The detection of antibiotic-resistant facultative pathogenic bacteria in surface waters is common in the present day. However, there is limited understanding of the factors that influence the spread and stabilization of resistance in this habitat, particularly regarding the role of biofilms. Despite the perceived differences between sediments, biofilms, and open water, their potential contribution to the long-term maintenance of resistances remains unclear. In this study, we investigated Escherichia coli isolates obtained from the Mur and Drava rivers in Austria. Samples were collected from both the water column and sediment at two locations per river: upstream and downstream of an urban area, including a sewage treatment plant. The iso-lates were subjected to antimicrobial susceptibility testing against 21 antibiotics belonging to seven distinct classes. Additionally, any isolates exhibiting an extended-spectrum beta-lactamase (ESBL) or carbapenemase phenotype were further analyzed for the presence of specific antimi-crobial resistance genes. E. coli isolates obtained from the two rivers exhibited resistance to at least one of the tested anti-biotics, with rates of 25.83% and 23.66% respectively. The most prevalent antimicrobial re-sistances observed were towards ampicillin, amoxicillin-clavulanic acid, tetracycline, and na-lidixic acid. Surprisingly, there was a similar proportion of resistant bacteria observed in both open water and sediment samples, contrary to expectations. The difference in resistance levels between samples collected upstream and downstream of the cities was minimal. Out of the total isolates, 13 E. coli were found to carry ESBL genes with one isolate carrying the gene for KPC-2 carbapenemase. There were no significant differences between the biofilm (sediment) and open water samples in the occurrence of antimicrobial resistance. Even the difference between the samples upstream and downstream of the cities and their wastewater treatment plants was minor. There seems to be no evidence of a large adaptive effect in this analysed biofilm population of E. coli. The un-typical phenotype of the KPC-producing and some of the ESBL-producing E. coli from this study could, however, be an indication that such adaptation effects generally exist in water.

Abstract: Background: Restless Legs Syndrome /Willis-Ekbom disease (RLS/WED) has occasionally -but not consistently- been associated with cognitive, and most notably, language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia, with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the partici-pants. Generalized estimating equations analysis was used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female, older (72.9 ±4.9 years) partici-pants, with follow-up evaluations after a mean of 3.09 ±0.85 years and without demen-tia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by 0.249 of a standard deviation, while demonstrating a mitigated language decline over time, by 0.063 of a standard deviation. The unadjusted models yielded similar results. Conclu-sions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

Grape production worldwide is increasingly threatened by grapevine trunk diseases (GTDs). No grapevine cultivar is known to be entirely resistant to GTDs, but susceptibility varies greatly. To quantify these differences, four Hungarian grape germplasm collections containing 305 different cultivars were surveyed to determine the ratios of GTDs based on symptom expression and mortality rate. The cultivars of monophyletic Vitis vinifera L. origin were amongst the most sensitive ones, and their sensitivity was significantly (p<0.01) higher than that of the interspecific (hybrid) cultivars assessed, which are defined by the presence of Vitis species other than V. vinifera (e.g. V. labrusca L., V. rupestris Scheele, V. amurensis Rupr.) in their pedigree. We conclude that ancestral diversity of the grape confers higher degrees of resilience against GTDs.

The possibility of using some warnings inside modern vehicles should be an aid to the driving activity. However, the information transferred to users is not always received in the expected way due to the variability and complexity of the road environment. This study, therefore, aims to identify a procedure that allows to ascertain whether drivers receive the data in an appropriate way even during particular manoeuvres, such as passing cyclists on a winding road or, on the contrary, if they represent an unnecessary overload. To answer this question, an experimentation in a simulated environment was set up with which the drivers’ visual behaviour was recorded in presence and absence of a driving aid device (On- Board Unit, OBU). The results show that, in some situation, the information provided by the OBU helps to maintain a more virtuous driving behaviour but, in the most complex ones, drivers acquire information from a smaller number of sources, excluding the aid devices present inside the cockpit. This procedure is useful for ADAS designers in order to refine these instruments but also for road managers who can improve safety by inserting appropriate signs or speed limits.

Age-related macular degeneration (AMD) is a complex, multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily its “dry” type, which is by far the most common (90% of all AMD cases). In recent years, AMD became younger: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review is to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.

Psychedelics extracted by plants have been used in religious, spiritual and mystic practices for millennia. In 1957, Dr. Hofmann have identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. Although the limitations related to the scientific design of many studies, clinical observations performed during the 1950s and the 1960s have shown a potential therapeutic effect of psilocybin in patients affected by depressive symptoms, anxiety, and conversion disorder. Psilocybin was classed as a schedule I substance in 1970, but the fascination for psychedelics remained almost unchanged over time promoting a new scientific interest starting from the 1990s. Recent studies provided further evidences supporting the suggestive hypothesis of a therapeutic use of psilocybin for treating various psychiatric disorders including: pathological anxiety, mood depressive disorder and addiction.

Abstract: Ultrasonic vocalizations (USVs) are one of the evolutionarily oldest forms of animal communication. In order to study the communication architecture in an aversive social situation, we used a behavioral model in which one animal, the observer, is witnessing as his cagemate, the demonstrator, is experiencing a series of mild electrical foot-shocks (aversive stimuli). We studied the effect of foot-shocks experience in the observer and the influence of a warning sound (emit-ted shortly before the shock is applied) on USVs communication. These experiments revealed that such a warning seems to increase the arousal level, which differentiates the responses depending on previous experience. It can be identified by the emission of characteristic, short 22-kHz calls, of a duration below 100 ms. Furthermore, by analyzing temporally overlapping USVs, we found that in ‘Warned’ pairs with a naive observer, 22-kHz were mixed with 50-kHz calls. This fact, combined with a high fraction of very high-pitched 50-kHz calls (over 75-kHz), suggests the presence of the phenomenon of social buffering. On the other hand, in ‘Warned’ pairs with an experienced observer, pure 22-kHz overlaps were mostly found, signifying possible fear contagion with dis-tress sharing. Hence the importance of differentiating 22-kHz calls to long and short.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PF4) autoantibodies.

Extracorporeal shock wave therapy (ESWT) is a well investigated and widely used treatment modality for a number of musculoskeletal disorders. A limitation of ESWT is its potential painfulness at higher, clinically relevant energy flux density (EFD), which may limit its applicability and, thus, effectiveness. Various studies in the literature demonstrated that neither application of a higher number of extracorporeal shock waves with lower EFD nor use of local anesthesia may solve this problem. Based on the results of several other studies in the literature it is hypothesized here that in patients suffering from musculoskeletal disorders that can be treated with ESWT, pretreatment with a pulsed, high power laser with a wavelength of 904 or 905 nanometers (hereafter: "laser pretreatment") does not only allow to apply higher EFDs in subsequent ESWT but actually results in faster and/or better treatment outcome than ESWT without laser pretreatment. Accordingly, it is hypothesized here that combining ESWT with laser pretreatment leads to synergistic effects and, thus, is superior to either treatment modality alone. Confirming this hypothesis in preclinical and clinical research may raise significance and increase the use of ESWT in physical and rehabilitation medicine, with immediate benefit for patients.

The coronavirus COVID-19 epidemic has wreaked havoc on inhabitants of earth killing thousands of humans from more than 150 countries. The epidemic has put a number of countries under complete lockdown and the deadly situation is still prevailing around the globe. Vaccines have been long known as the most effective means of preventing viral infections. However, the lack of vaccines against COVID-19 has further worsened the situation. In this time of health crisis, it is the duty of scientific research community to provide alternative, effective and affordable strategies to vaccinate human bodies against viral infections-COVID-19 based on focused experimental approaches. Growing evidence suggests that certain natural foods and lifestyle changes have potential to optimize immune functions against viral infections including improving defense function, resistance towards invading pathogens, while maintaining self-tolerance. Boosting immune system gives an edge in fending off viruses and staying healthy. This review presents the six smart steps to add to your to-do list which let the inner work of immunity take place against viral infections-COVID-19 by dissolving the powers of disease and illness. Many of these factors are associated in their functions to improve or properly maintain the immune function such as promoting anti-inflammatory functions, inhibiting pro-inflammatory mediators, modulating cell-mediated immunity, altering the antigen-presenting cellular functions as well as promoting communication between the innate and adaptive immune responses. Thus, a scientific illustration of boosting the immune system by proper sleep, moderate exercise, avoiding stress, utilizing vitamins enriched foods, intake of more water and use of fruits and vegetables will hopefully help the community to deal with the coronavirus by vaccinating the human systems naturally.

The Landauer principle supplies the estimation of the minimal mass of a particle which is capable to record/erase information within a thermal bath at the temperature of T. Particles lighter than ${\tilde{m}}_0=\frac{k_{B}Tln2}{c^2}$will not transform the information to the surrounding bodies and are well expected to be undetectable. The relation of the Landauer principle to the problem of “dark matter” is discussed. The maximal informational content of a particle at rest, estimated as $I_{max}=\frac{m_0{c}^2}{k_{B}Tkn2}$ is introduced. The Landauer principle also allows the estimation of minimal energy of the field which is capable to record/erase 1 bit of information in the surrounding at the temperature of T. The relativistic aspects of the Landauer principle and its relation to the relativistic transformation of temperature are addressed.

Luteinizing hormone receptor (LHR) is a member of the seven-transmembrane (TM) receptor family. Several mutations in LHR have been identified in many mammalian species, leading to either constitutive activation or inactivation of the receptor. Mutations in highly conserved regions of the TM domain have been reported. In this study, we analyzed signal transduction by three constitutively active mutants (designated M410T, L469R, and D590Y) and two inactivating mutants (D383N and Y546F) of eelLHR known as naturally occurring in human LHR . To directly assess the functional effects of these mutations, site-directed mutant receptors were transiently expressed in CHO-K1 cells and cAMP accumulation stimulated by recombinant eelLH (rec-eelLH) was measured by homogeneous time-resolved fluorescence (HTRF) assays. The cAMP response in cells expressing eelLHR wild-type (eLHR-WT) increased in a dose-dependent manner with rec-eelLH ligand stimulation. Cells expressing the activating eelLHR mutants, M410T, L469R, and D590Y, exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response, respectively. However, their maximal responses were approximately 73, 53, and 92%, respectively, of the maximal response of LHR-WT. The L469R mutant exhibited a particularly marked increase in cAMP production in the absence of agonist. The maximal responses of the inactivating mutants, D383N and Y546F, were 32 and 24% of LHR-WT, respectively. However, the inactivating mutations did not completely impair signal transduction. Thus, we report here the first characterization of activating and inactivating mutations in eelLHR and we show that these mutations have similar effects as those reported for mammalian LHRs. Moreover, eelLHR with activating mutations showed constitutive cAMP responses. These results provide important data on the signal transduction of constitutively active and inactive LHR mutants. Further studies should aim to identify the mechanism responsible for the significant increase in basal cAMP response in the constitutively activated eelLHR mutants.

In a recent Foundations of Physics paper [5] by the current author it was shown that, when the self-force problem of classical electrodynamics is properly solved, it becomes a plausible ontology underlying the statistical description of quantum mechanics. In the current paper we extend this result, showing that ordinary matter, thus represented, possibly suffices in explaining the outstanding observations currently requiring for this task the contrived notions of dark-matter, dark-energy and inflation. The single mandatory 'fix' to classical electrodynamics, demystifying both very small and very large scale physics, should be contrasted with other adhoc solutions to either problems. Instrumental to our cosmological model is scale covariance (and 'spontaneous breaking' thereof), a formal symmetry of classical electrodynamics treated on equal footing with its Poincare covariance, which is incompatible with the (absolute) metrical attributes of the GR metric tensor.

This study explores the determinants of ICO success, where success is defined as the amount of capital a project was able to raise. ICOs are a tool for startups in the blockchain ecosystem to raise early capital with relative ease. The market for ICOs has grown at a rapid pace since its start in 2013. We analyze a unique dataset of 278 projects that finished their ICOs by August 2017 to assess determinants of funding success that we derive from the crowdfunding and venture capital literature. Our results show that ICOs exhibit similarities to classical crowdfunding and venture capital markets. Specifically, we identify resemblances in determinants of funding success regarding human capital characteristics, business model quality, project elaboration and social media activity.

Geometric Akaike Information Criteria (G-AICs) for generalized noise-level dependent crystallographic symmetry classifications of two-dimensional (2D) images that are more or less periodic in either two or one dimensions as well as Akaike weights for multi-model inferences and predictions are reviewed. Such novel classifications do not refer to a single crystallographic symmetry class exclusively in a qualitative and definitive way. Instead, they are quantitative, spread over a range of crystallographic symmetry classes, and provide opportunities for inferences from all classes (within the range) simultaneously. The novel classifications are based on information theory and depend only on information that has been extracted from the images themselves by means of maximal likelihood approaches so that these classifications are objective. This is in stark contrast to the common practice whereby arbitrarily set thresholds or null hypothesis tests are employed to force crystallographic symmetry classifications into apparently definitive/exclusive states, while the geometric feature extraction results on which they depend are never definitive in the presence of generalized noise, i.e. in all real world applications. Thus, there is unnecessary subjectivity in the currently practiced ways of making crystallographic symmetry classifications, which can be overcome by the approach outlined in this review.

Ozonated sunflower oil (OSO) is renowned for its diverse therapeutic benefits. Nonetheless, the consequences of extended dietary intake of OSO have yet to be thoroughly investigated. Herein, the effect of 2-year dietary supplementation of OSO was examined on the zebrafish survivability, obesity, skeletal deformities, swimming behavior, and liver, kidney, ovary, and testis function. Results showed that the zebrafish feed supplemented with 20% (wt/wt) OSO for 2 years emerged with higher survivability and body weight management compared to sunflower oil (SO) and normal diet (ND) supplemented zebrafish. Radio imaging (X-ray) based analysis revealed 2.6o and 15.2o lower spinal curvature in the OSO-supplemented groups than in SO and ND-supplemented groups; consistently, OSO-supplemented zebrafish showed better swimming behavior. The histology analysis of the liver revealed a least fatty liver change and interleukin 6 (IL-6) generation in the OSO-supplemented group. Additionally, a significantly lower level of reactive oxygen species (ROS), apoptotic, and senescent cells were observed in the liver of the OSO-supplemented zebrafish. Also, no adverse effect on the kidney, testis, and ovary morphology was detected during 2 years of OSO consumption. Moreover, lower senescence with diminished ROS and apoptosis was noticed in the kidney and ovary in response to OSO consumption. The OSO supplementation was found to be effective in countering age-associated dyslipidemia by alleviating total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-C) and elevating high-density lipoproteins (HDL-C)/TC levels. Conclusively, prolonged OSO consumption showed no adverse effect on the morphology and functionality of vital organs; in fact, OSO supplementation displayed a protective effect against age-associated detrimental effects on spinal deformities, vital organ functionality, cell senescence, and survivability of zebrafish.

The photophysical properties of Cu(II) complexes with 5,10,15,20-meso-tetrakis(phenyl)porphyrin and 5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin were examined by luminescence and femtosecond time-resolved absorbance methods respectively. These studies were supported by DFT and TD-DFT calculations which highlight the important role played by a ligand-to-metal charge-transfer states in directing the system towards either intersystem crossing to the triplet hypersurface or coordinative expansion to a five-coordinate quasi-stable intermediate. The latter processes occurs when the porphyrin is photolyzed in the presence of suitably located Lewis bases. Femtosecond time resolved absorbance measurements on Cu(II)-5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin confirm that the coordinative expansion in water occurs in approximately 700 fs while crossing to the triplet hypersurface takes approximately 140 fs in the same solvent. These processes are mutually exclusive, but both can occur simultaneously depending on the environment of the porphyrin. The ratio of the two processes depends on the relative orientation of the Lewis base with respect to the copper atom at the time of excitation. As a consequence, copper porphyrins such as these, are excellent probes to the environment of the porphyrin, and can be used to identify the location of the porphyrin when interacting with DNA fragments.

This paper provides a new discovery that adds to the contemporary theory of modelling of non-stationary queues, by capturing analytically the behavior of the root parameter, for the G1/M/1 PSFFA model of non-stationary Ek/M/1 queue. Additionally, it has been also revealed that the resulting root parameter reduces to the PSFFA model of non-stationary queue. Potential applications of PSFFA to Computer engineering are provided. Some challenging open problems are addressed combined with closing remarks and future research directions.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

Accurate pathogenic detection in wastewater is critical for safeguarding public health and the environment. However, the presence of free nucleic acids in wastewater samples poses significant challenges to molecular detection accuracy. This comprehensive review explores the current status and future potential of pretreatment methods to remove free nucleic acids from wastewater samples. The study contributes a comprehensive analysis of the mechanisms, strengths, and limitations of various pretreatment approaches, including physical, chemical, and enzymatic processes. The effect of various factors on the removal efficiency of these pretreatment methods is also discussed. This review enhances our comprehension of pretreatment techniques and their vital role in achieving precise pathogenic detection in complex wastewater matrices. Furthermore, it outlines future perspectives and developments for improving the speed and effectiveness of pathogenic detection, contributing significantly to disease surveillance, early warning systems, and environmental protection.

The current work shows the optimization in the preparation of nanosized titanium carbide (TiC) in-situ through mechanical alloying (MA). Metallic titanium (Ti) powders, along with two carbon sources, carbon nanotubes (CNTs), and stearic acid (SA), were used to reduce the particle size using a high-energy Spex800 mill. The combined use of 2 wt % of these carbon sources and n-heptane as a liquid process control agent (PCA) proved crucial in generating nanoscale powder composites through a simple and scalable synthesis process within a 4-hour timeframe. The use of 20 wt % of both carbon sources was compared to determine the ability of CNTs to form carbides and the decomposition of PCAs during mechanical milling. The result reveals structures like nanoblocks and nanolumps with and important size reduction. The structure and morphology of the composites and starting materials were evaluated through x-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

During embryo development, the endoplasmic reticulum (ER) acts as an important site for protein biosynthesis, however, in vitro culture (IVC) can negatively affect ER homeostasis. Thereby, the aim of our study was to evaluate the effects of supplementation of tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, in the IVC of bovine embryos. Two experiments were carried out: Exp. 1: evaluation of blastocyst rate, hatching kinetics and gene expression of hatched embryos after being treated with different concentrations of TUDCA (50, 200 or 1,000 μM) in the IVC; Exp. 2: evaluation of the re-expansion, hatching, and gene expression of hatched embryos previously treated with 200 µM of TUDCA at IVC and submitted to vitrification. There was no increase in the blastocyst and hatched blastocyst rates treated with TUDCA in the IVC. However, embryos submitted to vitrification after treatment with 200 µM of TUDCA, increased hatching rate post-warming, together with a down-regulation in the expression of ER stress-related genes and the accumulation of lipids. In conclusion, this work showed that the addition of TUDCA during in vitro culture can improve the cryotolerance of the bovine blastocyst through the putative modulation of ER and oxidative stress.

The rye (Secale cereale L.) crop shows a high potential to collaborate in the sustainability of high Andean livestock because it supports the agroclimatic conditions and acid soils in the Peruvian Andes. The production of green forage, hay, and grain of the rye crop in acid soils was studied with the use of different levels of phosphorus and potassium fertilization in four local rye ecotypes (CBI-001, CSM-001, CJS-001, and CCE-001). The green forage yield (FV) ranged from 32.35 to 53.62 t ha-1, dry matter from 6.05 to 8.56 t ha-1, and hay from 7.0 to 10.36 t ha-1; nutritional levels ranged from 9.02 % to 13.56 % protein and 6.50 to 7.75 % ash levels, mainly with differences between ecotypes (p<0.05). No differences existed between fertilization levels for the number of stems per plant, and flowering stems per plant, and grains per ear (p>0.05). Also, CBI-001 and CCE-001 were superior with 1868.4 and 1797.8 kg ha-1 of grain, respectively (p=0.0072); the use of 60 kg ha of Nitrogen, 120 kg ha-1 of P2O5 and 80 kg ha-1 of K2O gave higher grain and residue yields. The high nutritional value and yield of the rye ecotypes studied in acid soil conditions and without irrigation can be an alternative for livestock feeding and grain production in the rainy season in the Andes as a dual-purpose crop.

The brown seaweed Alaria esculenta is the second most cultivated species in Europe and it is therefore of interest to expand its application in developing food products. In this study, a lactic acid bacteria consortium (LAB consortium) consisting of three Lactiplantabacillus plantarum strains (relative abundance ~ 94%) and a minor amount of a Levilactobacillus brevis strain (relative abundance of ~ 6%) was investigated for its ability to ferment carbohydrates available in brown seaweed. The consortium demonstrated ability in fermenting glucose, mannitol, galactose, mannose, and xylose, of which glucose and mannitol were the most favored substrates; no growth was observed on fucose, mannuronic and guluronic acid. The consortium used different pathways for carbohydrate utilization and produced lactic acid as the main metabolite. In glucose fermentations, only lactic acid was produced, but use of mannitol as carbohydrate source, resulted in co-production of lactic acid, ethanol and succinate. Xylose fermentation resulted in acetate production. The consortium was also able to utilize laminari-oligosaccharides (DP 2-4), obtained after enzymatic hydrolysis of laminarin, and produced lactic acid as metabolite. The consortium could grow directly on A. esculenta, resulting in a pH decrease to 3.8 after 7 days of fermentation. Incubation of the same seaweed at corresponding conditions without inoculation resulted in spoilage of the seaweed by endogenous bacteria.

The application of diffusion dialysis using various types of ion-exchange membranes for the separation of sulfuric acid and nickel sulfate has been evaluated. The process of dialysis separation of a real waste solution from an electroplating facility containing 252.3 g/L of sulfuric acid, 20.9 g/L of nickel ions and small amounts of zinc, iron, copper ions, etc. has been studied. Heterogeneous cation-exchange membrane containing sulfo groups and heterogeneous anion-exchange membranes with different thicknesses (from 145 μm to 550 μm) and types of fixed groups (4 samples with quaternary amino groups and 1 sample with secondary and tertiary amino groups) are used. The diffusion fluxes of sulfuric acid, nickel sulfate, and the total and osmotic fluxes of the solvent are determined. The use of a cation-exchange membrane does not allow separation of the components, since the fluxes of both components are low and comparable in magnitude. The use of anion-exchange membranes makes it possible to efficiently separate sulfuric acid and nickel sulfate. At the same time, the thin dialysis membrane turns out to be the most effective, as well as the membranes with quaternary amino groups, and the membrane with secondary and tertiary amino groups proved to be the least effective.

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.

A protocol was designed for plasmid curing using a novel counter-selectable marker, named pylSZK-pylT, in Escherichia coli. The pylSZK-pylT marker consists of the archaeal pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl) with modification, and incorporates an unnatural amino acid (Uaa), Nε-benzyloxycarbonyl-l-lysine (ZK), at a sense codon in ribosomally synthesized proteins, resulting in bacterial growth inhibition or killing. Plasmid curing is performed by exerting toxicity on pylSZK-pylT located on the target plasmid, and selecting only proliferative bacteria. All tested bacteria obtained using this protocol had lost the target plasmid (64/64), suggesting that plasmid curing was successful. Next, we attempted to exchange plasmids with the identical replication origin and an antibiotic resistance gene without plasmid curing using a modified protocol, assuming substitution of plasmids complementing genomic essential genes. All randomly selected bacteria after screening had only the substitute plasmid and no target plasmid (25/25), suggesting that plasmid exchange was also accomplished. Counter-selectable markers based on PylRS-tRNApyl, such as pylSZK-pylT, may be scalable in application due to their independence from the host genotype, applicability to a wide range of species, and high tunability due to the freedom of choice of target codons and Uaa’s to be incorporated.

Background: To date, FM using middle ear packing has rarely reported. In this study, we hypothesized that middle ear packing with dexamethasone soaked gelfoam and fibrin glue over the fat graft could promote the success rate of TMP closure regardless of perforation size. Methods: Between January 2005 and July 2020, a total of 209 patients who underwent fat myringoplasty due to chronic TMP at tertiary referral center were encountered and analyzed. The success rate and audiologic outcome was analyzed. Results: The mean successful TM closure rate was 88.0 %. The success rate by different age generation was not significant difference. The size of the perforation grade showed no significant difference. The perforation site by anterior or posterior was not significant. The preoperative mean threshold of AC, BC and ABG were 55.71, 12.98 and 42.73 dB respectively. The postoperative mean threshold of AC, BC and ABG were 23.67, 12.98 and 10.69 dB. The change of preoperative and postoperative hearing showed statistically significant. Conclusion: From our results, the simple trimming of the perforation edge and middle ear packing with external ear canal packing using fibrin glue induced the stable adhesion between the remnant TM and the fat graft.

The aim of this study was to investigate succinic acid production from lactose concentrate, a by-product of cheese-making, using Actinobacillus succinogenes and Basfia succiniciproducens. Although the capability of these strains to metabolize different sugars is already known, their application in the conversion of lactose bears high potential for optimization. With regard to B. succiniciproducens this approach is completely novel. In particular the influence of the mediums sugar concentration and its supplementation with yeast extract to prevent a lack of proteins and vitamins were examined. Lactose based media containing sugar concentrations between 20 and 65 g L-1 and 5 g L-1 yeast extract were fermented, whereby both strains showed comparable performances. The best results in succinic acid yield and acid concentration, 0.57 g g-1 initial sugar and 23 g L1, were achieved at an initial sugar concentration of 43 g L-1. The necessity of yeast extract was demonstrated using the sugar optimized medium without supplementation. As a result, yield and concentration of succinic acid dropped to 0.34 g g-1 and 13 g L-1, the sugar consumption decreased from more than 99 to less than 55 %. Therefore the supplementation amount of 5 g L-1 yeast extract can be regarded as well-balanced.

In the present study, we isolated and screened thirty strains of GABA-producing lactic acid bacteria (LAB) from Indonesian traditional fermented foods. Two strains were able to convert monosodium glutamate (MSG) to GABA after 24 h of cultivation at 37oC based on thin layer chromatography (TLC) screening. 16S rDNA sequencing and proteomic identification using MALDI-TOF MS identified these two strains as Lactobacillus plantarum designated as L. plantarum FNCC 260 and L. plantarum FNCC 343. The highest yield of GABA production obtained from the fermentation of L. plantarum FNCC 260 was 809.2 mg/l of culture medium after 60 h of cultivation. Supplementation of 0.6 mM pyridoxal 5’-phosphate (PLP) and 0.1 mM pyridoxine led to the increase in GABA production to 945.3 mg/l and 969.5 mg/l, respectively. The highest GABA production of 1226.5 mg/l of culture medium was obtained with 100 mM initial concentration of MSG added in the cultivation medium. The open reading frame (ORF) of 1410 bp of the gadB gene from L. plantarum FNCC 260 encodes 469 amino acids with a calculated molecular mass of 53.57 kDa. The production of GABA via enzymatic conversion of monosodium glutamate (MSG) using purified recombinant glutamate decarboxylase (GAD) from L. plantarum FNCC 260 expressed in Escherichia coli was found to be more efficient (5-fold higher within 6 h) than the production obtained from fermentation. L. plantarum FNCC 260 could be of interest for the synthesis of GABA.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

Novel collector lead(II)-benzohydroxamic acid (Pb(II)-BHA) complexes in aqueous solution were characterized by using experimental approaches, including Ultraviolet-visible (UV-Vis) spectroscopy and electrospray ionization–mass spectrometry (ESI-MS), as well as first-principle density functional theory (DFT) calculations with consideration for solvation effects. The Job plot delineated that a single coordinated Pb(BHA)⁺ should be formed first, and the higher coordination number complexes can be formed subsequently. Moreover, the Pb(II)-BHA species can aggregate with each other to form complicated structures, such as Pb(BHA)₂ or highly complicated complexes. ESI-MS results validated the existence of Pb-(BHA)_n=1,2 under different solution pH values. Further, the first-principles calculations suggested that Pb(BHA)⁺ should be the most stable structure, and the Pb atom in Pb(BHA)⁺ will act as an active site to attack nucleophiles. These findings are meaningful to further illustrate the adsorption mechanism of Pb(II)-BHA complexes in mineral processing.

1-[(4-ethyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-4-phenyl-1H-1,2,3-triazole (Ph4) and1-[(4-ethyl-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl)methyl]-5-phenyl-1H-1,2,3-triazole (Ph5) are new isomers of the triazole derivative family, were synthesized and tested on the corrosion of mild steel in molar hydrochloric acid molar media using weight loss, electrochemical polarization and impedance spectroscopy. Then the experimental results were confirmed by quantum chemical calculations using DFT at B3LYP /6-31G (d,p). The compound Ph4 is the best inhibitor and its inhibitory efficiency increased with increasing concentration and reaching 95% at 10⁻³ M. Polarization curves studies show that both compounds tested are mixed-type inhibitors. Nyquist curves presented a single capacitive loop, their diameter increases progressively with both inhibitors concentration. The change of the substitution phenyl from position 5 to position 4 in the triazole ring increases the inhibitory effect of the triazole compounds. The effect of temperature on the corrosion behavior of iron indicates that the inhibitory efficiency of the two inhibitors decreases with increasing temperature in the range of 308 to 338K. DFT study is in good correlationwith the experimental results.

Blackberry (Rubus fruticosus spp) is a fruit that has a significant antioxidant activity, due to its content in anthocyanins and antioxidant compounds. Emerging technologies are required as the thermoultrasound technique that ensures microbial reduction and release of compounds with antioxidant properties. The objective of this study was to evaluate changes in the antioxidant content and fatty acid profile of blackberry juice when it is subjected to conservation treatment (pasteurization and thermoultrasound). The blackberry juice and the extracted oil of blackberry juice with n-hexane (control, pasteurized and thermoultrasonicated) were evaluated in antioxidant activity, fatty acid profile and antioxidant content. The thermoultrasound juice had the highest (p < 0.05) amount of total phenols (1011 mg GAE/L), anthocyanins (118 mg Cy-3-GlE/L); antioxidant activity by ABTS (44 mg VCEAC/L) and DPPH (2665 µmol TE/L) compared to the control and pasteurized samples, as well as, as well as, oil extract of obtained of the thermoultrasound juice presented high antioxidant activity (177.54 mg VCEAC/L to ABTS and 1802.60 µmol TE/L to DPPH). The fatty acid composition of the oil extract showed the presence of myristic, linolenic, stearic, oleic, and linoleic acid, the fatty acid profile was similar in the different samples with the exception of stearic acid where this was higher in control sample. The thermoultrasound treatment can be an alternative to pasteurization treatments because keeps and releases antioxidant bioavailable compounds, preserving their fatty acids.

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by Agl, enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. We tested here the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model Agl-/-. We used open field, grip strength and rotarod tests for evaluating GHF-201’s effects on locomotion, biochemistry panel to quantify hematological biomarkers, indirect calorimetry to quantify in vivo metabolism, transmission electron microscopy to quantify glycogen in muscle, and fibroblast image analysis to determine cellular features affected by GHF-201. GHF-201 was able to improve all locomotion parameters and partially reversed hypoglycemia, hyperlipidemia and liver and muscle malfunction in Agl-/- mice. Treated mice burnt carbohydrates more efficiently and showed significant improvement of aberrant ultrastructural muscle features. In GSDIII patient fibroblasts, GHF-201 restored mitochondrial membrane polarization and corrected lysosomal swelling. In conclusion, GHF-201 is a viable candidate for treating GSDIII as it recovered a wide range of its pathologies in vivo, in vitro, and ex vivo.

Approximately 10–20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare cost vs controls without a COVID-19 diagnosis over ≥15 months, with a 7.6%–13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4–10% increase in long-term total HCRU over 6–8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.

Cardiovascular diseases (CVDs) and associated risk factors are a growing concern in Cameroon. Physiotherapists (PTs) can play a crucial role in prevention and management. However, the extent of Cameroonian PT involvement in health promotion (HP) activities remains unclear. This study assessed Cameroonian physiotherapists’ current HP practices for people at risk of developing or living with CVDs (pwCVDs). A cross-sectional survey was administered online to PTs practising in Cameroon. Out of 181 PT responses, 95% reported providing a variety of HP activities, including weight management (74%), dietary advice (73%), physical activity (69%), smoking cessation (69%), stress management (61%), and sleep promotion (48%). While PTs were confident in lifestyle assessments, they felt less confident about sleep interventions. Strong beliefs, confidence, team support, and time allocation enhanced HP practice. However, preference for passive modalities, patient adherence issues, organisational challenges within healthcare services, role ambiguity among healthcare providers, inadequate training opportunities, and the absence of established guidelines for CVD prevention negatively affect HP practice. These findings highlight the challenges and opportunities for enhancing HP delivery within the physiotherapy profession in Cameroon. Strategic investments and concerted efforts are necessary to address barriers and leverage facilitators effectively for scaling up HP initiatives, given the significant burden of CVDs in the country.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

Breast and prostate cancer lead incidence rankings in Chile, with obesity and overweight as important risk factors involved in prognosis. Nutritional interventions have shown to be beneficial therapies in patients with cancer, improving anthropometric and biochemical measurements. This study investigates the feasibility and effectiveness of Calorie Restriction and Time-Restricted Feeding in overweight or obese patients undergoing curative radiotherapy for breast and prostate cancer. The research was conducted as a prospective, interventional, non-randomized clinical trial, involving 27 participants, of whom 23 completed the study. Findings indicate that both interventions are feasible and effective. Notably, Time-Restricted Feeding demonstrated superior adherence and more significant improvements in weight loss and metabolic parameters. A mean weight reduction of 3.6 kg and waist circumference decrease of 4.9 cm was observed across participants. Serum levels of glucose, insulin, LDL, HDL and TG showed an average reduction, indicating positive metabolic changes. Results suggest that Time-Restricted Feeding could be a superior beneficial dietary intervention for cancer patients undergoing radiotherapy, due to its ease of adherence and positive impact on metabolic health. This research contributes to the growing evidence on the role of nutritional interventions in cancer treatment and underscores the need for more extensive studies to validate these findings.

Between 1942 and 1945, Jewish inmates of a forced labour camp and later Auschwitz subcamp at Blechhammer (Blachownia Śląska, Upper Silesia) worked alongside British prisoners of war on the construction site of a giant synthetic fuel facility, the Oberschlesische Hydrierwerke. The paper examines the multifaceted forms of interaction between these two groups, who were situated at the opposite ends of a spectrum ranging from high survival rates to certain death. By reframing the Jewish inmates’ perceptions of the POWs, it seeks to shed new light on a controversial debate on the nature of the relationship between them and British prisoners. The paper argues that important aspects have been missing from this debate, as the Jewish inmates were not sufficiently represented and not viewed as active protagonists. The relations between Jews and British POWs were not one-sided, but rather interdependent in complex ways. Both groups used these contacts to gain strategic information on the war and jointly contributed to the Allied resistance effort. The barter with British POWs played a crucial role in the collective and individual survival strategies of Jewish inmates, whereas the British increasingly depended on the Jewish inmates to procure basic foods when German rations ceased to be allocated. An analysis of the effects of British aid giving showed that the actual impact on the physical survival of the emaciated inmates was negligible. However, these humanitarian gestures significantly boosted their mental strength and equally helped them to cope better with post-traumatic stress disorders after the war. Altogether, the British were encouraging symbols of resistance against the Nazi regime in the eyes of the inmates. Negative experiences were rarely corroborated and were often linked to poor English language skills or a stronger identification with other nationalities.

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Or-thopoxvirus genu. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods & Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses: ACAM2000, JYNNEOS, and LC16, with the first being a replicating vaccine and the latter being non or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental im-munity to MPV. ACAM2000(a live‐attenuated replicating vaccine) and JYNNEOS (a live‐attenuated, non-replicating vaccine) are two US FDA‐approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer com-plications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or mRNA before monkeypox is declared a pandemic.

The interfacial polymerization (IP) of piperazine (PIP) and trimesoyl chloride (TMC) has been extensively utilized to synthesize nanofiltration (NF) membranes. However, it is still a huge challenge to monitor the IP reaction, because of the fast reaction rate and the formed ultra-thin film. Herein, two effective strategies were applied to reduce the IP reaction rate: (1) the introduction of hydrophilic interlayers between the porous substrate and the formed polyamide layer, and (2) the addition of macromolecular additives in the aqueous solution of PIP. As a result, in situ Fourier transform infrared (FT-IR) spectroscopy was firstly used to monitor the IP reaction of PIP/TMC with hydrophilic interlayers or macromolecular additives in the aqueous solution of PIP. Moreover, the formed polyamide layer growth on the substrate was studied in a real-time manner. The in situ FTIR experimental results confirmed that the IP reaction rates were effectively suppressed and that the formed polyamide thickness was reduced from 138 ± 24 nm to 46 ± 2 nm according to TEM observation. Furthermore, an optimized NF membrane with excellent performance was consequently obtained, which included boosted water permeation of about 141–238 (L/m²·h·MPa) and superior salt rejection of Na₂SO₄ > 98.4%.

Background: The maximal one-repetition test (1-RM) is widely used in scientific research; however, there are conflict results regarding its reproducibility in elderly population. The present study aimed to analyze the reproducibility the test both before and after a 12 week training period by using the bench press and leg press 45° 1-RM tests in the elderly taking into consideration the training experience and strength level of the women. Methods: Elderly women (n = 376; age, 68.5 ± 14.1 years; height, 162.7 ± 5.5 cm; body mass, 71.2 ± 16.0 kg) who underwent ≥3 months of resistance training performed an initial week of familiarization and a second week of testing and retest, with a 48–72 hour interval. Results: The results showed maximal and relative load strength of 39.3 kg and 0.59 kg/body mass for lower limbs and 20.9 kg and 0.31 kg/body mass for upper limbs. The Kappa indices were 0.93 and 0.95, and the intraclass correlation coefficients were 0.99 and 0.99 for the lower and upper limbs, respectively. Conclusion: Therefore, the present study confirms that the 1-RM test has high reliability and reproducibility in the elderly, for both upper and lower limbs.

Reducing sedentary behaviours can help prevent non-communicable diseases, particularly among young adolescents with long term illnesses or disabilities (LTID). Much of young people’s voluntary sedentary time is related to screen-time behaviours (STBs) such as TV viewing, playing computer games, and using the computer for other activities. Although public health data on adolescents’ STB is growing, information about adolescents with LTID is currently lacking in a European context. The purpose of this study is to compare time on STBs between adolescents with and without LTID in European Countries through the HBSC 2013/14 study. Young adolescents (n = 61,329; boys 47.8%) from 15 European countries reported the time spent on TV viewing, playing computer games, and using the computer for other purposes on weekdays and the weekend. STBs were dichotomised based on international recommendations of less than 2 h per day, and Chi-square tests of independence were performed to investigate differences. STB time was combined to produce a sum score as dependent variable in multiple analysis of covariance with age and family affluence as covariates. There were statistically significant differences in computer gaming among boys and other computer use among girls for both weekdays and weekends, whereby adolescents with LTID reported higher use. In addition, both boys and girls with LTID spent more time on STBs than their same sex peers without LTID (Boys, F = 28.17, p < 0.001; Girls, F = 9.60, p = 0.002). The results of this study indicate a need for preventive strategies to address high levels of STB among young adolescents with LTID and reduce the risk of poor health outcomes associated with higher levels of sedentary behaviour.

After axonal injury, chromatolysis (fragmentation of Nissl substance) occurs in both intrinsic neurons (whose processes are within the CNS) and extrinsic neurons (whose axons extend outside the CNS). Electron microscopy shows that chromatolysis involves fission of the rough endoplasmic reticulum. In intrinsic neurons (which do not regenerate axons) or in extrinsic neurons denied axon regeneration, chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust-like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by Ribophagy and Reticulophagy, respectively. In other words, chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no chromatolysis, severely injured neurons can remain chromatolytic and never again synthesise normal levels of protein; some may atrophy or die. What molecule(s) cause fragmentation or degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes? Ribonucleases can modify (and perhaps fragment) rough endoplasmic reticulum; various endoribonucleases can degrade mRNA causing polyribosomes to unchain and disperse; they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, rough endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases could be a profitable strategy.

Abstract: The spectral and dynamic properties of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

: Consumption of plant-based milk replacers has increased in recent years due to health benefits, benefits attributed mainly to the content of phenolic compounds, fatty acids, or bioactive compounds with antioxidant activity. In this context, we proposed to obtain two types of less studied plant-based beverages, namely lupine and chickpea beverages, as well as the possibility of getting these beverages using germinated seeds and even obtaining probiotic drinks through fermentation with Lactobacillus plantarum 299v. To evaluate the quality of the obtained products, we determined their content of proteins, fatty acids, organic acids, volatile compounds, and phenolic compounds. We evaluated the antioxidant activity of the obtained herbal drinks, and a load of probiotic microorganisms present after the fermentation process. Both lupine and chickpea drinks have the desired properties, high content of fatty acids and phenolic compounds, that bring probiotic benefits.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

Shrimp is the most important aquaculture industry. Therefore, we determined the effect of nitrifying-probiotic bacteria on water quality, growth, survival, immune response and intestinal microbiota of Litopenaeus vannamei cultured without water exchange. In vitro, only B. licheniformis used TAN, nitrites and nitrates since nitrogen bubbles were produced. TAN decreased significantly in the treatments with bacilli and LAB, but no differences were observed in nitrites. Nitrates were significantly higher in the treatments with bacteria. The final weight and survival of shrimp in the bacterial treatments increased significantly and superoxide anion increased significantly only in LAB treatment. The activity of phenoloxidase decreased significantly in the treatment with LAB and with the mixture of bacilli and LAB. Shrimp treated with bacilli in the water showed lower species richness. The gut bacterial community after treatments was significantly different from that of the control. Linoleic acid metabolism was positively correlated with final weight and superoxide anion, whereas quorum sensing was correlated with survival. Thus, bacilli and LAB in the water of hyperintensive culture systems act as nitrifers, modulate the intestinal microbiota and immune response, and improve the growth and survival of shrimp. This is the first report on Pediococcus pentosaceus and Leuconostoc mesenteroides as nitrifying bacteria.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. Cucumerinum (Foc) of cucumber is a destructive soil-borne disease in cucumber (Cucumis sativus.L). There is limited knowledge on molecular mechanisms to FW resistance-mediated defense responses in cucumber. In this study, metabolome and transcriptome profiling were carried out in two FW, resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. The NILs showed consistent and stable FW resistances in multiple greenhouse and laboratory screening tests. Widely targeted metabolomic analysis identified differentially accumulated metabolites (DMAs) with significantly more accumulation in NR in response to Foc infection including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway. Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis in or transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays in which two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, and the flavonoid compound gallocatechin 3-O-gallate were shown to have significant inhibitory effect on Foc growth. The antifungal effect of three compounds seems to be a novel finding. We conclude that phenolic acids and flavonoids play an important role in NR mediated FW resistance in cucumber.

Long-term storage may reduce the nutritional quality of brown rice, so the present study was aimed to evaluate the nutritive values and application in pig diets. In Exp.1, 18 Landrace × Yorkshire (L × Y) barrows with initial body weight (IBW) of 25.48 ± 3.21 kg were randomly assigned to three treatments, which included corn diet, one-year stored brown rice (BR1) diet and six-year stored brown rice (BR6) diet, to determine the digestible energy (DE) and metabolisable energy (ME) value of stored brown rice. In Exp. 2, 24 barrows (L × Y; IBW: 22.16 ± 2.42 kg) fixed with ileal T-cannula were randomly allotted to four dietary treatments, including corn diet, two stored brown rice diets and nitrogen-free diet, to evaluate the amino acid (AA) digestibility of stored brown rice. In Exp. 3 and 4, 108 crossbred weaned piglets (L × Y; IBW: 9.16 ± 0.89 kg) and 90 crossbred growing pigs (L × Y; IBW: 48.28 ± 3.51 kg) were allotted to 3 treatment diets, including control diet and two stored brown rice diets, respectively, to investigate the application of stored brown rice in weaned piglet and growing-finishing pig diets. Results showed that: 1) The DE and ME of corn and stored brown rice showed no significant differences (P > 0.05), while the apparent ileal digestibility (AID) of arginine, histidine, aspartic acid, and the standardized ileal digestibility (SID) of arginine and histidine were higher in stored brown rice compared to corn (P < 0.05). 2) Compared with the control diet, the stored brown rice diets showed no significant effects on growth performance, nutrient apparent total tract digestibility (ATTD) and serum biochemical indices (P > 0.05), but decreased digestive enzymes activities in duodenum, jejunum and ileum of piglets (P < 0.05). 3) Compared with the control diet, the stored brown rice diets showed no significant effects on growth performance, carcass traits, meat quality, fatty acids profiles in the longissimus dorsi muscle of growing-finishing pigs (P > 0.05). In conclusion, the brown rice stored for 6 years under good conditions has no obvious changes in available energy and nutrient values. Although it may reduce digestive enzyme activity in small intestine of the piglets, the stored brown rice showed no obvious adverse effect on growth performance and meat quality, and can be effectively used in pig diet.

Galanthus elwesii Hook is an important plant species of the Amaryllidaceae family and is used for medicinal purposes with its valuable bioactive compounds. The present study was conducted to investigate the effects of foliar salicylic acid (SA) and zinc (Zn) treatments on proline, carotenoid, chlorophyll content and anti-oxidant enzyme activity in G. elwesii. The ascorbate peroxidase (APX), catalase (CAT) enzyme activity, and protein contents were determined with ascorbate oxidation, hydrogen peroxide (H2O2), and Bradford experiments, respectively. The plants were treated with three different concentrations of SA (0.5, 1, and 2 mM) and, and Zn (40, 80, and 120 mM) were compared with the control. Fresh leaves were harvested in the study. APX (3.99 ± 0.58 EU/mg protein) and CAT (154.64 ± 4.10 EU/mg protein) were obtained from Zn 80 and 120 mM treatments at the highest level, respectively. Proline, chlorophyll b, and carotenoid content increased 12.4, 1.54 and 3.95-fold, respectively, in 0.5 mM SA treatments when matched with control group. It was found that increasing doses of SA and Zn increased the content of malondialdehyde (MDA), but this was not at a significant level. The total chlorophyll content increased 2.27-fold in Zn 120 mM + SA 2 mM treatment and the chlorophyll content increased 2.41-fold in Zn 40 mM + SA 1 mM treatment.

The objective of this study was to investigate the effects of ethyl nitroacetate, ethyl 2-nitropropionate and 3-nitropropionic acid on ruminal production of CH4, H2, volatile fatty acids (VFAs) and on dry matter digestibility of ground alfalfa under in vitro conditions. In vitro incubations were conducted as consecutive batch cultures. Total gas and amounts of methane produced by ruminal microbes were decreased by all nitrocompounds (P &lt; 0.05). Total production of VFAs was significantly reduced for all the nitrocompounds (P &lt; 0.05) except for NPA. DM disappearance was not affected (P &gt;0.05) by treatment.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H2O2), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H2O2 and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H₂O₂), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H₂O₂ and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

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.

In this work, we synthesized chitosan grafted-poly acrylic acid (CS-g-PA) through surface-initiated atom transfer radical polymerization (SI-ATRP). We also studied the adsorption process of copper and lead ions onto CS-g-PA surface. Adsorption equilibrium studies indicated pH 4.0 as the best pH for the adsorption process, while the maximum adsorption capacity for Pb2+ ions was 98 mg*g-1 and for Cu2+ was 164 mg*g-1, higher adsorption capacities than chitosan alone (CS), where Pb2+ was only 14.8 mg*g-1and Cu2+ was 140 mg*g-1, respectively. Furthermore, the adsorption studies indicated that Langmuir model describes all the experimental data. All these results suggest that the new CS-g-PA polymers had potential as adsorbent for hazardous and toxic metal ions produced by different industries.

Outlined is a proposal designed to culminate in the foundry fabrication of arrays of singly addressable quantum dot sources deterministically emitting single pairs of energy-time entangled photons at C-band wavelengths; each pair having negligible spin-orbit fine structure splitting; each pair being channeled into single mode pig-tail optical fibers. Entangled photons carry quantum state information among distributed quantum servers via I/O ports having two functions; the unconditionally secure distribution of decryption keys to decrypt publicly distributed, encrypted classical bit streams as input to generate corresponding qubit excitations, and to convert a stream of quantum nondemolition measurements of qubit states into a classical bit stream. Outlined are key steps necessary to fabricate arrays of on-demand quantum dot sources of entangled photon pairs, principal among are 1) foundry fabrication of arrays of isolated quantum dots, 2) generation of localized sub-surface shear strain in a semiconductor stack, 3) a cryogenic anvil cell, 4) channeling entangled photons into single mode optical fibers, 5) unconditionally secure decryption key distribution over the fiber network, 6) resonant excitation of a Josephson tunnel junction qubits from classical bits, and 7) conversion of a quantum nondemolition measurements of a qubit states into a classical bit.

The prototype misfit layer compound (SnS)1.17NbS2 consists of alternatively a metallic triatomic NbS2 layer in which Nb atoms are sandwiched by S atoms and an insulating SnS double-layer of NaCl-type structure. Here we investigate the effect of lattice misfit on the stability and chemical bonding in the misfit layer compound using a first-principles density-functional theory approach. The calculations show that for the (SnS)1+xNbS2 approximants, the most stable one has x = 0.167, close to the experimental observations. Charge analysis finds a moderate charge transfer from the SnS to NbS2. Sn or S vacancies in the SnS part affect the electronic properties and interlayer interactions. The obtained information here helps understand the mechanism of formation and stability of the misfit layer compounds and ferecrystals, and further to design of novel multilayer compounds and emerging van der Waals heterostructures.

Low dropout (LDO) regulators are widely used in portable electronic devices because they 1 occupy small chip and printed circuit board (PCB) areas. This work presents the design of a low 2 noise low dropout (LDO) linear voltage regulator using folded cascode operational amplifier and 3 source follower buffer for frequency compensation. The proposed design achieves low output noise 4 with feedback loops, which makes it possible to improve load and line regulations as well as the 5 transient response for voltage applications in comparison with the literature. The designed LDO 6 linear regulator works under the input voltage of 2.8-4.8 V and provides up to 100 mA load current 7 for an output voltage of 2.6 V. 8 9 Moreover, the operational amplifier design contributes to the major reduction in the frequency 10 noise, and make sure the stability of LDO under different conditions. Furthermore, the novel LDO 11 design topology has very less dropout voltage, fast transient response and minimized power dissi- 12 pation under maximum load current, worst process corner, and maximum temperature to achieve 13 high power efficiency, maintain output voltage in the presence of fast load changes, and to lower the 14 power loss across the pass element especially at high load. Design criteria are addressed in detail. 15 16 This LDO topology is able to achieve ultra-low noise i.e. 2 /muv/√Hz for frequency >1kHz. The 17 proposed LDO is implemented in the cadence virtuoso H9A with CMOS 130 μm technology.

With the aim to produce new heterocycle molecules, the previously reported 2-(aminomethyl)-2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one was converted efficiently by reacting with N,N’-dithiocarbonyldiimidazole (DTCI), to produce the substituted imidazolidine-2-thione moiety inserted in a three fused ring scaffold of the title compound. The molecular composition was confirmed by a high-resolution MS experiment, and its structure was elucidated by 1H, 13CNMR, and IR analyses. The thioacetamide form of the product was supported by density functional theory (DFT)-NMR analysis where 13C chemical shifts of thioacetamide form and of its iminothiol tautomer were calculated in chloroform at the BP86 /Jgauss-TZP2 level of theory. The very good linear correlation between 13C chemical shifts by experiment and by calculation for the NHC=S form confirmed the structure.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

This study investigates the potential of natural compounds against HIV-1 protease, a critical enzyme in the replication cycle of human immunodeficiency virus type 1 (HIV-1). HIV-1 protease is essential for cleaving large precursor proteins into smaller functional proteins necessary for viral maturation and infectivity. Protease inhibitors, specifically targeting HIV-1 protease, effectively suppress viral replication, aiding in the management of HIV infection. Using the SWISS DOCK Server, several natural compounds were investigated for their potential as inhibitors of HIV-1 protease. Docking results revealed that Amentoflavone showed excellent binding affinity with high Estimated ΔG values, suggesting its potential as an inhibitor of HIV-1 protease. Additionally, Amentoflavone exhibited similar promising results when tested against Roussarcoma virus protease. These findings indicate the potential of Amentoflavone as a natural compound against HIV and warrant further investigation into its therapeutic applications.

Diabetes Mellitus (DM) is a chronic metabolic disease consisting of Type 1 or Type 2 diabetes. Although treatment of Type 1 diabetes primarily involves insulin therapy, inhibitors of sodium glucose co-transporters (SGLT’s) are a promising new therapeutic. Of particular interest are the two family members, SGLT1 and SGLT2 that collectively contribute to 100% of filtered glucose reabsorption within the kidneys. Consequently, sole SGLT2 inhibitors (SGLT2i) and dual SGLT1/2 inhibitors (SGLT1/2i) contribute to reducing blood glucose levels by reducing glucose reabsorption and promoting glucosuria and natriuresis. Research from our team on SGLT2i, showed that there is a compensatory mechanism whereby SGLT1 is upregulated. This therefore may warrant the combined use of SGLT1/2i. Our in vitro results demonstrated that whilst both the sole SGLT2i empagliflozin (EMPA) and dual SGLT1/2i sotagliflozin (SOTAG) significantly reduce glucose uptake within HK2 cells, the latter was more effective. In addition, our in vitro results indicate significantly more pronounced upregulation of SGLT1 protein with EMPA compared to SOTAG. Our in vivo mechanistic findings demonstrated that SGLT1/2i significantly increased renal SOD1 levels, whilst SGLT2i significantly elevated renal SOD2 levels. Therefore, our study highlighted that SGLT2i and SGLT1/2i differentially regulate protective anti-oxidant proteins in the kidney.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

This paper presents a new method for parameterizing the Lorentz group based on coupled parameters. From the Euler–Hamilton equations, an additional angular rapidity and perpendicular rapidity are obtained, and the Hamiltonian and Lagrangian of a relativistic particle are expanded into rapidity spectra. A so-called passage to the limit is introduced that makes it possible to decompose physical quantities into spectra in terms of elementary functions when explicit decomposition is difficult. New rapidity-dependent Lorentz-invariant coordinates are obtained, and the descriptions of particle motion using the old and new Lorentz-invariant forms as applied to plane waves are compared. Based on a classical model of particle motion in the field of a plane monochromatic electromagnetic wave and in that of a plane laser pulse, the rapidity-dependent spectral decompositions into elementary functions are presented, and the Euler–Hamilton equations are derived as rapidity functions in 3+1 dimensions.

Sphingosine 1-phosphate (S1P) is a signaling lipid molecule involved in various cellular processes. It is important to develop a quantitative method for S1P to determine endogenous levels and to investigate its functions. Especially since S1P is a tiny lipid component of most biological samples, highly sensitive analysis by LC-MS/MS is required. The main challenge in S1P analysis by chromatography is peak broadening due to the presence of a polar phosphate and zwitterion formation in S1P. In this study, we used hydrogen fluoride (HF) to efficiently remove a phosphate and then analyzed the surrogate, sphingosine, as a sharp peak by LC-ESI-MS/MS. We optimized the dephosphorylation reaction in terms of reaction time, temperature, and HF concentration. Multiple reaction monitoring (MRM) for dephosphorylated form of S1P and C17-S1P as internal standard at m/z transition 300.4&gt;282.4 (quantification ion), 300.4&gt;262.4 (qualification ion), 286.3&gt;268.2 (internal standard). This method was validated by essential parameters such as specificity, linearity, range, LOQ, LOD, accuracy, precision, and repeatability. To confirm this new method, we quantified S1P levels in various serum products (100.02 ~ 284.38 nM). To apply the method in vivo, we analyzed S1P in plasma and kidney tissues obtained from a chronic kidney disease (CKD) mouse model. S1P levels were increased only in CKD kidney tissue but not in plasma. In conclusion, by applying the dephosphorylation step with HF, we established a new sensitive LC-MS/MS quantitative method for S1P that can be applied to biological samples.

Malignant melanoma is one of the most aggressive and resistant tumor types which is often accompanied by poor prognosis when spread to nearby or distant tissues. Even though an increasing number of second-line therapies are available for cancer patients, the 5-year survival rate of melanoma patients with regional and distant metastases is still rather low. Therefore, there is an urgent need to develop new, highly efficient treatments. Melanocortin-1-receptor (MC1R) is a cell surface receptor for α-MSH. It is responsible for melanogenesis and is shown to be overexpressed on the surface of cancer cells in a subset of melanoma patients. Here, we designed and synthesized α-MSH analogs and conjugated them to daunomycin through oxime linkage. Using our peptide-drug conjugates (Dau-α-MSHs), we performed comparative in vitro and in vivo evaluations to reveal their suitability for tumor targeting. Firstly, the expression level of MC1R was determined in various melanoma cell lines via RT-qPCR. Then, we examined the antiproliferative effect of our Dau-α-MSHs, moreover we determined the cellular uptake profile and intracellular localization of Dau-α-MSHs. The most efficient Dau-α-MSHs were investigated in vivo using a murine xenograft melanoma model. We found that various cell lines show differential expression on the mRNA levels. We also showed that healthy primary cells have lower expression of MC1R compared to tumor cell lines. Moreover, the concentration-dependent cellular uptake profile of Dau-α-MSHs was detected and the compounds exhibited a great antiproliferative effect on melanoma cell lines. We also provided evidence that our novel Dau-α-MSHs can inhibit tumor expansion significantly and are suitable for targeted tumor therapy.

With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include childhood infective dermatitis and adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. Since the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds may be active against HTLV-1. Here, we expand on our work showing that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formulation of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection in cell culture. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple redistribution of already widely available HIV pills to HTLV-1 endemic areas. Considering our findings with the old medical saying ‘it’s better to prevent than cure’, we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.

This paper aims to search for lump waves in a spatial symmetric (2+1)-dimensional dispersive wave model. Through an ansatz on positive quadratic functions, we conduct symbolic computations with Maple to generate lump waves for the proposed nonlinear model. A line of critical points of the lump waves is computed, whose two spatial coordinates travel at constant speeds. The corresponding maximum and minimum values are evaluated in terms of the wave numbers, and interestingly, all those extreme values do not change with time, either. The last section is the conclusion.

Aquaporins (AQPs; AQP0-AQP12) are water channels expressed in many and diverse cell types, participating in various functions of cells, tissues and systems, including the central nervous system (CNS). AQP dysfunction and autoimmunity to AQPs are implicated in several diseases. The best-known example of autoimmunity against AQPs is the antibodies to AQP4 which are involved in the pathogenesis of Neuromyelitis Optica spectrum disorder (NMOSD), a demyelinating disease of the CNS. The present review focuses on the discovery and the potential role of antibodies against AQP1 in the CNS, and their potential involvement in CNS demyelination and specifically in NMOSD. We describe (a) the several techniques developed for the detection of the AQP1-antibodies, with emphasis on methods that specifically identify antibodies targeting the extracellular domain of AQP1, i.e., those of potential pathogenic role, and (b) the available evidence supporting the pathogenic relevance of AQP1-antibodies.

Programmed-death-1 (PD-1) receptor plays a major physiological role in maintainance of im-mune tolerance, and, by interaction with its ligands (PD-L1 and PD-L2), prevents the develop-ment of multiple immune-mediated diseases. There is growing evidence of an important role of PD-1/PD-L1 pathway in pathogenesis of psoriasis. 84 subjects with psoriasis were included into the study, together with 29 healthy subjects as a control group. 28 of psoriatic patients were treated with biologice therapy (TNF-alpha, interleukin (IL)-12/23 or IL-17 inhibitors). Amounts of PD1 and PD-L1 positive T-cells in peripheral blood were evaluated using flow cytometry. Significantly lower levels of peripheral blood mononuclear cells (PBMCs) with the expression of PD-1 and PD-L1 were found in psoriatic patients when compared to healthy individuals, i.e. CD3/PD1, CD3/PDL1, CD4/PD1, CD4/PDL1, CD8/PDL1, CD19/PD1, CD19/PDL1 positive cells. Biologic treatment resulted in elevation of CD3/PDL1, CD8/PDL1 and decrease of CD8/PD1 posi-tive PBMCs. Our results confirm previous observations of disrupted PD-1/PD-L1 pathway in psoriasis, and that this disturbances may play an important role in development of the disease. Biologic drugs may reverse several abnormalities observed within this pathway, which may ex-plain their excellent efficacy in the treatment of psoriasis. Further research should be conducted to fully explain the results obtained.

High-resolution (2 km) high-frequency (hourly) SST data from 2015-2020 provided by the Advanced Himawari Imager (AHI) onboard the Japanese Himawari-8 geostationary satellite positioned over 140.7°E were used to study spatial and temporal variability of the China Coastal Front (CCF) in the East China Sea. The hourly SST data were processed with the Belkin and O’Reilly (2009) algorithm to generate long-term mean monthly maps of SST gradient magnitude (GM) and frontal frequency (FM) using a GM threshold of 0.1°C/km. Horizontal structure of SST field in the vicinity of the CCF was investigated from cross-frontal distributions of SST along 8 parallels from 31°N to 24°N. The high resolution (2 km) monthly distributions of SST along these 8 parallels were used to determine inshore and offshore boundaries of the CCF and calculate the CCF strength defined as the total cross-frontal SST step dSST=Offshore SST – Inshore SST. The CCF emerges in November, fully develops in December and peaks in strength in January-February. The front’s fragmentation and shrinking/weakening begins in February and March, respectively. In winter (December-February), the front’s strength dSST exceeds 5°C offshore the Zhejiang-Fujian coast and could be as high as 7.5°C when nearshore waters cool down to 7°C. In winter, the front’s strength decreases downstream from 31°N to 24°N. The CCF changes its physical nature as the seasons progress. In winter, the CCF is a water mass front between cold and fresh water coming from the north and warm and salty water coming from the south. In summer, the CCF becomes a coastal upwelling front maintained largely by southerly winds. In winter, the CCF’s cross-frontal structure in the SST field is ramp-shaped, with SST increasing monotonously in the offshore direction. In summer, the CCF’s cross-frontal structure in the SST field is V-shaped or U-shaped, featuring a minimum SST formed by cold upwelled water at some distance from the shore. Thus, the summer SST structure effectively consists of two fronts, a nearshore and offshore, with a minimum SST in-between. Across the inshore/offshore front, the SST decreases/increases in the offshore direction. The local bathymetry, especially the relatively steep shelf slope between 20-m and 50-m isobath, steers the front, which does not meander in winter offshore the Zhejiang-Fujian coast. As the cold season progresses, the front’s axis gradually shifts into deeper waters, from ~20 m to ~50 m.

Organophosphorus nerve agents are amongst the most toxic chemicals known to human beings. 9 They interfere with the central nervous system, resulting in continuous muscle contractions, 10 paralysis and even death. Prohibition by many countries around the world cannot disguise the 11 remaining presence of nerve agents in stockpile storage and governmental deployment, 12 highlighting the dire need for an efficient catalyst to degrade and detoxify nerve agents by 13 hydrolysis. Metal-organic frameworks (MOFs) have raised a few eyebrows for their permanent 14 porosity, precise tunability, and lasting stability. Modern Reticular Chemistry fosters the design and 15 synthesis of well-defined crystalline MOFs with open Lewis acidic metal sites that can catalytically 16 hydrolyze nerve agents both in aqueous solution and in solid state systems, unveiling unparalleled 17 potential for MOF-based personal protection gears. In this review, a summary of the representative 18 catalytically active MOFs in nerve agent hydrolysis is discussed. MOFs are categorized by their 19 reticular structure, emphasizing the capability and mechanistic insights of each single MOF in nerve 20 agent hydrolysis. The author’s perspective on the current challenges and future directions of MOF- 21 based catalysts in real-world protection applications is also provided, which hopefully could shed some 22 light on the future development of commercially available MOF protection suits.

HIV-1 protease (PR) is a viral enzyme that cleaves viral polyprotein precursors to convert them into functional forms, a process essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. While PR typically has low levels of intracellular activity prior to viral budding, induction of premature PR activation to trigger CARD8-mediated cell killing may help eliminate latent reservoirs in people living with HIV. In this review, we discuss the viral and host substrates of HIV-1 protease and highlight potential applications and advantages of targeting CARD8 sensing of HIV-1 PR.

As recommended in the ICH Guidelines (S5-R2 and S6-R1), and based on bioethical concerns, we chose bovine embryos (BE) to check the in vitro embryo development considering the use of different amounts of rHGAL-1 as supplementations of in vitro embryo culture (IVP) mediums. Based on procedures for commercial BE in vitro production, using oocytes aspirated from slaughterhouse ovaries, the rHGAL-1 supplementation performed in two experiments (#01 on the oocyte maturation - IVM medium supplemented and experiment #2 on culture step IVC, supplemented SOF medium). There were IVP commercial procedures done, with 3 IVP batches per experiment and distributed the oocytes in four groups of treatment (one control group and three different dosages of rHGAL-1 to supplement both IVM and SOF mediums, using (2, 20 and 40µg.mL-1 respectively). A total of 962 (experiment 1) and 1,213 (experiment 2) oocytes were aspirated and submitted to IVP procedure. There was no damage to in vitro bovine embryos growth, considering cleavage percentage (%CLE), blastocysts development on day 7 (BlD7, BxD7, BhD7), or hatching blastocysts maturation on day 8 (BhD8%), regardless of rHGAL-1 supplementation. The immunohistochemistry assay with D8 embryos cultivated with rHGAL-1 supplementation on the culture medium (SOF medium) could demonstrate the presence of exogenous GAL-1, distributed in mass cell and trophoblastic cells, and the profile observed is dependent of exogenous supplementation and it was more evident in hatched embryos. The findings reassure the use of a reasonable amount of rHGAL-1 for in vitro embryonic development and make using rHGAL-1 in assisted reproduction in humans more reliable and safer.

Age-related alterations in the gut microbiome composition and its impacts on the host’s health have been well described; however, detailed analyses of the gut microbial structure defining ecological microbe-microbe interactions is limited. One of the ways to determine these interactions is by understanding microbial co-occurrence patterns. We previously showed promising abilities of Lactobacillus acidophilus DDS-1 on the aging gut microbiome and immune system. However, the potential of the DDS-1 strain to modulate microbial co-occurrence patterns is unknown. Hence, we aimed to investigate the ability of L. acidophilus DDS-1 to modulate the fecal, mucosal and cecal-related microbial co-occurrence networks in young and aging C57BL/6J mice. Our Kendall’s tau correlation measures of co-occurrence revealed age-related changes in the gut microbiome, which were characterized by reduced number of nodes and associations across sample types when compared to younger mice. After four-week supplementation, L. acidophilus DDS-1 differentially modulated the overall microbial community structure in fecal and mucosal samples as compared to cecal samples. Beneficial bacteria such as Lactobacillus and Akkermansia acted as connectors in aging networks in response to L. acidophilus DDS-1 supplementation. Our findings provided the first evidence of the DDS-1-induced gut microbial ecological interactions revealing the complex structure of microbial ecosystems with age.

Gradient based methods are popularly used in training neural networks and can be broadly categorized into first and second order methods. Second order methods have shown to have better convergence compared to first order methods, especially in solving highly nonlinear problems. The BFGS quasi-Newton method is the most commonly studied second order method for neural network training. Recent methods have shown to speed up the convergence of the BFGS method using the Nesterov’s acclerated gradient and momentum terms. The SR1 quasi-Newton method though less commonly used in training neural networks, are known to have interesting properties and provide good Hessian approximations when used with a trust-region approach. Thus, this paper aims to investigate accelerating the Symmetric Rank-1 (SR1) quasi-Newton method with the Nesterov’s gradient for training neural networks and briefly discuss its convergence. The performance of the proposed method is evaluated on a function approximation and image classification problem.

The acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected. Antiretrovirals are only a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, new novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual-focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp3 atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available at https://figshare.com/s/ceb58d58e8f5585ce67e.

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism during fasting. The wild-type (WT) and LRH-1 liver-specific knockout (LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. During fasting, the LRH-1 LKO mice showed greater accumulation of triglycerides in the liver compared to that in WT mice. Interestingly, LRH-1 LKO liver decreased the perilipin 5 (PLIN5) expression and genes involved in β-oxidation. Additionally, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed to analyze the PLIN5 promoter sequence, which revealed −1620/−1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immuno-precipitation assays. Moreover, fasted WT primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted LRH-1 LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs and manage the cellular needs.

Background: A large percentage of deaths in an epidemic or pandemic can be due to overshoot of population (herd) immunity, either from the initial peak or from planned or unplanned exit from lockdown or social distancing conditions. Objectives: We study partial unlock or reopening interaction with seasonal effects in a managed epidemic to quantify overshoot effects on small and large unlock steps and discover robust strategies for reducing overshoot. Methods: We simulate partial unlock of social distancing for epidemics over a range of replication factor, immunity duration and seasonality factor for strategies targeting immunity thresholds using overshoot optimization. Results: Seasonality change must be taken into account as one of the steps in an easing sequence, and a two step unlock, including seasonal effects, minimizes overshoot and deaths. It may cause undershoot, which causes rebounds and assists survival of the pathogen. Conclusions: Partial easing levels, even low levels for economic relief while waiting on a vaccine, have population immunity thresholds based on the reduced replication rates and may experience overshoot as well. We further find a two step strategy remains highly sensitive to variations in case ratio, replication factor, seasonality and timing. We demonstrate a three or more step strategy is more robust, and conclude that the best possible approach minimizes deaths under a range of likely actual conditions which include public response.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients, compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and this is associated with cancer metastasis to the bone and poor prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression that may be linked to the pathogenic behavior of fibroblast-like synoviocytes, cartilage destruction, and bone erosion.

The paper proves that an odd composite integer $N$ can be factorized in at most $O( 0.125u(log_2N)^2)$ searching steps if $N$ has a divisor of the form $2^a{u} +1$ or $2^a{u}-1$ with $a > 1$ being a positive integer and $u > 1$ being an odd integer. Theorems and corollaries are proved with detail mathematical reasoning. Algorithms to factorize the kind of odd composite integers are designed and tested by factoring certain Fermat numbers. The results in the paper are helpful to factorize the related kind of odd integers as well as some big Fermat numbers

Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca²⁺ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway–regulated ERK1/2 and inositol trisphosphate (IP₃) signaling in NHDFs.

Based on a modified dice-and-fill technique, a PIN-PMN-PT single crystal 1-3 composite with the kerf of 12 μm and pitch of 50 μm was prepared. The as-made piezoelectric composite material behaved with high piezoelectric constant (d33 = 1500 pC/N), high electromechanical coefficient (kt = 0.81), and low acoustic impedance (16.2 Mrayls). Using lithography and flexible circuit method, a 48-element phased array was successfully fabricated from such a piezoelectric composite. The array element was measured to have a central frequency of 20 MHz and a fractional bandwidth of approximately 77% at −6 dB. Of particular significance was that this PIN-PMN-PT single crystal 1-3 composite-based phased array exhibits a superior insertion loss compared with PMN-PT single crystal and PZT-5H-based 20 MHz phased arrays. The focusing and steering capabilities of the obtained phased array were demonstrated theoretically and experimentally. These promising results indicate that the PIN-PMN-PT single crystal 1-3 composite-based high frequency phased array is a good candidate for ultrasound imaging applications.

A flavonoid Astragalin (kaempferol-3-O-β-D-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O- β-D-isomaltotrioside, Ast-Gal) on dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through up-regulation of surface markers, such as CD80, CD86, and MHC II in a dose-dependent manner, while Ast had little effects. Also, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as IL-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 mAb to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly increased IFN- γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs, and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

Background: Little is known about the decisional background of choosing an appropriate disease model. Therefore, this paper aims, (1) to identify a spectrum of reasons for choosing between animal and non-animal disease models and (2) provides an ethical analysis of these reasons. Methods: 13 researchers from basic and preclinical research were interviewed, the interviews were analyzed qualitatively and the results were categorized. The ethical analysis was based on the principlism approach and a value judgement model. Results: This paper presents 66 reasons why researchers use animal (41 %) or alternative, non-animal disease models (59 %). Most of the reasons were be assigned to the work environment (29 reasons) and scientific standards (22 reasons). Other reasons were assigned to personal attitudes (11 reasons) and animal welfare (4 reasons). Qualitative relevant normative differences are presented in the ethical analysis. Even if few reasons can be rejected outright from an ethical point of view, there are good reasons to give some more weight than others. Conclusions: The spectrum of reasons and its ethical assessment provide a framework for reflection for researchers who may have to choose between animal models and (investing in) alternatives. This can help to reflect on and justify decisions.

Sour rot, caused by Geotrichum citri-aurantii, is a significant post-harvest disease in citrus, resulting in economic losses due to the lack of effective fungicides. This study investigates the antifungal activity of essential oils from Late IAC 585 willowleaf and Pera IAC sweet orange in controlling sour rot in Tahiti acid lime fruits. Essential oils were extracted via hydrodistillation and tested in vitro and in vivo. In vitro, assays evaluated mycelial growth inhibition at concentrations ranging from 2 to 32 µl ml⁻¹. In vivo trials involved preventive and curative treatments on artificially inoculated fruits stored at 25°C ± 2. Results showed that Pera IAC sweet orange oil, at 32 µl ml⁻¹, reduced disease severity by 96% in curative treatments. In contrast, Late mandarin oil demonstrated moderate inhibition (44%) at the highest concentration in vitro. The oils did not affect key fruit quality parameters such as juice yield and total soluble solids. These findings suggest that citrus essential oils could be natural alternatives to synthetic fungicides for post-harvest sour rot management, combining effectiveness with maintaining fruit quality. Further research is needed to explore the mechanisms of action and commercial application potential.

Based on the electron-deficient property of picric acid (PA), two neutral Ir(III) complexes 1 and 2 modified with the electron-rich carbazolyl groups were synthesized and characterized. Both 1 and 2 exhibit aggregation-induced phosphorescence emission (AIPE) properties in THF/H2O. Among them, 2 is extremely sensitive for detecting PA with a limit of detection of 0.15 μM in THF/H2O. Furthermore, the selectivity for PA is significantly higher compared to other analytes, enabling efficient detection of PA in four common water samples. The density functional theory calculations and the spectroscopic results confirm that the sensing mechanism is photo-induced electron transfer.

The ultrasound guided viscosupplementation of the hip joint with hyaluronic acid(HA)is considered a standard procedure among the conservative treatments for hip arthritis.The aim of the study was to evaluate the clinical benefit and the incidence of adverse events of the technique in a obseravtional study at one year follow up. We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis that performed intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score(mHHS),WOMAC (Western Ontario and McMaster University),Hip Outcome Score (HOOS) with subscale Sport (HOOSs), for pain the Visual Analogic Scale (VAS).The patients were classified according to Tonnis’ radiological classification of arthrosis (range 0-3):20 patients(grade 0),32(grade 1),18(grade 2),15(grade 3).At last follow up all the scales increased:mHHS from 59.35 to 82.1,HOOS from 69.45 to 78.53,HOS Sport from 47.4 to 58.11,VAS from 6.09 to 3.97,WOMAC from 33.2 to 31.5 (p<0.05 for all the parameters);13/85 requested arthroplasty. Based on our findings, indication for use of hyaluronic acid is limited to patients with mild to moderate arthritis.Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term follow up.

An original approach has been proposed for designing a nanofibrous (NFs) layer using UV-cured polyvinylpyrrolidone (PVP) as a matrix, incorporating mesoporous graphene carbon (MGC) nanopowder both inside and outside the fibres, creating a sandwich-like structure. This architecture is intended to selectively adsorb and detect acetic acid vapours, which are known to cause health issues in exposed workers. The nanocomposite MGC-PVP-NFs layer was fabricated through electrospinning deposition onto interdigitated microelectrodes (IDEs) and stabilised under UV-light irradiation. To enhance the adhesion of MGC onto the surface of the nanocomposite polymeric fibres, the layer was dipped in a suspension of polyethylenimine (PEI) and MGC. The resulting structure demonstrated promising electrical and sensing properties, including rapid responses, high sensitivity, good linearity, reversibility, repeatability, and selectivity towards acetic acid vapours. Initial testing was conducted in a laboratory using a bench electrometer, followed by validation in a portable sensing device based on consumer electronic components (by ARDUINO®). This portable system was designed to provide a compact, cost-effective solution with high sensing capabilities. Under room temperature and ambient air conditions, both laboratory and portable tests exhibited favourable linear responses, with detection limits of 0.16 and 1 ppm, respectively.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield the Michael type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the reaction. The study of the variation of the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

1,3 Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with the promising anticancer active. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were firstly investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop» or using recently proposed diffusion mixing technique, which led to ~5-15% increasing of target compounds yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance to the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in nitrile imine structure and was significantly decreases at the reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.

Nanofibers are one of the most attractive materials that can modify functionalities for developing new kinds of specific applications, mainly used as a biomedical material. Herein, we designed and prepared the antibacterial nonwoven fiber mats of PLA and PLA composited with Ag nanoparticles by electrospinning. The effects of varying filler contents on their chemical, surface morphology, thermal, water absorbency, and antibacterial properties were investigated using FTIR, SEM/EDS, DSC, swelling ratio, and qualitative and quantitative antibacterial tests. FTIR and EDS spectra indicated that Ag nanoparticles were incorporated in the PLA without chemical bonding. SEM revealed that the average diameter of the PLA nanofibers containing the Ag nanoparticles was more significant than those without those particles. Besides, fiber diameters are proportionally the amount of Ag nanoparticle contents. DSC indicated that the Ag nanoparticles can be incorporated within the PLA-matrix without strongly affecting their thermal properties. Moreover, the crystallinity of the composite nonwoven fiber mats was higher than those of fiber mats in the neat PLA. Accordingly, the antibacterial activities revealed that all the composite nanofiber mats exhibited excellent against S. aureus and E. coli bacterial strains. In addition, in the cell toxicity study, all produced hybrids nonwoven fiber mats induced a reduction in cell viability for the L929 fibroblast cells. Our results suggest that the designed and prepared nonwoven fiber mats may have good potential for use in the biomedical field, particularly in wound dressing applications

This mini-review deals with some non-starter lactic acid bacteria (NSLAB) species with a controversial nature known to be both human and animal pathogens but also health-promoting and probiotic. The focus is put on Lactococcus garvieae, two Streptococcus species (Str. uberis and Str. parauberis), four Weissella species (W. hellenica, W. confusa, W. paramesenteroides and W. cibaria) and Mammalicoccus sciuri which worldwide are often found within the microbiotas of different kinds of cheese, mainly traditional artisanal ones made from raw milk and/or relying on environmental bacteria for their ripening. Based on literature data, their virulence and health-promoting effects are examined, and some of the mechanisms of these actions are investigated. Additionally, their possible roles in cheese ripening are also discussed. The analysis so far showed that, in general, the pathogenic and the beneficial strains, despite belonging to the same species, show pretty different genetic constitutions. Yet, when the safety of a given strain is assessed, genomic analysis on its own is not enough, and a polyphasic approach is needed including additional physiological and functional tests.

D-Glucaric acid is an important bio-based building block of polymers and is a high value-added chemical that can be used in a variety of applications. In the present study, the Udh target genes from Pseudomonas putida and Pseudomonas syringae were used together to construct the expression vector pETDuet-2×Udh. The transformants of BL21(DE3) with vector pETDuet-2×Udh was applied to produce glucaric acid from glucuronic acid. After optimization of induction conditions, the highest Udh expression were achieved when 0.4 mmol L-1 isopropyl-β-d–thiogalactoside (IPTG) was added to cell cultures at an OD600 value of 0.6 followed by culture at 26℃ for 6 hours. The production of glucaric acid substantially reached 5.24 ± 0.015 g L-1 in fed-batch cultures in a 30 L tank. In the present study, a new system for glucaric acid production was established, which was more economic and friendly to environment.

Purpose: The study aimed to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) in reducing blood loss in patients undergoing total knee replacement. Materials: A retrospective study on 530 individuals with a mean age of 71,44 years after posterior stabilized total knee arthroplasty was evaluated. Patients were divided into three groups, corresponding to the method of bleeding control: I - patients without additional bleeding protocol (control group); II - patients with iV TXA administration (TXA group); III - patients with exact TXA protocol combined with intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured as a substitute for blood loss by maximal Hb drop compared to preoperative Hb level. Results: The mean hospitalization for patients from the control group was 7.02 (SD 1.34) days, 6.08 (SD 1.06) days for the TXA group, and 5.56 (SD 0.79) for the TXA + LIA group. The most significant hemoglobin drop was found in the control group, which amounted to an average of 30.08% output value. In the TXA group, the decrease in hemoglobin was, on average, 25.17% (p<0.001), and in the TXA + LIA group, it was 23.67% (p<0.001). A decrease in the rate of allogeneic blood transfusions was observed, which was 24.4% in the control group, 9.9% in the TXA group, and 8% in TXA + LIA group (p<0.01). Conclusions: Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia statistically significantly reduces blood loss in patients after total knee replacement.

Knee Osteoarthritis (KOA), the most common knee degenerative disease, involve a slow destructive process, leading to disability and ultimately total knee replacement. The progression of KOA is related to the loss of rheological properties of the synovial fluid (SF), due to slow immunological, inflammatory and enzymatic processes that cleave the hyaluronic acid (HA) and decrease the concentration of specific proteins. Since no effective treatments have been found to halt the progression of KOA, injection of HA-based viscoelastic gels combined with physiotherapy (PT) is an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the SF characteristics, the SF aspirated from the KOA was spectrophotometrically and rheological analyzed, comparing the receiving groups of HA Kombihylan® and groups that received Kombihylan® and complex PT. In patients treated with PT, SF extracted 6 weeks after viscosupplementation had a superior elastic moduli (G') and viscous moduli (G") profile behavior, having a homogeneous distribution of proteins and polysaccharides in the SF, stimulating stronger interactions. In the absence of PT the G' and G" profiles are non-uniform, suggesting an unorganized supplemented SF with some clustering phenomena, proteins aggregation and a low level of entanglement between HA and macromolecular components in the SF.