The search for novel brewing strains from non-brewing environments represents an emerging trend to increase genetic and phenotypic diversities in brewing yeast culture collections. Another valuable tool is hybridization, where beneficial traits of individual strains are combined in a single organism. This has been used successfully to create de novo hybrids from parental brewing strains by mimicking natural Saccharomyces cerevisiae ale x Saccharomyces eubayanus lager yeast hybrids. Here, we integrated both these approaches to create synthetic hybrids for lager fermentation using parental strains from niches other than beer. Using a phenotype-centered strategy, S. cerevisiae sourdough strains and the S. eubayanus x Saccharomyces uvarum strain NBRC1948 (also referred to as Saccharomyces bayanus) were chosen for their brewing aptitudes. We demonstrated that, in contrast to S. cerevisiae x S. uvarum crosses, hybridization yield was positively affected by time of exposure to starvation, but not by staggered mating. In laboratory-scale fermentation trials at 20°C, one triple S. cerevisiae x S. eubayanus x S. uvarum hybrid showed a heterotic phenotype compared with the parents. In 2L wort fermentation trials at 12°C, this hybrid inherited the ability to consume efficiently maltotriose from NBRC1948 and, like the sourdough S. cerevisiae parent, produced appreciable levels of the positive aroma compounds 3-methylbutyl acetate (banana/pear), ethyl acetate (general fruit aroma) and ethyl hexanoate (green apple, aniseed, and cherry aroma). Based on these evidences, the phenotype-centered approach appears promising for design of de novo lager beer hybrids and may help to diversify aroma profiles in lager beers.

Longevity risk constitutes an important risk factor for life insurance companies and it can be managed through longevity-linked securities. The market of longevity-linked securities is at present far from being complete and does not allow to find a unique pricing measure. We propose a method to estimate the maximum market price of longevity risk depending on the risk margin implicit within the calculation of the technical provisions as defined by Solvency II. The maximum price of longevity risk is determined for a survivor forward (S-forward), an agreement between two counterparties to exchange at maturity a fixed survival-dependent payment for a payment depending on the realized survival of a given cohort of individuals. The maximum prices determined for the S-forwards can be used to price other longevity-linked securities, such as q-forwards. The Cairns-Blake-Dowd model is used to represent the evolution of mortality over time, that combined with the information on the risk margin, enables us to calculate upper limits for the risk-adjusted survival probabilities, the market price of longevity risk and the S-forward prices. Numerical results can be extended for the pricing of other longevity-linked securities.

S-licarbazepine was prepared by asymmetric reduction of oxcarbazepine with interface-assembled carbonyl reductase at the interface of oil/water biphasic system. The carbonyl reductase was conjugated with polystyrene in the surface of toluene/Tris-HCl biphasic system and formed a surfactant-like structure. The conversion and enantiometric excess of S-licarbazepine reached 97.39% and 99.6% when 3.97 mmol/L oxcarbazepine was reduced by interface-assembled carbonyl reductase with 60 g/L ethanol as co-substrate in toluene/Tris-HCl(12.5:10) biphasic system at 30 °C, 180 rpm for 6 h.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

Peptides of hydrolysates of food proteins are an easily digestible source of amino acids necessary for the body to adapt to physical stress. Commercially significant hydrolysates include whey protein, casein, and other animal proteins. Hydrolysates of plant proteins are gaining popularity, but they are less common, then animal ones. Soy protein isolate is promising for obtaining the hydrolysates due to its affordable price and balanced amino acid profile. However, there are no direct studies showing an improvement in the result of physical activity when eating soy protein isolate hydrolysate (SPIH). In this work, for the first time, the study was conducted on the safety and efficacy of SPIH during physical load on model animals (rats). It was shown that the hydrolysate did not lead to pathological changes in the viscera, food intake, and weight of animals did not differ from the control group (animals consumed whey protein). Under physical load rats enteral fed SPIH showed a tendency to adapt more quickly to physical stress than the control group and the group of animals that was fed by free amino acids. The metabolites of animal blood serum were studied by NMR spectroscopy. It was shown that by the 95th minute after feeding in the group of rats receiving SPIH, the difference of proteinogenic amino acids concentrations in blood between individuals was significantly less than in the groups receiving whey protein or a mixture of amino acids. In other words, individual biochemical and physiological characteristics of individuals did not affect the assimilation of amino acids of hydrolysate.

The less virulent human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 cause mild, self-limiting respiratory tract infections, while the more virulent SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. We, therefore, generated full-length E protein models for SARS-CoV-1, -2, MERS-CoV, HCoV-229E, and HCoV-NL63 and docked C-terminal peptides of each model to the PDZ domain of the human PALS1 protein. The PDZ-binding motif (PBM) of the SARS-CoV-1, -2, and MERS-CoV models adopted a more flexible, extended coil while the HCoV-229E and HCoV-NL63 models adopted a less flexible alpha helix. All the E peptides docked to PALS1 occupied the same binding site and the more virulent hCoV E peptides generally interacted more stably with PALS1 than the less virulent ones. We propose that the increased flexibility of the PBM in more virulent hCoVs may permit more stable binding to various host proteins, thereby possibly contributing to more severe disease. This is the first paper to model full-length 3D structures for both more virulent and less virulent hCoVs E proteins, providing novel insights for possible drug and/or vaccine development.

Intrinsically disordered proteins mediate crucial biological functions through their interactions with other proteins. Mutual synergistic folding (MSF) occurs when all interacting proteins are disordered, folding into a stable structure in the course of the complex formation. In these cases, the folding and binding processes occur in parallel, lending the resulting structures uniquely heterogeneous features. Currently there are no dedicated classification approaches that would take into account the particular biological and biophysical properties of MSF complexes. Here we present a scalable clustering-based classification scheme, built on redundancy-filtered features that describe the sequence and structure properties of the complexes, and the role of the interaction, which is directly responsible for structure formation. Using this approach, we define six major types of MSF complexes, corresponding to biologically meaningful groups. Hence, the presented method also shows that differences in binding strength, subcellular localization, and regulation are encoded in the sequence and structural properties of proteins. While current structure classification methods can also handle complex structures, we show that the developed scheme is fundamentally different, and since it takes into account defining features of MSF complexes, it serves as a better representation of structures arising through this specific interaction mode.

In this study, we utilized the UniProt database to extract breast cancer genes Total 2658 genes in Homo sapiens are obtain. Then 166 genes are taken and after delating duplicates 158 genes were remains. These genes were then analyzed for their biological pathways using Gene Ontology enrichment analysis through the Genecodis platform, resulting in the identification of 12 unique genes involved in disease pathways. Protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software, identifying ANLN,TREM1,LZTFL1,OXSM,PLA2G3,TAS2R13,ABCB10,ECT2,TRPC,BCAS3,PLA2G3,ZDHHC7 and ERBB2 as potential gene targets for breast cancer.

Proteomic analysis of purified rabies virus (RABV) revealed 47 entrapped host proteins within viral particles. Out of these, 11 proteins were highly disordered. Our study was particularly focused on five of the RABV-entrapped mouse proteins with the highest levels of disorder, Neuromodulin, Chmp4b, DnaJB6, Vps37B, and Wasl. We extensively utilized bioinformatics tools, such as FuzDrop, D2P2, UniProt, RIDAO, STRING, AlphaFold, and ELM for comprehensive analysis of the intrinsic disorder propensity of these proteins. Our analysis suggested that these disordered host proteins might play a significant role in facilitating the rabies virus pathogenicity, immune system evasion, and the development of the antiviral drug resistance. Our study highlighted the complex interaction of the virus with its host, with the focus on how the intrinsic disorder can play a crucial role in virus pathogenic processes and suggested that these intrinsically disordered proteins (IDPs) and disorder-related host interactions can also be a potential target for the therapeutic strategies.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

Inflammatory bowel disease (IBD) comprises systemic inflammatory conditions primarily affecting the gastrointestinal tract, including Crohn's disease and ulcerative colitis. This research aims to analyze the clinical symptoms and pathogenesis of Dextran sodium sulfate (DSS)-induced canine IBD model, and evaluate the restorative effect of ginsenoside from a pathogenesis perspective. We established the DSS-induced canine IBD model and studied the pathological mechanisms. Additionally, we examined the therapeutic effect of ginsenosides by assessing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI), C-reactive protein (CRP) levels, colonic tissue morphology, protein expression, and mucosal bacterial community analysis. Our findings revealed a total ginsenoside content of 22.7% in the ginsenoside extract. Animal experiments demonstrated that dogs with IBD exhibited decreased mental state, significantly increased CIBDAI and CRP levels, disrupted colonic epithelial tissue structure, decreased expression of mucin, tight junctions, and adherens junctions, as well as reduced diversity of the colonic mucosal bacterial community. Furthermore, correlation analysis highlighted a total of 38 bacterial strains correlated with physiological indices. Significantly, ginsenoside treatment could improve these symptoms and reverse the relative abundance of some bacterial communities. In conclusion, Alterations in the properties of the colonic mucus layer or the reduction of MUC2, its core component, in dogs with IBD can lead to bacterial penetration of the mucus layer and subsequent contact with intestinal epithelial cells, resulting in inflammation. Remarkably, ginsenoside intervention showcased the capacity to positively influence the relative abundance of bacteria and impact the colonic mucus layer properties, thereby offering promising prospects for IBD management and recovery.

Understanding the binding behavior and conformational dynamics of intrinsically disordered proteins (IDPs) is crucial for unraveling their regulatory roles in biological processes. However, their lack of stable 3D structures poses challenges for analysis. To address this, we propose an algorithm that explores IDP binding behavior with protein complexes by extracting topological and geometric features from the protein surface model. Our algorithm identifies a geometrically favorable binding pose for the IDP and plans a feasible trajectory to evaluate its transition to the docking position. We focus on IDPs from Homo sapiens and Mus-musculus, investigating their interaction with the Plasmodium Falciparum (PF) pathogen associated with malaria-related deaths. We compare our algorithm with HawkDock and HDOCK docking tools for quantitative (computation time) and qualitative (binding affinity) measures. Our results indicate that our method outperforms the compared methods in computation performance and binding affinity of experimental conformations.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

Specialized classes of proteins, working together in a tightly orchestrated manner, induce and maintain highly curved cellular and organelles membrane morphology. Due to the various ex- perimental constraints, including the resolution limits of imaging techniques, it is non-trivial to accurately elucidate interactions among the various components involved in membrane deformation. The spatial and temporal scales of the systems also make it formidable to investigate them using simulations with molecular details. Interestingly, mechanics-based mesoscopic models have been used with great success in recapitulating the membrane defor- mations observed in experiments. In this review, we collate together and discuss the various mechanics based mesoscopic models for protein-mediated membrane deformation studies. In particular, we provide an elaborate description of a mesoscopic model where the membrane is modeled as a triangulated sheet and proteins are represented as either nematics or fila- ments. This representation allows us to explore the various aspects of protein-protein and protein-membrane interactions as well as examine the underlying mechanistic pathways for emergent behavior such as curvature-mediated protein localization and membrane deforma- tion. We also put forward current efforts in the field towards back-mapping these mesoscopic models to finer-grained particle based models - a framework that could be used to explore how molecular interactions propagate to physical scales and vice-versa. We end the review with an integrative-modeling based road map where experimental imaging micrograph and biochemical data are combined with mesoscopic and molecular simulations methods in a theoretically consistent manner to faithfully recapitulate the multiple length and time scales in the membrane remodeling processes.

Herein, we are proposing two chalcone molecules, (E)-1-(4-methoxyphenyl)-3-(p-tolyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) prop-2-en-1-one, based on the anticancer bioactive molecule Xanthohumol, which are suitable for further in vitro and in vivo studies. Their ability to create stable complexes with the antiapoptotic X-linked IAP (XIAP) protein makes them promising anticancer agents. The calculations were based on ligand-based and structure-based virtual screening combined for the pharmacophore built. Additionally, the structures passed Lipinski's rule for drug use, and their reactivity was confirmed using density functional theory studies. The candidates were chosen between 10639400 compounds, and the docking protocols were evaluated using molecular dynamics simulations.

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

The description of protein disordered states is important for understanding protein folding mechanisms and their functions. In this short review, we briefly describe a simulation approach to modeling disordered protein interactions and unfolded states of globular proteins. It is based on the CABS coarse-grained protein model that uses a Monte Carlo (MC) sampling scheme and a knowledge-based statistical force field. We review several case studies showing that description of protein disordered states resulting from CABS simulations is consistent with experimental data. The case studies comprise investigations of protein-peptide binding and protein folding processes. The CABS model has been recently made available as the simulation engine of multiscale modeling tools enabling studies of protein-peptide docking and protein flexibility. Those tools offer customization of the modeling process, driving the conformational search using distance restraints, reconstruction of selected models to all-atom resolution and studies of large protein systems in a reasonable computational time. Therefore, CABS can be combined in integrative modeling pipelines incorporating experimental data and other modeling tools of various resolution.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

Studies carried out have revealed that every day around three thousand and twelve people lose their lives in the world due to traffic accidents and poor air quality. Large cities, with their millions of inhabitants and vehicles, face many problems relating to vehicular traffic. In 2015 the speed limit was modified on several roads in the city of São Paulo-Brazil. However, in 2017 the speed limits were increased again, but not on all previous routes. This study analyzed the impact of this change on the number of accidents and pollutant concentrations, over a period of ten years, comparing the periods before and after the implementation of the measure, using real data collected and provided by the authorities of the city and the state transit and environmental companies, on more than forty routes and two nearby air quality stations. The results show a clear reduction in the number of accidents without victims on the roads of the city of São Paulo starting in 2010. However, the restrictive measures imposed by government officials may have contributed to the decrease in the number of accidents, but the number of fatalities has not changed much. Air pollution has not improved substantially with speed changes, as new speed increases have been linked to new episodes of congestion. The average number of fatalities due to accidents has been increasing since 2010 and accidents are becoming more serious. The application of a general linear statistical model (GLM) estimated the impact of the speed reduction policy in terms of the number of injuries avoided per month: 43.4 and 14.1 on other roads and on Pinheiros marginal, respectively. The results highlight the need for a constant data collection by the authorities in cities with high vehicle traffic. The important temporal time trend in terms of reduction of injuries but not in terms of fatalities and air quality, shows the need to apply joint public policies, not only speed reduction, but also the use of new technologies and raising drivers’ awareness of the problem.

COVID-19 infection in high-risk populations is fatal and has a poor prognosis, necessitating a test to determine the protectiveness of immune response. Antibody testing is necessary to determine the body's immune response to COVID-19 infection and also vaccination strategies. Among the various methods available, chemiluminescent immunoassay (CLIA) test is more widely used and accessible to determine antibody levels. This study aimed to determine the protection level of S-RBD SARS-CoV-2 IgG using CLIA compared to Surrogate Virus Neutralization Test (SVNT). The population of this study comprised all healthcare professionals who experienced S-RBD SARS-CoV-2 IgG antibody level examinations. S-RBD SARS-CoV-2 IgG antibody levels were examined using CLIA and SVNT. The cut-off was determined using Receiver Operating Characteristic (ROC) curve and AUC (Area Under the Curve) measurements were evaluated. The result showed a strong positive correlation between S-RBD SARS-CoV-2 IgG CLIA and SVNT with a value of r=0.933 and p <0.001. The value ≥37.29 BAU/mL was determined as the cut-off based on SVNT 30% inhibition level with sensitivity, specificity, positive, and negative predictive values of 96.5%, 90.9%, 96.5%, and 90.9%, respectively. A titer of antibodies greater than or equal to 37.29 BAU/mL with CLIA showed the presence of protective antibodies compared to SVNT.

Drawing from literature and Geert Hofstede’s cultural dimensions, this study delves into the impact of cultural factors on family structures, roles, and relationships. Ghana and Latvia have different cultural and social orientations that influence family dynamics. Through a comparative lens, this paper will contribute to understanding how a country’s culture influences family dynamics, highlighting the influence of Power Dynamics of parenting style and Individualism vs. Collectivism on interaction levels within the family.

The appropriate concentration of vitamin D in the athlete’s body is essential for its proper functioning, especially in terms of muscular health, by enhancing recovery and oxygen consumption. Soccer players are required to perform frequent sprints and change of directions during training and competition. The aim of the present study was to establish whether the level of vitamin D (measured by 25-hydroxyvitamin D concentrations- 25(OH)D) in blood serum has any influence on speed (s) and change of direction (COD, s) performance. Material and methods: Twenty male soccer players from the top league in Poland participated in the study. All subjects' were evaluated for the serum concentration of 25(OH)D at the beginning of the preseason. . The linear sprint test was performed at 5m and 30m and COD (time and deficit), was evaluated at 30m at the beginning and after 6 weeks of preparatory period. Results: The results revealed that 50% of soccer players had an insufficient level or a deficit of 25(OH)D (≤ 30 ng/ml), with 20% having a significant deficiency of 30 ng/ml).There were no statistically significant correlations between the training effect for the variables ∆5m (before - after) and ∆30m (before - after). Statistically significant positive correlations were found between the training effect for the variables ∆COD (before - after) (R=0.62/p=0.003) and ∆deficit (before-after) (R=0.47/p=0.039). With a higher concentration of vitamin D in the blood, the training effect for COD and the deficit increased, which was visible in the faster performance of the COD test. No statistically significant differences were found for the mean values of the variables ∆5m (before - after) and ∆30m (before - after) in the group of subjects whose 25(OH)D concentration was 30mg /ml. Significant differences were noticed for the variables ∆COD (m=0.60 [s]) and ∆deficit (m=0.56[s]) in the group of subjects whose 25(OH)D concentration was 30mg /ml. The training effect was significantly higher for the group of subjects whose 25(OH)D concentration was above 30 mg/ml, which was observed by the faster performance of the COD test in this group of subjects. Conclusions: The serum concentration of vitamin D affects training adaptations of muscles. A lower concentration of Vitamin D seems to have a detrimental effect on the change of direction performance. Soccer players whose blood serum 25(OH)D concentrations were >30mg/ml achieved better results in the applied fitness tests.

A relativistic positioning system is a set of four emitters broadcasting their proper times by means of light signals. The four emitter times received at an event constitute the emission coordinates of the event. Covariant quantities associated with relativistic positioning systems are analysed relatively to an observer in Minkowski space-time by splitting them in their relative space-like and time-like components. The location of a user in inertial coordinates from a standard set of emission data (emitted times and satellite trajectories) is solved in the underlying 3+1 formalism. The analytical location solution obtained by Kleusberg for the GPS system is recovered and interpreted in a Minkowskian context.

. Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available model or natural S-glycosylated proteins significantly hampers the development of MS-based methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto Lys, Arg side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-furanosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a hydride ion shift.

Recent studies have shown that the endogenous cannabinoid system (ECS) of the brain is essentially involved in the pathogenesis of Parkinson's disease (PD), influencing its symptoms by regulating the level of endogenous cannabinoids and altering the activation of cannabinoid receptors (CBR). Therefore, modulation of ECS with new drugs developed for this purpose may prove to be a promising strategy in the treatment of PD. However, fine regulation of ECS is quite a challenge due to the functional diversity of CBR in the basal ganglia. Our review analyses the effects of ECS modulators on experimental PD models and in patients with PD, as well as presents the outlooks for the development of new cannabinoid drugs for the treatment of motor and non-motor symptoms in PD.

Objective: To explore motivation to exercise, support, and self-management needs among people with Parkinson’s (PwP), family-members and physiotherapists. Methods: Purposeful and maximum difference sampling methods (age, sex, geographical setting, and disease severity) were employed. PwP and family-members were recruited through physiotherapy services and local support groups. Semi-structured interviews with 12 PwP, focus groups with four family-members, and five physiotherapists were conducted. Interview guides were informed by patient-public input, and a recent systematic review. Interviews were recorded, transcribed, and analysed using thematic analysis. Results: Four common themes emerged: 1) The value of an intrinsic connection with exercise: but there are challenges. A greater connection to exercise led to long-term compliance. 2) Tailoring exercise is essential. Preferred exercises and environments were mixed, with differences emerging between sexes. 3) Physiotherapists’ aim to only maintain physical function led to frustration. Limited self-management opportunities, stigma and dehumanisation were discussed. 4) Non-motor symptoms, stigma, fear, and determination. Apathy, pain, and low mood were discussed. Conclusion: Exercise provided physical, emotional, and social rewards. Supports are necessary; however, challenges arise when PwP’s motivation are mismatched to family-members’ and physiotherapists’ goals. Co-created goals, tailored to their preferences, and exercise plans with supported self-management are recommended.

Defining integrals over volume element in curved spacetime together with the mass and energy densities within that region of spacetime is apparently equivalent to the given energy and mass of that body or particle. With this in mind equations involving energies and mass can be rewritten in terms of their densities and the integral over the volume element. The idea find its place in the Hamiltonian formulations, and can be carried over into quantum mechanical frameworks systematically accounting for the effect of spacetime volume structures and gravity on dynamics of quantum systems. This article briefly explores this concept and runs through various frameworks and equations relevant to this idea, particularly the schrodinger-Newton equation and discusses the cosmological constant as a vacuum energy density.

Ecuador is an important center of biodiversity of the plant family Amaryllidaceae, specially the subfamily Amaryllidoideae, known as a source of important bioactive molecules. The aim of this study was to assess the chemical and biological potential of four different species of Amaryllidoideae collected in Ecuador: Urceolina formosa, Urceolina ruthiana, Clinanthus incarnatus, and Stenomesson aurantiacum. Sixteen alkaloids were identified in the bulb extract of these species by GC-MS, which the extract of S. aurantiacum exhibiting the greatest structural diversity. The potential of these three genera against Alzheimer’s disease was evaluated by measuring their AChE and BuChE inhibitory activity, revealing that C. incarnatus and U. formosa (from Sucumbíos province) showed the best results with IC50 values of 1.73 ± 0.25 and 30.56 ± 1.56 g·ml-1, respectively. Molecular dynamic assays were conducted to elucidate the possible interactions that occurs among 2-hydroxyanhydrolycorine and AChE enzyme, suggesting some similarity with those observed for galanthamine. This study enhances our understanding of the biodiversity of Amaryllidoideae species from Ecuador, highlighting their potential as a source of chemical compounds with pharmaceutical potential.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

In Mexico viticulture represents the second source of employment in the agricultural area after the fruit and vegetable sector. In developed countries, remote sensing is widely used for vineyard monitoring, however, this tool is barely used in developing countries of Iberoamerica. In this re-search, our overall objective is to characterize two vineyards in the state of Queretaro (Mexico) using Sentinel-2 and meteorological data, specifically spectral and thermal indices. Results showed that spectral indices obtained from Sentinel-2 bands have characterized adequately the phenolog-ical evolution of the different varieties of the vineyards. The Modified Soil-Adjusted Vegetation Index (MSAVI) was adequately used to discriminate the first stages of vineyards, while the Nor-malized Difference Vegetation Index (NDVI) was useful to monitor vineyards during the rest stages of vineyards. Thermal indices have shown that the best grape varieties were those that can adapt to both cooler and warmer temperatures, have a reasonable ripening period, and can produce wines with balanced acidity and flavors. In conclusion, the combination of meteorological (including thermal indices) and remote sensing data (NDVI and MSAVI) provide information for choosing the suitable grape variety for this region.

Entropy as a mathematical concept is the first of its own kind, and second to none. Barely one or two papers in literature have investigated fractal dimensions of very basic entropies, such as Shannon, Tsallis, and Rényi entropic expressions. This was a thoughtful inspiration to delve into a step forward towards a unified information- theoretic fractal theory. The storytelling of this current paper starts by introducing my third entropy formula, namely Ismail’s entropy, , as a novel generalization to Shannonian entropy with a visionary link to both long- and short-range interactions, (LRIs), (SRIs) respectively. Clearly, this would generate a fourfold unification with statistical mechanics as well as contemporary physics. Hence, this adds more credibility and weight for this study. The fractal dimension of , is identified in this paper. As an essential part of this work, it was influential to spotlight the importance of fractal geometry to space industry as well as education, which is crucial to develop our societies. Thus, some potential fractal applications to CubeSat Technologies and Education are highlighted. So, will the deep search for more ground-breaking research has come to an end. Certainly, not. This was another inspiration to propose new open problems to widen research gates to the scientific community for more research pathways. Consequently, the paper ends with closing remarks combined with some challenging open problems and the next phase of research.

Vectorial Boolean functions and codes are closely related, and each corresponding domain gives been to each other. On the one hand, various requirements of binary linear codes are needed for their theatrical interests but, more importantly, for their practical applicants (such as few-weight codes or minimal codes for secret sharing, locally recoverable codes for storage, etc.). On the other hand, various criteria and tables have been introduced to analyse the security of S-boxes that are related to vectorial Boolean functions, such as the Differential Distribution Table (DDT), the Boomerang Connectivity Table (BCT), and the Differential-Linear Connectivity Table (DLCT). In previous years, two new tables have been proposed for which the literature was pretty abundant: the $c$-DDT to extend the DDT and the $c$-BCT to extend the BCT. In the same vein, we propose extended concepts to study further the security of vectorial Boolean functions, especially the $c$-Walsh transform, the $c$-autocorrelation, and the $c$-differential-linear uniformity, and its accompanying table, the $c$-Differential-Linear Connectivity Table ($c$-DLCT). We study these properties of the novel functions at their optimal level concerning these concepts and describe the $c$-DLCT of the crucial inverse vectorial (Boolean) function case. Finally, the derived functions could lead to new families of binary minimal codes, as the recent achievements on minimal codes from low differential uniformity. We draw new avenues for future research toward linear code designs.

Coagulase-Negative Staphylococci (CoNS) are commensal on human body surfaces and for years, they were not considered a cause of bloodstream infection and were often regardered as contamination. However, the association of CoNS with nosocomial infection is increasingly recognized. The insertion of cannulas and intravascular catheters represents the first source of CoNS entry into the bloodstream, causing bacteremia and sepsis. They owe their pathogenic power to their ability to produce biofilms on surfaces, such as medical devices. In this study, we evaluate the adhesive capacity of CoNS isolated from blood cultures by comparing spectrophotometric phenotypic assay with genotypic analysis based on the evidence of the ica operon. We retrospectively reviewed the database of CoNS isolated from blood cultures, that were considered to be responsible for 361 bloodstream infections. Among them, we selected 89 ones who had full records. Our data show that S. epidermidis was the predominant species isolated, and with greater adhesive capacities, especially those with the complete operon. Knowing the adhesive capabilities of a microorganism responsible for sepsis can be useful in implementing appropriate corrective and preventive measures, as conventional antibiotic therapy cannot effectively eradicate biofilms.

Staphylococcus aureus are commensal bacteria present on skin and mucosae in both humans and animals, but they can also be found in food, water and in various environments. They are also considered a major pathogen having a great morbidity leading to a wide range of infections. They are included in the list of most virulent and antimicrobic resistant bacterial pathogens (ESKAPE, Escherichia coli, Staphylococcus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecalis and faecium)) by the Center for Disease Control and Prevention (CDC), and S. aureus is part of the worldwide threat represented by the presence of antimicrobial resistance (AMR). The outcomes of an epidemiological investigation on 26,430 S. aureus isolates from a global public database (NPDIB; NCBI Pathogen Detection Isolate Browser) support the evidence of significant differences in the distribution of isolates and ARGs (Antimicrobial Resistance Genes) clusters among geographical areas of origin and among sources of the isolates. Moreover, the ARGs cluster patterns suggest an association between the isolates from human and animal populations. This outcome and the large diffusion of the pathogens among human and animal populations support the importance of gaining information on the epidemiology of these infections with a One Health approach.

Recently, we demonstrated the validity of anomalous numbers law, known as Newcomb-Benford´s law, at the mammalian neuromuscular transmission, considering different extracellular calcium concentrations . The present work continues to examine how alterations in extracellular solution modulate the first digit law in the context of the spontaneous release of acetylcholine from the neuromuscular junction. We investigated if the intervals of miniature potentials collected at the neuromuscular junction obey the law in a hyperkalemic environment. The analysis showed that the interval between the miniature potentials at high potassium concentrations follows Newcomb-Benford´s law. Also, our data allowed us to uncover a conformity fluctuation as a function of the number of intervals of the miniature potentials. Finally, we discuss the biophysical implications of the present findings.

Polymyositis is a rare condition with an unknown etiology occurring more frequently in adult women. There is a lack of evidence on the coexistence of PM and CMV infection in a patient with Hashimoto Thyroiditis hypothyroidism. However, the increasing incidence of CMV infection and autoimmune diseases overlapping points out a relationship, while the association direction remains unclear. Case outline: A 32-year-old woman recently treated for HT hypothyroidism was admitted to the hospital two weeks after being treated for common flu by the family doctor, complaining about a worsening condition with muscle pain, weakness, frequent falls, and fatigue. The first tests showed a normalized thyroid function, with elevated values of troponin and serum creatinine kinase (KC). The immunological tests revealed the presence of a high titer of CMV IgG antibodies and raised levels of CMV DNA. Pelvis MRI images demonstrated markedly elevated signals on the STIR sequences in the pelvis, thighs, and calves, indicating active and severe multifocal myositis. The diagnosis of PM was confirmed with the muscle biopsy on day 7 of hospitalization. The patient showed significant improvements within two weeks after the medical therapy and physiotherapy.

The humoral response of the COVID-19 vaccine varies from person to person. It largely depends on prior SARS-CoV-2 infection, obtaining an adequate immune response, and leaving a trace of changing antibody concentration over time. We retrospectively analyzed five clinical cases from selected patients and employees of the oncology hospital. All mild COVID-19 convalescents received the BNT162b2-Comirnaty mRNA vaccine three or four times. The levels of SARS-CoV-2 IgM- and IgG-specific antibodies, as well as S-RBD antibodies, were analyzed for two years. The concentration of antibodies was assessed in the laboratory using the chemiluminescent immunoassay CLIA, MAGLUMI. Results: (1) Active autoimmune disease stabilized the level of IgG-specific antibodies after systemic mRNA vaccination for at least six months. (2) Post-vaccination IgG and S-RBD levels decreased when vaccination was performed within three months of onset. (3) The booster dose administered only increased the S-RBD antibody levels. Declining IgG-specific antibodies were observed. (4) The S-RBD IgG levels were not correlated with the SARS-CoV-2 IgG levels in the vaccinated convalescents. (5) Subsequent reinfection with SARS-CoV-2 after vaccination three times released a more significant specific antibody response. Based on the collected data, we suggest that monitoring S-RBD antibodies is sensitive but not equivalent to a specific humoral response for SARS-CoV-2 IgG. We suggested that administering at least three doses of the mRNA vaccine should serve as the basis for immunization. The three-month interval may be the best alternative to an immunization schedule for non-immunocompromised people.

The relationship between Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per group) to better understand the role of protein palmitoylation in PD and the pathways altered in this disease. Data-mining of the cortical palmitome from PD patients and controls has allowed to: i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls, ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes, and iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we have partially characterized the altered palmitome in the cortex of PD patients which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study points out that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.

From the hospital wastewater, a novel bacteriophage was isolated and characterized. According to characterization properties, this bacteriophage belongs to the Siphoviridae family, the maximum bacteriophage titer was recorded at 37°C and a pH of 7.2, had a 44,789 bp linear double-strand DNA genome, and within the genome sequence, there are 61 genes, all of which are encoded into proteins. Although this bacteriophage does not have any virulence factors or antimicrobial resistance genes and had specific lytic activity against some antimicrobial resistance S. aureus clinical isolates.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and <100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p<0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p<0.01); vs LT=2.74±0.84; (p<0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p<0.001), and LAVi (r=0.70; p<0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

Much of the debate on Plan S seems to concentrate on how to make toll access journals open access, taking for granted that existing open access journals are Plan S compliant. We suspected this was not so, and set out to explore this using DOAJ's journal metadata. We conclude that an overwhelmingly large majority of open access journals are not Plan S compliant, and that it is small HSS publishers not charging APCs that are least compliant and will face major challenges with becoming compliant. Plan S need to give special considerations to smaller publishers and/or non-APC-based journals.

Adlay seed samples were collected from 3 adlay growing regions (Yeoncheon, Jeonnam and Eumseong regions) in Korea during 2012. Among all the samples collected, 400 seeds were tested for fungal occurrence by standard blotter and test tube agar methods and different taxonomic groups of fungal genera were detected. The most predominant fungal genera encountered were Fusarium, Phoma, Alternaria, Cladosporium, Curvularia, Cochliobolus and Leptosphaerulina. The occurrence of Fusarium species were 45.6% and based on the combined sequences of two protein coding genes, EF-1a, Beta-tubulin and phylogenetic analysis, 10 species were characterized as F. incarnatum (11.67%), F. kyushense (10.33%), F. fujikuroi (8.67%), F. concentricum (6.00%), F. asiaticum (5.67%), F. graminearum (1.67%), F. miscanthi (0.67%), F. polyphialidiom (0.33%), F. armeniacum (0.33%) and F. thapsinum (0.33%). The ability of these isolates to produce mycotoxins fumonisin (FUM) and zeralenone (ZEN) were tested by ELISA quantitative analysis method. The result revealed that fumonisin (FUM) was produced only by F. fujikuroi and zeralenone (ZEN) by F. asiaticum & F. graminearum. Mycotoxigenic species were then examined for their morphological characteristics to confirm their identity. Morphological observations of the species correlated well with their molecular identification and confirmed as F. asiaticum, F. fujikuroi and F. graminearum.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

A 52-day experiment was conducted to determine the crude protein (CP) requirements of juvenile matrinxã Brycon amazonicus, and to evaluate their resulting growth performance, hematological parameters and enzymatic activities. Sixty fish (29.03g ± 1.16g) were distributed in 12 tanks (310 L) with a completely randomized design, and maintained at four dietary crude protein levels (270, 320, 350, 390 g.kg-1) for 52 days. The results revealed that the fish fed diet 390 g.kg-1 CP had the best final weight, weight gain, feed conversion ratio, specific growth rate, protein efficiency ratio and lipid retention rate. The same could be stated for hematocrit, number of circulating erythrocytes, triglycerides and total proteins of the hematological profile (p<0.05). In the whole body composition, dry matter content was lower in the fish fed 390 g.kg-1 CP, while lipid content was higher in the fish fed 350-390 g.kg-1 CP (p<0.05). No differences were observed in CP and ash (p>0.05), or in the activities of digestive enzymes (p>0.05). In short, our findings suggest benefits of the 390 g.kg-1 CP feed for being the most adequate for this species’ juvenile stage.

Polyacrylamide gel electrophoresis (PAGE) is widely used for studying proteins and protein-containing objects. However, it is employed most frequently as a qualitative method rather than a quantitative one. In this paper, we show the feasibility of routine digital image acquisition and mathematical processing of electrophoregrams for protein quantification. Both the well-studied model protein molecules (bovine serum albumin) and more complex real-world protein-based products (casein-containing isolate for sports nutrition), which were subjected to mechanical activation in a planetary ball mill to obtain samples characterized by different protein denaturation degrees, were used as study objects. Protein quantification in the mechanically activated samples was carried out. The degree of destruction of individual protein was shown to be higher compared to that of protein-containing mixture after mechanical treatment for an identical amount of time. The methodological approach used in this study can serve as guidance for other researchers who would like to use electrophoresis for protein quantification both in individual form and in protein mixtures. The findings prove that photographic imaging of gels followed by mathematical data processing can be applied for analyzing the electrophoretic data.

The Rho guanine nucleotide exchange factor (RGNEF) protein encoded by the ARHGEF28 gene has been implicated in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Biochemical and pathological studies have shown that RGNEF is a component of the hallmark neuronal cytoplasmic inclusions in ALS-affected neurons. Additionally, a heterozygous mutation in ARHGEF28 has been identified in a number of familial ALS (fALS) cases that may give rise to one of two truncated variants of the protein. Little is known about the normal biological function of RGNEF or how it contributes to ALS pathogenesis. To further explore RGNEF biology we have established and characterized a yeast model and characterized RGNEF expression in several mammalian cell lines. We demonstrate that RGNEF is toxic when overexpressed and forms inclusions. We also found that the fALS-associated mutation in ARGHEF28 gives rise to an inclusion-forming and toxic protein. Additionally, through unbiased screening using the split-ubiquitin system, we have identified RGNEF interacting proteins, including two ALS-associated proteins. Functional characterization of other RGNEF interactors identified in our screen suggest that RGNEF functions as a microtubule regulator. Our findings indicate that RGNEF misfolding and toxicity may cause impairment of the microtubule network and contribute to ALS pathogenesis.

Wheat is the essential constituent of cereal-based diets and one of the most significant sources of calories. However, there is an inherently low bioavailability of proteins, mineral, and vitamins in modern wheat grains. Biofortification has earned recognition as an outstanding approach, at the same time as a cure for world hunger. The developments in the identifications of quantitative trait loci (QTL) analysis and understanding of the physiological and molecular basis of QTLs controlling the biofortification traits in wheat has revealed new horizons for the improvement of modern wheat varieties. Within this review, we have compiled the information from the studies carried out in wheat using QTL mapping methodologies that is among the best methods for biofortification traits. We hope this review will serve as an essential reference for the QTLs identified for the several important biofortification traits in wheat.

Nanotechnology is a multidisciplinary science covering matters involving nanoscale level that is being developed for a great variety of applications. Nanomedicine is one of these attractive and challenging uses focused on the employment of nanomaterials in medical applications such as drug delivery. However, the uses of these nanometric systems requires specific parameters to establish the possible advantages and disadvantages in specific applications. This review presents the fundamental factors of nanoparticles and it´s microenvironment that must be considered to make an appropriate design for medical applications: (i) Interactions between nanoparticles and their biological environment, (ii) the interaction mechanisms, (iii) and the physicochemical properties of nanoparticles. On the other hand, the repercussions of the control, alteration and modification of these parameters in the final applications. Additionally, we here briefly report the implications of nanoparticles in nanomedicine and provide perspectives for some particular applications which still are challenged

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

Due to the vast conformational space proteins can adopt, accurate and efficient prediction of protein structure remains still a challenging task, coupled with the intricacies of interatomic interactions and the limitations of current computational models in effectively navigating this complex molecular landscape. Additionally, the lack of comprehensive experimental data for all protein structures further exacerbates the difficulty in reliable machine learning-based prediction of the three-dimensional conformations of the proteios building block of life. Geometrically, Cartesian coordinate system (CCS, X, Y and Z) and spherical coordinate system (SCS, ρ, θ and φ) are two interconvertible coordinate systems, and are like two sides of one coin. Since the beginning of Protein Data Bank (PDB) in 1971, CCS has been the default approach to specify atomic positions with X, Y and Z in PDB. In this manuscript, therefore, I present a novel method for the reversible spherical geometric conversion of protein backbone structure coordinate matrices to three independent vectors: ρ, θ and φ. This reversible conversion facilitates lossless extraction of essential structural features from protein backbone structural data, enabling the development of advanced novel algorithms for protein structure prediction in future. In short, this inter-atomic SCS approach offers a comprehensive yet efficient means of representing protein backbone geometry, leveraging spherical coordinates to capture spatial relationships in a compact and intuitive inter-atomic manner, and to provide a robust framework for reversible feature extraction for the ongoing efforts in advancing the field of protein structure prediction, the holy grail of computational structural biology.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

The cell surface targeting of neo-synthesized G protein coupled receptors (GPCRs) involves recruitment of receptor into COPII vesicles budding at Endoplasmic Reticulum Exit sites (ERES). This process is regulated for some GPCRs by escort proteins, which facilitate their export, or by gatekeepers that retain the receptors in the ER. PRAF2, an ER gatekeeper of the heterodimeric GABAB receptor protomer GB1, which interacts with a tandem di-leucine / RXR retention motif in the carboxyterminal tail of GB1, also inhibits the plasma membrane export of the chemokine receptor CCR5. PRAF2 / CCR5 interactions involve the transmembrane domains of both proteins. The di-leucine / RXR motif contained in the third intracellular loop of CCR5 does not affect PRAF2-mediated retention but impairs instead the interaction between CCR5 and its private escort protein CD4. PRAF2 and CD4 thus display opposite roles on the cell surface export of CCR5, likely at the level of its recruitment into COPII vesicles, PRAF2 inhibiting and CD4 promoting this process.

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein's function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein-ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in-depth. Through the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drug binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes. This comparison enhanced our understanding of the structure-activity relationships of these inhibitors, underscoring the efficacy of the FMO method in identifying critical binding features and predicting binding modes for small-molecule ligands. Furthermore, Our research spotlighted "hot spot" residues instrumental for selective and robust PLK1 binding. Our findings offer profound insights, priming the rational design of innovative potential PLK1 inhibitors with significant implications for developing anticancer therapeutics.

Oyster mushroom( Pleurotus ostreatus) is belong to the group of healthy foods, as they contain high levels of proteins, vitamins and different classes of compounds, it is discovered that oyster mushrooms could play a key role in maintaining good health. Oyster mushroom (Pleurotus sp.) Class Basidiomycetes and Family Agaricaceae are widely known as ‘dhingri’ in India. Pleurotus Ostreatus have several medicinal properties including ; anti-arthritic , antitumor, immune modulatory , antioxidant, anticancer, anti-inflammatory, antigenotoxic, hypo-cholesterolaemic, antihyperglycaemic antihypertensive, antiplatelet aggregating, antiviral and antimicrobial activities.. In this paper studied that effects of chemical constituents of oyster mushroom(Pleurotus sp.) on DNA damaging protein which analyzed its activity of PARP inhibiting or vice – versa.For this analysis we choose the molecular docking technique to check the effects of different chemical constituents of oyster mushroom(Pleurotus sp.) on DNA damaging protein and compare their results to PARP inhibitory drugs which taken as standard . We perform the molecular docking in between chemical constituents of oyster mushroom(Pleurotus sp.) and 4UND protein compare to performance of molecular docking in between standard PARP inhibitory drugs and 4UND protein with the help of PyRx and BIOVIA Discovery studio software.The analysis of molecular docking shows that some chemical constituents of oyster mushroom(Pleurotus sp.) having more binding affinity than standard PARP inhibitory drugs .The Rutin shows better binding affinity than PARP inhibitory drugs on the same protein.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

G protein-coupled receptors (GPCRs) are critical drug targets. GPCRs convey signals from the extracellular to the intracellular environment through G proteins. There is evidence that some ligands that bind to the GPCRs activate different downstream signaling pathways. G protein activation or -arrestin biased signaling involves ligands binding to receptors and stabilizing conformations that trigger a specific pathway. Molecular dynamics (MD) simulations are especially valuable for obtaining detailed mechanistic information, including identification of allosteric sites and understanding modulators' interactions between receptors and ligands. Here, we highlight recent simulation studies and methods used to study biased G protein-coupled receptor signaling and their conformational dynamics. We also highlight applications of MD simulations to drug discovery.

VpStyA1 and VpStyA2B of Variovorax paradoxus EPS is annotated and characterized as the first representative of an E2-type styrene monooxygenase of proteobacteria. It comprises a single epoxidase (VpStyA1) and a fusion protein (VpStyA2B) which serves mainly as NADH:FAD-oxidoreductase. VpStyA2B had a Km of 33.6 ± 4.0 µM for FAD and a kcat of 22.3 ± 1.1 s-1. VpStyA2B and VpStyA1 showed monooxygenase activity on styrene of 0.14 U mg-1 and 0.46 U mg-1 as well as on benzyl methyl sulfide of 1.62 U mg-1 and of 3.11 U mg-1. A putative fusion region at position 408 (AREAV) was mutated to provide insights on VpStyA2B-function. The best mutant (408-AAAAA) obtained showed a 6.6-times higher affinity for FAD while keeping the NADH-affinity and -oxidation activity. Corresponding epoxidase activity increased (1.6-times). But, other mutants showed still NADH:FAD-oxidoreductase activity, but lost mostly their epoxidase activity indicating effects on the monooxygenase-part as well. Thus, this monooxygenase system represents an interesting candidate for biocatalyst development.

: This Systematic Review focused on the use of Bifidobacterium infantis and Bifidobacterium breve in neurodegenerative diseases. The study of metabolomics has demonstrated the relationship between dysbiosis and neuronal death. The modulation of the gut microbiota in the intervention of these pathologies has become a promising area of study, showing beneficial results such as the improvement of synaptic function, the reduction of neuroinflammation, as well as the improvement of associated neuropsychiatric symptoms. Several studies have addressed the administration of Bifidobacterium infantis and Bifidobacterium breve, alone, in conjunction or in combination with other strains, in the intervention of neurodegenerative diseases. This Systematic Review includes the results of 17 research articles (n=5 in humans and n=12 in animal models) and the main result was that the use of these Bifidobacterium strains, alone, in conjunction or in combination with other strains, produced improvements in neurodegenerative disease-related symptomatology and degenerative cellular processes. However, some studies shown neutral results in certain variables. These data suggest that the use of these probiotics has a neuroprotective effect that may delay the progression of the disease. This research provides relevant and updated information on the use of these Bifidobacterium strains in neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

The COVID 19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that preceded them. The characteristic mutant constellations of these VOCs increased viral transmissibility and infectivity. Their origin and evolution remain puzzling. With the help of data mining efforts and the GISAID database, a chronology of 22 haplotypes described viral evolution up until July 23, 2023. Since the 3-dimensional atomic structures of proteins corresponding to the identified haplotypes are not available, ab initio methods were here utilized. Regions of intrinsic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, followed by changes in structure and intrinsic disorder. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Our strategy of mapping the dynamic evolutionary landscape of genetically linked mutations to the N-protein structure demonstrates the utility of ab initio modeling and deep learning tools for therapeutic intervention.

Neurodegenerative protein conformational diseases are characterized by misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with increased risk for neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis  possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut-brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria’s effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host-bacteria interactions in the context of protein conformational diseases.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.

Study of RNA-protein interactions and identification of RNA targets are among the key aspects of understanding the RNA biology. Currently, various methods are available to investigate these interactions, in particular, RNA pulldown assay. In the present paper, a method based on the HaloTag technology is presented that is called Halo-RPD (HaloTag RNA PullDown). The proposed protocol uses plants with stable fusion protein expression and the MagneBeads magnetic beads to capture RNA-protein complexes directly from the cytoplasmic lysate of transgenic A. thaliana plants. The key stages described in the paper are as follows: 1) preparation of the magnetic beads 2) tissue homogenization and collection of control samples 3) precipitation and wash of RNA-protein complexes; 4) evaluation of protein binding efficacy; 5) RNA isolation; 6) analysis of the obtained RNA. Recommendations for better NGS assay designs are provided.

We report positive correlations between letter frequency and symmetry (more symmetric symbols are more frequent) in English and Russian languages and in four types of numerals (Western, Roman, Arabic, and Chinese) with the coefficients of determination of R2=0.899 (English), R2=0.693 (Russian) and R2=0.740 (numerals). For comparison, we studied "symbol-like" 2D colloidal clusters and found negative correlations between frequency and symmetry (R2=0.814 and R2=0.994). While in human-made systems the frequency of using of a symbol is the driving force which leads to symbols simplification and symmetrizing, in natural system, symmetry leads to lower frequency of occurrence because there are fewer ways of building symmetric clusters than asymmetric ones. We interpret these results as a correlation between the symbol as a type and as a token and we attribute this correlation to the inherent iconicity of symbols

Although a lot of research has been carried out on hand sanitizer as an effort to prevent Covid-19, there is still limited research on non-alcoholic hand sanitizer lotion from the brown algae Scytosiphon lomentaria (S. lomentaria) as a raw material that provides antibacterial effects and maintains healthy skin. Therefore, this study aimed to analyze microbial inhibitory ability, physical and chemical characteristics of hand sanitizer lotion made from S. lomentaria algae. S. lomentaria powder was tested for phytochemicals, total phenolic content, free radical scavenging activity (IC50), and antibacterial tests. S. lomentaria slurry was prepared by adding distilled water (1:1) for lotion preparations in four treatment groups, such as normal control (lotion base without adding algae), lotion with the addition of algae 20%, 30%, and 40%. The lotion preparations for each treatment group were tested for antibacterial activity of Staphylococcus aureus and Escherichia coli, phytochemicals, pH, adhesion, spreadability, homogeneity, emulsion type, and hedonic. S. lomentaria powder contains bioactive polyphenolic compounds with a total phenolic content of 117.70±1.40 mg GAE/g dry weight and an IC50 value of 455±3.4 ppm, while lotion with the addition of S. lomentaria contains polyphenols and saponins The best treatment was shown by 40% S. lomentaria hand sanitizer lotion with inhibition of 6.30 ± 0.64 mm E. coli, 6.85 ± 1.12 mm S. aureus, hedonic test for color, texture and absorption with likes to likes very much level, neutral pH, greenish-white color, O/W emulsion type, high adhesion, homogeneous, and easily absorbed by the skin. This research can be an alternative reference in making non-alcoholic hand sanitizer lotion that is safe for the skin.

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

The excessive and prolonged use of the electronic devices with digital screens may cause some serious health problems. The ocular surface problems particularly Dry Eye Syndrome may be the most common and preventable one of them. In this study, unfavourable and potentially harmful effects of digital screens on lacrimal system and tear functions were evaluated in 221 participants. Their ocular surface conditions were evaluated by Ocular Surface Disease Index (OSDI) scores and their lacrimal functioning was measured by Schirmer’s test.. A reciprocal and statistically significant relationship was found between dry eye symptoms and OSDI scores. This relationship was more prominent especially in long duration use of smartphones with brighter background lights..

To protect skin from harmful ultraviolet (UV), zinc oxide (ZnO) with tannin from gallnuts was treated on cotton and polyester fabrics in this study. Before the treatments, the fabrics were dyed with shikonin and xanthophyll from Gromwell and Cape Jasmine. First, this study found that xanthophyll was more effective at preventing light fade or discoloration than shikonin. Despite the highest K/S, the untreated cotton in violet faded the most intensely when exposed to UV. The color variation of untreated polyester was narrow, with little change in L, a*, and K/S. Due to the non-photochemical xanthophyll, the yellow-dyed samples treated with ZnO/polyphenol did not vary yellowness (b*: 28.838) significantly, while the violet fabrics displayed a significant decrease in K/S and an increase in b*. The combination of ZnO and polyphenol treatment improved UV absorption at 350 to 250 nm. Cu-mordanting after ZnO/polyphenols treatment caused the violet cotton to turn reddish from blueish (negative to positive b*), with a hue change of 316° to 59° and the highest ΔE (25.90±4.34) after UV exposure. In this study, the combination of ZnO/polyphenol with Cu-mordants contributed the xanthophyll-dyed polyester to achieve a minimum ΔE and keep chroma and hue after UV exposure.

Parkinson’s disease (PD) is the second most common degenerative disease which may cause blood pressure abnormalities due to autonomic dysfunction. Early morning rise of blood pressure which is called morning surge is found to be related with some cardiovascular diseases when it is exaggerated. We wanted to search the relation of Morning blood pressure surge (MBPS) and inflammation in PD. Method: Ambulatory blood pressure monitoring for 24 hours, fibrinogen to albumin ratio, hs-CRP are used in this retrospective study. Fifty idiopathic PD patients and 50 age and sex matched control cases were included. MBPS, it has been defined as the difference between morning BP (measured 2 hours after awakening) and the lowest night-time BP. Body mass index (BMI) is used as an independent variable. Results: Median value of MBPS for PD group (21,63) was significantly different from the control group values (18,63) (p

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

Cow’s Milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, 'lactase deficient' individuals cannot digest milk's carbohydrate lactose depriving themselves of highly beneficial milk proteins like casein, lactoalbumin and lactoglobulin, due to lactose intolerance (LI), while other individuals develop cow milk allergy specifically against these proteins (CMPA). The management of these conditions is distinctly different and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restriction or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of the nutrients over the genome, proteome and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and so increasing life expectancy. Here, we report the scientific community opinion proposing to replace the approach “one size fits all” with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety, often resulting from the individual perception of this condition as different from a normal state.

This research proposes an algorithm to sign messages using the ElGamal asymmetric cryptosystem, called: Digital signature algorithm based on ElGamal, Diffie-Hellman protocol and the number π (DSAπ). This proposal has a high level of security like the DSA standard, in addition, execution times are reduced in relation to it. The Diffie-Hellman protocol and the number π were used in the construction of the digital signature algorithm in conjunction with the Hash-Sha-512 function. Some experiments are presented to provide evidence that the bits on the right side of the decimal point of π appear randomly, such as: a color image was constructed of a string of consecutive bits chosen at random, of the number π. Subsequently, parameters such as: entropy, correlation, discrete Fourier transform, goodness-of-fit test χ2 were evaluated. It is mentioned that an S-box 8×8 is involved in the signature. The sensitivity of the signature was measured, that is, when small changes are made to the sender’s private key, or small changes to the message. Finally, an image was constructed using the signatures of random texts, and subsequently the randomness of its pixels was obtained, to verify that there is no relationship between the different signatures.

Intrusion detection is generally carried out by matching network traffic patterns with known attack patterns or by identifying abnormal network traffic patterns. One statistical methodological approach used in intrusion detection is Statistical Process Control (SPC) by constructing a control chart. Hotelling’s T2 control chart is a multivariate control chart commonly used to monitor the mean process. The performance of the T2 chart in monitoring mean shifts can be increased if a robust estimator is utilized. Based on previous research, T2 based on the Fast-MCD estimator has good performance in monitoring low to medium outlier contaminated data. Therefore, the MRCD estimator can be used to detect intrusion. On the other hand, this research focuses on developing a bootstrap-based robust Hotelling’s T2 charts with Fast-MCD and MRCD estimators for evaluating performance in detecting intrusion on intrusion detection datasets. Based application of UNSW-NB15, the proposed chart has better performance than the conventional T2 and Fast-MCD-based T2 despite the longer execution time.

The Sidi Bou Othmane (SBO) pegmatite district is in the Central Jebilet massif, Occidental Meseta domain, Morocco. The SBO district is hosted essentially in a volcano-sedimentary series composed of the Late-Devonian Sarhlef shales. Pegmatite bodies crop out as dykes, which are oriented from N-S to E-W and are generally variably deformed with ductile and/or brittle structures with ante, syn- or post kinematic criteria. Petrographic observations of pegmatite dykes show that feldspars (i.e., albite, microcline) are the most abundant mineral phases, followed by quartz, micas, with tourmaline and accessory mineral as garnet, and zircon and secondary minerals as clinochlore, sericite, and illite. The geochemical study indicates that, according to the major pegmatite elements dykes of SBO have mainly a S-type granitic composition and are peraluminous granite with calc-alkalic affinity. The study of trace elements pointed out that SBO pegmatite formed under post-orogenic syn-collision context during the Variscan orogeny, by the partial melting of argilliferous sediment and can be ascribed to the muscovite-bearing pegmatite; moreover, they have a good potential on ceramic and contain minerals, such as feldspar, recently assessed as Critical raw materials by European Union.

The work is devoted to the development of methods for constructing asymptotic formulas as x→∞ of a fundamental system of solutions of linear differential equations generated by a symmetric two-term differential expression of odd order. The coefficients of the differential expression belong to classes of functions that allow oscillation (for example, those that do not satisfy the classical Titchmarsh-Levitan regularity conditions). As a model equation, the 5th order equation i2p(x)y′′′′′+p(x)y′′′′′+q(x)y=λy, for which various cases of behavior of the coefficients p(x),q(x), is investigated. New asymptotic formulas are obtained for the case when the function h(x)=−1+p−1/2(x)∉L1[1,∞) significantly influences the asymptotics of solutions to the equation. The case when the equation contains a nontrivial bifurcation parameter is studied.

Blood biomarkers represent a promising future for studying cognitive impairment, particularly in Alzheimer's Disease (AD), as they offer a non-invasive alternative to cerebrospinal fluid tests and have potential as population screening tools. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations between Amyloid-β, Total Tau, Phosphorylated Tau (p-tau), Neurofilament Light (Nfl), and Glial Fibrillary Acidic Protein (GFAP) with cognition. The reviewed studies are heterogeneous, varying in design and population (mixed, cognitively impaired, or unimpaired), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-tau measures tend to show stronger associations with cognitive functions than other biomarkers, no single blood marker has emerged as predominantly associated with a specific cognitive domain. These findings add to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical evaluations of cognition.

It is important to develop new antibacterial drugs since the emergence of bacterial resistance to available antibiotics. Metal nanoparticles have the potential to combat antibiotic resistance and are effective antibacterial agents. Here, we demonstrate the biogenic production of zinc nanoparticles using Rhododendron arboreum stem bark. The biosynthesized ZnNPs were characterized through different analytical techniques such as UV-vis, FTIR, EDX, SEM, and XRD. Clinical isolates such as E. coli, S. aureus, and K. pneumonia were used to check the antibacterial efficacy of the biosynthesized zinc nanoparticles. The MIC and MBC values against K. pneumonia, S. aureu, and E. coli were found to be 34±0.21 and 11.71±0.47, 47±0.11 and 23.86±0.84 and 94±0.18 and 40.43±0.16 µg/mL, respectively. It dramatically decreased the integrity of the cell membrane and markedly increased the permeability of both inner and outer membranes. The green synthesized ZnNPs have good catalytic activity. It degraded 65% of methyl orange dye within 6h when the mixture was kept in direct sunlight, thus demonstrating good photodegradation potential and can be employed as a good photocatalyst. According to these results, biosynthesized zinc nanoparticles could be a potential therapy option for controlling bacterial pathogenesis and an effective photocatalyst for the elimination of hazardous water contaminants.

Following on from work already carried out in our laboratory on a new biomass-derived green solvent, eucalyptol, we are now turning our attention to sabinene as a new green solvent. Sabinene is also derived from biomass. We have shown that it can be used as such or distilled to synthesize thiazolo[5,4-b]pyridine heterocycles by thermal or microwave activation. This new solvent was compared with various conventional and green solvents. The conditions were optimized to enable us to carry out the syntheses in good yields, and we were able to show that sabinene, a natural bicyclic monoterpene, could be used effectively as a solvent.

Perinatal stress experienced by mothers of very premature newborns may influence the mother’s milk and the infant’s intestinal microbiota. This prospective study of mothers of very preterm infants fed with mother´s own milk (MOM) was carried out in a tertiary hospital over a 2-year period. Assessment of maternal stress in 45 mothers of 52 very preterm newborns using the parental stress scale (PSS:NICU) that revealed an inverse relationship between stress and MOM production in the first days of life (p=0.012). The greatest contributor to stress was the one related to the establishment of mother-child bond. Maternal stress was lower in mothers in whom the kangaroo method was established early (p=0.011) and in those with a higher educational level (p=0.032). Levels of fecal calprotectin (FC) decrease with the passage of days and were directly correlated with birthweight (p=0.044). FC levels 7 days post-delivery were lower in newborns that received postnatal antibiotics (p=0.027). High levels of maternal stress resulted in progressive decreases and increases in the proportions of Firmicutes and Proteobacteria species, respectively, over 15 days post-delivery, both in MOM and in fecal samples from premature newborns. These findings underscore the importance of recognizing and appropriately managing maternal stress in neonatal units, given its marked influence on both the microbiota of maternal milk and the intestinal microbiota of premature newborns.

Currently, a wide variety of velocity profiles are used in motion control. Thus, this paper compares the energy consumption of three parabolic, trapezoidal, and S-curve profiles. We studied the case of using embedded systems since they are a powerful solution to monitor and coordinate the movement of devices and machinery in various industries combined with motion control applications. These integrated systems allow precise and efficient control of motors and actuators through control and feedback algorithms. In addition, we propose an alternative methodology for implementing motion controllers using an Advanced RISC Machine (ARM) microcontroller, which computes the trajectory and the control action in real-time. We conducted an experiment using a linear plant composed of a direct current (DC) motor coupled to an endless screw where a carriage is mounted that can move mechanically along a rail a distance of 1.16m. In addition, a 4096 pulses per revolution (PPR) encoder is connected to the motor to measure position and angular velocity, which compute the distance the carriage has moved in meters. A current sensor is used to assess the energy consumption, and 40 tests for each profile were carried out to compare the energy consumption for the three-motion profiles considering cases with and without load on the carriage.

A simulation test system for the two-dimensional (2D) fuze overload loading process was designed to address the loading issues of recoil overload and centrifugal overload in fuze safety and arming (S&A) devices. By incorporating centrifuge rotation energy storage, impact acceleration simulation, and equivalent centrifugal rotation simulation, a block equipped with a fuze S&A device was accelerated instantly upon being impacted by a centrifuge-driven impact hammer, simulating recoil overload loading. The impact hammer was retracted instantaneously by adopting an electromagnetic brake, which resulted in the centrifugal rotation of the block around its track, to simulate the centrifugal overload loading. The dynamic equations of the simulation test system and the equations of impact hammer motions were established, whereby the rotation speed of the centrifuge and the braking force of the electromagnetic brake were calculated and selected. A dynamic model of the collision between the impact hammer and block was established using ANSYS/LS-DYNA software for simulation analysis. The acceleration curves of the recoil overload and centrifugal overload with variations in the centrifuge speed, cushion material, and buffer thickness were obtained, which verified the feasibility of the proposed loading simulation method. 2D overload loading simulation tests were performed using the developed simulation system, and the acceleration curves of the recoil overload and centrifugal overload were measured. The test results indicated that the proposed system can accomplish 2D overload loading simulations for a recoil overload of several 10000 g and centrifugal overload of several 1000 g.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency i.e. 5.13±0.10% and 82.36±4.01%, respectively. SC PLGA NPs showed a spherical morphology on an average size (134.8±4.61nm), PDI: 0.277±0.004, and −25.3±1.03mV zeta-potential is suitable for oral delivery. Development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameters examinations with 1.219-minutes RT, MS (162.00/73.10), and a total run-time was 2.0-minutes. 1.0–1000.0ng/mL was a linear-range with inter & intra-day accuracy (92.55–99.40%) followed by precision (1.88–4.23%). SC PLGA NPs oral bioavailability was significantly higher (**p<0.01) as compared to SC-S treated groups (iv & oral). We found that the antimicrobial activity of SC PLGA NPs was more effective than pure S-Allyl-L-Cysteine with significant results (p<0.01) as compared to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties which can be helpful for oral administration. On the basis of our observations, SC PLGA NPs suggested the highest potential for the improvement of oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and is the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described, a clinical isolate infection model, utilizing isolates obtained from patients with CF, an incomplete antibiotic clearance model, leading to bacterial bounce-back and the establishment of chronic infection, and an adapted water bottle chronic infection model. These models circumvent the requirement for surgical procedure and importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

The research is a deep study of the CBOE Volatility Index (VIX), which represent the market sentiments of the S & P 500 Index (SPX) over a period of 33 years. It evaluates how the two indexes perform in the stock market crash and how reliable VIX is in predicting market sentiments. The research distributes the market rally in two forms, and one is a trust rally, when investors are happy to see the market in a stable form, and investors' sentiments are positive towards the stock market. Second is a fear rally, where investors' sentiments are negative, and their outlook is bearish for various reasons. It observes the pattern of rallies, like the longest trust or fear rally, in which year and its duration. The research analyzes data to reach a meaningful conclusion and various inferences that can be drawn from the study of historical data.

Methyl Salicylate (MS), the principal constituent of Wintergreen oil (WO) was obtained from acetyl salicylic acid (ASA) by sequential transesterification-esterification reaction promoted by NbCl5for the first time. The reagents were added simultaneously, and the reaction process involved the transesterification and esterification reactions, which were accompanied by thin layer chromatography and gas chromatography. The conversion rate via GC was 100%, and the MS yield was 94%. A cytotoxicity of 50% and 64% for cultured S. aureus and metastatic melanoma cells, respectively, was observed for a concentration of 0.6 mg/mL, whereas no cytotoxicity for non-tumor cells was observed for this concentration, and it is considered to be the optimum concentration.

In response to the new concept of the impact of total climate production factors on plant phenology, this study will verify the feasibility of simulating plant phenology and triggering thresholds based on total climatic production factors by using the phenological and meteorological observation data of S. krylovii plant from 1985 to 2018 at the Xilinhot National Climate Observatory of China Meteorological Administration. The results indicate that the total climate production factors influencing plant phenological changes can be well used for phenological simulation and its triggering thresholds. The mutation of cumulative climate production potential based on total climate production factors can effectively indicate the green-up date and the wilting date of S. krylovii plant, and their triggering thresholds depend on the parameters of climate resource change and plant biology, which are (0.085, –5.363) and (0.086, –27.620), respectively. The cumulative climate production potential based on total climate production factors can effectively indicate the heading date of S. krylovii plant, and its triggering thresholds also depends on the parameters of climate resource change and plant biology, which is (394.632，–38026.268). Furthermore, the results support the viewpoint that the climate abrupt changes determine the beginning and the ending of plant growth, while the accumulative climate resources determine the other phenological dates. This study provides new ideas for the study of plant phenology.

With the explosion of the generation, transmission and sharing of image data over the Internet and other unsecured networks, the need and significance for the development of novel image encryption algorithms is unprecedented. In this research work, we propose a novel framework for image encryption that is based on two hyperchaotic maps, utilized in conjunction with the single neuron model (SNM). The framework entails three successive stages, where in every stage, a substitution box (S-box) is applied, then XORing with an encryption key is carried out. The S-boxes and the encryption keys are generated from the numerical solutions of the hyperchaotic maps and the SNM. The performance of the proposed framework is gauged through a number of metrics, reflecting superior performance and complete asymmetry between the plain images and their encrypted versions. However, the main advantages of this work are: (1) The attained width of the key space; and (2) The achieved efficiency in software implementation. The superior key space of 2^{2551} is the result of employing the two hyperchaotic maps, while the improved efficiency, resulting in an average encryption rate of 8.54 Mbps, is the result of the utilization of the single neuron model, as well as the employment of optimized parallel processing techniques. In addition, the proposed encryption framework is shown to output encrypted images that pass the NIST SP 800 suite.

From the merge of arts and crafts towards a practice for mass production of desirability, consumption and product development in a capitalist economy of scale, design has lost its natural ability of problem comprehension and tension alleviation. The modern world needs the creativity, flexibility, and responsiveness embedded into design practices, mostly when a behavioural change, either individual or organizational, is intended. Still, the informality nature of the field is creating a gap between the study, research, and industrial design practice. Here it is presented the Biology of Creativity Model (BoC) which is a design-by-analogy method that promotes an empowered design practice through analysis of mostly biology reference texts for enhanced creativity and innovation performance in a diverse array of contexts.

Cotton is one of the most important economic crops in the world, whereas insect attacks is a prime cause of its losses on yield and quality. Despite it is important, little is known about the mechanism of cotton response to insect. In this study, we simulated insect feeding by applying insect oral secretions (OS) to wounds, and combined transcriptome and metabolome analysis to comprehensively investigate how OS from two major pest species (Helicoverpa armigera and Spodoptera litura) affect cotton defense responses. Obvious differences were observed that 12,668 and 13,379 genes differently expressed respectively in cotton after being treated with different OS when compared with wounding along. Upon the addition of OS, JA-signaling pathway were rapidly and strongly induced, however SA-biosynthesis related gens were significantly down-regulated. By constructing the co-expression gene network, we identified a hub gene which encoding a leucine-rich repeat receptor kinase may play important role in recognition and signal transduction at early stage. We also found that OS from different insect species altered abundance of flavonoid related compound with different patterns. Interestingly, Gossypol which is a well-known anti-insect compound was kept a relative low content after OS application relative to wounding which implied the existence of the suppression effects of OS to cotton defense response. This study illustrated the transcriptional and metabolic changes of cotton in responding to OS from two chewing insect species, identified potential key gene during the interaction process and finds the evidence for OS’s inhibition effects on cotton defense response.

In this paper, we introduced many new notions and new contraction named as S-weakly contraction after that we obtained the p-common best proximity point theorems for different types of contractions in the setting of complete metric spaces by using weak P_p-property and proved the uniqueness of these points. Also we presented some examples to prove the validity of our results.

This article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic growth factors and how the technology can be used for the treatment of osteoarthritis (OA). Transfected and irradiated protein packaging cell lines may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage matrix regeneration. We discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging cell lines are superior to bacterial expression systems and are likely to have a significant impact on the development of new biological therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Sea cucumber peptides are small molecular peptides with biological function obtained from fresh sea cucumber as feedstock, which were hydrolyzed by protease, separated ,and purified. As the main product of sea cucumber refinement, it more accurately expresses the nutritional effect of sea cucumber and has a wide range of potential applications. It has been demonstrated that sea cucumber has a certain value-added effect on bone mineral density regulation, but the differences in bone mineral density regulation of extracts from different parts of sea cucumber and the techniques contributing to the efficient isolation of bone sea cucumber peptides have not been reported. Firstly, the aim of this study was to reveal the differences in osteogenic activities of enzymatic peptides from three major parts of sea cucumber: the body wall, the egg protein, and the intestinal protein. Then, the bone-enhancing sea cucumber peptides were isolated based on the characteristics of the dif-ferences in molecular weight distribution, hydrophilicity, and ionisation degree of sea cucumber, and to explore the possible mechanisms of their action. The findings indicated that sea cucumber peptides extracted from three distinct sites exhibited a dose-dependent enhancement of osteoblast proliferation and differentiation. Upon evaluating the three methods of sea cucumber peptide separation based on molecular weight distribution, hydrophilicity, and ionization, it was observed that the fraction isolated by hydrophobicity and

In this comprehensive survey, we delve into the multifaceted role of palmitoylation across vari-ous cell death modalities in the oncological context. From its intricate correlations with tumor-igenesis, steered by the DHHC family, to the counter-process of depalmitoylation mediated by enzymes like PPT1. Innovations in detection methodologies have paralleled our growing under-standing, transitioning from rudimentary techniques to sophisticated modern methods. Central to our discourse are agents like GNS561 and DC661, promising heralds in palmitoylation-targeted cancer therapy. Collectively, this review accentuates palmitoylation's transformative potential in oncology, foreshadowing groundbreaking therapeutic strategies and deepening our molecular comprehension of cancer dynamics.

Bioactive peptides are promising cosmetic active ingredients that can improve skin health and appearance. They exhibit a broad spectrum of activity, including anti–ageing, antioxidant, antimicrobial and anti–inflammatory. The aim of this study was to develop a safe, stable and efficacious environmentaly friendly ("green") emulsion using milk protein hydrolysate as a model active ingredient. Potential emulsions were formulated with biodegradable emollients, stabilised with a naturally-derived mixed emulsifier and prepared by cold process. They were evaluated for rheological behavior (continuous rotation and oscillation tests), physical stability (dynamic mechanical thermal analysis - DMTA test) and texture profiles, as well as for cytotoxic, antioxidant and antimicrobial effects. Rheological characterization revealed shear-thinning flow behaviour with yield point from continuous rotation tests and predominantly elastic character from oscillation (amplitude and frequency sweep) tests, with small structural change detected in the DMTA test. These results implied satisfactory rheological properties and good stability. Texture analysis revealed acceptable spreadability and substantivity of the emulsions. The protein hydrolysate showed antioxidant activity. The developed emulsions showed low antibacterial activity against selected microorganisms, but this was due to the action of preservatives, not peptides. All potential emulsions showed desirable safety profile. The results obtained provide the basis for the next stage of formulation development, i.e. in vivo efficacy tests.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.