In silico designing of multiepitope-based-peptide (MBP) vaccine against MAPK protein express for Alzheimer's disease in Zebrafish.

Understanding the role of the mitogen-activated protein kinases (MAPKs) signalling pathway is essential in advancing treatments for neurodegenerative disorders like Alzheimer's. In this study, we investigate in-silico techniques involving computer-based methods to extract the MAPK1 sequence. Our applied methods enable us to analyze the protein's structure, evaluate its properties, establish its evolutionary relationships, and assess its prevalence in populations. We also predict epitopes, assess their ability to trigger immune responses, and check for allergenicity using advanced computational tools to understand their immunological properties comprehensively. We apply virtual screening, docking, and structure modelling to identify promising drug candidates, analyze their interactions, and enhance drug design processes. We identified a total of 30 cell-targeting molecules against the MAPK1 protein, where we selected top 10 CTL epitopes (PAGGGPNPG, GGGPNPGSG, SAPAGGGPN, AVSAPAGGG, AGGGPNPGS, ATAAVSAPA, TAAVSAPAG, ENIIGINDI, INDIIRTPT, and NDIIRTPTI) for further evaluation to determine their potential efficacy, safety, and suitability for vaccine design based on strong binding potential. The potential to cover a large portion of the world's population with these vaccines is substantial-88.5 % for one type and 99.99 % for another. In exploring the molecular docking analyses, we examined a library of compounds from the ZINC database. Among them, we identified twelve compounds with the lowest binding energy. Critical residues in the MAPK1 protein, such as VAL48, LYS63, CYS175, ASP176, LYS160, ALA61, LEU165, TYR45, SER162, ARG33, PRO365, PHE363, ILE40, ASN163, and GLU42, are pivotal for interactions with these compounds. Our result suggests that these compounds could influence the protein's behaviour. Moreover, our docking analyses revealed that the predicted peptides have a strong affinity for the MAPK1 protein. These peptides form stable complexes, indicating their potential as potent inhibitors. This study contributes to the identification of new drug compounds and the screening of their desired properties. These compounds could potentially help reduce the excessive activity of MAPK1, which is linked to Alzheimer's disease.

Machine learning for cardiology.

This paper reviews recent cardiology literature and reports how artificial intelligence tools (specifically, machine learning techniques) are being used by physicians in the field. Each technique is introduced with enough details to allow the understanding of how it works and its intent, but without delving into details that do not add immediate benefits and require expertise in the field. We specifically focus on the principal Machine learning based risk scores used in cardiovascular research. After introducing them and summarizing their assumptions and biases, we discuss their merits and shortcomings. We report on how frequently they are adopted in the field and suggest why this is the case based on our expertise in machine learning. We complete the analysis by reviewing how corresponding statistical approaches compare with them. Finally, we discuss the main open issues in applying machine learning tools to cardiology tasks, also drafting possible future directions. Despite the growing interest in these tools, we argue that there are many still underutilized techniques: while neural networks are slowly being incorporated in cardiovascular research, other important techniques such as semi-supervised learning and federated learning are still underutilized. The former would allow practitioners to harness the information contained in large datasets that are only partially labeled, while the latter would foster collaboration between institutions allowing building larger and better models.

Corrigendum: Physical Organohydrogels With Extreme Strength and Temperature Tolerance.

[This corrects the article DOI: 10.3389/fchem.2020.00102.].

Physical Organohydrogels With Extreme Strength and Temperature Tolerance.

Tough gel with extreme temperature tolerance is a class of soft materials having potential applications in the specific fields that require excellent integrated properties under subzero temperature. Herein, physically crosslinked Europium (Eu)-alginate/polyvinyl alcohol (PVA) organohydrogels that do not freeze at far below 0°C, while retention of high stress and stretchability is demonstrated. These organohydrogels are synthesized through displacement of water swollen in polymer networks of hydrogel to cryoprotectants (e.g., ethylene glycol, glycerol, and d-sorbitol). The organohydrogels swollen water-cryoprotectant binary systems can be recovered to their original shapes when be bent, folded and even twisted after being cooled down to a temperature as low as -20 and -45°C, due to lower vapor pressure and ice-inhibition of cryoprotectants. The physical organohydrogels exhibit the maximum stress (5.62 ± 0.41 MPa) and strain (7.63 ± 0.02), which is about 10 and 2 times of their original hydrogel, due to the synergistic effect of multiple hydrogen bonds, coordination bonds and dense polymer networks. Based on these features, such physically crosslinked organohydrogels with extreme toughness and wide temperature tolerance is a promising soft material expanding the applications of gels in more specific and harsh conditions.

Chitin/chitosan derivatives and their interactions with microorganisms: a comprehensive review and future perspectives.

Chitosan, obtained as a result of the deacetylation of chitin, one of the most important naturally occurring polymers, has antimicrobial properties against fungi, and bacteria. It is also useful in other fields, including: food, biomedicine, biotechnology, agriculture, and the pharmaceutical industries. A literature survey shows that its antimicrobial activity depends upon several factors such as: the pH, temperature, molecular weight, ability to chelate metals, degree of deacetylation, source of chitosan, and the type of microorganism involved. This review will focus on the in vitro and in vivo antimicrobial properties of chitosan and its derivatives, along with a discussion on its mechanism of action during the treatment of infectious animal diseases, as well as its importance in food safety. We conclude with a summary of the challenges associated with the uses of chitosan and its derivatives.

Calcium homeostasis during hibernation and in mechanical environments disrupting calcium homeostasis.

To maintain calcium homeostasis during physical inactivity, precise coordination is necessary between different organs of the body. There are a number of factors which alter an organism's calcium balance, such as growth, aging, physical inactivity and acquired or inherited disorders which ultimately lead to bone loss. In non-hibernating mammals, physical inactivity causes bone loss which may not be completely recoverable during the lifespan of an individual despite a resumption of activity. Extreme physical inactivity and nutritional deprivation are two other important factors that lead to bone loss in non-hibernating mammals. The mechanism of bone loss is still poorly understood, however, there is some evidence which shows that during hibernation, smaller mammals (ground squirrels, bats, and hamsters) undergo bone loss. While on the other hand, hibernating bears do not show any sign of bone loss and retain their bone structure and strength. This may be due to differences in their hibernation patterns, as smaller mammals may excrete calcium throughout the hibernation period, which ultimately leads to bone loss, whereas bears seem to have a more developed and advanced mechanism to prevent calcium loss and maintain their bone structure. In this review, we summarize calcium homeostasis and its adaptive mechanisms with reference to bone loss in hibernating as compared to non-hibernating mammals. We also review the effect of microgravity and simulated microgravity on bone physiology and subsequent adaptation.

Functional, rheological, microstructural and antioxidant properties of quinoa flour in dispersions as influenced by particle size.

Nutritionally, particle size has significant impact on food digestibility in the gastrointestinal system. Controlling the rheological behaviors of particles in dispersion has been of major interest in the industry. In this work, the quinoa seed was ground into flour, followed by fractionating into a selected particle size [+30-mesh (>595-µm) to +200-mesh (>74-µm)]. The effect of particle size on composition, antioxidant, and several functional and mechanical properties of all particle fractions were studied. The protein, crude fat, crude fiber, dietary fiber contents increased with decreasing the particle size while the starch content decreased. The water holding capacity and sediment volume fraction increased with the reduction of particles. Rheological measurement indicated that there were significant differences among rheograms between coarser and finer particles of QF. The finest particles produced a lower complex viscosity and lower mechanical rigidity. The final and setback viscosities decreased as particle size decreased. Microscopy showed irregular-shaped polygon structure for the QF. The particle fractions ranged between +100 and +200-mesh showed compositional resemblances and, subsequently, the properties. The highest extractability of phenolics and antioxidant properties were observed for the finest particles. The information generated from this work would help the industry to develop products with the desired particle size with optimum functional and nutritional properties.

Novel findings on ultrastructural protection of skeletal muscle fibers during hibernation of Daurian ground squirrels: Mitochondria, nuclei, cytoskeleton, glycogen.

We examined ultrastructure protective phenomena and mechanisms of slow and fast muscles in hibernating Daurian ground squirrels (Spermophilus dauricus). Some degenerative changes such as slightly decreased sarcomere length and vacuolization occurred in hibernation, but periaxonal capsular borders in intrafusal fibers remained distinct and the arrangement of extrafusal fibers and Z-lines unscathed. In soleus samples, the number of glycogenosomes more than tripled during hibernation. The expression of phosphorylated glycogen synthase remained unaltered while that of glycogen phosphorylase decreased during hibernation. The number of extensor digitorum longus glycogenosomes decreased and the expression of phosphorylated glycogen synthase decreased, while glycogen phosphorylase expression remained unaltered. The nuclei number remained unchanged. Kinesin and desmin, preventors of nuclear loss and damage, were maintained or just slightly reduced in hibernation. The single-fiber mitochondrial concentration and sub-sarcolemmal mitochondrial number increased in both muscle types. The expression of vimentin, which anchors mitochondria and maintains Z-line integrity, was increased during and after hibernation. Also, dynamin-related protein 1, mitochondrial fission factor, and adenosine triphosphate synthase were elevated in both muscle types. These findings confirm a remarkable ultrastructure preservation and show an unexpected increase in mitochondrial capacity in hibernating squirrels.

Rheological, structural and functional properties of high-pressure treated quinoa starch in dispersions.

The impact of high-pressure treatment on the gelatinization of quinoa starch (QS) dispersions was investigated as a function of pressure (300, 450 and 600 MPa for 15 min) and starch to water (S/W) ratio (1:3 and 1:4 w/w). The structural changes of QS were characterized by rheological, DSC, SEM, XRD, and FTIR spectroscopy. The water holding capacity and granules particle size increased significantly with the intensity of pressure. The G' of the QS gradually improved as a function of pressure and S/W ratio. A complete gelatinization of QS occurred at 600 MPa by breaking down of amylopectin crystallites and transformation to the amorphous state, which was confirmed by rheometry, XRD, and DSC. Additional heat-treatment to pressure-treated samples greatly improved the gel rigidity except for the sample treated at 600 MPa. It can be inferred that the functional properties of QS could be significantly modified/improved with the application a pressure-treatment of 600 MPa.

miR-208a-3p Suppresses Osteoblast Differentiation and Inhibits Bone Formation by Targeting ACVR1.

Emerging evidence indicates that many microRNAs (miRNAs) are indispensable regulators of osteoblast differentiation and bone formation. However, the role of miRNAs in mechanotransduction of osteoblasts remains to be elucidated. This study aimed to identify a mechanosensitive miRNA that regulates Activin A receptor type I (ACVR1)-induced osteogenic differentiation. After 4 weeks of hindlimb unloading (HLU) suspension of 6-month-old male C57BL/6J mice, femurs and tibias were harvested to extract total bone RNAs. Elevated levels of miR-208a-3p correlated with a lower degree of bone formation in whole-bone samples of HLU mice. However, in vitro overexpression of miR-208a-3p inhibited osteoblast differentiation, whereas silencing of miR-208a-3p by antagomiR-208a-3p promoted expression of osteoblast activity, bone formation marker genes, and matrix mineralization under mechanical unloading condition. Bioinformatics analysis and a luciferase assay revealed that ACVR1 is a target gene of miR-208a-3p that negatively regulates osteoblast differentiation under mechanical unloading environment. Further, this study also demonstrates that in vivo pre-treatment with antagomiR-208a-3p led to an increase in bone formation and trabecular microarchitecture and partly rescued the bone loss caused by mechanical unloading. Collectively, these results suggest that in vivo, inhibition of miRNA-208a-3p by antagomiR-208a-3p may be a potential therapeutic strategy for ameliorating bone loss.

Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures.

Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives.

Active Chicken Meat Packaging Based on Polylactide Films and Bimetallic Ag-Cu Nanoparticles and Essential Oil.

Plasticized polylactide (PLA) composite films with multifunctional properties were created by loading bimetallic silver-copper (Ag-Cu) nanoparticles (NPs) and cinnamon essential oil (CEO) into polymer matrix via compression molding technique. Rheological, structural, thermal, barrier, and antimicrobial properties of the produced films, and its utilization in the packaging of chicken meat were investigated. PLA/PEG/Ag-Cu/CEO composites showed a very complex rheological system where both plasticizing and antiplasticizing effects were evident. Thermal properties of plasticized PLA film with polyethylene glycol (PEG) enhanced considerably with the reinforcement of NPs whereas loading of CEO decreased glass transition, melting, and crystallization temperature. The barrier properties of the composite films were reduced with the increase of CEO loading (P < 0.05). Their optical properties were also modified by the addition of both CEO and Ag-Cu NPs. The changes in the molecular organization of PLA composite films were visualized by FTIR spectra. Rough and porous surfaces of the films were evident by scanning electron microscopy. The effectiveness of composite films was tested against Salmonella Typhimurium, Campylobacter jejuni and Listeria monocytogenes inoculated in chicken samples, and it was found that the films loaded with Ag-Cu NPs and 50% CEO showed maximum antibacterial action during 21 days at the refrigerated condition. The produced PLA/Ag-Cu/CEO composite films can be applied to active food packaging. PRACTICAL APPLICATION: The nanoparticles and essential oil loaded PLA composite films are capable of exhibiting antimicrobial effects against Gram (+) and (-) bacteria, and extend the shelf-life of chicken meat. The bionanocomposite films showed the potential to be manufactured commercially because of the thermal stability of the active components during the hot-press compression molding process. The developed bionanocomposites could have practical importance and open a new direction for the active food packaging to control the spoilage and the pathogenic bacteria associated with the fresh chicken meat.

Polylactide/graphene oxide nanosheets/clove essential oil composite films for potential food packaging applications.

Antimicrobial nanopackaging films were developed by incorporating clove essential oil (CLO) (15-30% w/w) and graphene oxide (GO) nanosheets (1% w/w) into polylactide (PLA), suitable for use as food packaging, via solution casting. Addition of CLO into PLA matrix improved the flexibility of the composite films by lowering tensile stress, complex viscosity (η*), and glass transition temperature (Tg). GO improved the Tg, η* and lowered the oxygen permeability of the plasticized PLA matrix. Optical and anti-UV properties of the film were influenced by both GO and CLO incorporation. FTIR spectra exhibited a change in the molecular organization of the plasticized PLA film after incorporation with CLO. Microstructural studies revealed that the reinforcement of GO prevented porosity of plasticized PLA/CLO film surface. The developed composite film showed excellent antibacterial activity against Staphylococcus aureus and Escherichia coli and therefore, has a potential to be used as active packaging material for food safety and preservation.

Stress-responsive microRNAs are involved in re-programming of metabolic functions in hibernators.

Mammalian hibernation includes re-programing of metabolic capacities, partially, encouraged by microRNAs (miRNAs). Albeit much is known about the functions of miRNAs, we need learning on low temperature miRNAs target determination. As hibernators can withstand low body temperatures (TB) for a long time without anguish tissue damage, understanding the means and mechanisms that empower them to do as such are of restorative intrigue. Nonetheless, these mechanisms by which miRNAs and the hibernators react to stressful conditions are not much clear. It is evident from recent data that the gene expression and the translation of mRNA to protein are controlled by miRNAs. The miRNAs also influence regulation of major cellular processes. As the significance of miRNAs in stress conditions adaptation are getting clearer, this audit article abridges the key alterations in miRNA expression and the mechanism that facilitates stress survival.

Remarkable plasticity of Na+, K+-ATPase, Ca2+-ATPase and SERCA contributes to muscle disuse atrophy resistance in hibernating Daurian ground squirrels.

We investigated cytosolic calcium (Ca2+) and sarcoplasmic reticulum Ca2+ regulation in skeletal muscle fibers of hibernating Daurian ground squirrels (Spermophilus dauricus), non-hibernating hindlimb-unloaded (HLU) squirrels, and HLU rats to clarify the molecular mechanisms involved in preventing muscle atrophy in hibernators. The Na+, K+-ATPase and Ca2+-ATPase activities in the soleus muscle (SOL) of squirrels were maintained in hibernation, decreased during interbout arousal (IB-A), and increased to autumn/pre-hibernation (AUT/Pre-H) levels in torpor after interbout arousal (Post-IBA), whereas activities in the extensor digitorum longus muscle (EDL) were stable during hibernation, but increased during post-hibernation (Post-H). Activities increased in the SOL of HLU rats, but were stable in HLU squirrels. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity in the SOL decreased in IB-A squirrels, but returned to AUT/Pre-H levels in the Post-IBA group; no significant changes were found in the EDL. SERCA activity increased in the EDL of HLU squirrels and SOL of HLU rats. Compared with AUT/Pre-H, SERCA type 2 protein expression increased in the SOL and EDL of IB-A and Post-IBA squirrels, but increased in the SOL only in HLU animals. We also describe the protein kinase A changes in this paper. Thus, hibernating ground squirrels displayed remarkable Na+, K+-ATPase, Ca2+-ATPase, and SERCA plasticity.

Comparative effects of untreated and 3-methacryloxypropyltrimethoxysilane treated ZnO nanoparticle reinforcement on properties of polylactide-based nanocomposite films.

Polylactide (PLA) nanocomposites characterized by antimicrobial properties are gaining increasing attention for food packaging. In this contribution, the PLA based nanocomposite films with multifunctional end-use properties were achieved by incorporating ZnO nanoparticles (NPs) [untreated: ZnO(UT) and 3-methacryloxypropyltrimethoxysilane treated: ZnO(ST)] into polymer matrix via solvent casting method. The ZnO(ST) prevented the degradation of PLA at higher temperature and improved the mechanical property. Color, transparency, and anti-UV properties of composite films were influenced by the incorporation of ZnO NPs. Contrary to untreated ZnO, the treated NPs were more effective in enhancing the tortuosity of the diffusive path for the oxygen molecules to diffuse through the film. The glass transition (Tg) and crystallization (Tc) temperatures of composites were improved by the addition of ZnO, whereas a higher Tg was recorded for ZnO(ST) loaded films. XRD demonstrated the change in crystallinity of the films with NPs addition. Nanoparticles well distributed in the composite films as observed through SEM however spots of agglomeration were observed for PLA/ZnO(UT) films. Developed films especially incorporated with ZnO(ST) were found to be active against both Gram-negative (Salmonella Typhimurium) and Gram-positive (Listeria monocytogenes) bacteria. Therefore, PLA/ZnO nanocomposite films could be considered as environment-friendly active packaging material for food preservation.

Tetramethylpyrazine ameliorated disuse-induced gastrocnemius muscle atrophy in hindlimb unloading rats through suppression of Ca2+/ROS-mediated apoptosis.

The purpose of this study was to examine the possible mechanism underlying the protective effect of tetramethylpyrazine (TMP) against disuse-induced muscle atrophy. Sprague-Dawley rats were randomly assigned to receive 14 days of hindlimb unloading (HLU, a model of disuse atrophy) or cage controls. The rats were given TMP (60 mg/kg body mass) or vehicle (water) by gavage. Compared with vehicle treatment, TMP significantly attenuated the loss of gastrocnemius muscle mass (-33.56%, P < 0.01), the decrease of cross-sectional area of slow fiber (-10.99%, P < 0.05) and fast fiber (-15.78%, P < 0.01) during HLU. Although TMP failed to further improve recovery of muscle function or fatigability compared with vehicle treatment, it can suppress the higher level of lactate (-22.71%, P < 0.01) induced by HLU. Besides, TMP could effectually reduce the increased protein expression of muscle RING-finger protein 1 induced by HLU (-14.52%, P < 0.01). Furthermore, TMP can ameliorate the calcium overload (-54.39%, P < 0.05), the increase of malondialdehyde content (-19.82%, P < 0.05), the decrease of superoxide dismutase activity (21.34%, P < 0.05), and myonuclear apoptosis (-78.22%, P < 0.01) induced by HLU. Moreover, TMP significantly reduced HLU-induced increase of Bax to B-cell lymphoma 2 (-36.36%, P < 0.01) and cytochrome c release (-36.16%, P < 0.05). In conclusion, TMP attenuated HLU-induced gastrocnemius muscle atrophy through suppression of Ca2+/reactive oxygen species increase and consequent proteolysis and apoptosis. Therefore, TMP might exhibit therapeutic effect against oxidative stress, cytosolic calcium overload, and mitochondrial damage in disuse-induced muscle atrophy.

Deciphering the potential of guar gum/Ag-Cu nanocomposite films as an active food packaging material.

Guar gum (GG) based nanocomposite (NC) films were prepared by incorporating silver-copper alloy nanoparticles (Ag-Cu NPs) through solution casting method. Effect of NP loadings (0.5-2%) on the thermo-mechanical, optical, spectral, oxygen barrier and antimicrobial properties of the GG/Ag-Cu NC films were investigated. Tensile testing showed an improvement in the mechanical strength, and a decrease in elongation at break for all NP loadings. NP incorporation into GG films showed a marked influence on the color values. The NC films showed excellent UV, light and oxygen barrier capability. Thermal properties of the NC films were improved as evidenced from the differential scanning calorimetry and the thermal conductivity data. NC films became rough and coarse over neat GG film as visualized through the scanning electron microscopy. A strong antibacterial activity was exhibited by NC films against both Gram-positive and Gram-negative bacteria, and therefore, the film could be considered as an active food packaging.

Preparation and characterization of agar-based nanocomposite films reinforced with bimetallic (Ag-Cu) alloy nanoparticles.

Agar-based active nanocomposite films were prepared by incorporating silver-copper (Ag-Cu) alloy nanoparticles (NPs) (0.5-4wt%) into glycerol plasticized agar solution. Thermo-mechanical, morphological, structural, and optical properties of the nanocomposite films were characterized by texture analyzer, differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transforms infrared (FTIR) spectroscopy, and surface color measurement. Tensile strength and the melting temperature of the film increased linearly with NPs loading concentration. Color, transparency and UV barrier properties of agar films were influenced by the reinforcement of Ag-Cu NPs. XRD analysis confirmed the crystalline structure of the Agar/Ag-Cu nanocomposite films, whereas the smoothness and the homogeneity of film surface strongly reduced as observed through the SEM. The nanocomposite films exhibited a profound antibacterial activity against both Gram-positive (Listeria monocytogenes) and Gram-negative (Salmonella enterica sv typhimurium) bacteria. Overall, the agar nanocomposite films could be used as packaging material for food preservation by controlling foodborne pathogens and spoilage bacteria.

Mechanical, structural and thermal properties of Ag-Cu and ZnO reinforced polylactide nanocomposite films.

Plasticized polylactic acid (PLA) based nanocomposite films were prepared by incorporating polyethylene glycol (PEG) and two selected nanoparticles (NPs) [silver-copper (Ag-Cu) alloy (<100 nm) and zinc oxide (ZnO) (<50 and <100 nm)] through solvent casting method. Incorporation of Ag-Cu alloy into the PLA/PEG matrix increased the glass transition temperature (Tg) significantly. The crystallinity of the nanocomposites (NCs) was significantly influenced by NP incorporation as evidenced from differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The PLA nanocomposite reinforced with NPs exhibited much higher tensile strength than that of PLA/PEG blend. Melt rheology of NCs exhibited a shear-thinning behavior. The mechanical property drastically reduced with a loading of NPs, which is associated with degradation of PLA. SEM micrographs exhibited that both Ag-Cu alloy and ZnO NPs were dispersed well in the PLA film matrix.