In the last decades droughts, deforestation and wildfires have become recurring phenomena that have affected both human activities and natural ecosystems in Amazonia. The time an ecosystem requires to recover from carbon losses is a crucial metric to evaluate disturbance impacts on forests. However, the factors influencing and controlling the recovery time and its spatiotemporal patterns at the regional scale are still poorly understood. In this study, we combined forest growth model, remote sensing and field plots, to map Amazonia-wide (300-ha resolution) impact and recovery time of aboveground biomass (AGB) after drought, fire and a combination of logging and fire. Our simulated results indicate that AGB decreases by 4%, 19% and 46% in forests disturbed by drought, fire and logging + fire, respectively, with an average AGB recovery time of 27 years for drought, 44 years for burned and 63 years for logged + burned areas and with maximum values reaching 184 years in areas of high fire intensity. Our findings provide two major insights in the spatial and temporal patterns of drought and wildfire in the Amazon: 1) the recovery time of the forests takes longer in the southeastern part of the basin, and, 2) as droughts and wildfires become more frequent – since the intervals between the disturbances is getting shorter than forest regeneration – potentially causing a long-lasting damage in these fragile ecosystems and a permanent degradation.

This paper reports on the fabrication of alumina doped preforms using MCVD-vapor phase chelate delivery system with Al(acac)3 as the precursor. The objectives of the work are to study the deposition process, the efficiency of the fabrication process, and the quality of the fabricated fiber preforms. Two parameters are studied, Al(acac)3 sublimator temperature (TAl°C) and deposition direction (i.e. downstream and upstream). Other parameters such as oxygen flow and deposition temperature are fixed. The results showed that a high uniformity of refractive index difference (%RSD < 2%) and core size (%RSD < 2.4%) was obtained along the preform length using downstream deposition while for the combined upstream and downstream deposition the uniformity was deteriorated. The process efficiency was found to be about 21% for TAl°C of 185°C and downstream deposition. From the EDX elemental analysis, the refractive index was found to increase by 0.0025 per mole percent of alumina.

This document describes the theoretical basis of the algorithms used to determine properties of snow and ice from the measurements of the Ocean and Land Color Instrument (OLCI) onboard Sentinel-3 satellites within the Pre-operational Sentinel-3 snow and ice products (SICE) project: http://snow.geus.dk/. The code used for the SICE retrieval and its documentation can be found at https://github.com/GEUS-SICE/pySICE. The algorithms were developed after the work from Kokhanovsky et al. (2018, 2019, 2020).

Here we present an overview of speleothem δ18O records from South America, which mostly are available in the Speleothem Isotopes Synthesis and Analysis (SISAL_v1) database. South American tropical and subtropical δ18O time series are primarily interpreted as being driven by the amount effect and, consequently show the past history of the convection intensity of convergence zones such as the Intertropical Convergence Zone and the South America Monsoon System. We investigate past hydroclimate scenarios in South America related to the South American Monsoon System in three different time scales: Late Pleistocene, Holocene and the last two millennia. The precession driven insolation is the main driver of convective variability over the continent during the last 250 kyrs, including the Holocene period. However a dipole is observed between the west and east portions of the continent. Records located in the central region of Brazil appear to be weakly affected by insolation driven variability and more susceptible to the South Atlantic Convergence Zone. Cold episodic events in Northern Hemisphere increase the activity of the South American Monsoon System on all time scales, in turn increasing rainfall amounts in South America, as was documented during Heinrich events in the late Pleistocene and Bond events in the Holocene, as well as during the Little Ice Age.

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.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA. However, several are under development, and the FDA anticipates their fast entry, as evidenced by the FDA's actions of issuing GE-specific guidelines. The potential of GE in treating diseases far supersedes any other modality due to the recognized role of genes in most human diseases. While GT products add missing genes, GE tools can overcome many aberrations. However, GE presents many safety challenges, including off-target impact, delivery consistency, and long-term effects of gene-fixing. However, most of these concerns will be resolved once the FDA begins approving them, leading to hundreds of products capable of treating untreatable diseases.

A series of penta-1,4-dien-3-one containing a H-phosphonate scaffold were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and HRMS. Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compounds 3c and 3o exhibited substantial antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In addition, compounds 3c, 3f, and 3r showed remarkable curative activities against tobacco mosaic virus (TMV), with 50% effective concentration (EC50) values of 290.0, 234.0, and 373.6 μg/mL, respectively. These were superior to that of ningnanmycin (386.2 μg/mL). Compound 3r exhibited comparative protective activity against TMV, with an EC50 value of 291.1 μg/mL, which was better than that of ningnanmycin (297.1 μg/mL). Notably, the solubility of all title compounds improved relative to the lead compound curcumin. These results suggest that penta-1,4-dien-3-one containing a H-phosphonate scaffold may be considered as an activator for antibacterial and antiviral agents.

An oceanic radar altimeter such as TOPEX/Poseidon (T/P) is typically for observing elevation changes over the open oceans or large inland lakes/rivers, with limited applications over solid earth due to its large footprint and susceptibility to waveform contamination and slope effect. Here we demonstrate that it is possible to construct a long-term time series of glacier elevation change from T/P-series radar altimeters over two flat surfaces near a glacier terminus and an icefield (Sites A and B, with slopes of 2° and 0.8°) in Mt. Tanggula, Tibet, at elevations over 5400 m. We retracked radar waveforms using the subwaveform threshold algorithm, selected quality altimeter data (1/4 of the original) with nearly the same slope and adjusted the original elevations by fitting with a time-varying, 2nd order surface. The glacier elevation changes at the two sites from T/P (1993–2002) show seasonal elevation oscillations with linear rates at about −3 m/year and abnormal seasonal changes around the 1997–98 El Niño. Site A is over a deep valley in southern Tanggula. Its elevation dropped about 30 m over 1993–2002 (from T/P) and the glacier almost disappeared by 2016 (from altimeters and satellite images). Despite the sporadic Jason-2 and Jason-3 altimeter data, we also derived long-term rates of glacier elevation change over 1993–2017. Landsat-derived glacier area and elevation changes near the two sites confirm the rapid glacier thinning from the altimeters. The glacier meltwater near Site A supplied increasing source water to Chibuzhang Co west of Mt. Tanggula, contributing partially to its accelerated rising lake level. The glacier thinning at Site B (icefield) was correlated with the increased discharge of the Tuotuo River in eastern Mt. Tanggula, a source region of the Yangtze River. The successful detection of glacier thinning at the two sites shows that T/P-series altimeters can serve as a virtual station at a flat glacier spot to monitor long-term glacier elevation changes in connection to climate change. This virtual station concept is particularly useful for inaccessible glaciers, but its implementation faces two challenging issues: increasing the volume of quality altimeter data and improving the ranging accuracy over a targeted mountain glacier spot.

Porcine circovirus type 2 (PCV2) is a small non-enveloped DNA virus that causes swine immunosuppression by inducing apoptosis in lymphocytes. The ORF3 protein plays a major role in PCV2-induced apoptosis in porcine kidney cells, but there is little information regarding this protein in PCV2-infected lymphocytes. In this study, hybridoma screening and epitope mapping were determined by using an indirect ELISA. The mAb 7D3 against ORF3 peptide (residues 35–65) of PCV2 were generated in this study. In vivo situation, the mAb 7D3 recognized ORF3 protein existed in PCV2-infected apoptotic porcine PBMCs. It is noteworthy that thimerosal interfered with the binding of mAb 7D3 to epitope and it was diminished by adding cysteine. Additionally, thimerosal interacting with cysteine-containing peptide was demonstrated by the PTI assay. Furthermore, thimerosal specifically interacted with the antigen-binding sites of mAb 7D3. This study suggested that thimerosal blockade the occlusion of the antigen-binding sites of mAb 7D3 to bind ORF3 peptide (residues 35–65) via thimerosal interacting with cysteine residues which should be located within the antigen-binding sites of mAb 7D3. Overall, the mAb 7D3 has been characterized and it will be a valuables tool in future studies of ORF3 function and the wider mechanism of cell apoptosis caused by PCV2 infection. Similarly, these techniques will be useful for applications in detecting thimerosal too.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids like total cholesterol (TCH), LDL- and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. This study aimed to investigate the relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities and erythrocyte membrane fluidity in 58 depressive children and adolescents, as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. We are the first to report that omega-3 FAs increase after 12 weeks of supplementation large HDL subfractions (anti-atherogenic) and decrease small HDL subfractions (pro-atherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder.

The search for economical and sustainable sources of PUFAs within the framework of the circular economy is encouraged by their proven beneficial effects on health. The extraction of monkfish liver oil (MLO) for the synthesis of omega-3 ethyl esters was performed evaluating two blending systems and four green solvents. Moreover, the potential solubility of the MLO in green solvents was studied using the predictive simulation software COSMO-RS. The production of the ethyl esters was performed by one or two step reactions. Novozym 435, two resting cells (Aspergillus flavus and Rhizopus oryzae) obtained in our laboratory and mix of them were used as biocatalysts in a solvent-free system. The yields for Novozym 435, R. oryzae and A. flavus in the one-step esterification were 63%, 61% and 46%, respectively. The hydrolysis step in the two-step reaction led to 83%, 88% and 93% of free fatty acids (FFA) for Novozym 435, R. oryzae and A. flavus respectively. However, Novozym 435 showed the highest yield in the esterification step (85%) followed by R. oryzae (65%) and A. flavus (41%). Moreover, selectivity in front of polyunsaturated fatty acids of R. oryzae lipase was evidenced, since it did slightly esterified docosahexaenoic acid (DHA) in all the esterification reactions tested.

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.

A novel effective vibrational mode was discovered in the conventional transducer with an array of orthogonal (square) regular piezoelectric rods in 1-3 piezocomposite, containing the damping backing and front matching layers. The operational resonance in the structure was determined as the Surface Acoustic Wave (SAW) on the backing boundary excited by the adjacent piezo-rods, with its frequency typically near 3 times lower the fundamental half-lambda conventional piezocomposite resonance. Pulse-echo sensitivity and transmitting sound-pressure-level (SPL) in air showed that the signal strength is roughly comparable to the industrial similar air transducers at the frequency range 100…700 kHz, where at these frequencies the lateral and longitudinal piezoelement dimensions in the conventional transducer design are typically close to each other causing interference with unwanted coupling modes. As was determined theoretically and proved in experiments, the backing SAW resonance effect in the transducer performance is inherent just to the regular periodic 1-3 piezocomposite structure, and does occur neither with randomly located/oriented piezo-rods, nor in the homogeneous piezo-plate at least with the same lateral cross-section as the connected to it backing. The purpose of the article is to investigate a newly discovered operational vibrational mode of a SAW type in 1-3 regular piezocomposite, other than piezoelectric resonance. The investigated phenomena can improve the transceiver sensitivity, bandwidth, providing lower drive voltage, and smaller and lighter weight ultrasonic transducers. Based on the piezocomposites with thickness’ 1…1.5 mm (rod resonance near 2…3 MHz), pillar width 0.2…0.8 mm, kerf width 0.1…0.4 mm, the transceivers with an operating frequency from 140 kHz to 650 kHz were designed and fabricated with a conventional backing of a mixture of high-density tungsten powder and epoxy, and a matching layer of a mixture of low-density glass bubbles and epoxy. Experimental evaluation of their acoustical performance showed expected characteristics suitable for practical applications.

An introductory course of Arka Dhyana, also known as Intuitive Meditation (IM), consisting of five sessions, was offered to an international audience via Zoom technology. Participants were shown how to connect to their deeper self, essence or soul by bringing their I-ego-awareness from the thinking mind, often associated with the frontal part of the brain, to 19 energetic stations in the body including the heart centre. In this limited study, evaluation was both process and outcome orientated and included HeartMath (HM) Inner Balance or emWave2 electronic technology to measure mean coherence and achievement before and after each session. A highly significant increase in both coherence and achievement in six participants was found, which was also reflected in a reported increase in wellbeing related to feelings in qualitative statements indicating changes in levels of consciousness and individual transformative experiences as predicted by the Theory of the Six Main Levels of Consciousness.

The co-circulation of duck hepatitis A virus subtypes 1 (DHAV-1) and 3 (DHAV-3) in ducklings has resulted in significant economic losses. Because ducklings infected with DHAV-1 or DHAV-3 show similar clinical signs and gross lesions, it is important to discriminate these subtypes as early as possible for better clinical management. On the basis of multiple alignments of the 5′-noncoding region sequences of strains DHAV-1 and DHAV-3, universal and type-specific primers were designed and synthesized. Using the primers in a one-tube reverse transcription-PCR (RT-PCR) assay, reference strains of DHAV-1 and DHAV-3 (isolated over a span of 60 years and covering many different countries) were successfully amplified, indicating that the primer sequences were completely conserved. The amplicon sequences results and the sizes of amplicons from reference DHAV-1 and DHAV-3 isolates correlated completely with their genotypes. Moreover, with this one-tube RT-PCR system, the amplicon sizes of liver samples of reference DHAV-1- or DHAV-3-infected birds matched perfectly with their respective genotypes, as determined by virus isolation and neutralization tests. No other RNA viruses of duck origin were detected with the synthesized primers. The sensitivity of viral RNA detection was 10 pg. With this system, 20% genotype 1, 45% genotype 3, and 9% co-infection of the two genotypes were detected in 55 clinical samples. This novel approach could be used for the rapid genotyping DHAV-1 and/or DHAV-3 infection in routine clinical surveillance or epidemiologic screening.

Two novel core-shell composites SiO2@PMDA-Si-Tb, SiO2@PMDA-Si-Tb-phen with SiO2 as the core and terbium organic complex as the shell, were successfully synthesized. The terbium ion was coordinated with organic ligand forming terbium organic complex in the shell layer. The bi-functional organosilane ((HOOC)2C6H2(CONH(CH2)3Si(OCH2CH3)3)2 (abbreviated as PMDA-Si) was used as the first ligand and phen as the second ligand. Furthermore, the silica-modified SiO2@PMDA-Si-Tb@SiO2, SiO2@PMDA-Si-Tb-phen@SiO2 core-shell-shell composites were also synthesized by sol–gel chemical route. An amorphous silica shell was coated around the SiO2@PMDA-Si-Tb and SiO2@PMDA-Si-Tb-phen core-shell composites. The core-shell and core-shell-shell composites both exhibited excellent luminescence in solid state. The luminescence of core-shell-shell composites was stronger than that of core-shell composites. Meanwhile, an improved luminescence stability property for the core-shell-shell composites was found in the aqueous solution. The core-shell-shell composites exhibited bright luminescence, high stability, long lifetime, and good solubility, which may present potential applications in the field of bio-medical.

Detailed kinetics for a 3-wavelength photopolymerization confinement (PC) system is presented for both numerical solutions and analytic formulas. The dynamic profiles are simulated for oxygen, free radical, and conversion for various situations of: blue-light only, 2-light (red and UV), and 3-light (red, blue, UV). An effective PC requires two conditions: (i) a strong N-inhibition for uncured regime with a low conversion (triggered by the UV-light); and (ii) a weak S-inhibition (oxygen-induced) for high conversion under the blue-light or blue and red-light initiation. Good PC candidates are governed by collective factors of: (i) the double ratio of light-intensity and initiator-concentration, (ii) monomers rate-constant; and (iii) effective absorption constants at specific wavelength and initiators. A new reverse feature for the role of N-inhibition on the blue-conversion is found. Higher oxygen concentration leads to a lower conversion, which could be enhanced by reducing the S-inhibition via a red or blue-light pre-irradiation, having a pre-irradiation time TP=200 s for red-light only, and reduced to 150 s, when both red and blue-light. System under UV-only leads a conversion lower than that of blue-only. However, conversion could be improved by the dual-light (blue and UV), and further enhanced by the pre-irradiation of red-light. The two competing factors, N-inhibition and S-inhibition, could be independently and selectively tailored to achieve: (a) high conversion of blue-light (without UV-light), enhanced by red-light pre-irradiation for minimal S-inhibition; and (b) efficient PC initiated by UV-light produced N-inhibition for reduced confinement thickness and for high print speed.

We live in the time of profound transformations commonly labelled with the word “globalization”. The rise of one ecological-technological-social system encompassing our whole planet is an important element of these processes. Solving big global problems demands knowledge of two complementary sorts: on the one hand – going “in depth”, on the other – going “in breadth”. The present paper assumes the second (in a sense: philosophical) perspective. It tries to analyze some relations between the development of technology (IT) and the development of democracy. The notion of democracy, its various forms and axiological reasons for it are considered first. In the subsequent chapter different consequences (both positive and negative) the IT development has for contemporary democracy are discussed. In the next chapter the evolutionary nature of the technological development is debated as well as the question of (democratic) control of this process. The development of Artificial General Intelligence is presented as a challenge for democracy

The main goal of our work is the revealing of problematic issues related to estimates of the absorption coefficient of colored organic matter in the northern seas from data of the Ocean and Land Color Instrument (OLCI) on the Sentinel-3 satellites. In particular, a comparison of the OLCI standard error estimates ADG443_NN_err., relating to the measurement and retrieval of the geophysical products, with the uncertainties in the real situation of the northern seas, where the natural conditions are extremely unfavorable (first of all, frequent cloudiness, low Sun heights). We conducted a comprehensive multi-sensor study of the uncertainties using various approaches, first at all, directly comparing the data from satellite (OLCI Sentinel-3 and four other ocean color sensors) and field measurements in five sea expeditions 2016-2019, by using the different processing algorithms. Our analysis has shown that the real uncertainties of the final product are significantly higher than the calculated errors of the ADG443_NN_err., which is 100% and ~10%. The main reason for that is the unsatisfactory atmospheric correction. We present the results of the analysis of the different effecting factors (satellite sensors, processing algorithms, use of the other parameters), and formulate the tasks of future work.

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).

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Atlantic salmon (Salmo Salar) is one of the fish species that rich in omega-3 fatty acids. Consumption of omega-3 fatty acids can lower down the risk of cardiovascular disease and coronary heart disease. The extraction of omega-3 fish oil from Atlantic salmon by using hexane and isopropanol was conducted in this research. Response Surface Methodology (RSM) was used to study the impact of parameters which were temperature (50-90°C), centrifuge speed (1000-3000rpm) and solvent ratio of hexane to isopropanol (0.5-1.5) to the percentage of oil yield. The results obtained shows that 15.23%± 0.61 of oil yield from Atlantic salmon under an optimum condition of 70°C, 3000 rpm and solvent ratio of hexane to isopropanol of 1.5. The acid value, peroxide value and p-anisidine value of the fish oil obtained were 7.48 mg KOH/g, 1.94 meq/kg and 5.56 respectively which were all within the acceptable limit which stipulated by Global Organization for EPA and DHA (GOED) and Food and Agricultural Organization of the United Nations (FAO). The FTIR analysis proved the presence of alkane and carboxylic acid in the fish oil. Furthermore, GC-MS analysis showed that the fish oil contains higher monounsaturated fatty acids (MUFA) contents followed by polyunsaturated fatty acids (PUFA) and 4.5525% of total omega-3 fatty acids.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

In the energy-momentum density expressions for a relativistic perfect fluid with a bulk motion, one comes across a couple of pressure-dependent terms, which though well known, are to an extent, lacking in their conceptual basis and the ensuing physical interpretation. In the expression for the energy density, the rest mass density along with the kinetic energy density of the fluid constituents due to their random motion, which contributes to the pressure as well, are already included. However, in a fluid with a bulk motion, there are, in addition, a couple of explicit, pressure-dependent terms in the energy-momentum densities, whose presence to an extent, is shrouded in mystery, especially from a physical perspective. We show here that one such pressure-dependent term appearing in the energy density, represents the work done by the fluid pressure against the Lorentz contraction during transition from the rest frame of the fluid to another frame in which the fluid has a bulk motion. This applies equally to the electromagnetic energy density of electrically charged systems in motion and explains in a natural manner an apparently paradoxical result that the field energy of a charged capacitor system decreases with an increase in the system velocity. The momentum density includes another pressure-dependent term, that represents an energy flow across the system, due to the opposite signs of work being done by pressure on two opposite sides of the moving fluid. From Maxwell's stress tensor we demonstrate that in the expression for electromagnetic momentum of an electric charged particle, it is the presence of a similar pressure term, arising from electrical self-repulsion forces in the charged sphere, that yields a natural explanation for the famous, more than a century old, 4/3 factor in the electromagnetic mass.

Every protein consists of a linear sequence over an alphabet of $20$ letters/amino acids. The sequence unfolds in the $3$-dimensional space through secondary (local foldings), tertiary (bonds) and quaternary (disjoint multiple) structures. The mere existence of the genetic code for the $20$ letters of the linear chain could be predicted with the (informationally complete) irreducible characters of the finite group $G_n:=\mathbb{Z}_n \rtimes 2O$ (with $n=5$ or $7$ and $2O$ the binary octahedral group) in our previous two papers. It turns out that some quaternary structures of protein complexes display $n$-fold symmetries. We propose an approach of secondary structures based on free group theory. Our results are compared to other approaches of predicting secondary structures of proteins in terms of $\alpha$ helices, $\beta$ sheets and coils, or more refined techniques. It is shown that the secondary structure of proteins shows similarities to the structure of some hyperbolic $3$-manifolds. The hyperbolic $3$-manifold of smallest volume --Gieseking manifold--, some other $3$ manifolds and the oriented hypercartographic group are singled out as tentative models of such secondary structures. For the quaternary structure, there are links to the Kummer surface.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Fish oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), vitamin D₃ and natural astaxanthin sustainably extracted from anchovy fillet leftovers using biobased limonene only, can be conveniently stabilized by adsorption on periodic mesoporous silicas. The simplicity of the process, the high load of entrapped fish oil, and the biocompatible nature of silica support numerous forthcoming applications of this new class of “Omeg@Silica” materials.

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.

Galectin-3 is considered a cancer biomarker and bioindicator of fibrosis and cardiac remodeling, and, therefore, it is desirable to develop convenient methods for its detection. Herein, an approach based on the development of multivalent electrochemical probes with high galectin-3 sensing abilities is reported. The probes consist of multivalent presentations of lactose–ferrocene conjugates scaffolded on poly(amido amine) (PAMAM) dendrimers and gold nanoparticles. Such multivalent lactose–ferrocene conjugates are synthesized by coupling of azidomethylferrocene-lactose building blocks on alkyne-functionalized PAMAM, for the case of the glycodendrimers, and to disulfide‐functionalized linkers that are then used for the surface modification of citrate-stabilized gold nanoparticles. The binding and sensing abilities towards galectin 3 of both ferrocene-containing lactose dendrimers and gold nanoparticles have been evaluated by means of isothermal titration calorimetry, UV-vis spectroscopy, and differential pulse voltammetry. The highest sensitivity by electrochemical methods to galectin-3 was shown by lactosylferrocenylated gold nanoparticles, which are able to detect the lectin in nanomolar concentrations.

This paper continues the review study on antimicrobial properties relevant to the periodontal diseases. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response has been covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies has been analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there is still much less studies using animal models and only a few clinical studies. Most of the studies, regardless of the used model indicated efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontitis is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

Investigation of sea-level positions during the highly-dynamic Marine Isotope Stage 3 (MIS 3: 29-61 kyrs BP) proves difficult because: i) in stable and subsiding areas, coeval coastal sediments are currently submerged at depths of few to several tens of meters below present sea level; ii) in uplifting areas, the preservation of geomorphic features and sedimentary records is limited due to the erosion occurred during the Last Glacial Maximum (LGM) with sea level at depth of -130 m, followed by marine transgression that determined the development of ravinement surfaces. This study discusses previous research in the Mediterranean and elsewhere, and describes new fossiliferous marine deposits laying on metamorphic bedrock of Cannitello (Calabria, Italy). Radiocarbon ages of marine shells (about 43 kyrs cal BP) indicate that these deposits, presently between 28 and 30 meters above sea level, formed during MIS 3.1. Elevation correction of the Cannitello outcrops (considered in an intermediate-to-far-field position with respect to the ice sheet) with the local vertical tectonic rate and Glacial Isostatic Adjustment (GIA) rate allows to propose a revision of the eustatic depth for this highstand. Our results are consistent with recently proposed estimates based on a novel ice sheet modelling technique.

We show that given a Lie superalgebra and an element of its dual space one can construct the 3-Lie superalgebra. We apply this approach to Lie superalgebra of (m,n)-block matrices taking supertrace of a matrix as the element of dual space. Then we also apply this approach to commutative superalgebra and the Lie superalgebra of its derivations to construct 3-Lie superalgebra. The graded Lie brackets are constructed by means of a derivation and involution of commutative superalgebra, and we use them to construct 3-Lie superalgebras.

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.

Forest degradation is known to be widespread in the tropics, but is currently very poorly mapped, in part because there is little quantitative data on which satellite sensor characteristics and analysis methods are best at detecting it. To improve this, we used data from the Tropical Forest Degradation Experiment (FODEX) plots in the southern Peruvian Amazon, where different numbers of trees had been removed from four 1 ha forest plots, carefully inventoried by hand and Terrestrial Laser Scanning before and after the logging to give a range of biomass change (ΔAGB) values. We conducted a comparative study of six multispectral optical satellite sensors (WorldView-3, SkySat, SPOT-7, PlanetScope, Sentinel-2 and Landsat 8) at 0.3 – 30 m spatial resolution, to find the best combination of sensor and remote sensing indicator for change detection. Spectral reflectance, the Normalized Difference Vegetation Index (NDVI) and texture parameters were extracted after radiometric calibration and image preprocessing. The strength of the relationships between the change in these values and field-measured ΔAGB (computed in % ha−1) was analysed. The results demonstrate that: (a) texture measures correlates more with ΔAGB than simple spectral parameters; (b) the strongest correlations are achieved for those sensors with spatial resolutions in the intermediate range (1.5 - 10 m), with finer or coarser resolutions producing worse results, and (c) when texture is computed using a moving square window ranging between 9 - 14 m in length. Maps predicting ΔAGB showed very promising results using a NIR-derived texture parameter for 3 m resolution PlanetScope (R2 = 0.97 and RMSE = 1.80 % ha−1), followed by 1.5 m SPOT-7 (R2 = 0.74 and RMSE = 5.25 % ha−1) and 10 m Sentinel-2 (R2 = 0.71 and RMSE = 5.55 % ha−1). Texture models derived from 0.3 m WorldView-3 improved with increasing window size, with highest R2 of 0.62 and RMSE = 6.35 % ha−1 for a window of 14 m in length. The degradation in our field plots is invisible to the 30 m resolution Landsat data. Our findings imply that, at least for lowland Peru, low-medium intensity disturbance can be detected best in optical wavelengths using a texture measure derived from 3 m PlanetScope data. That such data are being collected daily, and currently released free as monthly mosaics over tropical forests as part of the Norway’s International Climate and Forest Initiative (NICFI), is excellent news for monitoring such degradation.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

According to the risk investigations of being involved in an accident, alcohol-impaired driving is one of the major causes of motor-vehicles accidents. Preventing highly intoxicated persons from driving would potentially save many lives. This paper proposes a lightweight in-vehicle alcohol detection that processes the data generated from 6-alcohol sensors (MQ-3 Alcohol Sensors) using an optimizable shallow neural network (O-SNN). The experimental evaluation results exhibit a high-performance detection system scoring a 99.8% of detection accuracy with a very short inferencing delay of 2.22 µ seconds. Hence, the proposed model can be efficiently deployed and used to discover in-vehicle alcohol with high accuracy and low inference overhead as a part of the driver alcohol detection system for safety (DADSS) system aiming at massive deployment of alcohol sensing systems that could potentially save thousands of lives annually.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

Toward the standardization of O. biennis sprout extract (OBS-E), we aimed to obtain indicator compounds, using a validated method. HPLC-UVD allowed simultaneous quantification of indicator compounds quercetin 3-glucuronide and ellagic acid. The method was validated in terms of specificity, linearity, precision, accuracy, and limit of detection/limit of quantification (LOD/LOQ). High specificity and linearity was demonstrated, with correlation coefficients of 1.0000 for quercetin 3-glucuronide and 0.9998 for ellagic acid. The LOD/LOQ values were 0.486/1.472 μg/mL for quercetin 3-glucuronide and 1.003/3.039 μg/mL for ellagic acid. Intra-day and inter-day variability tests produced relative standard deviation for each compound of &lt;2%, a generally accepted precision criterion. High recovery rate were also obtained, indicating accuracy validation. The OBS-E prepared using various concentrations of ethanol were then analyzed. The 50% ethanol extract had highest content of quercetin 3-glucuronide, whereas the 70% ethanol extract possessed the lowest. However, the ellagic acid content was highest in the 70% ethanol extract and lowest in the 90% ethanol extract. Thus, quercetin 3-glucuronide and ellagic acid can be used industrially as indicator compounds for O. biennis sprout products, and our validated method can be used to establish indicator compounds for other natural products.

Bacterial indole-3-acetic acid (IAA), an effector molecule in microbial physiology, plays an important role in plant growth-promotion. Here, we comprehensively analyzed about 7282 prokaryotic genomes representing diverse bacterial phyla, combined with root-associated metagenomic data to unravel the distribution of tryptophan-dependent IAA synthesis pathways and to quantify the IAA synthesis-related genes in the plant root environments. We found that 82.2% of the analyzed bacterial genomes were potentially capable of synthesizing IAA from tryptophan (Trp) or intermediates. Interestingly, several phylogenetically diverse bacteria showed a preferential tendency to utilize different pathways and tryptamine and indole-3-pyruvate pathways are most prevalent in bacteria. About 45.3% of the studied genomes displayed multiple coexisting pathways, constituting complex IAA synthesis systems. Furthermore, root-associated metagenomic analyses revealed that rhizobacteria mainly synthesize IAA via IAM and tryptamine (TMP) pathways and might possess stronger IAA synthesis abilities than bacteria colonizing other environments. The obtained results refurbished our understanding of bacterial IAA synthesis pathways and provided a faster and less labor-intensive alternative to physiological screening based on genome collections. The better understanding of IAA synthesis among bacterial communities could maximize the utilization of bacterial IAA to augment the crop growth and physiological function.

Marine sponges, a well documented prolific source of natural products, harbors numerous microbial communities believed to possess N-acyl homoserine lactones (AHLs) mediated Quorum sensing (QS) as one of the mechanisms of interaction. Bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the potential for production of both QS signal molecules as well as QS interfering molecules (QSI) in the same sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six putative unsaturated acyl chain AHLs. Bioassay guided purification led to the isolation of two brominated metabolites with QS-interfering activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and was identified as 3-Br-N-methyltyramine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 were evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075 and E. coli pSB401) and was confirmed by measuring dose dependent inhibition of proteolytic activity and pyocyanin production in P. aeruginosa PAO1. The obtained results showed the co-existence of QS and QSI in S. spinosulus, a complex network which may mediate the orchestrated function of the microbiome within the sponge holobiont.

Gold clusters protected by 3-MBA ligands (MBA = mercaptobenzoic acid, -SPhCO2H) have attracted recent interest for their unusual structures and advantageous ligand-exchange and bioconjugation properties. Azubel et al. first determined the core structure of an Au68-complex, which was estimated to have 32 ligands (3-MBA groups). To explain the exceptional structure-composition and reaction properties of this complex, and its larger homologs, Tero et al. proposed a “dynamic stabilization” via carboxyl O-H--Au interactions. Herein, we report the first results of an integrated LC/MS analysis of unfractionated samples of gold / 3-MBA clusters, spanning the narrow size range 13.4 to 18.1 kDa. Using high-throughput procedures adapted from bio-macromolecule analyses, we show that integrated capillary HPLC-ESI-MS, based upon aqueous-methanol mobile phases and ion-pairing reverse-phase chromatography, can separate several major components from the nanoclusters mixture that may be difficult to resolve by standard native gel electrophoresis due to their similar size and charge. For each component, one obtains a well-resolved mass spectrum, nearly free of adducts or signs of fragmentation. A consistent set of molecular mass determinations is calculated from detected charge-states tunable from 3- (or lower), to 2+ (or higher). One thus arrives at a series of new compositions (n, p) specific to the Au/3-MBA system. The smallest major component is assigned to the previously unknown (48, 26); the largest one is evidently (67, 30), vs. the anticipated (68, 32). Various explanations for this discrepancy are considered. A prospective is given for the several members of this novel series, along with a summary of the advantages and present limitations of the micro-scale integrated LC/MS approach to characterize such metallic-core macro-molecules, and their derivatives.

Abstract. The purpose of this review is to investigate the nature of privacy concerns in the context of Smart Local Energy Systems (SLES) to understand how SLES providers can minimize both users’ concern, and cause for concern, around privacy. We conducted a rapid realist review and thematic framework analysis against Bronfrenbrenner’s socio-ecological model to understand privacy concerns in different contexts. A common privacy concern was that sharing detailed energy use data had the potential to reveal information about home life, and to intrude upon people’s sense of autonomy, choice and control. Evidence suggests that people are willing to accept newdata sharing technologies if the benefits of doing so are clear, anticipated, and mutually beneficial. Building trust, through increasing knowledge and understanding was a mechanism for overcoming privacy concerns, but this was mediated by the organization providing the information. Non-profit organizations were more trusted to ensure appropriate safeguards to privacy were in place. One key barrier to participation with good supporting evidence was that people can resist perceived intrusions on their privacy. This could be actively resisted by refusing to install data collection technologies or passively by non-participation in adapting energy use behaviors: both of which are necessary for SLES to achieve their goals of managing energy demand and building resilience in smart grids.

Despite the publication in 2009 of a paper on ‘terms and definitions of immune thrombocytopenia’, (ITP) some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, a ‘consensus’ to classify the different lines of treatment for primary ITP in adults according to their indications and goals was proposed in October 2018 to the XIX annual meeting of the Italian Gruppo di Studio delle Piastrine (GSP), a non-profit platelet study group of scientists and physicians. Having approved the project, 60 potential co-authors and experts in the world were invited to take part to a consensus through e-Delphy method and nine of the 12 who initially accepted the invitation completed the work. Agreement was reached on a classification of four lines of treatment for primary ITP in adults based on their indications and goals. The consensus obtained regarded also the criteria, ‘timing’ included, to consider practicable elective splenectomy in these patients. In our opinion, the classification of the lines of treatment for primary ITP in adults here proposed could facilitate the realization of better shared evidence-based guidelines for the treatment of the disease.

Genetic activation of the class I PI3K pathway is very common in cancer. This mostly results from oncogenic mutations in PIK3CA, the gene encoding the ubiquitously expressed PI3Kα catalytic subunit, or from inactivation of the PTEN tumour suppressor, a lipid phosphatase which opposes class I PI3K signalling. The clinical impact of PI3K inhibitors in solid tumours, aimed at dampening cancer-cell-intrinsic PI3K activity, has thus far been limited. Challenges include poor drug tolerance, incomplete pathway inhibition and pre-existing or inhibitor-induced resistance. The principle of pharmacologically targeting cancer-cell-intrinsic PI3K activity also assumes that all cancer-promoting effects of PI3K activation are reversible, which might not be the case. Emerging evidence suggests that genetic PI3K pathway activation can induce and/or allow cells to tolerate chromosomal instability, which – even if occurring in a low fraction of the cell population – might help to facilitate and/or drive tumour evolution. While it is clear that such genomic events cannot be reverted pharmacologically, a role for PI3K in the regulation of chromosomal instability could be exploited by using PI3K pathway inhibitors to prevent those genomic events from happening and/or reduce the pace at which they are occurring, thereby dampening cancer development or progression. Such an impact might be most effective in tumours with clonal PI3K activation and achievable at lower drug doses than the maximum-tolerated doses of PI3K inhibitors currently used in the clinic.

The carbonized elastomer-based composites (CECs) possess a number of attractive features in terms of thermomechanical and electromechanical performance, durability in aggressive media and facile net-shape formability, but their relatively low ductility and strength limit their suitability for structural engineering applications. Prospective applications such as structural elements of MEMS can be envisaged, since smaller principal dimensions reduce the susceptibility of components to residual stress accumulation during carbonization, and to brittle fracture in general. We report the results of operando in-SEM study of micro-deformation and fracture behavior of CECs based on NBR elastomeric matrices filled with carbon and silicon carbide. Nanostructured carbon composite materials were manufactured via compounding of elastomeric substance with carbon and SiC fillers using mixing rolling mill, vulcanization, and low-temperature carbonization. Double Edge Notched Tensile (DENT) specimens of vulcanized and carbonized elastomeric composites were subjected to in situ tensile testing in the chamber of the scanning electron microscope (SEM) Tescan Vega 3 using Deben Microtest 1 kN Tensile Stage. The series of acquired SEM images were analyzed by means of Digital Image Correlation (DIC) using Ncorr open source software to map the spatial distribution of strain. These maps were correlated with Finite Element Modelling (FEM) simulations to refine the values of elastic moduli. Besides, the elastic moduli were derived from unloading curve nanoindentation hardness measurements carried out using NanoScan-4D tester and interpreted using the Oliver-Pharr method. Carbonization causes significant increase of elastic moduli from 0.86 ± 0.07 to 14.12 ± 1.20 GPa for the composite with graphite and carbon black fillers. Nanoindentation measurements yield somewhat lower values, namely, 0.25 ± 0.02 GPa and 9.83 ± 1.10 GPa before and after carbonization respectively. The analysis of fractography images suggests that crack initiation, growth and propagation may occur both at the notch stress concentrator and relatively far from the notch. Possible causes of such response are discussed, namely, (1) residual stresses introduced by processing; (2) shape and size of fillers; and (3) the emanation and accumulation of gases in composites during carbonization.

Open-source 3-D printing has played a pivotal role in revolutionizing the additive manufacturing (AM) landscape, by making distributed manufacturing economic, democratizing access, and fostering far more rapid innovation than antiquated proprietary systems. Unfortunately, some 3-D printing manufacturing companies began deviating from open-source principles and violating licenses for the detriment of the community. To determine if a pattern has emerged of companies patenting clearly open-source innovations, this study presents three case studies from the three primary regions of open-source 3-D printing development (EU, U.S. and China) as well as three aspects of 3-D printing technology (AM materials, an open-source 3-D printer, and core open-source 3-D printing concepts used in most 3-D printers). The results of this review have shown that non-inventing entities called patent parasites are patenting open-source inventions already well-established in the open source community and in the most egregious cases commercialized by one (or several) firms at the time of the patent filing. Patent parasites are able to patent open-source innovations by using a different language, vague patent titles and broad claims that encompass enormous swaths of widely diffused open-source innovation space. This practice poses a severe threat to innovation and several approaches to irradicate the threat are discussed.

The regioselectivity in non-polar [3+2] cycloaddition (32CA) reactions has been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) level. To this end, the 32CA reactions of nine simplest three-atom-components (TACs) with 2-methylpropane were selected. The electronic structure of the reagents has been characterised through the Electron Localisation Function (ELF) and the Conceptual DFT. The energy profiles of the two regioisomeric reaction paths and ELF of the transition state structures are studied to understand the origin of the regioselectivity in these 32CA reactions. This MEDT study permits to conclude that the least electronegative ends X1 atom of these TACs controls the asynchronicity in the C-X (X = C,N,O) single bond formation, and consequently, the regioselectivity. This behaviour is a consequence of the fact that the creation of the non-bonding electron density required for the formation of the new CX single bonds has a lesser energetic cost at the least electronegative X1 atom than that at the Z3 one.

Bioactive glass (BG) represents a promising biomaterial for bone healing; here injectable BG pastes biological properties were improved by 25 wt% gelatin or chitosan, as well as mechanical resistance was enhanced by adding 10 or 20 wt% 3-Glycidyloxypropyl trimethoxysilane (GPTMS) cross-linker. Composites exhibited bioactivity as apatite formation was observed by SEM and XRD after 14 days immersion in SBF; moreover, polymers did not enhance degradability as weight loss was &gt;10% after 30 days in physiological conditions. BG-gelatin-20 wt% GPTMS composites demonstrated the highest compressive strength (4.8±0.5 MPa) in comparison with 100% BG control (1.9±0.1 MPa). Cytocompatibility was demonstrated towards human mesenchymal stem cells (hMSC), osteoblasts progenitors and endothelial cells. The presence of 20 wt% GPTMS conferred antibacterial properties thus inhibiting the joint pathogens Staphylococcus aureus and Staphylococcus epidermidis infection. Finally, hMSC osteogenesis was successfully supported in a 3D model as demonstrated by alkaline phosphatase release and osteogenic genes expression.

Flavan-3-ols and their oligomeric forms called proanthocyanidins are polyphenolic compounds occurring in several foodstuffs and in many medicinal herbs. Their consumption is associated with numerous health benefits. Their bioactivities include antioxidant, anti-inflammatory, cytoprotective, as well as antimicrobial. The latter property is important in prevention and treatment of periodontal diseases. Periodontitis is a multifactorial polymicrobial infection characterized by a destructive inflammatory process affecting the periodontium. Using non-toxic and efficient natural products such as flavanol derivatives can significantly contribute to alleviating of periodontitis symptoms and prevent the disease progress. In this paper, we systematically review the state-of-the art in antibacterial effects of these compounds from the viewpoint of gum health. There is a significant evidence supporting an importance of antibacterial action exerted by proanthocyanidins from edible fruits, tea and medicinal herbs in inhibition of periodontitis-causing pathogens.

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2) and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2 and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53-/- cells are insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis is promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulting in endoplasmic reticulum (ER) stress-mediated DR5 expression, which is upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with TRAIL synergistically enhanced I3M-induced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53-/- cells were resistant to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells.

The enhancement of health-beneficial omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly assigned into a split-plot design with pasture type as the main plot effect and pellet supplementation as a sub-plot effect in a feeding trial that lasted for nine weeks. The n-3 LC-PUFA content in Longissimus dorsi muscle of all lambs was well above the 30 mg threshold for “omega-3 source” nutrition claim under the Australian Food Standards and Guidelines. Pasture type impacted the fatty acid contents in muscle, heart and kidney of prime lambs. Lambs grazing cocksfoot only had the highest 18:3n-3 (ALA) and n-3 LC-PUFA contents (67.1 mg/100g and 55.2 mg/100 g, respectively). Supplementation of pellets with or without oil infusion to grazing lambs decreased the ALA and n-3 LC-PUFA contents and increased n-6/n-3 ratio in Longissimus dorsi muscle. The fatty acid content in internal organs of grazing lambs was also affected by pellet supplementation. The liver and kidney of grazing lambs were both “good sources” (60 mg/100 g) of omega-3. The cocksfoot grass showed considerable potential for producing healthy, premium quality meat with high contents of n-3 and n-3 LC-PUFA which may consequently enhance the omega-3 intake of Australian lamb consumers.

The paper briefly reviews the Clifford algebras of space Cl(3,0) and anti-space Cl(0,3) with a particular focus on the paravector representation, emphasizing the fact that both algebras have an isomorphic center represented just by two coordinates. Since the paravector representation allows assigning the scalar element of grade 0 to the time coordinate, we consider the relativity in such two-dimensional spacetime for a uniformly accelerated frame with the constant acceleration 3Hc. Using the Rindler coordinate transformations in two-dimensional spacetime and then applying it to Minkowski coordinates, we obtain the FLRW metric, which in the case of the Clifford algebra of space Cl(3,0) corresponds to the anti-de Sitter (AdS) flat (k=0) case, the negative cosmological term and an oscillating model of the universe. The approach with anti-Euclidean Clifford algebra Cl(0,3) leads to the de Sitter model with the positive cosmological term and the exact form of the scale factor used in modern cosmology.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

Within the scope of observed materialistic physical systems, without addressing the roots of H-Bar and big G, it is impossible to construct a workable model of final unification. With reference to our earlier proposed three large atomic gravitational constants, it is possible to reform and compactify the 10 dimensional String theory to 3+1 dimensions

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 goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease, and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease-specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2,200 with a range from 69 to 7,944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of new discoveries into clinical practice.

This paper proposes a new structure of the dual-rotor hybrid-excited axial-flux permanent magnet vernier machine (DR-HEAFPMVM) with the modular stator and the consequent-pole PM (CPM) rotor for low-speed, high torque density applications such as in-wheel electric vehicles. The tooth-wound non-overlapping armature windings and direct current (DC) excitation windings are respectively arranged in stator main-teeth and split-teeth to obtain the modulated and adjustable air-gap flux densities, which result in the high torque density and outstanding flux-weakening capability. First, the design consideration, operation principle, and the air-gap flux density distributions of the proposed machine are elaborated based on the air-gap permeance function. Then, the influence of the pole ratios (PRs) and the DC excitation currents on the main electromagnetic performances of the DR-HEAFPMVM, such as the flux-weakening capability, back-electromotive force (back-EMF), on-load electromagnetic torque, loss distribution, and efficiencies, is investigated using the 3-D finite-element method (FEM). Results verify the feasibility of the flux adjustment of the DC excitation windings equipped in the split-tooth, and the design with a pole ratio of 8/1 tends to have higher torque density, higher machine efficiency, and considerable flux-weakening capability compared with the other two PRs.

Background and Objectives: In the current Covid-19 pandemic, children below the age of 12 could manifest Covid-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. Subjects and Methods: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. Results: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to Covid-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to Covid-19. Children with previous Covid-19 exposure had higher averages of anti-S (2379 U/ml compared to 409.1), anti-N (177.6 U/ml compared to 30.9) and neutralizing antibody (93.7 U/ml compared to 77.1) than children with no prior exposure at day 35. Conclusions: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.

We reported previously that poly (3-hydroxybutyrate) (PHB) oligomer is an effective antimicrobial agent against gram-positive bacteria, gram-negative bacteria, fungi and multi-drug resistant bacteria. In this work, it was further found that polyethylene glycol (PEG) can promote the antimicrobial effect of PHB oligomer synergistically. Three hypothetic mechanisms were proposed, that is, generation of new antimicrobial components, degradation of PHB macromolecules and dissolution/dispersion of PHB oligomer by PEG. With a series of systematic experiments and characterizations of HPLC-MS, it was deducted that dissolution/dispersion of PHB oligomer dominated the synergistic antimicrobial effect between PHB oligomer and PEG. This work demonstrates a way for promoting antimicrobial effect of PHB oligomer and other antimicrobial agents through improving hydrophilicity.

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

Plants are constantly exposed to a variety of different environmental stresses, including drought, salinity, and elevated temperatures. These stress cues are assumed to aggravate in the future driven by the global climate change scenario which we are currently experiencing. These stressors have largely detrimental effects on plant growth and development and, therefore, put global food security in jeopardy. For this reason, it is necessary to expand our understanding of the underlying mechanisms by which plants respond to abiotic stresses. Especially boosting our insight into the ways by which plants balance their growth and their defense programs appears to be of paramount importance, as this may lead to novel perspectives that can pave the way to increase agricultural productivity in a sustainable manner. In this review, our aim was to present a detailed overview of different factettes of the crosstalk between the antagonistic plant hormones abscisic acid (ABA) and auxin, two phytohormones that are the main drivers of plant stress responses, on the one hand, and plant growth, on the other.

Multi- and hyper-spectral, multi-angular top-of-canopy reflectance data call for an efficient retrieval system which can improve the retrieval of standard canopy parameters (as albedo, LAI, fAPAR), and exploit the information to retrieve additional parameters (e.g. leaf pigments). Furthermore consistency between the retrieved parameters and quantification of uncertainties are required for many applications. % (2) methods We present a retrieval system for canopy and sub-canopy parameters (OptiSAIL), which is based on a model comprising SAIL, PROSPECT-D (leaf properties), TARTES (snow properties), a soil model (BRDF, moisture), and a cloud contamination model. The inversion is gradient based and uses codes % created by Automatic Differentiation. The full per pixel covariance-matrix of the retrieved parameters is computed. For this demonstration, single observation data from the Sentinel-3 SY_2_SYN (synergy) product is used. The results are compared with the MODIS 4-day LAI/fPAR product and PhenoCam site photography. OptiSAIL produces generally consistent and credible results, at least matching the quality of the technically quite different MODIS product. For most of the sites, the PhenoCam images support the OptiSAIL retrievals. The system is computationally efficient with a rate of 150 pixel per second (7 millisecond per pixel) for a single thread on a current desktop CPU using observations on 26 bands. Not all of the model parameters are well determined in all situations. Significant correlations between the parameters are found, which can change sign and magnitude over time. OptiSAIL appears to meet the design goals, puts real-time processing with this kind of system into reach, seamlessly extends to hyper-spectral and multi-sensor retrievals, and promises to be a good platform for sensitivity studies. The incorporated cloud and snow detection adds to the robustness of the system.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

Distinctive strains of Pantoea are used as soil inoculants for their ability to promote plant growth. Pantoea agglomerans strain C1, previously isolated from the phyllosphere of lettuce, can produce indole-3-acetic acid (IAA), solubilize phosphate, and inhibit plant pathogens, such as Erwinia amylovora. In this paper, the complete genome sequence of strain C1 is reported. In addition, experimental evidence is provided on how the strain tolerates arseniate up to 100 mM, and on how secreted metabolites like IAA and siderophores act as biostimulants in tomato cuttings. The strain has a circular chromosome and two prophages for a total genome of 4,846,925-bp, with a GC content of 55.2%. Genes related to plant growth promotion and biocontrol activity, such as those associated with IAA and spermidine synthesis, solubilization of inorganic phosphate, acquisition of ferrous iron, and production of volatile organic compounds, siderophores and GABA, were found in the genome of strain C1. Genome analysis also provided better understanding of the mechanisms underlying strain resistance to multiple toxic heavy metals and transmission of these genes by horizontal gene transfer. Findings suggested that strain C1 exhibits high biotechnological potential as plant growth-promoting bacterium in heavy metal polluted soils.

Either stereo reactants or stereo catalysis from achiral or chiral molecules are prerequisite to obtain pure enantiomeric lipid derivatives. We reviewed a few plausible organic syntheses of phospholipids under prebiotic conditions with a special attention to the starting materials as pro-chiral dihydroxyacetone and dihydroxyacetone phosphate (DHAP), which are the key molecules to break symmetry in phospholipids. The advantages of homochiral membranes compared to those of heterochiral membranes were analysed in term of specific recognition, optimal functions of enzymes, membrane fluidity and topological packing. All biological membranes contain enantiomeric lipids in modern bacteria, eukarya and archaea. The contemporary archaea, comprising of methanogens, halobacteria and thermoacidophiles are living under extreme conditions reminiscent of primitive environment and may indicate the origin of one ancient evolution path of lipid biosynthesis. The analysis of lipid metabolism reveals that all modern cells including archaea synthetize enantiomeric lipid precursors from prochiral DHAP. sn-glycerol-1-phosphate dehydrogenase (G1PDH), usually found in archaea, catalyses the formation of sn-glycerol-1-phosphate (G1P), while sn-glycerol-3-phosphate dehydrogenase (G3PDH) catalyses the formation of sn-glycerol-3-phosphate (G3P) in bacteria and eukarya. The selective enzymatic activity seems to be the main strategy that evolution retained to obtain enantiomeric pure lipids. The occurrence of two genes encoding for G1PDH and G3PDH, served to build up an evolution tree and the basis of our review focusing on the evolution of these two genes. Gene encoding for G3PDH in Eukarya may originate from G3PDH gene found in rare archaea indicating that archaea appeared earlier in the evolution tree than eukarya. Archaea and bacteria evolved probably separately, due to their distinct respective genes coding for G1PDH and G3PDH. The suggested hypothesis is that catalysis of homochiral G1P or G3P from DHAP are more efficient than those leading to racemic G1P and G3P, since there are no enzymes able to synthesize racemic G1P and G3P from DHAP. We propose that G1PDH or G3DPH, which are not “image mirror enzymes” but belonging to distinct family of proteins, emerged separately during evolution. They were probably selected for their efficient catalytic activities during evolution from large libraries of vesicles containing various biopolymers, including amino acids, carbohydrates, nucleic acids, lipids, and meteorite components to induce chemical imbalance.

Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

This paper presents an innovative testing framework, testFAILS, designed for the rigorous evaluation of AI Linguistic Systems, with a particular emphasis on various iterations of ChatGPT. Leveraging orthogonal array coverage, this framework provides a robust mechanism for assessing AI systems, addressing the critical question, "How should we evaluate AI?" While the Turing test has traditionally been the benchmark for AI evaluation, we argue that current publicly available chatbots, despite their rapid advancements, have yet to meet this standard. However, the pace of progress suggests that achieving Turing test-level performance may be imminent. In the interim, the need for effective AI evaluation and testing methodologies remains paramount. Our research, which is ongoing, has already validated several versions of ChatGPT, and we are currently conducting comprehensive testing on the latest models, including ChatGPT-4, Bard and Bing Bot, and the LLaMA model. The testFAILS framework is designed to be adaptable, ready to evaluate new bot versions as they are released. Additionally, we have tested available chatbot APIs and developed our own application, AIDoctor, utilizing the ChatGPT-4 model and Microsoft Azure AI technologies

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

After a long limbo, RNA has gained its credibility as a druggable target, fully earning its de-served role in the next-generation area of pharmaceutical R&D. We have recently probed the Trans-Activation Response element (TAR), a RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabiliz-ing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analyti-cal approaches for the study of multicomponent RNA-based interactions.

The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (300-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 leads to a significant reduction in tumoroid size and to the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. These weakened phenotypes by MMP3 KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated into recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3 resulting in increasing the proliferation and CD9+ tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

Recently, the Third Generation Partnership Project (3GPP) introduced the New Radio (NR) technology for Vehicle-to-everything (V2X) communication to enable delay-sensitive and bandwidth-hungry applications in vehicular communication. The NR system is strategically crafted to complement the existing Long Term Evolution (LTE) Cellular-Vehicle-to-Everything (C-V2X) infrastructure, particularly to support advanced services such as the operation of automated vehicles. It is widely anticipated that the 5th generation (5G) NR system will surpass LTE C-V2X in terms of achieving superior performance in scenarios characterized by high throughput, low latency, and enhanced reliability, especially in the context of congested traffic conditions and a diverse range of vehicular applications. This article will provide a comprehensive literature review on vehicular communications from Dedicated Short Range Communication (DSRC) to NR V2X. Subsequently, it delves into a detailed examination of the challenges and opportunities inherent in NR V2X technology. Finally, we proceed to elucidate the process of creating and analyzing an open-source 5G NR V2X module in network simulation-3 (ns-3) and then demonstrate the NR V2X performance in terms of different key performance indicators implemented through diverse operational scenarios.

Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.

We present a cost- and time-efficient method for the controlled preparation of single phase La(IO3)3 nanoparticles via a simple soft-chemical route which takes a matter of hours, thereby providing an alternative to the common hydrothermal method which takes days. Nanoparticles of pure α-La(IO3)3 and pure δ-La(IO3)3 were synthesised via the new method depending on the source of iodate ions, thereby demonstrating the versatility of the synthesis route. The crystal structure, nanoparticle size-dispersal and chemical composition were characterised via angle- and energy-dispersive powder X-ray diffraction, scanning electron microscopy and Fourier-transform infrared spectroscopy.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Disordered eating is a serious health concern globally. The etiology is complex and multidimensional and differs somewhat for each specific eating disorder. Several risk factors have been identified which include psychological, genetic, biochemical, environmental, and sociocultural factors. Poor body image, low self-esteem, teasing, family dynamics, and exposure to media images have also been identified as risk factors. While it is enticing to consider a single behavioral risk factor, doing so fails to consider the documented environmental, social, psychological, biological, and cultural factors that contribute to the development of an eating disorder in a multidimensional and complex integration that is undoubtedly unique to everyone. Focusing only on any one factor without taking the complex etiology into account is remiss. For example, it has been suggested that the use of dietary supplements may lead to eating disorders, despite a lack of evidence to support this conjecture. Therefore, the purpose of this review is to examine the evidence-based risk factors for eating disorders and discuss why connecting dietary supplements to eating disorder etiology is not supported by the scientific literature and may interfere with treatment. Established, effective prevention and treatment approaches for eating disorders should be the focus of public health initiatives in this domain.

Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination in considered the only sustainable method for global trypanosomosis control. Unfortunately, not a single field applicable vaccine solution has been successful so far. Active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here we show Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and diminazene diaceturate anti-parasite treatment scheme, our result demonstrate that while the latter ensured the full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-pertussis vaccine recall response. DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-pertussis antibody ratio in favor of the latter, and a striking impact on all spleen immune cell populations. Interestingly, an increased plasma IFNy level in DTPa vaccinated trypanosome infected mice did result in a temporary antibody-independent improvement of early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome inflicted immune damage is permanent, and is not restored by successful anti-parasite treatment.

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in RGD (arginine-glycine-aspartic acid) sequences, with good processability that is being investigated for regenerative medicine applications. Recently, the biocompatibility and osteogenic ability of β-TCP/RCP (RCP granules combined with β-tricalcium phosphate (TCP) submicron particles) were demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects (three-walled bone defect) created in beagle dogs to investigate tissue responses and subsequent regenerative effects. Micro computed tomography image analysis at 8 weeks postoperatively showed that the amount of new bone after β-TCP/RCP graft was significantly greater (2.2 fold, P&lt;0.05) than that of the control (no graft) group. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including TRAP-positive and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control, and significantly suppressed gingival recession and epithelial downgrowth (P&lt;0.05). These results suggest that β-TCP/RCP is effective as a periodontal tissue regenerative material.

Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs) involved in the regulation of 60% of human gene activity remains poorly explored. Similar to what we have previously done with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 hours post-infection, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h while at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. By RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17 and FURIN), in renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2.

Accumulating literature demonstrates that omega-3 polyunsaturated fatty acid (N3PUFA) can be incorporated into the phospholipid bilayer of cell membrane in the human body to positively affect the cardiovascular system, including improving epithelial function, decreasing coagulopathy, and attenuating uncontrolled inflammatory responses and oxidative stress. Moreover, it has been proven that the N3PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of some potent endogenous bioactive lipid mediators that mediate some favorable effects attributed to their parent substances. A linear dose-response relationship between increased EPA and DHA intake and reduced thrombotic outcomes have been reported. The excellent safety profile of dietary N3PUFA makes them a prospective adjuvant treatment for people exposed to a higher risk of cardiovascular problems associated with COVID-19. This review presented the potential mechanisms that might contribute to the beneficial effect of N3PUFA and the optimal form and dose applied.

The evolutionary success of land plants largely relies on their ability to cope with constant environmental fluctuations, which negatively impact their reproductive fitness and trigger adaptational responses to biotic and abiotic stresses. In this challenging scenario, comprehensive research efforts so far aimed at depicting the roles of well-known phytohormones, mainly auxins, along with brassinosteroids, jasmonates, and abscisic acid, although the signaling networks coordinating the crosstalk among them remains vaguely understood. Accordingly, this review focuses on the Arabidopsis Amidase Signature (AS) superfamily members, highlighting the hitherto relatively underappreciated functions of AMIDASE1 (AMI1) and FATTY ACID AMIDE HYDROLASE (FAAH), as crucial coordinators of the growth-defense response trade-off by modulating auxin and ABA homeostasis.

Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ols (FL), a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FL possibly activates sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1α were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

Let $\mathcal{N}$ be an arbitrary class of matroids, closed under isomorphism. For $k$ a positive integer, we say that $M \in \mathcal{N}$ is \emph{$k$-minor-irreducible} if $M$ has no minor $N \in \mathcal{N}$ such that $1\leq\left|E\left(M\right)\right|-\left|E\left(N\right)\right|\leq k $. Tutte's Wheels and Whirls Theorem establish that, up to isomorphism, there are only two families of 1-minor-irreducible matroids in the class of 3-connected matroids. More recently, Lemos classified the 3-minor-irreducibles with at least 14 elements in the class of triangle-free 3-connected matroids. Here we prove a local characterization for the 2-minor-irreducible matroids with at least 11 elements in the class of triangle-free 3-connected matroids. This local characterization is used to establish two new families of 2-minor-irreducible matroids in this class.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

Japan Aerospace Exploration Agency (JAXA) is going to launch Advanced Land Observing Satellite 3 (ALOS-3) after 2022. ALOS-3 satellite is capable of observing global land areas with wide swath (4000 km along-track direction and 70 km cross-track direction) at high spatial resolution (panchromatic: 0.8m, multispectral: 3.2m). Maintenance and updating of land cover and vegetation information at national level is one of the major goals of the ALOS-3 mission. This paper presents the potential of simulated ALOS-3 images for the classification and mapping of land cover and vegetation types at Genus-Physiognomy-Ecosystem (GPE) level. We acquired and simulated WorldView-3 images according to the configuration of the ALOS-3 satellite sensor and the simulated ALOS-3 images were utilized for the classification and mapping of land cover and vegetation types in three sites (Hakkoda, Zao, and Shiranuka) in northern Japan. This research dealt with 17 land cover and vegetation types in Hakkoda site, 25 land cover and vegetation types in Zao site, and 12 land cover and vegetation types in Shiranuka site. Ground truth data were newly collected in three sites, and we employed eXtreme Gradient Boosting (XGBoost) classifier with the implementation of 10-fold cross-validation method for assessing the potential of ALOS-3S images. The classification accuracies obtained in Hakkoda, Zao, and Shiranuka sites in terms of f1-score were 0.810, 0.729, and 0.805 respectively. The fine scale (3.2m) land cover and vegetation maps produced in the study sites showed clear and detailed view of the distribution of plant communities. Regardless of the limited number of the temporal images, ALOS-3S images showed high potential (at least 0.729 F1-score) for the land cover and vegetation classification in all three sites. The availability of more cloud free temporal scenes is expected for improved classification and mapping in the future.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. In this study, the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in liver were investigated. Rats were fed the diets with (0.54 %) or without EGCG supplementation for four weeks and were then intraperitoneally injected with acetaminophen (1g/kg). Results showed EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by increasing the Bax/Bcl2 ratio in liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen-glutathione and acetaminophen-protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in liver after acetaminophen treatment. Our results indicate that EGCG may lower oxidative stress and reduce the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in liver and thus lower hepatotoxicity

GPR4, a member of proton activated GPCRs group. Previously we have reported that GPR4 is constitutively active at physiological pH and knockout of GPR4 has shown to protect dopaminergic neuronal cells from caspase-dependent mitochondrial apoptotic cell death. In this study we have investigated the role of GPR4 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice model of Parkinson’s disease. Subchronic administration of MPTP in mice produces oxidative stress induced apoptotic cell death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor deficits. Treatment with NE52-QQ57, a selective antagonist of GPR4 reduced dopaminergic neuronal loss MPTP-intoxicated C57BL6/J mice and improved motor deficit and memory impairment. Co-treatment with NE52-QQ57 significantly decreases the protein level of proapoptotic marker (Bax), and increases the antiapoptotic marker (Bcl-2) in the SNpc and striatum tissue collected from the brain of MPTP inflicted mice. Further, MPTP induced activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP) was significantly decreased in the SNpc and striatum tissue of NE52-QQ57 cotreated mice. Further mice receiving both MPTP and NE52-QQ57 mice showed significantly higher TH positive cells in the SNpc and striatum than MPTP treated mice alone. Moreover, NE52-QQ57 cotreatment improved the motor activity in the rotarod test and pole test and also improved spatial memory in Y maze test. Our findings suggest GPR4 as a potential therapeutic target for PD whereas the activation GPR4 is involved in the caspase mediated apoptotic cell death in SNpc and striatum of MPTP-intoxicated mice.

A patient in her early 20s presented with constant and progressive lower abdominal and back pain, mainly on the right side of the abdomen, purulent vaginal discharge and pyrexia. Radio-logical assessment revealed a possible tuboovarian abscess and incidental diagnosis of ipsilateral renal agenesis. The patient was treated for pelvic inflammatory disease (PID), however after antibiotic administration and since the symptoms were not resolving, an abdominal MRI was requested which revealed a uterus didelphys with two cervices, an obstructed haemivagina and evidence of haematocolpos. The diagnosis of OHVIRA syndrome was confirmed and the patient underwent an excision of the vaginal septum, drainage of the haematopyocolpos and laparoscopic drainage of the tuboovarian abscess. She achieved a good recovery.