Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

Radiolabelled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection we recently developed the fluorine-18 labelled PSMA-ligand [¹⁸F]PSMA-1007 as next generation radiofluorinated Glu-ureido PSMA inhibitor after [¹⁸F]DCFPyL and [¹⁸F]DCFBC. Since radiosynthesis so far was suffering for rather poor yields novel procedures for the automated radiosyntheses of [¹⁸F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly used radiosynthesisers. Using the novel one-step procedure the [¹⁸F]PSMA-1007 was produced in good radiochemical yields ranging from 30-70 % and synthesis times less than 55 minutes. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and at the same time high yielding production pathway for the next generation PSMA radioligand [¹⁸F]PSMA-1007. Actually it turned out that the radiosynthesis is as easily realised as the well-known [¹⁸F]FDG synthesis and thus transferable onto all currently available radiosynthesisers. Using the new procedures, clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

A specific HPLC method has been developed and validated for the determination of vanillyl butyl ether in cosmetic products. The extraction procedure with an isopropanol water 1:1 mixture is described. The method uses a RP-C-18 column with isocratic elution and a UV detector. The mobile phase consists of a mixture of acetonitrile and buffer (Na2HPO4 20mM in water) (30:70 v/v) with a variable flow rate. The method was validated with respect to accuracy, precision (repeatability and reproducibility), specificity and linearity. The procedure described here is simple, selective and reliable for routine quality control analysis and stability tests of commercially available cosmetic products.

The activity and cyclability of Cu-MOF-74 as catalyst was studied for the ligand-free C-O cross-coupling reaction of 4-nitrobenzaldehyde (NB) with phenol (Ph) to form 4-formyldiphenyl ether (FDE). Cu-MOF-74 is characterized by unsaturated copper sites in a highly porous metal-organic framework. The influence of solvent, reaction temperature, NB/Ph ratio, catalyst concentration and basic agent (type and concentration) were evaluated. High conversions were achieved at 120°C, 5 mol% of catalyst, NB/Ph ratio of 1:2, DMF as solvent and 1 equivalent of K2CO3 base. The activity of Cu-MOF-74 material was higher than other ligand-free copper catalytic systems tested in this study. This catalyst was easily separated and reused in five successive runs, achieving a remarkable performance without significant porous framework degradation. The leaching of copper species in the reaction medium was negligible. The O-arylation between NB and Ph took place only in the presence of Cu-MOF-74 material, being negligible without the solid catalyst.

One of the rare diseases throughout the world is Glycogen Storage Disease, which appears due to problems in glycogen metabolism. Among various subtypes of GSD, GSD Type 1a is the most abundant one of GSD Type 1, seen in approximately 80% and caused by different kinds of mutations in the Glucose-6-Phosphatase Catalytic Subunit (G6PC) gene in human chromosome 17q21. G6PC gene encodes for glucose-6-phosphatase (G6Pase) protein, which cleaves glucose-6-phosphate into glucose and inorganic phosphate (Pi), and GSD Type 1a patients fail to breakdown glucose-6-phosphate due to several mutations in the G6PC gene. In our study, we aim to create new therapeutic approaches for GSD 1a. We collected mutation data of 57 GSD Type 1a patients from Turkey. According to the data, 16 types of mutations were observed in the G6PC gene. Allele frequencies of these mutations are calculated as 59% for R83C/H, 11% for W160*, 7% for G270V, and 28% for others which have less frequency. Up to now, the tertiary protein structure of G6Pase has not been structured yet. To understand the possible impacts of these mutations, we statistically obtained possible tertiary structure predictions of G6Pase by running 5 different tools. At the end of the study, we suggest two effective and promising gene therapy methods for GSD Type 1a, Prime Editing for R83C/H mutations, and mRNA delivery for other mutations, in addition to a promising, commercially available drug suggestion for patients with W160*, W86*, and S15* mutations, although the drug belongs to another disease.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

Glucose-6-phosphatase (G6Pase), an enzyme found mostly in the kidneys and the liver, acting significant role of supplying glucose through starvation. This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups according to their type of anti diabetic therapy : (23) newly diagnosed group without therapy (Group1), (20) with metformin therapy (Group2) and (21) with metformin plus glibenclamide therapies( Group3). The study found that G-6-Pase activity is increased, thereby leading to an increase in endogenous glucose production (EGP) in patients with type 2 diabetes and, therefore FPG will increase. The result found that increasing G-6-Pase activity will increase the concentration of glucose in the blood and that will increase the long-term glycemic control (HbA1c%).

The objective of this study is to investigate the aquatic-toxic effects of glyoxal-containing cellulose ether with four different glyoxal concentrations (0, 1.4, 2.3 and 6.3%) in response to global chemical regulations, e.g., European Union Classification, Labeling and Packaging (EU CLP). Tests of the aquatic-toxic effects of glyoxal-containing cellulose ether on 11 freeze-dried microbial strains, Microcystis aeruginosa, Daphnia magna and zebrafish embryos were designed as an initial stage for toxicity screening, and were performed with the standardized toxicity test guidelines. Glyoxal-containing cellulose ether showed no significant toxic effects in the toxicity tests for the 11 freeze-dried microbial strains, Daphnia magna and zebrafish embryos. Alternatively, 6.3% glyoxal-containing cellulose ether led to more than a 60% reduction of Microcystis aeruginosa growth after 7 days of exposure. Approximately 10% developmental abnormalities (e.g., bent spine) in zebrafish embryos were also observed in the group exposed to 6.3% glyoxal-containing cellulose ether after 6 days of exposure. These results imply that <6.3% glyoxal-containing cellulose ether results in non-toxic effects on the acute toxicity of aquatic organisms. However, ≥6.3% glyoxal-containing cellulose ether may affect the health of aquatic organisms with long-term exposure. In order to better evaluate the eco-safety of cellulosic products contained in glyoxal, further studies regarding the toxic effects of glyoxal-containing cellulose ether with long-term exposure are required. The results from this study allow us to evaluate the auatic-toxic effects of glyoxal-containing cellulosic products, under EU chemical regulations, on the health of aquatic organisms.

The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

Arylmagnesium and -calcium reagents are easily accessible, however, ether degradation processes limit the storability especially of the calcium-based heavy Grignard reagents. Ortho-bound substituents with phosphanyl donor sites usually block available coordination sites and stabilize such complexes. The reaction of bromo-2,6-bis(diphenylphosphanylmethyl)benzene (1a) with magnesium in tetrahydrofuran yields [Mg{C₆H₃-2,6-(CH₂PPh₂)₂}₂] (2) after recrystallization from 1,2-dimethoxyethane. However, the similarly performed reduction of bromo- (1a) and iodo-2,6-bis(diphenylphosphanylmethyl)benzene (1b) with calcium leads to ether cleavage and subsequent degradation products. α-Deprotonation of THF yields 1,3-bis(diphenylphosphanylmethyl)benzene. Furthermore, the insoluble THF adducts of dimeric calcium diphenylphosphinate halides, [(thf)₃Ca(X)(µ-O₂PPh₂)]₂ [X = Br (3a), I (3b)], precipitate verifying ether decomposition and cleavage of P-C bonds. Ether adducts of calcium halides [such as [(dme)₂(thf)CaBr₂] (4)] form supporting the initial Grignard reaction and a subsequent Schlenk-type dismutation reaction.

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

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.

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.

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

According to some authors, the serum selenium level is strongly associated with the severity of liver diseases including liver cirrhosis. The aim of the study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines – interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in serum of 99 alcoholic liver cirrhosis patients divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Nanotechnology is an emerging field of modern science based on the use of nanoparticles (NPs) with a huge potential in many sectors, including nanomedicine. Their small size confers them unique properties because they are subject to physical laws that are in the middle between classical and quantum physics. In this context, NPs project plays a pivotal role because the composition, size, shape and surface proprieties need to be carefully considered for their optimal design and application. As reported in this review, NPs are classified in inorganic (metallic NPs; quantum dots; carbon-based nanostructures; mesoporous silica nanoparticles) and organic (liposomes and micelles, dendrimers and polymer nanoparticles) ones. Here, we report an accurate description of the potential of each NPs type focusing on their multiple areas of application like theranostics drug delivery, imaging, tissue engineering, antimicrobial techniques and nanovaccines, and therefore they represent a promise to revolutionize the new era of nanomedicine, especially in cancer research.

Starting from the environmental issues related to global warming, climate change and reduction of greenhouse gas emissions, this review paper describes how CO₂ recycling can represent a challenging strategy suitable to explore new concepts and opportunities for catalytic and industrial development. In this view, the production of dimethyl ether (DME) from catalytic hydrogenation of CO₂ appears as a viable technology, able to meet also the ever-increasing need for alternative environmentally-friendly fuels and energy carriers. Basic considerations on thermodynamic aspects controlling DME production from CO₂ are presented, then summarizing the main catalytic systems developed in such a field. Special attention is paid on the role assumed during last years by zeolite-based systems, either in the methanol-to-DME dehydration step or in the one-pot CO₂-to-DME hydrogenation. On the whole, the productivity of DME results significantly to be dependent on several catalyst features, linked not only to the metal-oxide phase responsible for CO₂ activation/hydrogenation, but also to specific properties of the zeolites (i.e., topology, porosity, surface area, acidity, interaction with active metals, distributions of metal particles, …) influencing activity and stability of hybridized bifunctional heterogeneous catalysts.

The alkylation of 1,1,2-trimethyl-1H-benzo[e]indole with 2-chloroacetamide, followed by work-up of the reaction mixture with a base and the subsequent treatment of a crude product with acetic acid gives 10a,11,11-trimethyl-10a,11-dihydro-8H-benzo[e]imidazo[1,2-a]indol-9(10H)-one. The structure assignments were based on data from ¹H, ¹³C and ¹⁵N NMR spectroscopy. The optical properties of the obtained compound were studied by UV-vis and fluorescence spectroscopy.

The premise regarding COVID-19 disease is that it is a spectrum which begins with infection with viral SARS-CoV-2 exposure via airborne or oral virus particles. The individual response to it depends on many factors including co-morbid conditions. An important aspect of SARS-CoV-2 virus infection is the cytokine storm that develops after the infection. The immuno-chemical chaos created in this cytokine storm is to the benefit of the virus. In this meta analysis the authors explore ways to let the cytokine storm die down by looking into the role of histamine. Histamine is a metabolic product of the essential aminoacid histidine. Histamine has 4 known receptors: H1, H2, H3 and H4. The immunoglobulines IgE and IgM are indicative for a COVID-19 infection. This immune response is related to inflammation. Inflammation, in turn, runs mainly via histamine after e.g. virus inoculation. The goal of the meta-study is to gather evidence to primarily block the H4 receptor (H4R) in gastrointestinal cells to diminish the cytokine overproduction in the $\approx$ 30\% of the patients suffering from gastrointestinal problems caused by SARS-CoV-2. Our concept is as follows. If we can strike a careful balance between hampering the gastrointestinal spreading of the virus and histamine antagonists to tackle the cytokine storm, then the natural immunity can later on come on line again and attack the virus without being led astray by cytokine chaos. We will concentrate on H4R but also look at H1R and H2R related effects. The proposed substances in our systemic approach can be balanced for an effective early treatment. The nature of our work is by its method and results theoretical. In that respect we also may note the structural chemistry indol skeleton resemblance among a number of different drugs.

The coronavirus disease 2019 (COVID-19) is now a global pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unlike other known coronaviruses, such as the Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 reveals new clinical, immunological, and pathologic features. The lymphocyte depletion, macrophage and neutrophil hyperactivation, cytokine dysregulation, thrombophilia, delayed antiviral response, and immune exhaustion are key immunological findings linked to the clinical progression of this disease. Understanding and identifying the underlying immunological basis of COVID-19 is crucial to designing effective therapies. Here, we provide an overview of immunopathogenesis driven by SARS-CoV-2 after its interactions with the immune system.

This study examines the improvement in coupled intercomparison project phase six (CMIP6) models against the predecessor CMIP5 in simulating mean and extreme precipitation over the East Africa region. The study compares the climatology of the precipitation indices simulated by the CMIP models with the CHIRPS dataset using robust statistical techniques for 1981 – 2005. The results display the varying performance of the general circulation models (GCMs) in the simulation of annual and seasonal precipitation climatology over the study domain. CMIP6-MME shows improved performance in the local annual mean cycle simulation with a better representation of two peaks, especially the MAM rainfall relative to its predecessor. Moreover, simulation of extreme indices is well captured in CMIP6 models relative to its predecessor. The CMIP6-MME performed better than the CMIP5-MME with lesser biases in simulating SDII, CDD, and R20mm over East Africa. Remarkably, most CMIP6 models are unable to simulate extremely wet days (R95p). A few CMIP6 models (e.g., NorESM2-MM and CNRM-CM6-1) depicts robust performance in reproducing the observed indices across all analyses. Conversely, OND season shows the overestimation of some indices (i.e., R95p, PRCPTOT), except for SDII, CDD, and R20mm. Consistent with other studies, the mean ensemble performance for both CMIP5/6 shows better performance due to the cancellation of some systematic errors in the individual models. Generally, the CMIP6 depicts improved performance in the simulation of MAM season akin CMIP5 models. However, the new model generation is still marred with uncertainty, thereby depicting substandard performance over the East Africa domain. This calls for further investigation of attribution studies into the sources of persistent systematic biases and a prerequisite for identifying individual models with robust features that can accurately simulate observed patterns for future usage.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been found to be modulators of immune function. Additionally, they may affect the growth of colorectal cancer (CRC). With the advent of novel treatment approaches in oncology targeting immune checkpoint inhibition and aiming to boost the immune response against tumors the exact role of n-3 and n-6 PUFA in inflammation as well as in CRC needs to be re-evaluated in order to understand potential interactions with these new treatment paradigms. Interestingly, for the cyclooxygenase (COX) inhibitor aspirin a possible synergistic effect together with a PD1-Ligand antibody has been shown. However, could n-3 PUFA be disadvantageous in the context of immune tumor therapy due to an immune suppressive effect that has been described for these fatty acids in the past, or could they also enhance the effect of immune checkpoint inhibition? In this paper, we discuss the current data regarding the immune modulatory as well as the anti-CRC effect of n-3 PUFA. Arguing towards an immune-activating effect of n-3 PUFA, we demonstrate the results of a pilot study. Here, we show that incubation of human peripheral blood mononuclear cells (PBMCs) with the n-3 PUFA docosahexaenoic acid (DHA) significantly decreases CRC-cell supernatant-triggered secretion of IL-10 and increases secretion of TNF-a, while the omega-6 polyunsaturated fatty acid (n-6 PUFA) arachidonic acid (AA) reduced TNF-a secretion. These changes in cytokine secretion upon incubation with DHA demonstrate a possible enhancing effect of n-3 PUFA on an anti-tumor immune response.

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL^-1 s^-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, I have hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of ACE2 pathway for SARS-CoV-2 patients who are suffering from critical, advanced and untreatable stages of the disease.

For more than one hundred years, scientists dispute the correct interpretation of Lorentz transformations within the framework of the special theory of relativity of Albert Einstein. On the one hand, the changes in length, time and mass with increasing velocity are interpreted as apparent due to the observer dependence within special relativity. On the other hand, real changes are described corresponding to the experimental evidence of mass increase in particle accelerators or of clock delay. This ambiguity is accompanied by an ongoing controversy about valid Lorentz-transformed thermodynamic quantities such as entropy, pressure and temperature. In this paper is shown that the interpretation problem of the Lorentz transformations is genuinely anchored within the postulates of special relativity and can be solved on the basis of the thermodynamic approach of matter-energy equivalence, i.e. an energetic distinction between matter and mass. It is suggested that the velocity-dependent changes in state quantities are real in each case, in full agreement with the experimental evidence.

A series of Si-bearing MgAl₂O₄-spinels were synthesized at 1500-1650 °C and 3–6 GPa. These spinels had SiO₂ contents up to ~1.03 wt%, and showed a substitution mechanism of Si⁴⁺ + Mg²⁺ = 2Al³⁺. Unpolarized Raman spectra were collected from polished single grains, and displayed a set of well-defined Raman peaks at ~610, 823, 856 and 968 cm^-1 which had not been observed before. Aided with the Raman features of natural Si-free MgAl₂O₄-spinel, synthetic Si-free MgAl₂O₄-spinel, natural low quartz, synthetic coesite, synthetic stishovite and synthetic forsterite, we infer that these Raman peaks should belong to the SiO₄ groups. The relations between the Raman intensities and SiO₂ contents of the Si-bearing MgAl₂O₄-spinels suggest that at some P-T conditions some Si must adopt the M-site. Unlike the SiO₄ groups with very intense Raman signals, the SiO₆ groups are largely Raman-inactive. We have further found that the Si cations primarily appear on the T-site at P-T conditions ≤ ~3–4 GPa and 1500 °C, but attain a random distribution between the T-site and M-site at P-T conditions ≥ ~5–6 GPa and 1630–1650 °C. This Si-disordering process observed for the Si-bearing MgAl₂O₄-spinels hints that similar Si-disordering might happen to the (Mg,Fe)₂SiO₄-spinels (ringwoodite), the major phase in the lower part of the mantle transition zone of the Earth and the index mineral for the very strong shock stage experienced by extraterrestrial materials. The likely consequences have been explored.

Poor understanding of malnutrition burden is a common reason for not prioritizing the care of small and nutritionally at-risk infants aged under-six months (infants u6m). We aimed to estimate the anthropometric deficit prevalence in infants u6m attending health centres, using the Composite Index of Anthropometric Failure (CIAF); and to assess the overlap of different individual indicators. We undertook a two-week survey of all infants u6m visiting each of 18 health centres in two zones of the Oromia region, Ethiopia. We measured weight, length, and MUAC (Mid upper arm circumference); and calculated weight-for-length (WLZ), length-for-age (LAZ), and weight-for-age z-scores (WAZ). Overall, 21.7% (95% CI: 19.2; 24.3) of infants u6m presented CIAF and of these, 10.7% (95% CI: 8.93; 12.7) had multiple anthropometric deficits. Low MUAC overlapped with 47.5% (95% CI: 38.0; 57.3), 43.8% (95% CI: 34.9; 53.1), and 42.6% (95% CI: 36.3; 49.2) of the stunted, wasted and CIAF prevalence, respectively. Underweight overlapped with 63.4% (95% CI: 53.6; 72.2), 52.7% (95% CI: 43.4; 61.7), and 59.6% (95% CI: 53.1; 65.9) of the stunted, wasted and CIAF prevalence, respectively. Anthropometric deficits, single and multiple, are prevalent in infants attending health centres. WAZ overlaps more with other forms of anthropometric deficits than MUAC.

Injuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to OA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible). Right knee joints of the mice were injured using a non-invasive tibial compression injury model that closely mimics ACL rupture in humans and global gene expression was quantified before and at 1-day, 1-week, and 2-weeks post-injury using RNA-seq. Following injury, STR/ort displayed severe cartilage degeneration while MRL/MpJ had little cartilage damage. Gene expression analysis suggested that prolonged inflammation and elevated catabolic activity in STR/ort injured joints, compared to the other two strains may be responsible for the severe PTOA phenotype observed in this strain. MRL/MpJ had the lowest expression values for several inflammatory cytokines and catabolic enzymes activated in response to ACL injury. Furthermore, we identified several genes highly expressed in MRL/MpJ compared to the other two strains including B4galnt2 and Tpsab1 which may contribute to enhanced healing in the MRL/MpJ. Overall, this study has increased our knowledge of early molecular changes associated with PTOA development.

Drinking water contamination of lead from various environmental sources, leaching consumer products and intrinsic water-pipe infrastructure is still today a matter of great concern. Therefore, new highly sensitive and convenient Pb²⁺ measurement schemes are necessary, especially for in-situ measurements at a low-cost. Within this work dye/ionophore/Pb²⁺ co-extraction and effective water phase de-colorization was utilized for highly sensitive lead measurements and sub-ppb naked-eye detection. A low-cost ionophore Benzo-18-Crown-6-ether was used, and a simple test-tube mix and separate procedure was developed. Instrumental detection limits were in the low ppt region (LOD=3, LOQ=10), and naked-eye detection was 500 ppt. Note, however, that this sensing scheme still has improvement potential as concentrations of fluorophore and ionophore were not optimized. Artificial tap-water samples, leached by a standardized method, demonstrated drinking water application. Implications for this method are convenient in-situ lead ion measurements.

Two 2,2':6',2''-terpyridine-based Schiff bases (TPySSB and TPySB) have been synthesized. The TPySSB shows remarkable selective ‘off-on’ fluorescence for Al³⁺ by photoinduced electron transfer (PET) mechanism of sensing. Chemosensor TPySSB binds Al³⁺ in a 1:2 ratio with an association constant 6.8×10⁵ (R²=0.98) and this 1:2 stoichiometric model is established on Job’s plot and ¹H NMR. Compared TPySSB and TPySB, it is of great importance of the existence of salicylidene unit due to its strong binding abilities of both phenol and C=N structure to the Al³⁺.

The search for improved therapeutic approaches to breast cancer are still on going. Breast tumor kinase (BRK, also known as PTK6) is one of the targets, it is highly expressed in breast carcinomas while displaying low or no expression in the normal mammary gland, which hints at the oncogenic role of this enzyme in breast cancer. In these twenty years, an increasing number of studies have focused on understanding the cellular roles of BRK in breast cancers. This review outlines the advances made towards understanding the cellular and physiological role of BRK, the molecular and chemical inhibitors and its therapeutic significance in breast cancer.

“Non-Locality is most naturally incorporated into a theory in which there is a special frame of reference. One possible candidate for this special frame of reference is the one in which the Cosmic Microwave Background (CMB) is isotropic. However, other than the fact that a realistic interpretation of quantum mechanics requires a preferred frame and the CMB provides us with one, there is no readily apparent reason why the two should be linked” (L. Hardy). Starting from this remark we first argue that, given the present view of the vacuum, the basic tenets of Quantum Field Theory cannot guarantee that Einstein Special Relativity, with no preferred frame, is the physically realized version of relativity. Then, to try to understand the nature of the hypothetical preferred Σ−frame, we consider the so called ether-drift experiments, those precise optical measurements that try to detect in laboratory a small angular dependence of the two-way velocity of light and then to correlate this angular dependence with the direct CMB observations with satellites in space. By considering all experiments performed so far, from Michelson-Morley to the present experiments with optical resonators, and analyzing the small observed residuals in a modern theoretical framework, the long sought Σ− frame tight to the CMB naturally emerges. Finally, if quantum non-locality reflects some effect propagating at vastly superluminal speed vQI→∞, its ultimate origin could be hidden somewhere in the infinite speed cs→∞ of vacuum density fluctuations.

E-commerce businesses employ recommender models to assist in identifying a personalized set of products for each visitor. To accurately assess the recommendations’ influence on customer clicks and buys, three target areas—customer behavior, data collection, user-interface —will be explored for possible sources of erroneous data. Varied customer behavior misrepresents the recommendations’ true influence on a customer due to the presence of B2B interactions and outlier customers. Non-parametric statistical procedures for outlier removal are delineated and other strategies are investigated to account for the effect of a large percentage of new customers or high bounce rates. Subsequently, in data collection we identify probable misleading interactions in the raw data, propose a robust method of tracking unique visitors, and accurately attributing the buy influence for combo products. Lastly, user-interface issues discuss the possible problems caused due to the recommendation widget’s positioning on the e-commerce website and the stringent conditions that should be imposed when utilizing data from the product listing page. This collective methodology results in an exact and valid estimation of the customer’s interactions influenced by the recommendation model in the context of standard industry metrics such as Click-through rates, Buy-through rates, and Conversion revenue.

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

For the majority of lipophilic compounds adipose tissue is traditionally considered as storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposures may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) is a group of lipophilic flame retardants found in majority of human samples in North America. Their ability to alter physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using RNA-seq approach with subsequent bioinformatic analysis. Genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism were altered in expression in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.

Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signalling pathway and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodelling and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukaemia, and iron overload is compounded by blood transfusions given to improve anaemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumour activity against leukaemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

Autism Spectrum disorder (ASD) and intellectual disability (ID) are the most frequent develop-mental disorders with a prevalence between 3% and 5% of the population. In addition, both ASD and ID can be found in the same patient. Mutations in several genes involved in the epigenetic regulation of gene expression have been linked to different ID associated with ASD features including alterations of the ly-sine-acetyltransferase 6A (KAT6A) gene in KAT6A syndrome. KAT6A enzyme participates in a wide range of critical cellular functions such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiolog-ical alterations in fibroblasts derived from three patients harboring KAT6A mutations. We ad-dressed survival in stress medium, histone acetylation, protein expression patterns and tran-scriptome analysis as well as cell bioenergetics. In addition, we evaluated the therapeutic effec-tiveness of epigenetic modulators and mitochondrial boosting agents such as pantothenate and L-carnitine in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly correct the mutant phe-notype in cellular models of KAT6A syndrome.

Recent times have witnessed an increasing number of countries and private firms pledging carbon neutrality by mid-century. Whilst representing a significant improvement in intentions to tackle climate change, such pledges lack substance and structure. For instance, individual pledges lack coordination and aggregation among peers, while strategies and measures to achieve ambitious targets are largely absent. Moreover, current disagreements obstructing progress in international climate change negotiations further undermine the reliability of carbon neutrality objectives. Effective international policies are needed to foster aggregate mitigation ambitions and the creation of adequate supporting mechanisms. This theoretical paper describes a governance innovation aimed at overcoming such shortfalls and disagreements through a unifying yet customizable pathway towards carbon neutrality. It does so by first outlining a political governance framework based on a climate club interpretation of Article 6 of the Paris Agreement. Secondly, it proposes carbon emission mitigation effort sharing on a per capita basis to ensure efficiency, equity and political feasibility. Thirdly, this paper describes how the supply of certified mitigations of carbon emissions required to satisfy effort sharing-based demand can be assetized as carbon credits by operationalizing Article 6 as a joint certification mechanism. The resulting governance architecture for managing demand and supply of mitigations shifts efforts to tackle climate change from a ‘problem-driven’ cost approach to ‘opportunity-driven’ value creation pathways towards carbon neutrality.

This study aimed to determine whether camelina oil is safe for use in canine diets, using canola oil and flax oil as controls as they are similar and generally regarded as safe (GRAS) for canine diets. Thirty privately-owned adult dogs of various breeds (17 females; 13 males), with an average age of 7.2 ± 3.1 years (mean ± SD) and body weight (BW) of 27.4 ± 14.0 were used. After a 4-week wash-in period using sunflower oil and kibble, dogs were blocked by breed, age, and size, and randomly allocated to one of three treatment oils (camelina (CAM), flax (FLX), or canola (OLA)) at a level of 8.2 g oil/100g total dietary intake. Body condition score (BCS), BW, food intake (FI), and hematological and select biochemical parameters were measured at various timepoints over a 16-week feeding period. All data were analyzed with ANOVA using PROC GLIMMIX of SAS. No biologically significant differences were seen between treatment groups for BW, BCS, FI, hematological and biochemical results. Statistically significant differences noted among some serum biochemical results were considered small and due to normal biological variation. These results support a conclusion that camelina oil is safe for use in canine nutrition.

Natural products are an important source of antibacterial agents. Canthin-6-one alkaloids have displayed potential antibacterial activity based on our previous work. In order to improve the activity, twenty-two new 3-N-benzylated 10-methoxy canthin-6-ones were designed and synthesized through quaternization reaction. The in vitro antibacterial activity against three bacteria was evaluated by double dilution method. Four compounds (6f, 6i, 6p and 6t) displayed 2-fold superiority (minimum inhibitory concentration (MIC) = 3.91 µg/mL) against agricultural pathogenic bacteria R. solanacearum and P. syringae than agrochemical propineb. Moreover, the structure–activity relationships (SARs) were also carefully summarized in order to guide the development of antibacterial canthin-6-one agents.

The ascomycete Trichoderma atroviride is well known for its mycoparasitic lifestyle. Similar to other organisms, light is an important cue for T. atroviride. However, besides triggering of conidiation, little is known on the physiological responses of T. atroviride to light. In this study, we analyzed how cultivation under different light wavelengths and regimes impacted the behavior of two T. atroviride wild-type strains, IMI206040 and P1. While colony extension of both strains was slightly affected by light, massive differences in the photoconidation response between the two strains became evident. T. atroviride P1 colonies conidiated under all conditions tested including growth in complete darkness, while IMI206040 required white, blue or green light to trigger asexual reproduction. Interestingly, deletion of the stress-activated MAP kinase-encoding gene tmk3 abolished the ability of strain P1 to conidiate in red and yellow light as well as in darkness. Furthermore, light-dependent differences in the mycoparasitic activity of T. atroviride and in the biosynthesis of the secondary metabolite 6-pentyl--pyrone (6-PP) became evident. 6-PP production was highest upon dark incubation while light, especially exposure to white light as light/dark cycles, had an inhibitory effect on its biosynthesis. We conclude that the response of T. atroviride to light is strain-dependent and impacts differentiation, mycoparasitism and 6-PP production and hence should be considered in experiments testing the mycoparasitic activity of these fungi.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Introduction: In rural communities in regions with limited resources the provision of clean water remains challenging. Fecal contamination of water is very common and results in a high incidence of diarrhea, subsequent acute kidney injury and mortality particularly in the very young and old. Membrane filtration is a practical solution to this problem and recent innovation allows membrane filtration using recycled hemodialyzers. We, Easy Water for Everyone, have quantified the systematic effect on health outcomes. Material and Methods: Between 02/2018 and 12/2018, 4 communities in rural Ghana (in the Greater-Accra region) were each provided with a high-volume membrane filtration devices (NUF 500; NuFiltration using recycled hemodialyzers). Health data from montly household surveys and chart review in local healthcare facilities were collected with approval from Ghana Health Services. Specifically, data was collected on gastrointestinal disease, acute kidney injury and therapeutic interventions. Incidence rates for a five-months period before and after implementation of the device were calculated and compared to rates during the same months from 4 neighboring communities that were not yet provided with the device. Results: Acceptance of the devices and the purified water in the studied villages was good and self-reported data of 1130 villagers over 10 months from 9 studied communities in rural Ghana (11% younger than 5 years and 14 % older than 65 years) were included in this analysis. The overall monthly incidence rate of diarrhea showed a decline following the implementation of the device in the 4 study villages from a mean of 0.18 to 0.05 cases per person-month for a reduction in rates by 72% (rate ratio = 0.27). By contrast, the control group of 4 villages in the same region showed no decline in mean rates during the same months as the study period with mean rates changing not significantly from 0.11 to 0.08 cases per person-month. Discussion: Provision of a hemodialyzer membrane filtration device markedly improves health outcomes as measured by diarrhea incidence within rural communities. While our data awaits confirmation in a larger population and further statistical analyses accounting for village characteristics, seasonality and subject demographics, the obvious decline in incidence rates supports widespread use of hemodialyzer membrane filtration devices, particularly in rural regions. Rollout of the device in further sites will likely increase our understanding in terms of risk and other preventive factors modifying the incidence of diarrhea and subsequent acute kidney injury.

Most of the commonly used Ionic Liquids (ILs) contain bulky organic cations with suitable anions. With our COMPLET (Concept of Melting Point Lowering due to Ethoxylation), we follow a different approach. We use simple, low-toxic, cheap and commercially available anions of the type Cx(EO)yCH2COO– to liquefy presumably any simple metal ion, independently of its charge. In the simplest case, the cation can be sodium or lithium, but synthesis of Ionic Liquids is also possible with cations of higher valences such as transition or rare earth metals. Anions with longer alkyl chains are surface active and form surface active ionic liquids (SAILs), which combine properties of ionic and nonionic surfactants at room temperature. They show significant structuring even in their pure state, i.e. in the absence of water or any other added solvent.

Remote sensing is one of the modern methods that have significantly developed over the last two decades and nowadays provides a new means for forest monitoring. High spatial and temporal resolutions are demanded for accurate and timely monitoring of forests. In this study multi-spectral Unmanned Aerial Vehicle (UAV) images were used to estimate canopy parameters (definition of crown extent, top and height as well as photosynthetic pigment contents). The UAV images in Green, Red, Red-Edge and NIR bands were acquired by Parrot Sequoia camera over selected sites in two small catchments (Czech Republic) covered dominantly by Norway spruce monocultures. Individual tree extents, together with tree tops and heights, were derived from the Canopy Height Model (CHM). In addition, the following were tested i) to what extent can the linear relationship be established between selected vegetation indexes (NDVI and NDVIred edge) derived for individual trees and the corresponding ground truth (e.g., biochemically assessed needle photosynthetic pigment contents), and ii) whether needle age selection as a ground truth and crown light conditions affect the validity of linear models. The results of the conducted statistical analysis show that the two vegetation indexes (NDVI and NDVIred edge) tested here have a potential to assess photosynthetic pigments in Norway spruce forests at a semi-quantitative level, however the needle-age selection as a ground truth was revealed to be a very important factor. The only usable results were obtained for linear models when using the 2nd year needle pigment contents as a ground truth. On the other hand, the illumination conditions of the crown proved to have very little effect on the model’s validity. No study was found to directly compare these results conducted on coniferous forest stands. This shows that there is a further need for studies dealing with a quantitative estimation of the biochemical variables of nature coniferous forests when employing spectral data acquired by the UAV platform at a very high spatial resolution.

Human milk fat is a concentrated source of energy and provides essential and long chain polyunsaturated fatty acids. According to previous experiments, human milk fat is partially lost during continuous enteral nutrition. However, these experiments were done over relatively short infusion times, and a complete profile of the lost fatty acids was never measured. Whether this lost happens considering longer infusion times or if some fatty acids are lost more than others remain unknown. Pooled breast milk was infused through a feeding tube by a peristaltic pump over a period of 30 minutes and 4, 12 and 24 hours at 2 ml/hour. Adsorbed fat was extracted from the tubes, and the fatty acid composition was analyzed by Gas chromatography-mass spectrometry. Total fat loss (average fatty acid loss) after 24 hours was 0.6 ± 0.1%. Short-medium chain (0.7%, p=0.15), long chain (0.6%, p=0.56) saturated (0.7%, p=0.4), monounsaturated (0.5%, p=0.15), polyunsaturated fatty (0.7%, p=0.15), linoleic (0.7%, p=0.25), and docosahexaenoic acids (0.6%, p=0.56) were not selectively adsorbed to the tube. However, very long chain fatty (0.9%, p=0.04), alpha-linolenic (1.6%, p=0.02) and arachidonic acids (1%, p=0.02) were selectively adsorbed and therefore lost in a greater proportion than other fatty acids. In all cases, the magnitude of the loss was clinically low.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.

We describe a selective and sensitive fluorescence platform for the detection of trinitrophenol (TNP) based on competitive host–guest recognition between pyridine-functionalized pillar[6]arene (PCP6) and probe (acridine orange, AO) that used PCP6-functionalized reduced graphene (PCP6-rGO) as the receptor. TNP is an electron-deficient and negative molecule which is captured by PCP6 via electrostatic interactions and π-π interactions. Therefore, a selective and sensitive fluorescence sensor for TNP detection is developed. It has a low detection limit of 0.0035 μM (S/N=3) and a wider linear response of 0.01−5.0 and 5.0−125.0 for TNP. The sensing platform is also used to test TNP in two water and soil samples with satisfying results. This suggests that this approach has potential applications for the determination of TNP.

Background: Persistent up regulation of NF-κB leads to chronic inflammation and subsequent microglial activation and takes neurons towards death by activating death receptor domains and the p53 pathway. Thus, inhibition of NF-κB may lead to more effective treatment for Parkinson’s disease. Therefore, we have used mangiferin, specific inhibitor of NF-κB in this study. Method: The study utilized male Wistar rats weighing 200-250 gm (n=8 in each group). Stereotactic surgery of rats was done to induce 6-OHDA lesioning in rats. On day 42, rats were subjected to behavioural studies to evaluate effect of mangiferin and their brains were taken out after euthanasia to perform biochemical and molecular studies. Results: Mangiferin significantly increases locomotor parameters in 6-OHDA lesioned rats. It also decreases activity of Cyclooxygenase enzyme which then leads to decrease concentration of inflammatory cytokines. Microglial inflammation was also substantially reduced by reducing MPO concentration. Oxidative stress burden was also reduced after treatment with mangiferin as indicated by increase in Total Antioxidant Capacity, SOD and Catalase and reduction in concentration of MDA. Treatment with mangiferin also reduces burden of oxidative stress by increasing the activity of NRF2/ARE pathway. Activity of Caspase 3 and 9 was also significantly reduced after treatment with mangiferin. Significant decrease in activity of both Cox1 and Cox 2 was also observed. Maximum improvement in all parameters was observed in rats treated with grouping of mangiferin 45mg.kg-1 and levodopa 10mg.kg-1. Treatment with levodopa alone has no significant effect on biochemical and molecular parameters though it significantly improves behavioural parameters. Conclusion and Implications: Results of this study suggest that mangiferin has protective effect in hemi-parkinsonian rats by inhibiting NF-κB. Current treatment of Parkinson’s disease does not target the underlying problem of the disease. Therefore, combination therapy of mangiferin and levodopa can be helpful in better management of Parkison’s.

Background. The characterization of new biomarkers of COVID-19 is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium and magnesium in COVID-19. Aims: To measure sRAGE, ACE2, interleukin (IL)-6, IL-10, CRP, calcium, magnesium, and albumin in COVID-19 patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2, IL-6, IL-10, CRP using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 patients and 30 healthy controls.Results. COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients with calcium being the most important predictor followed by IL-6, and CRP. COVID-19 patients with CCTAs showed lower SpO₂ and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.Conclusion. The results show that immune-inflammatory and RAGE pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19.

I present an experimental paradigm to explore the interpersonal dynamics generating a collective mind. I hypothesized that collective organization is based on dual interpersonal modes: (1) symmetrical and (2) anti‑symmetrical. I specified the geometric topology of these modes by detecting the spatiotemporal patterns that embed cooperative agents in a three‑dimensional matrix. I found that the symmetrical mode is executed automatically and without guidance. Conversely, the anti‑symmetrical mode required explicit direction and recruited attention for execution. I demonstrate that self‑other mirror‑symmetry stabilized group dynamics, enabled fast and efficient symmetrical imitation that optimized information transmission, whereas anti‑symmetrical imitation was comparatively slow, inefficient, and unstable. I determined that the anti‑symmetrical mode spontaneously transitioned to the symmetrical mode under perturbations. Crucially, this renormalization mechanism never transitioned from symmetrical to anti‑symmetrical. These self-organizing dynamics speak to interpersonal symmetry‑breaking. In the present work, spontaneous group choice mandated that agents synchronize cooperative cycles in symmetrical space under internal or external perturbations. I provide examples to illustrate that this self-regulating pullback attractor manifests in invertebrates and vertebrates alike. I conclude by suggesting that inter‑agent symmetry provides the social stability manifold through which attention-driven interactions enable intrapersonal and interpersonal change.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

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.

Microplastics (MPs) quantification in benthic marine sediments is typically performed by time-consuming and moderately accurate mechanical separation and microscopy detection. In this paper we describe the results of our innovative Polymer Identification and Specific Analysis (PISA) of microplastic total mass, previously tested on either less complex sandy beach sediment or less demanding (because of the high MPs content) wastewater treatment plant sludges, applied to the analysis of benthic sediments from a sublittoral area north-west of Leghorn (Tuscany, Italy). Samples were collected from two shallow sites characterized by coarse debris in a mixed seabed of Posidonia oceanica, and by a very fine silty-organogenic sediment, respectively. After sieving at &lt;2 mm the sediment was sequentially extracted with selective organic solvents and the two polymer classes polystyrene (PS) and polyolefins (PE and PP) were quantified by pyrolysis-GC/MS. A contamination in the 8-65 ppm range by PS could be accurately detected. Acid hydrolysis on the extracted residue to achieve total depolymerization of all natural and synthetic polyamides, tagging of all aminated species in the hydrolyzate with a fluorophore, and reversed-phase HPLC (RP-HPLC) analysis, allowed to quantify within the 137-1523 ppm range the individual mass of contaminating Nylon 6 and Nylon 6,6, based on the detected amounts of the respective monomeric amines 6-aminohexanoic acid (AHA) and hexanediamine (HMDA). Finally, alkaline hydrolysis of the residue from acid hydrolysis followed by RP-HPLC analysis of the purified hydrolysate showed contamination by polyethylene terephthalate (PET) in the 12.1-2.7 ppm range, based on the content of its comonomer, terephthalic acid.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the molecular characteristics of the HDAC6 protein, as well as its overexpression in CML leukemic stem cells, which make it a promising therapeutic target for the treatment of CML.

Background: Cytokines are multifunctional glycoproteins playing a vital role in the tumor microenvironment and in the progression of breast cancer. The immune responses in the tumors restrained by pro- and anti-inflammatory cytokine expressions could be influenced by genetic polymorphisms. Hence, the present study evaluated the contribution of IL6 (rs1800797, rs1800796, and rs1800795), and IL18 (rs1946518, rs187238, and rs549908) genotypes and its haplotypes with risk and progression of breast cancer in south Indian population. Methods: The polymorphisms of IL6 gene -597G>A, -572G>C, -174G>C and IL18 gene -607C>A, -137G>C, and 105A>T were genotyped through PCR-RFLP and As-PCR assays in blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression and Kaplan-Meier analyses for the obtained data. Results: The frequency of AA genotype & A-allele of IL6 -597G>A, and CC genotype & C allele of IL6 -174G>C polymorphism was higher in breast cancer patients and was found to be significantly associated with TNM staging, late (advanced) stage, metastasis, etc. While, CG and GG genotypes of IL6 -572 C>G polymorphism had a protective role against breast cancer. Further, IL18 -607C>A, -137G>C & 105A>T polymorphisms were found to be associated with lobular carcinoma subtype, PR-ve and HER2+ve breast cancer patients. Perfect LD was observed between all SNPs of IL6 & IL18 genes under study; G-C-C, A-G-G and A-C-C haplotype combination of IL6 genes had conferred 2.09, 2.25 and 4.72 folds risk for breast cancer respectively. In survival analysis, we observed that the C allele of rs 1800795 was found to be significantly associated with 5years overall survival in breast cancer subjects. Conclusions: Overall, our results suggest the importance of genotypic and haplotype analysis of IL6, and IL18 gene variants in progression and risk identification of breast cancer.

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Stabilized melanocortin analog peptide ACTH(6-9)PGP (FRWGPGP) possess a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we studied the pro-proliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6-9 (FRWG) linked with the peptide Prolyl-Glycyl-Proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN. The mechanism of its action was the modu-lation of proliferation-related (NF-kB and Nrf-2) and antioxidant-related (HO-1, Nqo1, Gclc) genes and apoptosis decrease.

This paper presents the values of several mechanical characteristics for two blends: H (60% PP + 12% PA6 + 8% EPDM + 20% Polybond 3200) and G (20% PP + 42% PA6 + 28% EPDM + 10% Polybond 3200) (%wt), comparing them to those of PP (polypropylene) and PA6 (polyamide 6). The adding of EPDM (ethylene propylene diene monomer rubber) and Polybond 3200 help reducing the disadvantages of simple blends made of PP+PA6, when the PA6 concentration allows for having a PA6 matrix with droplets of PP. SEM analysis helps for understanding the performance of material G as compared to the neat polymers. EDX analysis proved that there was a matrix inversion, material H having a PP matrix and material G a matrix made of PA6 with droplets of PP. Strain at break for PP and material H were proved to be insensitive to test speed, but materials G and PA6 had large value for strain at break and energy at break for v = 10 mm/min. Taking at basis the values for polyamide 6 (PA6), material G has greater values for energy at break: with 97.8% for v = 10 mm/min, with 29.5% for v= 250 mm/min and with 98% for 1000 mm/min, without exhibiting the micro and macro cavitation of PA6. This means that the recipe, the technology and the mechanical characteristics make material G a potential candidate for applications where a low and moderate impact resistant material is required.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare and potentially life-threatening systemic drug reaction with skin involvement. We present the unusual case of DRESS in a 16-year-old male that was treated with TMP-SMX for acne and was initially misdiagnosed with Steven Johnson Syndrome. Our case serves as an example to healthcare providers treating adverse drug reactions to having a high clinical suspicion for DRESS as delay in diagnosis and treatment can result in disseminated disease and higher patient mortality risk.

Fire-tolerant eucalypt forests of south eastern Australia are assumed to fully recover from even the most intense fires but surprisingly very few studies have quantitatively assessed that recovery. Accurate assessment of horizontal and vertical attributes of tree crowns after fire is essential to understand the fire’s legacy effects on tree growth and on forest structure. In this study, we quantitatively assessed individual tree crowns 8.5 years after a 2009 wildfire that burnt extensive areas of eucalypt forest in temperate Australia. We used airborne lidar data validated with field measurements to estimate multiple metrics that quantified the cover, density, and vertical distribution of individual-tree crowns in 51 plots of 0.05 ha in fire-tolerant eucalypt forest across four wildfire severity types (unburnt, low, moderate, high). Significant differences in the field-assessed mean height of fire scarring as a proportion of tree height, and in the proportions of trees with epicormic (stem) resprouts were consistent with the gradation in fire severity. Linear mixed-effects models indicated persistent effects of both moderate- and high-severity wildfire on tree crown architecture. Trees at high-severity sites had significantly less crown projection area and live crown width as a proportion of total crown width than those at unburnt and low-severity sites. Significant differences in lidar-based metrics (crown cover, evenness, leaf area density profiles) indicated that tree crowns at moderate- and high-severity sites were comparatively narrow and more evenly distributed down the tree stem. These conical-shaped crowns contrasted sharply with the rounded crowns of trees at unburnt and low-severity sites, and likely influenced both tree productivity and the accuracy of biomass allometric equations for nearly a decade after the fire. Our data provide a clear example of the utility of airborne lidar data for quantifying the impacts of disturbances at the scale of individual trees. Quantified effects of contrasting fire severities on the structure of resprouter tree crowns provide a strong basis for interpreting post-fire patterns in forest canopies and vegetation profiles in lidar and other remotely-sensed data at larger scales.

Direct Behavior Rating (DBR) as a behavioral progress monitoring tool can be designed as longitudinal assessment with only short intervals between measurement points. The reliability of these instruments has been evaluated mostly in observational studies with small samples based on generalizability theory. However, for standardized use in the pedagogical field, a larger and broader sample is required in order to assess measurement invariance between different participant groups and over time. Therefore, we constructed a DBR with multiple items to measure the occurrence of specific externalizing and internalizing student classroom behaviors on a Likert scale (1 = never to 7 = always). In a pilot study, two trained raters observed 16 primary school students and rated the student behavior over all items with a satisfactory reliability. In the main study, 108 regular primary school students, 97 regular secondary school students and 14 students in a clinical setting were rated daily over one week (five measurement points). IRT analyses confirmed the instrument’s technical adequacy, and latent growth models demonstrated the instrument’s stability over time. Further development of the instrument and study designs to implement DBRs are discussed.

The paper considers the symmetries of a bit of information corresponding to one, two or three qubits of quantum information and identifiable as the three basic symmetries of the Standard model, U(1), SU(2), and SU(3) accordingly. They refer to “empty qubits” (or the free variable of quantum information), i.e. those in which no point is chosen (recorded). The choice of a certain point violates those symmetries. It can be represented furthermore as the choice of a privileged reference frame (e.g. that of the Big Bang), which can be described exhaustively by means of 16 numbers (4 for position, 4 for velocity, and 8 for acceleration) independently of time, but in space-time continuum, and still one, 17th number is necessary for the mass of rest of the observer in it. The same 17 numbers describing exhaustively a privileged reference frame thus granted to be “zero”, respectively a certain violation of all the three symmetries of the Standard model or the “record” in a qubit in general, can be represented as 17 elementary wave functions (or classes of wave functions) after the bijection of natural and transfinite natural (ordinal) numbers in Hilbert arithmetic and further identified as those corresponding to the 17 elementary of particles of the Standard model. Two generalizations of the relevant concepts of general relativity are introduced: (1) “discrete reference frame” to the class of all arbitrarily accelerated reference frame constituting a smooth manifold; (2) a still more general principle of relativity to the general principle of relativity, and meaning the conservation of quantum information as to all discrete reference frames as to the smooth manifold of all reference frames of general relativity. Then, the bijective transition from an accelerated reference frame to the 17 elementary wave functions of the Standard model can be interpreted by the still more general principle of relativity as the equivalent redescription of a privileged reference frame: smooth into a discrete one. The conservation of quantum information related to the generalization of the concept of reference frame can be interpreted as restoring the concept of the ether, an absolutely immovable medium and reference frame in Newtonian mechanics, to which the relative motion can be interpreted as an absolute one, or logically: the relations, as properties. The new ether is to consist of qubits (or quantum information). One can track the conceptual pathway of the “ether” from Newtonian mechanics via special relativity, via general relativity, via quantum mechanics to the theory of quantum information (or “quantum mechanics and information”). The identification of entanglement and gravity can be considered also as a ‘byproduct” implied by the transition from the smooth “ether of special and general relativity’ to the “flat” ether of quantum mechanics and information. The qubit ether is out of the “temporal screen” in general and is depicted on it as both matter and energy, both dark and visible.

Electricity demand forecasting has been a real challenge for power system scheduling in the different levels of the energy sectors. Various computational intelligence techniques and methodologies have been employed in the electricity market for load forecasting; although, scant evidence is available about the feasibility of each of these methods considering the type of data and other potential factors. This work introduces several scientific, technical rationale behind intelligent forecasting methods, based on the work of previous researchers in the field of energy. The fundamental benefits and main drawbacks of the aforementioned methods are discussed in order to depict the efficiency of each approach in various situations. In the end, a proposed hybrid strategy is represented.

Background and Objective: Although whole body-electromyostimulation (WB-EMS) has been shown to favorably improve body composition in several research studies, it has not been confirmed how it affects adipose tissue-derived biomarkers and circumferences of the abdomen and thighs. Materials and Methods: Twenty participants of obese elderly women were randomly classified into an EMS group (EMSG; n = 10) or a non-EMS group (CON; n = 10). The WB-EMS suits used in this study enabled the simultaneous activation of 8 muscle groups with selectable intensities for each phase. Stimulation frequency was selected at 85 Hz, impulse-width at 350 μ seconds, and impulse-rise as a rectangular application. Impulse duration was 6 seconds with a 4-second break between impulses. The EMS sessions were combined with aerobic dancing 3 times a week for 12 weeks. Both groups received the same program; however, the CON did not receive electrical stimuli. Biomarkers and body composition including circumferences of the abdomen and thighs were measured on Week 0 and Week 12. Results: Compared with the CON, 1) a significant effect of the EMS-intervention concerning decreased body weight (p = 0.032) and increased basal metabolic rate (p = 0.029) were evident. The thigh subcutaneous fat and total fat of EMSG were not significantly changed, but those of CON were significantly increased after 12 weeks. 2) The biomarkers of CON either increased or showed no change, although the interleukin (IL)-6 was significantly (p = 0.028) decreased in EMSG. Specifically, C-reactive protein (CRP; p = 0.005) and alpha-fetoprotein (p = 0.050) of CON were significantly increased after 12 weeks. In addition, the IL-6 (p = 0.034), CRP (p = 0.001), carcinoembryonic antigen (p = 0.017), and low density lipoprotein (p = 0.005) of EMSG were lower than those of CON in the end of experiment. 3) Conclusions: The results indicate that EMS intervention improved body composition and reduced negative biomarkers, thus highlighting its effectiveness.

Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. After the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“Oral Turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.

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. ¬¬

The paper interprets a comparison of two mostly used techniques of a field-oriented control for 6-phase electric drives, with their pros and cons, as well as their differences in construction and behaviour. Both of these approaches have been realized. Frequency and step responses analysis have been demonstrated with a 6-phase permanent magnet synchronous machine. Experimental results have been compared with simulations based on a mathematical model.

A series of Ni/KIT6 catalystprecusors with 25wt.%Ni loading amount were reduced in H₂ at 400, 450, 500, and 550ºC, respectively. The studied catalysts were investigated by XRD, Quasiin-situ XPS, BET, TEM, and H₂-TPDanalysis methods.It was found that reduction temperature is an important factor affecting the hydrodeoxygenation (HDO) performance of the studied catalysts. The reduction temperature influences mainly the content of active components, crystal size, and the abilityfor adsorbing and activatingH2. The developed pore structure and large specific surface area of the KIT-6 support favored the Ni dispersion.The RT450 catalyst, which was prepared in H₂ atmosphere at 450 ºC, has the best HDO performance. Ethyl acetate can be completely transformed, and maintain 96.8% ethane selectivity and 3.2% methane selectivity at 300 ºC. The calculated apparent activation energies of the prepared catalysts increased in the following order: RT550 > RT400 > RT500 > RT450.

The current pandemic is urgently demanding to discover alternative materials capable of inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its negative charge density that may bind to viral envelopes inactivating membrane receptors.

We are all similar, but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly and yeast panels with insightful applications for translational research.

This paper seeks to investigate the questions of: How does the constancy of the speed of light come about? Why does time dilation and length contraction occur? Are they physical effects with a mechanism? Does mass have a role is in these effects? Is Relativity an emergent phenomenon? The enquiry is along a different tact than the standard Lorentzian invariance canon but in the realm of readily known experimental facts or analogies and theory in the domain of wave propagation and solid state physics. These analogies, to almost prosaic physics, have a small following and are called Ether Theories, which modern physics has implicitly reinstated by General Relativity and Quantum Field Theories. In the category of Ether Theories based on analogies to solid state physics, this presentation is unique in not being Lorentz invariant; it is based on earlier papers by the author enquiring into the speed of coincidence counting of the Bell Inequality and a communication protocol. It is believed that Lorentz invariance emerges from the Ether and all Relativistic Mechanics can be built from the bottom up. The conclusion is that space-time is not really curved but the effects are all ascribable to mass gain.

In this work, nylon 6/ P(N-phenylmaleimide-alt-styrene) blends were prepared by melt blending, and the mechanical, heat-resistant, crystallographic and dynamical mechanical properties of nylon 6/ P(N-phenylmaleimide-alt-styrene) blends with different contents were investigated and analyzed. The results showed that the mechanical properties decreased with increasing PNS, while the heat deflection temperature (HDT), relative crystallinity (Xn), and storage modulus (G’) increased with increasing PNS. The results of differential Scanning Calorimetry (DSC) proved the PNS played the positive role of nucleating PA6. And the results of dynamic mechanical analysis (DMA) proved the PNS could improve the rigidity of PA6/PNS blends. From the SEM, these PNS domains were between 0.2 and 4 μm in diameter. The experimental results indicated that the addition of PNS improved the rigidity of PA6/PNS blends, and then improved the heat-resistant property.

.Functionalization of multi-walled carbon nanotubes (MWNTs) surface with sulfonated poly(ether ether ketone) SPEEK chains using hexane diamine (HAD) as the interlinking molecule was investigated. MWNTs were first oxidized by nitric acid to generate carboxyl groups on their surface. Grafting of SPEEK chains on the MWNTs surface was achieved using hexane diamine as a cross-linking molecule. The attachment took place after the reaction of amine groups with carboxyl groups of oxidized MWNTs and sulfonate groups of SPEEK as confirmed by infrared (FTIR) analysis. Scanning electron microscopy (SEM) showed that MWNTs were packed into a dense and compact structure. Transmission electron microscopy (TEM) showed that the nanotubes were wrapped by polymer chains and arranged in a bundle like structure. These observations reveal that some of MWNTs were interconnected by SPEEK chains.

Advanced paternal age at fertilization has been suggested to be a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental factors that modify such changes. In this study, we characterize age-dependent changes in sperm DNA methylation profiles between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). Reduced representation bisulfite sequencing (RRBS) libraries were prepared from caudal epididymal sperm DNA and differentially methylated regions (DMRs; ≥ 10x coverage depth, ≥ 3 CpGs per cluster, ≥ 5% methylation change, q < 0.05) were identified via MethPipe package. In control animals, 5,319 age-dependent DMRs were identified, with 99.3% DMRs hypermethylated in mature animals compared to young pubertal rats. These age-related DMRs were enriched for functional categories essential for embryonic development, such as pattern specification, forebrain and sensory organ development, Hippo and Wnt pathways. Age-related changes in sncRNA, reported in different study, target similar list of genes and biological categories.In BDE-47 exposed rats, sperm DNA methylation was higher in young pubertal and lower in mature animals when compared to controls, which resulted in a significant attenuation in the number of age-dependent DMRs (N = 189) identified in the exposed group. In conclusion, our results indicate that the natural aging process has profound effects on sperm methylation levels and this effect may be modified by environmental exposures. Moreover, our results further support the role of epigenetic mechanisms as a likely link betwen paternal age and offspring health and development.

From the wide range of engineering materials traditional Stellite 6 alloy exhibits excellent cavitation erosion (CE) resistance. In this work, the effect of nitrogen ion implantation of HIPed Stellite 6 on the improvement of CE resistance and both cobalt-rich matrix phase transformation due to nitrogen implantation and CE were stated. The CE resistance of stellites ion-implanted by 120 keV N+ ions two fluences: 5x1016 cm-2 and 1x1017 cm-2 were comparatively analysed with the unimplanted stellite and AISI 304 stainless steel. CE tests were conducted according to ASTM G32 with stationary specimen method. Erosion rate curves and mean depth of erosion confirm that the nitrogen implanted HIPed Stellite 6 two times exceeds the resistance to CE than unimplanted stellite, and has almost 10 times higher CE reference than stainless steel. The X-ray diffraction (XRD) confirms that HIPed Stellite 6 nitrogen ion implantation favours transformation of the ɛ(hcp) to γ(fcc) structure. Unimplanted stellite ɛ-rich matirx is less prone to plastic deformation than γ and consequently, increase of γ phase effectively holds carbides in cobalt matrix and prevents Cr7C3 debonding. This phenomenon elongates three times the CE incubation stage, slows erosion rate and mitigates the material loss. Metastable γ structure formed by ion implantation consumes the cavitation load for work-hardening and γ → ɛ martensitic transformation. In further CE stages, phases transform as for unimplanted alloy namely, the cavitation-inducted recovery process, removal of strain, dislocations resulting in increase of fcc phase. The CE mechanism was investigated using a surface profilometer, atomic force microscopy, SEM-EDS and XRD. HIPed Stellite 6 wear behaviour relies on the plastic deformation of cobalt matrix, starting at Cr7C3/matrix interfaces. Once the Cr7C3 losing their restrain, are debonding and removed. Carbides detachment creates cavitation pits which initiate cracks propagation through cobalt matrix, the loss of matrix phase and CE proceeds with a detachment of massive chunk of materials.

Carcinoembriogenic antigen (CEA) is a routine marker for follow-up of colo-rectal cancers. We aimed to determine whether a CEA increase within the normal range can be linked to a recurrence risk. We included 78 consecutive patients with colo-rectal cancer, who underwent curative surgical treatment with or without chemo- or radiotherapy. As reference, we used the smallest value of the CEA during follow-up. A total of 34/78 patients (43.6%) had fluctuations of CEA of at least 1.1 ng/ml, with or without increases above 5 ng/ml. In 27/34 patients (79.4%) increases of CEA were explained either by recurrence (15/34 patients, 44.1%), adjuvant chemotherapy (7/34 patients, 20.6%) or benign pathology (5/34 patients, 14.7%). In 5 of 22 recurrences (23%) a CEA increase of at least 1.1 ng/ml, but below 5 ng/ml preceded the clinical relapse by a median of 8 months (range 3-22 months). The 4-year disease-free survival was 89% in patients with postoperative CEA <2.5 ng/ml, and 55% in patients with CEA >2.5 ng/ml. CEA increase by at least 1.1 ng/ml within the normal range, after curative treatment of colorectal cancer can be either an early sign of relapse or can be usually explained by other pathological processes.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

Emotions are indicators of affective states and play a significant role in human daily life, behavior, and interactions. Giving emotional intelligence to the machines could, for instance, facilitate early detection and prediction of (mental) diseases and symptoms. Electroencephalography (EEG) -based emotion recognition is being widely applied because it measures electrical correlates directly from the brain rather than the indirect measurement of other physiological responses initiated by the brain. The recent development of non-invasive and portable EEG sensors makes it possible to use them in real-time applications. Therefore, this paper presents a real-time emotion classification pipeline, which trains different binary classifiers for the dimensions of Valence and Arousal from an incoming EEG data stream. After achieving a 23.9% (Arousal) and 25.8% (Valence) higher f1-score on the state-of-art AMIGOS dataset, this pipeline was applied to the dataset achieved by an emotion elicitation experimental framework developed within the scope of this thesis. Following two different protocols, 15 participants were recorded using two different consumer-grade EEG devices while watching 16 short emotional videos in a controlled environment. For an immediate label setting, the mean f1-score of 87% and 82% were achieved for Arousal and Valence, respectively. In a live scenario, while continuously being updated on the incoming data stream with delayed labels, the pipeline proved to be fast enough to achieve predictions in real time. However, the significant discrepancy from the readily available labels on the classification scores leads to future work to include more data with frequent delayed labels in the live settings.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines TNF- and IL-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-17, IL-23, GM-CSF, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

We investigated the effect of helium atmospheric-pressure plasma (PL) and deep-ultraviolet (UV) light treatments on the adhesive properties of fiber-reinforced poly(ether-ether-ketone)polymer (PEEK). PEEK disks reinforced with carbon (CPEEK) or glass (GPEEK) fibers were polished, modified with PL and UV for 60 s, and the surface energy was calculated by measuring the contact angles. The disk surfaces were analyzed by X-ray photoemission spectroscopy. Shear bond strength testing was performed using a universal testing machine, and the fracture surfaces were observed by electron probe microanalyzer. Data were analyzed with one and two-way ANOVA and Tukey’s post-hoc test (p < 0.05). The surface energies were increased by the modifications, which created OH functional groups on the surfaces. The bond strengths of CPEEK were increased by PL and those of GPEEK were increased by PL and UV, owing to chemical bonding at the interface.

In this paper I will address Dr. Sonne’s questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas and is more immature and more symptomatic while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions that Dr. Sonne presented and will discuss also my published theory on the physical nature of subjective experience and its relation to the brain and how that theory interacts with DBP, and how the 2 theories relate to subjective experience, will, behavior, psychopathology and its treatment.

Nonwovens made of recycled carbon fibers (rCF) and thermoplastic (TP) fibers have excellent economic and ecological potential. In contrast to new fibers, recycled carbon fibers are significantly cheaper and the CO2 footprint is mostly compensated by energy savings in the first product life cycle. The next step for this promising material is its industrial serial use. Therefore the process chain from fiber to composite material is analyzed. Initially rCF length at different positions during the carding process is measured. Thereafter the influence of the TP fibers onto processing, fiber shortening and mechanical properties is evaluated. At last several nonwovens with different TP fibers and fiber volume contents between 15 vol.-% and 30 vol.-% are produced, consolidated by hot pressing and tested by 4-point bending to determine the mechanical values. The fiber length reduction ranges from 20.6 % to 28.4 %. TP fibers cushion the rCF against mechanical stress but hold rCF fragments back due to their crimp. The resulting bending strength varies from 301 MPa to 405 MPa and the stiffness from 16.3 GPa to 30.1 GPa. Design recommendations for reduced fiber shortening are derived as well as material mixtures which offer better homogeneity and higher mechanical properties.

A particular challenge in the conceptual design of direct-from orbit delivery systems is the seemingly well-known kinematics retain fallacies whose efficacies are reduced over great distances. Rotation about the local wing of an aerospace vehicle is almost never the pitch angle, yet modern application of kinematics often assumes such (with accompanying angular error). The same assertion is usually true about the nature of roll and yaw angles. Expressing motion in coordinates of rotating reference frames necessitates transformation between reference frames, and one such transformation is embodied in the Direction Cosine Matrices (DCM) formed by a sequence of three successive frame rotations. One of two ubiquitous sequences of three rotations used to construct the DCM involves first a rotation around the inertial z-axis, then intermediate y-axis, then finally about the body’s x-axis; a sequence commonly called the “aerospace sequence” or the a “3-2-1 rotation sequence”. The second ubiquitous sequence is the so-called “orbital sequence” or “3-1-3 rotation sequence” with rotations about the inertial z axis first, then about the intermediate x-axis, then finally about the body z-axis. This manuscript evaluates which sequence is the most advantageous for an object starting in space and then travels through the atmosphere to a target on the Earth’s surface. Six degrees of freedom of vehicle motion were simulated starting in orbit with a given thrust and commanded maneuver. The simulation performs all twelve possible rotation sequences (transforming inertial coordinates to body coordinates) with comparison by computational burden and error representing rotations about body axes (roll, pitch, and yaw respectively). Simulation precision is validated using the quaternion normalization condition indicating near machine precision (0.9\times{10}^{-15}) and reveals the so-called 132 rotation is the most accurate with an average error of 0.14° and a computational time of 0.013 seconds: resulting in a 97.95% increase in accuracy over the so-called 321 rotation and a 99.84% increase over the so-called 313 rotation.

The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.

Stable isotope concentrations in the soil, rain and ground water have been used to trace the water extraction zones of plants in different environments. The need to identify the plant water use by plants in afforestation programs to control desertification increases the importance of sap water partitioning of plants in sand dune areas. However, the introduction of new plant covers exerts pressure on the water resources and can affect the local soil water conditions. In this study, we analyzed the isotope concentrations in rain, soil, sap, and ground water after the summer of 2010. Two experimental plots established in the Hailiutu catchment (Shaanxi province, northwest China) were selected to gather the water samples between September and October 2010. One plot is dominated by Salix bushes (Salix psammophila C. Wang \& Chang Y. Yang) and the other by the tree species Willow (Salix matsudana Koidz.). The total precipitation at the experimental site was 401 mm/yr during 2010, while 88.7 mm was collected in total for the period September to October. Willow trees transpired 12.82 kg/d being almost three times larger than Salix shrubs (4.57 kg/d). Despite the transpiration rates of both plant species and the few rain events in the region, the soil water beneath the plant covers is not depleted. Stable isotope signature of soil water beneath both covers shows the fractionation front in Salix at 20 cm depth and at Willow at 40 cm depth. However, soil water signature is closer to the groundwater than the collected rain water.

Silicatein-α (Silα), a hydrolytic enzyme derived from siliceous marine sponges, is one of the few enzymes in nature capable of catalysing the metathesis of silicon-oxygen bonds. It is therefore of interest as a possible biocatalyst for the synthesis of organosiloxanes. To further investigate the substrate scope of this enzyme, a series of condensation reactions with a variety of phenols and aliphatic alcohols were carried out. In general, it was observed that Silα demonstrated a preference for phenols, though the conversions were relatively modest in most cases. In the two pairs of chiral alcohols that were investigated, it was found that the enzyme displayed a preference for the silylation of the S-enantiomers. Additionally, the enzyme’s tolerance to a range of solvents was tested. Silα had the highest level of substrate conversion in the non-polar solvents n-octane and toluene, although the inclusion of up to 20% of 1,4-dioxane was tolerated. These results suggest that Silα is a potential candidate for directed evolution towards future application as a robust and selective bi-ocatalyst for organosiloxane chemistry.

The study examined the effect of noninvasive crown retrieval/reuse process using erbium-doped yttrium aluminum garnet laser (Er:YAG). Twenty-six extracted human teeth were prepared for a crown. The crown was milled using lithium disilicate (LD) and zirconia (Z) materials, n=13 per group, 3 for scanning electron microscopy (SEM). The crown was luted using composite resin cement and subjected to a laser retrieval process. After the retrieval process, the crown was cleaned, recemented and laser-retrieved two more times, without and with additional tooth reduction mimicking clinical refreshment of dentin. Retrieval time and temperature were analyzed using analysis of variance (ANOVA). Surface changes were observed through SEM. The retrieval times were 267.1±130.43, 220±79.09, 277.1±126.44, 368.4±136.14, 355±159.39, and 419.2±121.36 seconds for first, second, third LD and Z groups, respectively (p=.009). The maximal temperatures were 23.95.1±1.89°C, 24.86±2.01°C, 24.17±1.53°C, 22.88±1.51°C, 24.03±1.74°C, and 21.99±1.32°C for for first, second, third LD and Z groups, respectively (p=.006). Er:YAG laser crown removal is an effective retrieval tool for all-ceramic crowns. Minimal changes to teeth and crowns were observed following laser irradiation.

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

The excessive use of synthetic insecticides in modern agriculture has led to the contamination of the environment and the development of insect resistance. In this study, we evaluated the potential of tangerine (Citrus reticulata L.) peel essential oil (EO) as a natural insecticide against greenhouse whitefly (Trialeurodes vaporariorum W. (Homoptera: Aleyrodidae)), a common pest in greenhouse production. Petroleum ether (PET) and n-hexane (HEX) were used as solvents to extract essential oil (EO) from tangerine peels. The yield of EO was 1.59 % and 2.00 % (m/m) for PET and HEX, respectively. The insecticidal activity of EO was evaluated by measuring the mortality rate (MR) of greenhouse whiteflies at different time intervals. The results showed that PET and HEX extracts of tangerine EO effectively controlled the greenhouse whitefly. With both solvents, it was observed that with doses of 12.5% (v/v), similar results were achieved as with the positive control (corresponding to the commercial insecticide imidacloprid). Additionally, the FTIR analysis found that the EO contained d-limonene, which may be the source of its insecticidal properties. Therefore, tangerine peel essential oil is an excellent natural insecticide candidate for controlling greenhouse whiteflies effectively and sustainably.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).