinchoninic acid (BCA), as well as AAAA of the supernatant. For both particle types, these indirect quantification techniques show a protein overestimation of up to 1700% compared to the direct AAAA measurements. In addition, protein coating on latex particles was performed both passively through adsorption and covalently through EDC/sulfo-NHS chemistry. Our results showed no difference between the immobilization methodologies. This finding suggests that usual protein determination methods are no unambiguous proof of a covalent conjugation on particles or beads.

In the Republic of Moldova, nearly 90% of all deaths are due to noncommunicable diseases (NCDs), tha majority of which (58%) are caused by cardiovascular disease (CVD). Excess salt (sodium) and inadequate potassium intakes are associated with high CVD. Moreover, salt iodisation is the preferred policy to prevent iodine deficiency and associated disorders. However, there is no survey that has directly measured sodium, potassium and iodine consumption in adults in the Republic of Moldova. The aim is to estimate population sodium, potassium and iodine intakes and explore knowledge, attitudes and behaviour (KAB) towards the use of salt, amongst the adult population in the Republic of Moldova. Proportional random samples of adults were obtained from 28 of the 37 Districts and Municipalities and one Administrative Territorial Unit of Moldova. Participants attended a screening including demographic, anthropometric and physical measurements. Dietary sodium, potassium and iodine intakes were assessed by 24h urinary sodium (UNa), potassium (UK) and iodine (UI) excretions. Creatinine was measured. KAB was collected by questionnaire. Eight hundred and fifty-eight participants (326 men and 532 women, 18–69 years) were included in the analysis (response rate 66%). Mean age was 48.5 yrs (SD 13.8). Mean UNa was 172.7 (79.3) mmoL/day, equivalent to 10.8 g of salt/day and potassium excretion 72.7 (31.5) mmoL/day, equivalent to 3.26 g/day. Men ate more sodium and potassium than women. Only 11.3% of the sample had a salt intake below the World Health Organization (WHO) recommended target of 5 g/day and approximately 39% met WHO targets for potassium excretion (>90 mmoL/day). Whilst 81.7% declared limiting their consumption of processed food and over 70% declared not adding salt at the table, only 8.8% looked at sodium content of food, 31% still added salt when cooking and less than 1% took other measures to control salt consumption. Measures of awareness were significantly more common in urban compared to rural areas. Mean urinary iodine was 225 (SD: 152; median 196) mcg/24h, with no difference between sexes. According to WHO criteria, 41.0% had adequate iodine intake, 28.6% had intake below requirements and 17.8% and 12.6% had above requirement or excessive levels, respectively. Iodine content of salt table was 21.0 (SD: 18.6) mg/kg, with no difference between men and women. However, the content was lower in rural than urban areas (16.7 [SD: 18.6] vs 28.1 [SD: 16.5] mg/kg, p<0.001). There were weak or no correlations between urinary sodium and iodine excretions, and between urinary iodine excretion and iodine concentration in the table salt used in the participants’ households, indicating that in most cases participants were not using iodised salt as their main source of salt, more so in rural areas. In the Republic of Moldova, salt consumption is unequivocally high, potassium consumption is lower than recommended, both in men and in women, whilst iodine intake is still inadequate in 1 in 3 people, although severe iodine deficiency is rare. Salt consumed is often not iodised, with less iodised salt being used in rural areas.

Background: Sodium intake has been related to several adverse health outcomes; such as, hypertension, and cardiovascular diseases. Processed foods are major contributors to the population’s dietary sodium intake. The aim of the present study was to determine sodium levels in Mexican packaged foods; also to evaluate the proportion of foods that comply with sodium benchmark targets set by the UK Food Standards Agency (UK FSA) and those set by the Mexican Commission for the Protection of Health Risks (COFEPRIS). We also evaluated the proportion of foods that exceeded the Pan American Health Organization (PAHO) targets. Methods: This was a cross-sectional study that comprised data collected from the package of 2,248 processed foods from selected supermarkets of Mexico. Results: Many processed food categories contained excessive amount of sodium, being the processed meats (ham, bacon and sausages) those that have the highest concentrations. The proportion of foods classified as compliant in our sample was lower for international targets (FSA UK and PAHO) compared to the Mexican COFEPRIS criteria. Conclusions: These data provide a critical baseline assessment for monitoring sodium levels in Mexican processed foods.

Risk of cardiovascular disease (CVD), common in childhood cancer survivors (CCSs), may be affected by diet. We assessed sodium (Na) and potassium (K) intake, estimated from food frequency questionnaires (FFQs) and morning urine spots, and its associations with cardiovascular risk in CCSs. We stratified CCS into three risk profiles based on A) personal history (CVD, CVD risk factors, or CVD risk free), B) body mass index (obese, overweight, or normal/underweight), and C) cardiotoxic treatment (anthracyclines and/or chest irradiation, or neither). We obtained a FFQ from 802, and sent a spot urine sample collection kit to 212, of which 111 (52%) returned. We estimated Na intake 2.9 g/day based on spot urine and 2.8 g/day based on FFQ; estimated K intake was 1.6 g/day (spot urine) and 2.7 g/day (FFQ). CCSs with CVD risk factors had a slightly higher Na intake (3.3 g/day), than CCSs risk free (2.9 g/day) or with CVD (2.7 g/day, p = 0.017), and obese participants had higher Na intake (4.2 g/day) than normal/underweight CCSs (2.7 g/day, p<0.001). Daily Na intake was above, and daily K intake below national recommended levels. Adult survivors of childhood cancer need dietary assistance to reduce Na and increase K intake.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct N^ɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

This work presents a novel approach to construct surrogate models of parametric Differential Algebraic Equations based on a tensor representation of the solutions. The procedure consists in building simultaneously, for every output of the reference model, an approximation given in tensor-train format. A parsimonious exploration of the parameter space coupled with a compact data representation allows to alleviate the curse of dimensionality. The approach is thus appropriate when many parameters with large domains of variation are involved. The numerical results obtained for a nonlinear elasto-viscoplastic constitutive law show that the constructed surrogate model is sufficiently accurate to enable parametric studies such as the calibration of material coefficients.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

The objective of this study was to assess the ability of producing laminated edible films manufactured using the following proteins; gelatin (G), whey protein isolate (WPI), and polysaccharide; sodium alginate (SA), and to evaluate their physical properties. Additionally, films’ preparation employing these ingredients was optimized through the addition of corn oil (O), Overall, 8-types of laminated films (G-SA, G-WPI, SA-WPI, SA-G-WPI, GO-SAO, GO-WPIO, SAO-WPIO, SAO-GO-WPIO were developed in this study. The properties of the prepared films were characterized through the measurement of; tensile strength (TS), elongation at break point (EB), puncture resistance (PR), tear strength (TT), water vapour permeability (WVP) and oxygen permeability (OP). The microstructure of cross-sections of laminated films was investigated by scanning electron microscopy (SEM). Mechanical properties of films were dramatically enhanced through the addition of film layers. GO-SAO laminate showed the best barrier properties to water vapour (22.6 ± 4.04 g mm/kPa d m2) and oxygen (18.2 ± 8.70 cm3 mm/kPa d m2). SAO-GO-WPIO laminate film was the strongest of all laminated films tested, having the highest TS of 55.77 MPa, PR of 41.36 N and TT of 27.32 N. SA-G-WPI film possessed the highest elasticity with an EB value of 17.4%.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

We propose an iterative scheme for feature-based positioning using a new weighted dissimilarity measure with the goal of reducing the impact of large errors among the measured or modeled features. The weights are computed from the location-dependent standard deviations of the features and stored as part of the reference fingerprint map (RFM). Spatial filtering and kernel smoothing of the kinematically collected raw data allow efficiently estimating the standard deviations during RFM generation. In the positioning stage, the weights control the contribution of each feature to the dissimilarity measure, which in turn quantifies the difference between the set of online measured features and the fingerprints stored in the RFM. Features with little variability contribute more to the estimated position than features with high variability. Iterations are necessary because the variability depends on the location, and the location is initially unknown when estimating the position. Using real WiFi signal strength data from extended test measurements with ground truth in an office building, we show that the standard deviations of these features vary considerably within the region of interest and are neither simple functions of the signal strength nor of the distances from the corresponding access points. This is the motivation to include the empirical standard deviations in the RFM. We then analyze the deviations of the estimated positions with and without the location-dependent weighting. In the present example the maximum radial positioning error from ground truth are reduced by 40% comparing to kNN without the weighted dissimilarity measure.

RNA interference (RNAi) is one of the main mechanisms for disease resistance and small RNA production in plants. The main proteins involved in RNAi include Dicer-like (DCL), RNA-dependent RNA polymerase (RDR), double-stranded RNA-binding (DRB), and Argonaute (AGO). Juglandaceae contains a variety of important woody plants, and walnuts are one of the four major woody plant groups and one of the four major dried fruits in the world. To clarify the evolution and functional differentiation of RNAi-related proteins in the walnut (Juglans regia) genome, this study integrated various web resources from gene family acquisition to structural analysis and transcriptome data to correlate walnuts and their congeners. The walnut genome has 5 DCL, 13 RDR, 15 DRB and 15 AGO genes, similar genes encoding conserved protein structural domains and conserved motifs with similar subcellular localization. Walnut AGO proteins are classified into three classes and seven subclasses. The DCL is divided into four categories, while RDR is mainly divided into four categories, and DRB can be divided into six categories. The exception is that the copy number of walnut RDR1 is 9, in which seven RDR1 are distributed in clusters on chromosome 16. Purifying selection drove the formation of walnut genes, but protein classes were subjected to varying degrees of purifying selection. Additionally, these results showed some similarity in other plants of the walnut family. Moreover, different RNAi-related genes of walnut produced abundant selective expression in response to different tissues and stresses. In this study, DCL, RDR, DRB and AGO gene families were identified and analysed in the genome of the walnut family for the first time and preliminarily examined the evolution, structure and expression characteristics of these families to provide a preliminary basis for the evolution of the walnut RNAi pathway and breeding research.

The synthesis of magnetic nanoparticles (MNPs) coated with hydrophilic poly-sodium-acrylate ligands (PSA) was studied to assess PSA-MNP complexes as draw solution (DS) solutes in forward osmosis (FO). For MNP-based DS, the surface modification and the size of the MNPs are two crucial factors to achieve a high osmolality. Superparamagnetic nanoparticles (NP) with functional groups attached may represent the ideal DS where chemical modifications of the NPs can be used in optimizing the DS osmolality and the magnetic properties allows for efficient recovery (DS re-concentration) using an external magnetic field. In this study MNPs with diameters of 4 nm have been prepared by controlled chemical co-precipitation of magnetite phase from aqueous solutions containing suitable salts of Fe2+ and Fe3+ under inert atmosphere and a pure magnetite phase could be verified by X-ray diffraction. Magnetic colloid suspensions containing PSA coated MNPs with three different molar ratios of PSA : MNP = 1:1, 1:2 and 1:3 were prepared and assessed in terms of osmotic pressure, aggregation propensity and magnetization. FTIR confirmed the presence of PSA on coated MNPs and pristine PSA-MNPs with a molar ratio PSA : MNP = 1:1 exhibited an osmotic pressure of 30 bar. Molar ratios of PSA : MNP = 1:2 and 1:3 lead to formation of less stabile magnetic colloid solutions which led to formation of aggregates with larger average hydrodynamic sizes and modest osmotic pressures (5.5 bar and 0.2 bar respectively). After purification with ultrafiltration, the 1:1 nanoparticles exhibited an osmotic pressure of 9 bar with no aggregation and a sufficient magnetization of 25 emu/g to allow for DS regeneration using an external magnetic field. However, it was observed that the amount of PSA molecules attached to the MNPs decreased during DS recycling steps leaving only strong chelate bonded core-shell PSA as coating on the MNPs. This demonstrates the crucial role of MNP coating robustness in designing an efficient MNP-based DS for FO.

Understanding the detailed timing of crop phenology and their variability enhances grain yield and quality by providing precise scheduling of irrigation, fertilization, and crop protection mechanisms. Advances in information and communication technology (ICT) provide a unique opportunity to develop agriculture-related tools that enhance wall-to-wall upscaling of data outputs from point-location data to wide-area spatial scales. Because of the heterogeneity of the worldwide agro-ecological zones where crops are cultivated, it is unproductive to perform plant phenology research without providing means to upscale results to landscape-level while safeguarding field-scale relevance. This paper presents an advanced, reproducible, and open-source software for plant phenology prediction and mapping (PPMaP) that inputs data obtained from multi-location field experiments to derive models for any crop variety. This information can then be applied consecutively at a localized grid within a spatial framework to produce plant phenology predictions at the landscape level. This software supports the development of process-oriented and temperature-driven plant phenology models by intuitively and interactively leading the user through a step-by-step progression to the production of spatial maps for any region of interest. Maize (Zea mays L.) was used to demonstrate the robustness, versatility, and high computing efficiency of the resulting modeling outputs of the PPMaP. The framework is implemented in R, providing a flexible and easy‐to‐use GUI interface. Since this allows appropriate scaling to the larger spatial domain, the software can effectively be used to determine the spatially explicit length of growing period (LGP) of any variety.

Here, I introduce a concept called autonomous selection to refer to a source of selection that is part of the individuals upon which it acts. The concept is motivated by a set of phenomena with the following characteristics: Natural selection shaped a variant (e.g., gene, epigenetic mark, or combination thereof) to act in a manner that reduces the frequency of one or more heritable traits of the individual in which it is located if those traits are detrimental to individual or group fitness. Phenomena with these characteristics are peculiar to traditional evolutionary theory but have been identified rather frequently in recent decades. They are also relevant to adaptive evolution: By reducing the frequency of a trait detrimental to fitness, the variant accelerates the evolution of adaptations, which allows its holders to adapt better to constantly changing environments. The variant is shaped by (natural) selection, but also does (autonomous) selection. Several phenomena with these characteristics have been invoked by proponents of the extended evolutionary synthesis (EES). The concept of autonomous selection helps resolve some of the controversy surrounding the EES: EES proponents call attention to the incompleteness of contemporary theory, emphasizing individuals’ processes that influence which adaptations those individuals evolve. I argue for the special importance of individuals’ processes that do not just influence those individuals’ adaptations, but also accelerate the adaptive evolution of those individuals. All known phenomena that fit this description are examples of autonomous selection. Other phenomena raised by EES proponents do not meet this threshold.

To understand the evolution of the human norovirus GII.P6-GII.6 and GII.P7-GII.6 strains, we analyzed both the RdRp region and VP1 gene in globally collected strains using authentic bioinformatics technologies. A common ancestor of the P6- and P7-type RdRp region emerged approximately 50 years ago and a common ancestor of the P6- and P7-type VP1 gene emerged approximately 110 years ago. Subsequently, the RdRp region and VP1 gene evolved. Moreover, the evolutionary rates were significantly faster for the P6-type RdRp region and VP1 gene than the P7-type RdRp region and VP1 genes. Large genetic divergence was observed in the P7-type RdRp region and VP1 gene compared with the P6-type RdRp region and VP1 gene. The phylodynamics of the RdRp region and VP1 gene fluctuated after the year 2000. Positive selection sites in VP1 proteins were located in the antigenicity-related protruding 2 domain, and these sites overlapped with conformational epitopes. These results suggest that the GII.6 VP1 gene and VP1 proteins evolved uniquely due to recombination between the P6- and P7-type RdRp regions in the HuNoV GII.P6-GII.6 and GII.P7-GII.6 virus strains.

Population studies have demonstrated an association between sodium (Na) and po-tassium (K) intake and levels of blood pressure (BP) and cholesterol. The aim of this study was to describe the dietary intake and distribution of Na and K in Mexicans, and their as-sociation with metabolic risk outcomes. We analyzed a national survey that included 4,219 participants. Dietary information was obtained through a 24-hour recall. Foods and beverages were classified based on the degree of processing. BP and biomarkers in blood and urine were measured. The mean intake (mg/d) of Na was 1512 in pre-schoolchildren, 2844 in schoolchildren, 3743 in adolescents, and 3132 in adults. The mean intake of K was 1616 in pre-schoolchildren, 2256 in schoolchildren, 2967 in adolescents, and 3401 in adults. Processed and ultra-processed foods (UPF) contribute to sodium intake: 49% in preschool and schoolchildren, 47% in adolescents, and 39% in adults. Adults in the fourth quartile of sodium intake had lower serum concentrations of cholesterol (181.4 mg/dL) and HDL-c (35.5 mg/dL). The Mexican population has high Na and low K intakes. There is a relationship between Na sodium consumption and cholesterol, and LDL levels. UPF contributes to almost 40% of the sodium consumed by Mexicans.

In order to improve the performance of soft plantation wood, an environmentally friendly inorganic-organic hybrid wood modifier was developed. First, using urea and melamine as crosslinking agents, the waterborne glucose silicone resin (MUG) was prepared with glucose under the catalysis of inorganic acid and metal ions. Then MUG resin was diluted to 10% and 20% mass fraction, and compounded with sodium silicate (S) of 20% and 10% mass fraction, so the inorganic-organic hybrid G10S20 and G20S10 wood modifier were obtained respectively. Then plantation poplar wood (Populus tomentosa) were impregnated and modified with them. Their physical and mechanical properties were tested and compared with those of the wood treated with S of 20% mass fraction (S20). Infrared analysis showed that amino resin characteristic structure (CO-NH-) existed in MUG resin. The resin has good permeability. Compared with S20 modified wood, the degree of shrinkage of G10S20 or G20S10 modified wood is reduced, their moisture absorption is reduced, and their dimensional stability is improved. Waterborne glucose silicone modifier can effectively improve the wood density, modulus of elasticity, modulus of rapture and compression strength. SEM analysis showed that the cell wall of G20S10 modified wood was significantly thicker than the untreated wood, and there were columnar and granular solid substances attached in some cell cavities, ducts and corners, etc. EDX showed that the number of Si elements on the cell wall was significantly increased compared with the control, indicating that the modifier effectively entered the wood cell wall. The waterborne glucose silicone resin can greatly improve the physical and mechanical properties of wood through organic-inorganic hybridization. It is a green, non-formaldehyde, eco-friendly, low cost, compound wood modifier with broad application prospects.

Time evolution operators of a strongly ionizing medium are calculated by a time-dependent unitary transformation (TDUT) method. The TDUT method has been employed in quantum mechanical system composed of discrete states. This method is especially helpful for solving molecular rotational dynamics in quasi-adiabatic regimes because the strict unitary nature of the propagation operator allows us to set the temporal step size large; a tight limitation on the temporal step size ($\delta t <<1$) can be circumvented by the strict unitary nature. On the other hand, in a strongly ionizing system where the Hamiltonian is not Hermitian, the same approach cannot be directly applied because it is demanding to define a set of field-dressed eigenstates. In this study, the TDUT method was applied to the ionizing regime using the Kramers-Henneberger frame, in which the strong-field-dressed discrete eigenstates are given by the field-free discrete eigenstates in a moving frame. Although the present work verifies the method for a one-dimensional atom as a prototype, the method can be applied to three-dimensional atoms, and molecules exposed to strong laser fields.

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: i) primary dengue infection, ii) secondary dengue infection with the same (homologous) dengue virus and iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production, and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights on the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

Neuropsychiatric disorders are globally public-health concern, in which diagnosis might be based on symptoms that often vary across individuals. Schizophrenia is one of the major neuropsychiatric disorders, which may affect millions worldwide. Detection of predictive biomarkers is the most intensively developing approach for the disease. However, the biochemical alterations have not been comprehensively distinguished up to the present time. In addition, there is less confidence of finding a specific biomarker for neuropsychiatric disorders including schizophrenia, but rather a specific characteristic behavioral pattern. Maternal immune activation has been considered to be one of the important factors for the development of neuropsychiatric disorders. Here, the mouse model of neuropsychiatric disorders has been built, in which poly-I:C, sodium dextran sulfate (DSS) and κ-carrageenan (CGN) were used for the maternal immune activation during the pregnancy of individuals. Subsequently, we challenged to link some of biochemical changes of p62 and GLAST in the offspring mice brain to the alteration of several pathological behaviors. Consequently, it has been shown that autophagy might be involved in the development of neuropsychiatric disorders including schizophrenia. To our knowledge, this is the first report of the significant correlation between pathological behavior and the biochemical alterations in neuropsychiatric disorder model animals. The relative ease of conducting these evaluation-tasks would make them useful for testing novel therapeutics designed to ameliorate the symptoms of several psychiatric disorders.

Objective: To investigate the protein expression levels of cyclin‑dependent kinase subunit 2 (CKS2) and cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significances. Methods: A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumor, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analyzed the clinical significance of the expression of the two factors. Results: (1) The positivity rates for CKS2 in benign gastric tumor tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, i.e., 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumor diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=0.625, P=0.000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the overall survival rate for patients in the CKS2 (+) group was significantly worse (25.0% vs 64.0%, 2=15.67, P=0.000) and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse overall survival (30.1% vs 60.5%, 2=15.67, P=0.000). (4) The overall survival rates of CKS2(+)CD47(+) group, CKS2(+)CD47(-) group, CKS2(-)CD47(+) group, and CKS2 (-)CD47 (-) group were 20.0%(13/65), 58.3%(7/12), 57.1%(8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2(+)CD47(+) group was significantly poor. Conclusion: High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

Hydrogels obtained from the combination of different polymers are an interesting strategy for the development of controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using different concentration of the components. The hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling degree; betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay shown that almost all hydrogels are cytocompatibles and an increase the proliferation in both cell types after one week of incubation was observed by Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics and biocompatibility.

The present study was conducted to investigate the comparative effects of organic and inorganic forms of sulfur, methyl sulfonyl methane (MSM) and sodium sulfate (SS), on laying performance, egg quality, ileal morphology, ileal volatile fatty acids, and antioxidant and stress markers in various biological samples in aged laying hens. A total of 144, 73-week-old Lohman Brown-Lite laying hens were randomly assigned to one of three experimental diets: basal diet (CONT), CONT + 0.2% MSM (MSM), and CONT + 0.3% SS (SS). The trial lasted for 12 weeks. MSM and SS groups contained 0.07% of sulfur, either organic or inorganic. Dietary MSM did not affect egg production and feed conversion ratio at 12 weeks compared with the CONT group. Dietary sulfur did not affect egg quality except for Haugh unit at 4 weeks which was lowered (P &lt; 0.05) in the SS group. Compared with the CONT group, higher (P &lt; 0.05) villus height and crypt depth ratio was observed in the SS group. None of dietary sulfur affected the percentages of short-chain fatty acids in the ileum. Total antioxidant capacity of liver increased (P &lt; 0.05) in laying hens fed MSM- and SS-added diets compared with the CONT group. The MSM and SS groups lowered (P &lt; 0.05) malondialdehyde (MDA) concentration in serum samples compared with the CONT. Finally, dietary MSM had the lowest (P &lt; 0.05) MDA concentrations in yolk samples. Taken together, our study showed that dietary organic and inorganic sulfur have positive effects on ileal morphology and antioxidant capacity in laying hens. However, SS-mediated inhibition in laying performance needs to be clarified.

In recent years, the photophysical properties of crystalline metal-organic frameworks (MOFs) have become increasingly relevant for their potential application in light-emitting devices, photovoltaics, nonlinear optics and sensing. The availability of high-quality experimental data for such systems makes them ideally suited for a validation of quantum mechanical simulations, aiming at an in-depth atomistic understanding of photophysical phenomena. Here we present a computational DFT study of the absorption and emission characteristics of a Zn-based surface-anchored metal-organic framework (Zn-SURMOF-2) containing anthracenedibenzoic acid (ADB) as linker. Combining band-structure and cluster-based simulations on ADB chromophores in various conformations and aggregation states, we are able to provide a detailed explanation of the experimentally observed photophysical properties of Zn-ADB SURMOF-2: The unexpected (weak) red-shift of the absorption maxima upon incorporating ADB chromophores into SURMOF-2 can be explained by a combination of excitonic coupling effects with conformational changes of the chromophores already in their ground state. As far as the unusually large red-shift of the emission of Zn-ADB SURMOF-2 is concerned, based on our simulations, we attribute it to a modification of the exciton coupling compared to conventional H-aggregates, which results from a relative slip of the centers of neighboring chromophores upon incorporation in Zn-ADB SURMOF-2.

Soil water loss by evaporation influences the sodium adsorption ratio (SAR) of irrigation drainage water. Evaporation concentrates sodium and magnesium but calcite precipitation has a more complicated effect on soluble calcium and alkalinity. Here we propose a revised sodicity hazard assessment that quantifies the impact of evaporative water loss and calcite precipitation on drainage water SAR. This paper shows sodicity hazard is determined by the initial composition of irrigation water as originally suggested by previous researchers, and provide a simple, accurate way to identify the potential sodicity hazard of any irrigation water. In particular, the initial equivalent concentration of alkalinity and calcium determine the salinization pathway followed during evaporation. If the irrigation water alkalinity exceeds soluble calcium expressed as equivalent concentrations, drainage water SAR approaches an upper limit determined by the initial relative concentration of sodium and magnesium. If irrigation water alkalinity is less than soluble calcium, drainage water SAR approaches a lower limit determined by the initial calcium, magnesium and sodium. In both cases the SAR is scaled by the square root of the concentration factor √Fc quantifying soil water loss. To assess the impact of evaporation and calcite precipitation on the SAR and test the accuracy of the new sodicity hazard assessment, we evaluated data from previously published lysimeter studies. We plotted water composition boundaries for each source water, comparing these boundaries to the drainage water composition recorded in the lysimeter studies. As salinity increased by evaporation, each drainage water followed a distinct salinization path.

This paper presents sufficient conditions for almost global stability of nonlinear switched systems consisting of both stable and unstable subsystems. Techniques from the stability analysis of switched systems have been combined with the multiple Lyapunov density approach - recently proposed by the authors for the almost global stability of nonlinear switched systems composed of stable subsystems. By using slow switching for stable subsystems and fast switching for unstable subsystems lower and upper bounds for mode-dependent average dwell times are obtained. In addition to that, by allowing each subsystem to perform slow switching and using some restrictions on total operation time of unstable subsystems and stable subsystems, we have obtained a lower bound for an average dwell time.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.