For several millennia, doctors and healers used therapeutic ingredients extracted from minerals, plants, and animals. Among the active remedies derived from animals, the placenta was among the most popular ones. The use of placenta-based remedies has retained its significance in our time. The placenta-based therapeutics are indicated for stimulating immunity, wound healing, reduction of skin pigmentation, treatment of various patients suffering from gynecological disorders, etc. By the beginning of the 21st century, the majority of specific functions and chemical ingredients of the placenta were identified and described. However, only now active proteins and peptides with molecular weight of about ten kDa were revealed. Presumably, they play an essential role during the therapeutic application of placental extract. Hopefully, this discovery will start a new era in the research and clinical application of organotherapeutic remedies, including placenta.

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides are a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interact with metal ions to potentiate their antimicrobial effectiveness, as such they have been termed metalloAMPs. In this work, we review the scientific literature of metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion, zinc (II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate their activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics.

Nano medicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future. The current medical field is in dire need of new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging. Here in this experimental study, the nano materials used in DNA biosensors like silver nano dots were incorporated as nano biosensors are used for both therapeutic and diagnostic applications. The most important step while preparing a DNA biosensor is the immobilization of DNA probe on the surface of a sensing device such as an electrode. The amount of immobilized DNA probe will influence the accuracy sensitivity, selectivity and life of a DNA biosensor directly. Because of the high surface to volume ratio and excellent biological compatibility, nano materials can enlarge the sensing surface area to increase the amount of immobilized DNA and the DNA mixed with nano materials can keep its biologically activity well.In this study,silver nano dots created in our lab were functionalized with thio nucleides and were used as nano sensor probes in bio bar code assays.

In 2020, the WHO established a road map for neglected tropical diseases 2021−2030 that aims to control and eradicate 20 diseases, including Leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions such as those caused by Trypanosoma cruzi and Leishmania spp infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, avoiding the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes, as well as to stimulate the host immune defenses or even serve as a vector of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of Leishmaniosis and Chagas disease.

Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, it was seen a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics. These reductions lead to the inhibition of DNA repair, inhibition of cell wall turnover, protein turnover, and ROS accumulation leading to cell death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. The major interaction site is formed by the unusually long complementarity determining region (CDR) H3. The CDRH3 residue Tyr100H is known to represent a tyrosine sulfation site; however, this modification is not present in the experimental complex structure of PG16 with full-length HIV-1 Env. To investigate the role of sulfation for this complex, we modeled the sulfation of Tyr100H and compared the dynamics and energetics of the modified and unmodified complex by atomistic molecular dynamics simulations. Our results show that sulfation does not affect the overall conformation of CDRH3, but still enhances gp120 interactions both at the site of mutation and for the neighboring residues. This stabilization affects not only protein-protein contacts, but also the interactions between PG16 and the gp120 glycan shield. Further, we also investigated whether PG16-CDRH3 is a suitable template for the development of peptide mimetics. For a peptide spanning residues 93-105 of PG16 we obtained an experimental EC50 value of 3nM for the binding of gp120 to the peptide. This affinity can be enhanced by almost one order of magnitude by artificial disulfide bonding between residues 99 and 100F. In contrast, any truncation results in significantly lower affinity, suggesting that the entire peptide segment is involved in gp120 recognition. Their high affinity makes PG16-derived peptides useful building blocks for further optimization to obtain a potent inhibitor that efficiently blocks HIV-1 infection.

Urinary peptides are the products of systemic protein turn over which are excreted out of the body and hence can serve as an important biomarker for various pathophysiology. These peptides in other species of bovine have been reported to possess several bioactive properties. To investigate the potential of urinary peptides we generated a peptidome profile from the urine of Murrah Buffaloes (n=10). Urine samples were processed using <10 kDa MWCO filter, filtrate obtained was used for peptide extraction using Solid Phase Extraction (SPE). Eluate, obtained after SPE was extracted using ethyl acetate and the peptide-containing aqueous phase was collected. We extensively assessed the antimicrobial properties of the urinary aqueous phase. The nLC-MS/MS of the aqueous phase from 10 animals resulted in the identification of 8165 peptides originating from 6041 parent proteins. 76 Proteases responsible for the release of these sequences from precursor proteins were also identified. We further analyzed these peptide sequences to identify bioactive peptides and classify them into anti-cancerous, anti-hypertensive, anti-microbial, and anti-inflammatory groups with a special emphasis on antimicrobial properties. With this in mind, we simultaneously conducted experiments to evaluate antimicrobial properties of urinary aqueous extract on three pathogenic bacterial strains S. aureus, E. coli, & S. agalactiae.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

This work emphasizes to use silver decorative method to enhance the antibacterial activity of TiO₂ and ZnO nanoparticles. These silver decorated nanoparticles (hybrid nanoparticles) were synthesized by using sodium borohydride as a reducing agent, with the weight ratio of Ag precursors: oxide nanoparticles = 1: 30. The morphology and optical property of these hybrid nanoparticles were investigated using transmission electron microscopy (TEM) and UV–vis spectroscopy. The agar-well diffusion method was used to evaluate their antibacterial activity against both Staphylococcus aureus and Escherichia coli bacteria, with or without light irradiation. The TEM images indicated clearly that silver nanoparticles (AgNPs, 5-10 nm) were well deposited on the surface of nano-TiO₂ particles (30-60 nm). Besides, smaller AgNPs (< 2 nm) were dispersed on the surface of nano-ZnO particles (20-50 nm). UV-vis spectra confirmed that the hybridization of Ag and oxide nanoparticles led to shift the absorption edge of oxide nanoparticles to the lower energy region (visible region). The antibacterial tests indicated that both oxide pure nanoparticles did not exhibit inhibitory against bacteria, with or without light irradiation. However, the presence of AgNPs in their hybrids, even at low content (< 40 mg/mL) leads to a good antibacterial activity and the higher inhibition zones under light irradiation as compared to that in dark was observed.

The three-point bending behavior of a single Au nanowire deformed with an atomic force microscope was monitored by coherent X-ray diffraction using a sub-micrometer sized hard X-ray beam. While three-dimensional reciprocal-space maps were recorded before and after deformation by standard rocking curves, they were measured by scanning the energy of the incident X-ray beam during deformation at different loading stages. The mechanical behavior of the nanowire is visualized in reciprocal space and a complex deformation mechanism is described. In addition to the expected bending of the nanowire, torsion is detected. Bending and torsion angles are quantified from the high resolution diffraction data.

The enormous influence in terms of bioactivity, affinity, and selectivity represented by the replacement of (L)-2,6-dimethyl tyrosine (Dmt) instead of Phenylalanine (Phe) into Nociceptin/orphanin (N/OFQ) neuropeptide analogues, has been well documented in literature. More recently, the non-natural amino acid (L)-2-methyl tyrosine (Mmt), with steric hindrance among Tyr and Dmt, has been studied because of the modulation of steric effects in opioid peptide chains. Here we report a new synthetic strategy to obtain Mmt based on the well-known Pd-catalyzed ortho-C(sp2)–H activation approach, since there is a paucity of other synthetic routes in literature, to achieve it. The aim of this work was to force only the mono ortho-methylation process over the double ortho-methylation one. In this regard we are pleased to report that the introduction of the dibenzylamine moiety on Tyr aromatic nucleus is a convenient and traceless solution to achieve such a goal. Interestingly, our method provided the aimed Mmt either as N-Boc or N-Fmoc derivatives ready to be inserted into peptide chains through solid phase peptide synthesis (SPPS). Importantly, the introduction of Mmt in place of Phe1 in the sequence of N/OFQ(1-13)-NH2 was very well tolerated in terms of pharmacological profile and bioactivity.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

In recent years, antimicrobial resistance in many human pathogens has become a serious health concern. Since infections with resistant pathogens cannot be treated with traditional antimicro-bial drugs, new strategies are necessary to fight bacterial infections. Hybrid nano-systems may provide a solution to this problem, by combining multiple mechanisms for killing bacteria to synergistically increase the effectiveness of the antimicrobial treatment. In this review, we high-light recent advances in the development of hybrid nano-systems for the treatment of bacterial infections. We discuss the use of hybrid nano-systems for combinational therapy, focusing on various triggering mechanisms for drug release and the development of biomimetic nanomateri-als. We also examine inherently antimicrobial nano-systems and their uses in preventing infec-tions due to wounds and medical implants. This review summarizes recent advances and pro-vides insight into the future development of antimicrobial treatments using hybrid nanomateri-als.

Drought is one of the leading abiotic factors limiting morphological and physiological activities in blackberry cultivation. We investigated the effect of silver nanoparticles (AgNPs) on morphological and physiological processes in the boysenberry crop (Rubus ursinus Chamisso &amp; Schlenhtendal) under drought stress. The experiment was performed with three drought stress levels (0% PEG, 4% PEG and 8% PEG) and three AgNPs treatments (0, 0.1, 0.2 mg L−1) invitro conditions. The results showed that drought stress induced by PEG, reduced root and shoot development of boysenberry plants grown invitro. The addition of AgNPs is significantly alleviated the adverse effect of drought stress and increased the plant growth parameters. Antioxidant activity of SOD and CAT enzymes increased in boysenberry leaves when treated with AgNPs under drought conditions, while the amount of MDA decreased. Therefore, the results obtained in this study suggest that 0.1 mg L-1 AgNPs added to the medium improve the growth and development of invitro boysenberry plants under drought stress.

Ultra-short 230 fs laser pulses of 515 nm wavelength were tightly focused into 700 nm focal spots and utilised in opening ~ 400 nm nano-holes in a Cr etch mask that was tens-of-nm thick. Nano-holes ablated at slightly above the threshold of ablation irradiance became nano-disks and nano-rings at slightly lower pulse energies. Subtle sub-1 nJ pulse energy control was harnessed to pattern large surface areas with controlled nano-alloying of Si and Cr. This technique is extendable to vacuum-free large area patterning of nanolayers by alloying them at distinct locations with sub-diffraction resolution. Such metal masks with nano-hole opening can be used for formation of random patterns of nano-needles with sub-100 nm separation when applied to dry etching of Si.

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versa-tile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for under-standing the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other, non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer’s, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal com-plexes have potential applications as radiopharmaceuticals. The examination of these complexes was done by preforming UV-Vis, IR, EPR, NMR spectroscopy, and X-ray analysis.

Coronaviruses are highly transmissible and pathogenic viruses for humans and animals. The vast quantity of information collected about SARS-CoV-2 during the pandemic helped to unveil details on the mechanisms behind the infection, which are still largely elusive. Recent research demonstrated that different class I/II human leukocyte antigen (HLA) alleles might define an individual susceptibility to SARS-CoV-2 spreading, contributing to the differences in the distribution of the infection through different populations; additional studies suggested that the homolog of the HLA in cats, the Feline Leukocyte Antigen (FLA), plays a pivotal role in the transmission of viruses. With these premises, this study aimed to exploit a bioinformatic approach for the prediction of the transmissibility potential of two distinct Feline Coronaviruses (FCoVs) in domestic cats (Feline enteric Coronavirus, FeCV and Feline Infectious Peritonitis Virus, FIPV) using SARS-CoV-2 as the reference model. We performed an epitope mapping of nonapeptides deriving from SARS-CoV-2, FeCV and FIPV glycoproteins and predicted their affinities for different alleles included in the three main loci in class I FLAs (E, H and K). The predicted complexes with the most promising affinities were then subjected to molecular docking and molecular dynamics simulations to provide insights into the stability and binding energies in the cleft. Results showed the FLA proteins encoded by alleles in FLA-I H (H*00501 and H*00401) and E (E*01001 and E*07001) loci are largely responsive to several epitopes deriving from replicase and spike proteins of the analyzed coronaviruses. The analysis of the most affine epitope sequences resulting from the prediction can stimulate the development of anti-FCoV immunomodulatory strategies based on peptide drugs.

In our modern days, macromolecular biomolecules are dethroning classical small molecule therapeutics because of improved targeting and delivery properties. Protamine – a small polycationic peptide represents such a promising candidate. In nature, it binds and protects DNA against degradation during spermatogenesis due to electrostatic interaction between the negatively charged DNA-Phosphate backbone and the positively charged protamine. Researchers are mimicking this technique in order to develop innovative nanopharmaceutical drug delivery systems, incorporating protamine as carrier for biologically active components such as DNA or RNA. The first key part of this review highlights ongoing investigation in the field of protamine-associated nanotechnology, discussing the self-assembling manufacturing process and nanoparticle engineering. Immune-modulating properties of protamine are referred which lead to the second key part protamine in novel vaccine technologies. Protamine-based RNA delivery systems in vaccines (some of them belong to the new class of mRNA-vaccines) against infectious disease and their use in cancer treatment are reviewed and an update on the current state of latest developments with protamine as pharmaceutical excipient for vaccines is given.

Alterations in myelin, the protective and insulating sheath surrounding axons, affect brain function, as is evident in demyelinating diseases where the loss of myelin leads to cognitive and motor dysfunction. Recent evidence suggests that changes in myelination, including both hyper- and hypo-myelination, may also play a role in numerous neurological and psychiatric diseases. Protecting myelin and promoting remyelination is thus crucial for a wide range of disorders. Oligodendrocytes (OLs) are the cells that generate myelin, and oligodendrogenesis (OLgenesis), the creation of new OLs, continues throughout life and is necessary for myelin plasticity and remyelination. Understanding the regulation of OLgenesis and myelin plasticity within disease contexts is therefore critical for the development of novel therapeutic targets. In our companion manuscript [1], we review literature demonstrating that multiple hormone classes are involved in the regulation of OLgenesis under physiological conditions. The majority of hormones enhance OLgenesis, increasing oligodendrocyte precursor cell differentiation and inducing maturation and myelin production in OLs. Thus, hormonal treatments present a promising route to promote remyelination. Here, we review literature on hormonal regulation of OLgenesis within the context of disorders. We focus on steroid hormones, including glucocorticoids and sex hormones, peptide hormones such as insulin-like growth factor 1, and thyroid hormones. For each hormone, we describe whether they aid in OL survival, differentiation, or remyelination, and we discuss their mechanisms of action, if known. Several of these hormones have yielded promising results in both animal models and in human conditions; however, a better understanding of hormonal effects, interactions, and their mechanisms will ultimately lead to more targeted therapeutics for myelin repair.

The brain’s capacity to respond to changing environments via hormonal signaling is critical to fine-tuned function. An emerging body of literature highlights a role for myelin plasticity as a prominent type of experience-dependent plasticity in the adult brain. Myelin plasticity is driven by oligodendrocytes (OLs) and their precursor cells (OPCs). OPC differentiation regulates the trajectory of myelin production throughout development, and importantly, OPCs maintain the ability to proliferate and generate new OLs throughout adulthood. The process of oligodendrogenesis (OLgenesis), the creation of new OLs, can be dramatically influenced during early development and in adulthood by internal and environmental conditions such as hormones. Here, we review the current literature describing hormonal regulation of OLgenesis within physiological conditions, focusing on several classes of hormones: steroid, peptide, and thyroid hormones. We discuss hormonal regulation at each stage of OLgenesis and describe mechanisms of action, where known. Overall, the majority of hormones enhance OLgenesis, increasing OPC differentiation and inducing maturation and myelin production in OLs. The mechanisms underlying these processes vary for each hormone but may ultimately converge upon common signaling pathways, mediated by specific receptors expressed across the OL lineage. However, not all of the mechanisms have been fully elucidated, and here, we note the remaining gaps in the literature, including the complex interactions between hormonal systems and with the immune system. In the companion manuscript in this issue [1], we discuss the implications of hormonal regulation of OLgenesis for neurological and psychiatric disorders characterized by white matter loss. Ultimately, a better understanding of the fundamental mechanisms of hormonal regulation of OLgenesis across the entire lifespan, especially in vivo, will progress both basic and translational research.

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

Electro-spun ultra-fine fibers exhibit two significant properties: a high surface-to-volume ratio and a relatively defect-free molecular structure. Due to the high surface-to-volume ratio, electro-spun materials are well suited for activities requiring increased physical contact, such as providing a site for a chemical reaction or filtration of small-sized physical materials. However, electrospinning has many shortcomings, including difficulties in producing inorganic nanofibers and a limited number or variety of polymers used in the process. The fabrication of nanofiber bundles via electrospinning is explored in this analytical study, as well as the relationship between extrinsic electrospinning parameters and the relative abundance of various fiber morphologies. Numerous variables could impact the fabrication of nanofibers, resulting in a variety of morphologies; therefore, adequate ambient conditions and selecting the appropriate solvent for achieving a homogenous polymer solution and uniform electro-spun materials are examined. Finally, common polymers suitable for electrospinning and the promising applications of ultra-fine fibers achieved via electrospinning are studied in this paper.

The research progress of nano-hydroxyapatite and its composite biomaterials, which are widely used, is summarized. The preparation techniques and applications of nano-hydroxyapatite and its composites in tissue engineering scaffolds, sustained and controlled release drug carriers, targeting drug delivery and environmental functional materials show that nano-hydroxyapatite and its composites will have good prospects in the field of biomedicine. The nano-hydroxyapatite composite biomaterial is a first phase or multi-phase material added to the nano-hydroxyapatite to obtain a favorable histological reaction, satisfactory strength and rigidity, and to synthesize a scaffold material for tissue regeneration. As a scaffold for guiding bone tissue regeneration, nano-hydroxyapatite composite material can also be used as a targeted drug release system for drug delivery system. It has good biocompatibility and degradability and has become a research hotspot in bone tissue engineering. The complex is expected to be applied to medical diagnostic fields such as tumor cell detection and nano biological probes.

Milk is newborn’s food and an emulsion full of all necessary components for neonatal growth. Its consumption is worldwide and is the base for all dairy products. Because of the latter, many new technologies are growing, among them proteomics; in order to give new insights in milk’s compounds and to maximize the beneficial potential for consumers’ health. In this review, we aimed to gather data of proteomics studies for the majority of dairy animals and elucidate the role of milk bioactive compounds. Furthermore, special reference was made to milk fat globule membrane (MFGM) peptides and the result of thermal treatment in milk proteins. Finally, the proteomic approach regarding adulterations was included in the review.

One of the main families of antimicrobial peptides (AMPs) derived from the skin secretions of Hylidae frogs are dermaseptins. Among them, dermaseptin S4 (DS4) is characterized by its broad spectrum of activity against bacteria, protozoa and fungi. This study determined the physicochemical properties of the native peptide DS4(1-28) and its derivatives [DS4(1-28)a and DS4(1-26)a] isolated from the skin of the frog Phyllomedusa sauvagii and examined their antimicrobial properties against two marine pathogenic bacteria (Vibrio harveyi and V. anguillarum). The results indicate that DS4(1-26)a has high bacteriicdal activity against the tested strains and low hemolytic activity (&gt; 30 % lysis at the highest tested concentration of 100 µg mL-1) compared to the other two peptides. In addition, all three peptides affected the membrane and cell wall integrity of both pathogenic bacteria, causing leakage of cellular contents, with DS4(1-26)a having the most severe impact. These properties were corroborated by tansmission electron microscopy and by the variation of cations in their binding sites due to the effect of AMPs. These results suggest that DS4 and its derivatives, particularly the truncated and amidated peptide DS4(1-26)a, could potentially be effective in the treatment of infections caused by these marine pathogenic bacteria. Future experiments are required to validate the use of DS4 in vivo in the prevention of fish bacterial diseases.

The receptor tyrosine kinase (EphB4), which produces erythropoietin, was identified as a molecular target for cancer. We identified six peptides as potential inhibitors of EphB4 using an integrated approach combining online bioinformatics tools. According to PeptideRanker, CSM-peptides, SCMTHP, and AcPEP analysis, all peptides are effective against cancer, with the exception of LTAPGQATLPT and VEQNLVPGLK. Furthermore, Toxin-Pred predicts that none of the peptides are toxic, and that only VQLPGWRVFP and TMKGPPDTLQ are potentially allergenic using AllerTop server. PepSite2, HPEPDOCK, and MDockPeP servers were utilized to perform molecular docking, and PacDock was used to examine molecular interactions. The docking score (kcal/mol) range of six promising anticancer peptides against EphB4 was recorded as follows: VQLPGWRVFP (-240.72), FTKDDEWSCFPF (-201.74), SYLPPLSAEVTAK (-177.52), LTAPGQATLPT (-162.23), VEQNLVPGLK (-157.30), TMKGPPDTLQ (-149.67). The main bindings on the allosteric site to VQLPGWRVFP were with R706, S815, R819 and P843 on EphB4. Collectively, our results demonstrated that M. oleifera peptides ameliorate cancer by inhibiting EphB4, and they are promising candidates for the prevention and treatment of cancer.

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.

Fungal infections pose a significant threat to human health, particularly in immunocompromised individuals. Due to several factors, such as the inappropriate use of antimicrobial drugs, the emergence of resistance in microorganisms, and increasing demand for less cytotoxic antifungal agents for immunocompromised patients, antifungal research has gained significant attention in recent years. Antifungal peptides, and among them, cyclic peptides, are a class of antifungal agents that have been under development since the 1960s. Using cyclic peptides as a promising approach for combating antifungal resistance in pathogenic fungi has gained significant attention in recent years. The identification of antifungal cyclic peptides from various sources has been possible due to the widespread interest in peptide research in recent decades. It is increasingly important to evaluate the narrow to broad-spectrum antifungal activity and the mode of action of synthetic and natural cyclic peptides for both synthesized and extracted peptides. This short review aims to highlight some of the antifungal cyclic peptides isolated from bacteria, fungi, and plants, taking into consideration the progress made in peptide research. Additionally, it provides a summary of synthetic cyclic peptides with antifungal activity and discusses the potential future of utilizing combinations of antifungal peptides from different sources. The review underscores the need for further exploration of the novel therapeutic applications of these abundant and diverse cyclic peptides.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

In this study, an extracellular metalloprotease from Pseudoalteromonas sp. H2 was purified and identified. The EH2 maintained more than 80% activity over a wide pH range of 5-10 and the stability was also nearly independent of pH. More than 65% of activity was detected in a wide temperature of 20-70℃. The high stability of the protease in presence of different surfactants and oxidizing agent was also observed. Moreover, we also investigated the antioxidant activities of the hydrolysates generated from porcine and salmon skins collagen by EH2. The results show that salmon skins collagen hydrolysates demonstrated higher DPPH (42.88%±1.85) and hydroxyl radical (61.83%±3.05) scavenging activity compared to those produced with porcine skins collagen. For oxygen radical absorbance capacity, the hydrolysates from porcine skins collagen had higher efficiency (7.72±0.13 μmol·TE/μmol). Even 1 nM mixed peptides can effectively reduce the levels of intracellular ROS. And the two type of substrates exerted the best antioxidant activity when hydrolyzed for 3 hours. Hydrolysis time and type of substrate exerted important effect on the antioxidant property of hydrolysates. This study may have implications for the potential application of marine protease in biocatalysis industry. In addition, the hydrolyzed peptides from meat waste containing beneficial collagen by protease have good antioxidant activity indicating it may be a potential additive in the food processing industry and cosmetics industry.

Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.

In a recent paper discussing Newton’s third law in the framework of special relativity for charged bodies, it was suggested that one can construct a practical relativistic motor provided high enough charge and current densities are available. As on the macroscopic scale charge density is limited by the phenomena of dielectric breakdown, it was suggested to take advantage of the high charge densities which are available on the microscopic scale. A preliminary analysis of this option denoted "nano relativistic scale" is studied in the current paper.

Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), Contact lenses, Dental Applications, AMP-Incorporated Bone Grafts, Urinary tract infections (UTIs), Medical Implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings.

Cruor, the main component responsible for the red color of blood in mammals, contains 90% hemoglobin, a protein that is considered a rich source of bioactive peptides. The aim of the present study is to evaluate the potential of human hemoglobin as a source of bioactive peptides, compared to bovine hemoglobin, which has been widely studied in recent years. More specifically, the study focused on neokyotorphin, a natural antimicrobial peptide and meat preservative, which corresponds to the α137-141 fragment of bovine hemoglobin produced by enzymatic hydrolysis. Firstly, the results of the in-silico analysis showed that the two types of hemoglobin have a high similarity for the α and β chains (identities of 88% and 91%, respectively). Secondly, both types of hemoglobin were subjected to similar enzymatic hydrolysis conditions, which showed that the hydrolysis of human hemoglobin followed the same reaction mechanism as the hydrolysis of bovine hemoglobin, the 'Zipper' mechanism. The hydrolysis conditions (23°C, pH 3.5) made it possible to obtain α137-141 in significant quantities to allow for significant valorization from an industrial point of view. The hydrolyses were able to take place at high initial substrate concentrations, allowing for faster and more efficient processing of the co-product in the same amount of time, with over 65% of this production achieved in just 30 min. Increasing the substrate concentration (from 1% to 10% (w/v)) resulted in a proportional increase in α137-141 production. Regardless of the concentrations tested, the kinetic pattern remained similar. Finally, the results of the mass spectrometry analysis revealed the presence of several bioactive peptides in cattle and humans. Although some were known before, new bioactive peptides were discovered in human hemoglobin, such as four antibacterial peptides (α37-46 PTTKTYFPHF; α36-45 FPTTKTYFPH; α137-141 TSKYR; α133-141 STVLTSKYR), four opioid peptides (α137-141 TSKYR; β31-40 LVVYPWTQRF; β31-37 LVVYPWT), an ACE inhibitor (β129-135 KVVAGVA), an anticancer agent (β33-39 VVYPWTQ) and an antioxidant (α137-141 TSKYR). These peptides have never been found in human hemoglobin before, according to our knowledge. These results highlight the potential of human hemoglobin as a source of bioactive peptides useful for the food or pharmaceutical industry.

Bacillus licheniformis produce several classes of antimicrobial substances which are mainly either peptides or proteins. Among of them bacteriocins - peptides or proteins of different structural composition including synthesized by bacteria ribosomally; non-ribosomally synthesized peptides and cyclic lipopeptides; exopolysaccharides. Different representatives of these classes act against Gram-positive, Gram-negative bacteria, fungal pathogens and amoebae cells. In this review, a detailed classification of antimicrobial substances produced by B. licheniformis based on their chemical structure and mode of the synthesis and activity is presented. For some (rather limited number) of secreted antimicrobials mechanism of their harmful effect on the target cells is established, however, for many of them it remains unknown. The antimicrobial activity for most substances was studied in vitro only, however some substances were characterized in vivo and are found practical applications in medicine and veterinary. The cyclic lipopeptides with surfactant properties are applied in industry. In this review, a special attention on antimycobacterials produced by B. licheniformis is made as a possible approach to combat multidrug resistant and latent tuberculosis. Indeed, a number of peptides and proteins revealed strong antimycobacterial activity. However, medical application of some bacteriocins with promising in vitro antimycobacterial activity is limited by their toxicity for animals and humans. In this connection, similarly with the enhancement of the antimycobacterial activity of natural bacteriocins using genetic engineering, reduction of the toxicity by the same approach looks feasible. A unique capability of B. licheniformis to synthesize and produce a bouquet of different antibacterial compounds allow to consider this organism as a universal natural vehicle for antibiotic substances in form of probiotic cultures strains to combat various types of pathogens including mycobacteria.

Cryptococcus neoformans is a human multidrug-resistant yeast with high mortality rates in immunocompromised patients. Recently, the synthetic peptide Mo-CBP3-PepII emerged as a potent anticryptococcal molecule with an MIC50 at low concentration. Here, the mechanisms of action of Mo-CBP3-PepII were deeply analyzed to provide new information about how it led C. neoformans cells to death. Light and fluorescence microscopies, analysis of enzymatic activities, and proteomic analysis were employed to understand the effect of Mo-CBP3-PepII on C. neoformans cells. Light and fluorescence microscopies revealed Mo-CBP3-PepII induced the accumulation of anion superoxide and hydrogen peroxide in C. neoformans cells. In addition to a reduction in the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) in the cells treated with Mo-CBP3-PepII. In the presence of Ascorbic acid (AsA), no ROS were detected and Mo-CBP3-PepII lost the inhibitory activity against C. neoformans. Yet, Mo-CBP3-PepII inhibited the activity of lactate dehydrogenase (LDH), ergosterol biosynthesis, and induced the decoupling of cytochrome c from the mitochondrial membrane. Proteomic analysis revealed a reduction in the abundance of proteins related to energetic metabolism, DNA and RNA metabolism, pathogenicity, protein metabolism, cytoskeleton, and cell wall organization and division. Our findings indicated that Mo-CBP3-PepII might have multiple mechanisms of action against C. neoformans cells, mitigating the development of resistance and thus being a potent molecule to be employed in the production of new drugs against C. neoformans infections.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

Nervous necrosis virus (NNV) has spread throughout the world, affecting more than 120 freshwater and marine fish species. While vaccination effectively prevents disease outbreaks, the difficulty of producing sufficient viruses using cell lines continues to be a significant disadvantage for producing inactivated vaccines. This study, therefore, explored the application of synthetic peptides as potential vaccine candidates for the prevention of NNV in Asian seabass (Lates calcarifer). Using the epitope prediction tool and molecular docking, three predicted immunogenic B cell epitopes (30-32 aa) derived from NNV coat protein were selected and synthesised, corresponding to amino acid positions 5 to 34 (P1), 133 to 162 (P2) and 181 to 212 (P3). All the predicted peptides interact with Asian sea bass’s MHC class II by docking. The antigenicity of these peptides was determined through ELISA and all peptides were able to react with NNV-specific antibodies. Subsequently, the immunogenicity of these synthetic peptides was investigated by immunisation of Asian seabass with individual peptides (30 μg/fish) and a peptide cocktail (P1+P2+P3, 10 μg each/fish) by intraperitoneal injection, followed by a booster dose at day 28 post-primary immunisation. There was a subset of immunised fish that were able to induce upregulation of CD4 in the head kidney and spleen. Importantly, antibodies derived from fish immunised with synthetic peptides reacted with whole NNV virions. Taken together, these findings indicate that synthetic linear peptides based on predicted B cell epitopes exhibited both antigenic and immunogenic properties, suggesting that they could be potential vaccine candidates for the prevention of NNV in fish.

Both ricin and R. communis agglutinin (RCA120), belonging to the type II ribosome-inactivating proteins (RIPs-Ⅱ), are derived from the seeds of castor bean plant. They share very similar amino acid sequences, but ricin is much more toxic than RCA120. It is urgently necessary to distinguish ricin and RCA120 in response to public safety. Currently, mass spectrometric assays are well established for unambiguous identification of ricin by accurate analysis of differentiated amino acid residues after trypsin digestion. However, diagnostic peptides are relatively limited for unambiguous identification of trace ricin, especially in complex matrices. Here, we demonstrate a digestion strategy of multiple proteinases to produce novel peptide markers for unambiguous identification of ricin. LC-HRMS was used to verified the resulting peptides, among which only the peptides with uniqueness and good MS response were selected as peptide markers. Seven novel peptide markers were obtained from tandem digestion of trypsin and endoproteinase Glu-C in PBS buffer. From the chymotrypsin digestion under reduction and non-reduction conditions, eight and seven novel peptides were selected respectively. Using pepsin under pH 1~2 and proteinase K digestion, 6 and 5 peptides were selected as novel peptide markers. In conclusion, the obtained novel peptides from the established digestion methods can be recommended for the unambiguous identification of ricin during the investigation of illegal use of the toxin.

Polydiacetylene (PDA) inserted in films or in vesicles have received increasing attention due to PDA property to undergo a blue-to-red colorimetric transition along with a change from non-fluorescent to fluorescent upon application of various stimuli. In this review paper, the principle of the detection of various microorganisms (bacteria: directly detected or detected through the emitted toxins or through their DNA, and viruses) and of antibacterial and antiviral peptides based on these responsive PDA vesicles are detailed. The obtained analytical performances, when vesicles are in suspension or immobilized, are given and compared to those of the responsive vesicles mainly based on the vesicle encapsulation method. Many future challenges are then discussed.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

Nano-titanium has excellent corrosion resistance and can be widely used in the field of corrosion resistant coatings. This paper introduces nano-weight titanium modified phenolic resin coatings and their anti-corrosion properties to explore the principle of nano-titanium modification and the mechanism of anti-corrosion to further develop more advanced corrosion resistant coatings. The article uses scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and UV-Vis spectrophotometer to characterise the morphology and structure of the nano-titanium modified phenolic resin coatings and to determine the corrosion resistance properties of the modified phenolic resin coatings. The results show that the 4% nano-titanium modified phenolic resin coating, nano-titanium powder and phenolic resin will maximize the dispersion and combination, and the structure is good; nano-titanium grafted on phenolic resin, the successful preparation of nano-titanium modified phenolic resin; modified nano-titanium added to improve the coating's ability of UV absorption. The corrosion resistance of the coating is much better than that of the unmodified phenolic resin coating.

It is important to add second- or third-phase materials to improve the physical, mechanical, and biodegradable properties of polypropylene (PP) nanocomposites. A unique hybrid bio-nanocomposite was fabricated using microparticle cellulose powder from wastepaper with a polypropylene (PP) polymeric matrix using a low-shear chaotic mixing method. A small amount (2-5%) of layered micro clay was also added to investigate the hybrid effect of nanocomposite fabrication on the mechanical properties. A low-shear chaotic melt mixing method induces the formation of nano cellulose structures and layered clay nanoparticles by via exfoliation. The nanoparticles were characterized using Fourier transform infrared (FTIR) spectroscopy. Mechanical properties such as the flexural strength (FS) and tensile strength (TS) were investigated using an Izod impact tester (IZ), and a dynamic mechanical testing analyzer (DMTA). Further, scanning electron microscopy (SEM) was used to observe the microstructure of the nanocomposite. In addition, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were conducted to investigate the crystallinity and degradation of the samples, respectively. The addition of wastepaper cellulose powder below 2.5 wt. % did not improve the mechanical properties, however, improvements were observed when more than 5wt.% wastepaper cellulose powder was added. With the addition of a small amount of nano-clay, the mechanical properties were significantly improved, and a synergistic effect could be noticed. The observed results were then compared with PP-clay nanocomposites used in automotive industries to replace cellulose nanocomposites. The application areas can also cover lead production in paper cups and vacuum foaming.

It is important to add second- or third-phase materials to improve the physical, mechanical, and biodegradable properties of polypropylene (PP) nanocomposites. A unique hybrid bio-nanocomposite was fabricated using microparticle cellulose powder from wastepaper with a polypropylene (PP) polymeric matrix using a low-shear chaotic mixing method. A small amount (2-5%) of layered micro clay was also added to investigate the hybrid effect of nanocomposite fabrication on the mechanical properties. A low-shear chaotic melt mixing method induces the formation of nano cellulose structures and layered clay nanoparticles by via exfoliation. The nanoparticles were characterized using Fourier transform infrared (FTIR) spectroscopy. Mechanical properties such as the flexural strength (FS) and tensile strength (TS) were investigated using an Izod impact tester (IZ), and a dynamic mechanical testing analyzer (DMTA). Further, scanning electron microscopy (SEM) was used to observe the microstructure of the nanocomposite. In addition, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were conducted to investigate the crystallinity and degradation of the samples, respectively. The addition of wastepaper cellulose powder below 2.5 wt. % did not improve the mechanical properties, however, improvements were observed when more than 5wt.% wastepaper cellulose powder was added. With the addition of a small amount of nano-clay, the mechanical properties were significantly improved, and a synergistic effect could be noticed. The observed results were then compared with PP-clay nanocomposites used in automotive industries to replace cellulose nanocomposites. The application areas can also cover lead production in paper cups and vacuum foaming.

In today’s world, it is the need of the hour to adopt new technology to sustain the production of the future. Nanotechnology is gaining popularity for its efficiency in various applied fields of science. In agriculture, nanomaterials have a huge impact on the efficiency of fertilizers pesticides, etc. As it requires very fewer quantities and has a negligible residual effect the environment is safe with the innovation of Nano fertilizer. Keeping this view into account an experimental Trial at a farmer’s field was carried out at Berui village in the Hooghly District of West Bengal during the winter (rabi) season of 2019 – 20 under the supervision of Berui Cooperative, KVK-Hooghly, BCKV, and IFFCO with nano-Urea, nano-Zn and nano-Cu using RBD design with 10 treatments and 3 replications. Experimental results revealed that the highest tuber yield was obtained in T-7 (50% N+100% P & K+ 2 spray of nano-Urea), and that was followed by T-10 (50% N + 100% P & K + 50% Zn + 1 spray each of Nano-Urea, Zn and Cu) and T-8 (100% N-P-K + 50% Zn + 2 spray of Nano-Zn). The performance of nano fertilizers, Nano- Urea, was quite promising and economically viable as compared to the 100% recommended dose with commercial fertilizers (RDF).

In this review, the following information describes the manifestation of sleep deprivation by human beings and its adverse effect on their health. Sleep deprivation has been demonstrated into namely two types known as REM sleep and NREM sleep affecting our health in so a problematic way that it is making our body immune to many diseases leading to lethal problems. Therefore, great research by many scientists has discovered that the turmeric “Curcuma longa” which is been used in every Indian kitchen since ancient times, has shown a remarkable effect on the problem caused by sleep deprivation but due to its poor solubility and low bioavailability drawn it into a great disadvantage. But the help of the study of nanotechnology and the evolution of curcumin into nano–curcumin made the possibility of the remarkable effect by making the curcumin more potent and enhancing its stability. Immunological changes due to sleep deprivation lead to Alzheimer’s disease, glioma, neuropathic pains, and many more. Therefore, this review has been summarized as it is been providing information related to curcumin and its affection for sleep deprivation.

Rubber-based composites are widely used especially in transportation. The goal of this paper is to study the mechanical properties of rubber-based composites of carbon black and Nano Aluminum trioxide additive (50 nm). Various percentage of carbon black was used (20,40, and 60 phr). The increase in Carbon black percentage shows an increase in mechanical properties of the composites (for 60 phr properties tensile test improve by 49%, for hardness resistance the improve was 21%, and for the wear test the composite improve by 22%). Various wetting percentage of nano Aluminum trioxide was used (1,1.5,2, and 2.5 %). Increasing the wetting percentage increase tensile strength (27%, hardness resistance increase by 28%, and wear resistance increase nonlinearly with a percentage reaching 70%). Selecting the optimal composition of the two fillers, then study different irradiances for it with the ultraviolet laser of moderately low energy after the vulcanization process. Post ultraviolet laser of (345 nm). Furthermore, laser vulcanization shows improvement in mechanical properties.

The thermal properties of novel nanomaterials play a significant role in determining the performance of the material in technological applications. Herein, direct measurement of the temperature diffusivity of cellulose nanocomposite films was carried out by the micro-contact method. Polymer films containing up to 2%wt. of nanocellulose were synthesised by a simple chemical process. Films of a high optical transmittance T ≈ 80 % (for a 200- μ m-thick film), which were up to 44% crystalline, were characterised. Two different modalities of temperature diffusivity based on: 1) a resistance change and 2) micro-thermocouple detected modulation of a heat wave, were used for the polymer films with cross-sections of ∼ 100 μ m thickness. Twice different in-plane α ‖ and out-of-plane α ⊥ temperature diffusivities were directly determined with high fidelity: α ‖ = 2 . 12 × 10 − 7 m 2 /s and α ⊥ = 1 . 13 × 10 − 7 m 2 /s. An amorphous polyethylene terephthalate (PET) fiber was measured for comparison α ‖ = 1 . 15 × 10 − 7 m 2 /s. This work provides an example of a direct contact measurement of thermal properties of nanocellulose composite films. The thermal diffusivity, which is usually high in strongly interconnected networks and crystals, was investigated for the first time in this composite.

Microbolometer is the most common uncooled infrared technique that allows to achieve 50mK-temperature resolution on the scene. However, this approach has to struggle with both the self-heating inherent to the resistive readout principle and the 1/f noise. We present an alternative approach that consists in using micro / nanoresonators vibrating according to a torsional mode, and whose resonant frequency changes with the incident IR-radiation. Dense arrays of such electromechanical structures were fabricated with a 12µm-pitch at low temperature allowing their integration on CMOS circuits according to a post-processing method. H-shape pixels with 9 µm-long nano-rods and a cross-section of 250 × 30 nm² were fabricated to provide large thermal responses, whose experimental measurements reached up to 1024 Hz/nW. These electromechanical resonators featured a noise equivalent power of 140pW for a response time of less than 1 ms. To our knowledge, these performance are unrivaled with such small dimensions. We also showed that a temperature sensitivity of 20 mK within 100ms-integration time is conceivable at a 12µm-pitch by co-integrating the resonators with their readout electronics and suggesting a new readout scheme. This sensitivity could be reached at short-term by depositing on top of the nano-rods a vanadium oxide layer having a phase-transition that could possibly enhance the thermal response by one order of magnitude.

The BRightest Target Explorer (BRITE) is the pioneering nanosatellite mission dedicated for photometric observations of the brightest stars in the sky. The BRITE CCD sensors are poorly shielded against extensive flux of energetic particles which constantly induce defects in the silicon lattice. In this paper we investigate the temporal evolution of the generation of the dark current in the BRITE CCDs over almost 4 years after launch. Utilizing several steps of image processing and employing normalization of the results it was possible to obtain useful information about the progress of thermal activity in the sensors. The outcomes show clear and consistent linear increase of induced damage despite the fact that only about 0.14% of CCD pixels were probed. By performing the analysis of temperature dependencies of the dark current, we identified the observed defects as phosphorus-vacancy (PV) pairs, which are common in proton irradiated CCD matrices. Moreover, the Meyer-Neldel empirical rule was confirmed in our dark current data, yielding E_MN=24.8 meV for proton-induced PV defects.

Europium (Eu)-doped fluorapatite (FA) nanorods has a similar biocompatibility with hydroxyapatite (HA) in terms, attracted much attention as cell imaging biomaterials due to their luminescent property. Here, we will discuss the new feature of europium doped fluorapatite (Eu-FA) nanorods as anticancer drug carrier. Eu-FA nanorods was prepared using a hydrothermal method. The morphology, crystal structure, fluorescence and composition are investigated. The specific crystal structure, enabling an effective loading of drug molecules. Doxorubicin (DOX), used as an anticancer model drug, was shown to be effectively loaded onto the surface of the nanorods. The DOX release was fairly pH-dependent, occurring more rapidly at pH 5.5 than pH 7.4 was observed. The intracellular penetration of the DOX-loaded Eu-FA nanorods (Eu-FA/DOX) can be imaged in situ due to the self-fluorescence property. Treatment of melanoma A375 cells with Eu-FA/DOX elicited a more effective apoptosis rate than direct DOX treatment. Overall, Eu-FA show great promise for tracking and treating tumor, may potentially useful as a multifunctional carrier system to effectively load and sustainably deliver drugs.

TNF cytokine receptor TNFR1 protein plays an important role in immune response and autoimmune diseases. Previously, we demonstrated that the peptide of the innate immunity protein Tag7 (PGLYRP1), designated as 17.1, is able to perform the functions of a full-size Tag7 protein, namely, to inhibit the transmission of a signal through the TNFR1 receptor and activate this receptor in complex with the major heat shock protein Hsp70. In this study, we show that two peptides derived from 17.1 – 17.1A and 17.1B have different affinities to the TNFR1 receptor and the Hsp70 protein, and each of them is able to perform only one of the above functions: peptide 17.1A is only able to inhibit signal conduction through the TNFR1 receptor, and peptide 17.1B can only activate this receptor is in complex with Hsp70. Thus, it is possible to modulate the activity of TNFR1 receptor and further perform its specific inhibition or activation in the treatment of various autoimmune or oncological diseases.

Proteins, as gifts from nature, provide structure, sequence, and function templates for designing biomaterials. Here, we reported an engineered toolkit derived from a natural block copolymer, RfA1. RfA1 is composed of positively charged polyelectrolyte linker regions interspersed with highly conserved polyampholyte motifs. These linkers and motifs are constructional fragments and ready-to-use building blocks for synthetic design and construction. One functional and editable feature of RfA1 derivatives is their preferential distribution to cytoplasm or nucleoplasm, in a fragment-replication-determined manner. Based on this property, a prices spatiotemporal Tet-on demo was established, which effectively transports cargo peptides into nuclei at selective time points. Moreover, the functional homogeneities of either motifs or linkers were also verified, making them standardized building blocks for synthetic biology. In summary, this study provides a modularized, orthotropic and well-characterized toolkit for precise and spatiotemporal regulation of protein nucleocytoplasmic localization.

Pain is a natural bioassay for detecting and quantifying biological activities of venoms. The painfulness of stings delivered by ants, wasps, and bees can be easily measured in the field or lab using the stinging insect pain scale that rates the pain intensity from 1 to 4, with 1 being minor pain, and 4 being extreme, debilitating, excruciating pain. The painfulness of stings of 96 species of stinging insects and the lethalities of the venoms of 90 species was determined and utilized for pinpointing future promising directions for investigating venoms having pharmaceutically active principles that could benefit humanity. The findings suggest several under- or unexplored insect venoms worthy of future investigations, including: those that have exceedingly painful venoms, yet with extremely low lethality – tarantula hawk wasps (Pepsis) and velvet ants (Mutillidae); those that have extremely lethal venoms, yet induce very little pain – the ants, Daceton and Tetraponera; and those that have venomous stings and are both painful and lethal – the ants Pogonomyrmex, Paraponera, Myrmecia, Neoponera, and the social wasps Synoeca, Agelaia, and Brachygastra. Taken together, and separately, sting pain and venom lethality point to promising directions for mining of pharmaceutically active components derived from insect venoms.

Prostanoids modulate the pathogenesis of vascular diseases such as atherosclerosis, in which inflammation has an important role. It is well known that inducible Ciclooxygenase-2 (COX-2) is responsible for prostanoid production associated with inflammation. Angiotensin II may be implicated through the expression of COX-2 in the vascular wall. The purpose of this study was to examine in angiotensin II-stimulated adventitial fibroblasts the anti-inflammatory activity of different food peptides by inhibiting COX-2 expression, and the production of pro-inflammatory prostanoids. Fibroblasts from aorta of Sprague-Dawley rats were incubated with different food derived peptides followed by incubation with Angiotensin II. COX-2 expression was determined by western blot, transcriptional activity by luciferase assays and prostaglandin E2 by enzyme immunoassay. COX-2 expression was inhibited in the presence of Val-Pro-Pro (bovine β-casein 84–86), Arg-Asp-Ile-Leu-Asn-Gln (ovalbumin 84–89) and Tyr-Arg-Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe (ovalbumin 125–134). Angiotensin II-induced prostaglandin E2 production was also reduced by all the above-mentioned sequences. The incubation with ovalbumin-derived peptides displayed a significant reduction of COX-2 promoter activity compared to the stimuli with Angiotensin II in transiently transfected cells. These three sequences could potentially be used as functional food ingredients to reduce inflammation related to cardiovascular diseases.

Oral mucositis is most frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in oral mucositis. The mucositis of which was induced by the protocol of Sonis. 40 hamsters were used, divided into two groups: Group I- control; Group II- supplemented with 5% intraperitoneal glycine, 2,0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation collagen expression and the growth factors: EGF and PDGF. It was observed that the group supplemented with glycine higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

This study introduces an innovative integration of hyperbolic metamaterials (HMMs) and photonic crystals (PtCs), each possessing unique dispersion properties that effectively manipulate the propagation of light. We present a PtC waveguide consisting of arrays of HMM nanorods, denoted as HMM PtCs. This waveguide configuration enables the realization of a high figure of merit (FOM) nano-sensor. By modifying the refractive indices of the surrounding materials, the PtC waveguide exhibits alterations in absorption and transmission, allowing for the detection of temperature, pressure, and material variations. Numerical methods were employed to demonstrate the remarkable efficiency of this proposed system, achieving a sensitivity of 324.16 nm/RIU (refractive index unit) and an impressive FOM of 469.58 RIU−1. These results signify a substantial improvement over surface plasmonic sensors, which typically exhibit limited FOMs. As a consequence, the HMM PtC waveguide sensor emerges as an exceptionally appealing option for photonic sensing applications. The proposed HMM PtC waveguide holds vast potential across diverse fields, including biology, medicine, and clinics, representing an exciting advancement for both industry and scientific research.

Current spacecraft mass are mostly fuel, this is dictated by the lack of fueling stations in space and also by the Tsiolkovsky rocket equation which defines the mass ratio needed to escape earths gravity. The Tsiolkovsky rocket equation gives a relationship between the mass ratio and the final velocity in multiples of the exhaust speed, and dictates a high mass ration for current exhaust speeds. A relativistic motor exchanging momentum and energy with the electromagnetic field may mitigate such considerations, enabling efficient interplanetary travel. In this paper we will discuss the advantages and challenges of this novel mover for space transportation.

This study reports the preparation of silica and nano-fructosome encapsulated Candida antarctica lipase B particles (CalB@NF@SiO2) and demonstration of their enzymatic hydrolysis and acylation. CalB@NF@SiO2 particles were prepared as a function of TEOS concentration (3-100 mM). Their mean particle size was 185 nm by TEM. Enzymatic hydrolysis was performed to compare catalytic efficiencies of CalB@NF and CalB@NF@SiO2. Catalytic constants (Km, Vmax, and Kcat) of CalB@NF and CalB@NF@SiO2 were calculated with Michaelis-Menten equation and Line-weaver Burk plot. Optimal stability of CalB@NF@SiO2 was found at pH 8 and temperature of 35 ℃. Moreover, CalB@NF@SiO2 particles were reused for seven cycles to evaluate their reusability. In addition, enzymatic synthesis of benzyl benzoate was demonstrated by an acylation reaction with benzoic anhydride. The efficiency of CalB@NF@SiO2 for converting benzoic anhydride to benzyl benzoate by the acylation reaction was 97%, indicating that benzoic anhydride was almost completely converted to benzyl benzoate. Consequently, CalB@NF@SiO2 particles are better than CalB@NF particles for enzymatic synthesis. In addition, they are reusable with high stability at optimal pH and temperature.

Advanced Nano structural hard coatings are thin materials films that range in thickness from a few nanometers to a few micrometers and are applied to different surfaces to increase their hardness and wear resistance. Physical vapor deposition (PVD) or chemical vapor deposition (CVD) methods are frequently used to deposit these coatings. These coating’s distinctive characteristics result from their microstructure, which is made up of material columns or grains with a diameter of only a few nanometers. Increased hardness, higher wear resistance, and improved tribological properties result from these short dimensions. In applications with significant wear and/or high contact pressures, such as cutting tools, bearings, and engine parts, the usage of sophisticated Nano structural hard coatings is crucial. Advanced Nano structural hard coatings include, 1. Amorphous carbon coatings with high hardness, low friction, and exceptional wear resistance are known as diamond-like carbon (DLC) coatings. DLC coatings are frequently used in a variety of industries, including the automotive, aerospace, and biomedical ones. 2. Coatings made of titanium nitride (TiN): These metallic coatings have high hardness and wear resistance. Cutting tool, machining, and aerospace industries frequently use TiN coatings. 3. Chromium nitride (CrN) coatings: These coatings have great corrosion resistance, good wear resistance, and high hardness. Cutting tools, gears, and bearings are just a few of the objects that use CrN coatings. 4. Tungsten carbide (WC) coatings: These coatings, which have a high degree of hardness and wear resistance, are frequently employed in cutting tools and other applications that require wear resistance. Advanced Nano structural hard coatings provide many advantages over conventional coatings, including better hardness, increased wear resistance, and improved tribological qualities. The automotive, aerospace, and biomedical industries are just a few that could use these coatings. In this paper the author will explain about the design synthesis and applications of advanced Nano structural hard coating in aerospace and automotive applications.

Reaction of 2-mercapto-3-phenylquinazolin-4(3H)-one (MPQ) with both 4-vinyl benzyl chloride and allyl bromide furnished the reactive heterocyclic monomers 3-phenyl-2-((4-vinylbenzyl) thio) quinazolin-4(3H)-one (PVTQ) and 2-(allylthio)-3-phenylquinazolin-4(3H)-one (APQ), respectively. Copolymerization of PVTQ monomer with styrene and methyl methacrylate in the presence of 2,2′-azobisisobutyronitrile (AIBN) afforded the copolymers PS-co-PPVTQ and PMMA-co-PPVTQ, respectively. Similarly, copolymerization of monomer APQ with styrene and methyl methacrylate (MMA) afforded the copolymers PS-co-PAPQ and PMMA-co-PAPQ, respectively. The resulted copolymers were characterized by using FT-IR, 1H-NMR and GPC techniques. Silver nanocomposites of PS, PMMA, PS-co-PPVTQ, PMMA-co-PPVTQ, PS-co-PAPQ and PMMA-co-PAPQ were synthesized by the addition of silver nitrate into the polymer solution. The reduction of silver ions into silver nanoparticles was performed in DMF and water. Thermogravimetric (TGA) analysis was used to determine the thermal stability of the copolymers and their silver nanocomposites. The X-ray diffraction (XRD) analysis indicated the amorphous structures of the co-polymers and confirmed the formation of silver nanoparticles. The antitumor and antibacterial activities were screened for the copolymers and enhanced by the formation of their silver nanocomposites. In vivo antitumor activity in Ehrlich Ascitic Carcinoma (EAC) mice model showed that PS-co-PPVTQ/Ag NPs, PMMA-co-PPVTQ/Ag NPs, and PMMA-co-PAPQ/Ag NPs displayed promising inhibitory effects against EAC and induce apoptosis against MCF-7 cells.

Natural products endowed of biological activity represent a primary source of commodities ranging from nutrition to therapeutic agents, as well as cosmetic tools, and recreational principles. These natural means have been used by mankind since centuries if not millennia. They are commonly used all over the world and socio-economical contexts but are particularly attractive in disadvantaged area or economically emerging situations all over the world. This is very likely due to the relatively easy recovery of these bioactive principles from the environment, to the low if any cost as well as ease of administration and to the general popular compliance concerning their consumption/ingestion. In this concise review, we focus on some popular bioactive principles of botanical origin which find a wide use in the Madagascan populations. But, due to space limitations only some most common and largely diffused principles in this country are considered. Finally, a possible nanotechnological administration is discussed in the case where a potential therapeutic usage is envisaged.

Nowadays, we can observe a worldwide trend towards the development of synthetic biomaterials. Numerous researches have been carried out in order to better understand the cellular behavior involved in the inflammation and bone healing processes related to living tissues. The aim of this study is to evaluate the tissue behavior of two different types of biomaterials: synthetic nano-hydroxyapatite / beta-tricalcium phosphate and hydroxyapatite in non-critical bone defects in rat calvaria. Twenty four rats underwent surgery in which two 3 mm defects in each cavity were performed. The rats were divided into 2 groups: Group 1, using xenogen hydroxyapatite (Bio oss ™); Group 2, using synthetic nano-hydroxyapatite / beta-tricalcium phosphate (Blue Bone ™). Sixty days after the surgery, the calvaria bone defect was filled with biomaterial, the animals were sacrificed and marked with Masson's trichrome and PAS staining, and immunohistochemistry (TNF-α, MMP-9) and electron microscopy analyzes were performed. Histomorphometric analysis indicates a greater presence in the protein matrix in Group 2, in addition to higher levels of TNF-α, MMP-9. The ultrastructural analysis shows an association of material with fibroblasts in the tissue regeneration stage. Paired statistical data indicates that Blue Bone ™ can improve bone formation / remodeling when compared to biomaterials of xenogenous origin.

A highly dirt resistant paint for building facades without chemicals harmful to nature and environment, is developed which resolves the unattractive disfigurement of building walls caused by dirt. The experimentation is scientifically and statistically planned with the aid of computer programming. It consists of a sequence of phases which include the selection of appropriate raw materials, adopting of Basic Language computer programming to generate a target population of paint formulations. The average PVC percentage is computed using theory and found to be 54.98% for the target population of 543143 paint formulations hence verifies the literature results. Experimentation and statistical analysis are performed to compare the classical conventional agitator with latest lab equipment like Nano mill and it is concluded that Nano mill performs better on the average than conventional agitator in preparation of paint formulations. Hence the sample of paint formulations is prepared on Nano mill and tested in laboratory using advanced available technology for the analysis and comparison of paint properties to determine the best paint formulation. The results are analyzed using Analysis Of Variance Technique (ANOVA) and it is concluded that the paint formulation named “O3” has the highest dirt resistance on the average. The final selected formula O3 is compared with three other competitor paints in market under natural environment for a period of almost one year. A regression model is also constructed to study the effect of environmental factors like time, temperature and humidity on dirt resistance of paints. It is found that O3 formulation is the best environment friendly which performs equally well with one competitor paint and has higher dirt resistance than two other competitor paint formulations containing harmful chemicals. The regression model of dirt resistance on variables including time, temperature and humidity shows that these factors are significantly affecting the dirt resistance of a given paint at 5% level of significance. 95.34% variation in the dirt resistance of a given paint is due to and explained by the given factors. The regression model is useful to predict the average dirt resistance of a given paint with a certain level of confidence. The project exemplifies the work of an applied research from conceptualization to successful commercialization for the paint industry.

In this work, pure TiO₂ and nano-magnetic of Fe₃O₄/TiO₂ were synthesized for degradation of 2,4-dichlorophenol (2, 4-DCP) as an organic pollutant. A range of analytical techniques including XRD, DRS, FESEM, and VSM were employed to reveal the crystal structure, morphology and property of the nanocomposite. The XRD results showed the prepared samples including 100% anatase phase. We obtained the band gap energy 2.9 and 2.8 eV for pure TiO₂ and Fe₃O₄/TiO₂ respectively. VSM results demonstrate that easy, fast separation and redispersion of Fe₃O₄/TiO₂ sample can be realized. We obtained 62% and 31% degradation of 2,4-DCP in the presence of Fe₃O₄/TiO₂ and pure TiO₂ under visible light respectively.

A compact 2-DOF (two degrees of freedom) piezoelectric-driven platform for 3D cellular bio-assembly systems has been proposed based on “Z-shaped” flexure hinges. Multiple linear motions with high resolution both in x and y directions are achieved. The “Z-shaped” flexure hinges and the parallel-six-connecting-rods structure are utilized to obtain the lowest working stress while compared with other types of flexure hinges. In order to achieve the optimized structure, matrix-based compliance modeling (MCM) method and finite element method (FEM) are used to evaluate both the static and dynamic performances of the proposed 2-DOF piezoelectric-driven platform. Experimental results indicate that the maximum motion displacements for x stage and y stage are lx=17.65 μm and ly=15.45 μm, respectively. The step response time for x stage and y stage are tx=1.7 ms and ty =1.6 ms, respectively.

The present study aims at deposition of zinc phosphate coatings with the incorporation of nano Titanium dioxide particles by chemical phosphating method. Zinc phosphate coatings were developed on low carbon steel by using nano TiO2 in the standard phosphating bath. The Coated low carbon steel samples were assessed for corrosion studies using electrochemical impedance spectroscopy and potentiodynamic polarisation techniques in 3.5% NaCl solution. Chemical composition of the coatings was analysed by energy dispersive X-ray spectroscopy (EDX). Significant variations in the coating weight, porosity and corrosion resistance were observed with the addition of nano TiO2 in the phosphating bath. Corrosion rate of nano TiO2 incorporated chemical phosphate coated samples was found to be 3.5 mpy which was 4 times less than the bare uncoated low carbon steel (~14 mpy). Electrochemical impedance spectroscopy studies revels in the reduction of porosity in nano TiO2 phosphate coated samples. It was found that nano TiO2 particles in the phosphating solution yielded phosphate coatings of higher coating weight, greater surface coverage and enhanced corrosion resistance than the normal zinc phosphate coatings (developed using normal phosphating bath).

Background: Functional beverages are ordinary foods with components or ingredients able to provide specific health effects other than purely nutritional effect. Aim: This study aims to formulate a new functional beverage obtained from the recovery of YoAlp® whey, a bovine fermented milk obtained using autochthonous starter cultures, added with Renetta Canada/Golden Delicious-Raspberry (YWL), Renetta Canada-Aronia (YWA) and Ravèntse (YWR) fruit juices to improve the functionality of the beverage. Methods: Microbiological analysis and chemical characterization, by a proteomic approach and spectrophotometric microassay, have been conducted on beverages to investigate the expected shelf-life and potential health promoting effects. Results: The microbiological assessment confirmed the safety of the beverages and the probiotic bacteria vitality over a shelf life of seven days. Biochemical analysis performed highlight the presence of different bioactive peptides (ACE inhibitory and antioxidant), and the betacasomorphin 9 (BCM-9), marker of A2 variant of β-casein typically present in Aosta Valley cattle breeds. Moreover, high amounts of total polyphenols, which concur to the antioxidant activity values observed, have been found. Furthermore, ACE inhibitory activity is well correlated to the bioactive peptides detected. Finally, a consumer test confirmed the YoAlp® whey-based beverages appreciation. Conclusions: The production of these beverages could represent a huge opportunity for Aosta Valley’s farms to increase their income and competitiveness, creating a circular economy by recovering a by-product like whey and following sustainability and healthy trends, which are driving the food sector.

(1) Background: We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules on celiac disease. We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of celiac disease; (2) Methods: CD200, CD200R and Elafin distribution was determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection; (3) Results: We characterized the expression and function of the CD200–CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200, CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type Th1 and Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752, were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD; (4) Conclusions: In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will led to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Sporothrix brasiliensis is the most pathogenic species, responsible for the Brazilian cat-transmitted sporotrichosis hyperendemics. In this scenario, investigation of pathogen-host interaction can provide relevant information for future treatment strategies. To this end, the invertebrate Galleria mellonella has proven to be a suitable alternative to evaluate the virulence of pathogenic fungi since the insect immune system is similar to the mammalian innate immune response. The aim of this work was to investigate phenotypic and molecular aspects of the immune response of G. mellonella throughout the S. brasiliensis infection. Hemocyte density and the evolution of the fungal load were evaluated. In parallel, RT- qPCR expression analysis of genes encoding antimicrobial peptides (Gallerimycin and Galiomycin) and stress management genes (C7 Contig 15362 and C8 Contig 1910) was conducted. Fungal load and hemocyte densities were proportionally increasing simultaneously to the deleterious morphological events and larvae mortality. Gallerimycin, C7 Contig 15362, and C8 Contig 19101 genes were positively regulated (p&lt;0.05) at distinct moments of S. brasiliensis infection, characterizing a time-dependent and alternately modulated profile. Galiomycin gene expression remained unchanged. Our results contribute to the future proposal of potential alternative pathways to treat and, consequently, control S. brasiliensis zoonosis, a major public Health in Latin America.

Spinal cord injury is a traumatic injury that causes a catastrophic state in patients due to neuronal deficits, loss of motor and sensory function, and this is due to secondary deleterious events subsequent to mechanical damage that expands the death of neural cells beyond the initial trauma. One of the most important events is inflammation, which activates molecules like pro-inflammatory cytokines (IL-1beta, IFN-gamma, TNF-alpha) that provoke a toxic environment, inhibiting axonal growth and exacerbating CNS damage. As there is no effective treatment, one of the strategies developed is neuroprotection to preserve healthy neural tissue and reduce neuroinflammation. Some of the neuroprotective treatments that have been practiced are the use of cell therapy, the administration of peptides and molecules or supplements that have been shown to favor an anti-inflammatory environment, and help to preserve the cells and tissues surrounding the injured area, favoring axonal growth and improving locomotor function. In this review we will explain some of these strategies used in different animal models of spinal cord injury, their activity as modulators of the immune system and the benefits they have shown.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

Cell-penetrating peptides (CPPs) have been evaluated as enhancers in drug delivery, their addition in medical formulations favors absorption allowing obtaining the pharmacological effect with lower drug doses. In vaccine formulations their inclusion has been also explored with interesting results. Currently mucosal vaccination constitutes a promising alternative with the main advantage of inducing both systemic and mucosal immune responses, which are crucial for control tumors and infections at mucosal tissues. The known CPP Penetratin was recently evaluated in vaccine formulations designed for nasal administration. The authors demonstrated that this non-covalent linked CPP could improve the antigen-specific systemic and mucosal antibody responses. In the present work we evaluate in Balb/C mice the nasal immune-enhancing effect of four CPPs. Animals were intranasally immunized with CPP and the recombinant hepatitis B surface protein (HBsAg) as model antigen. The IgG antibody response in sera and the mucosal IgA response were measured by ELISA. The IFN-g secretion response at spleen was also evaluated by ELISPOT and ELISA. Among the CPPs studied one novel peptide stand out by its ability to potentiate the humoral and cellular immune response against the co-administered antigen. Considering that the use of mucosal routes is a promising strategy in vaccination against infectious diseases and cancer, which are gaining special relevance nowadays in the development of novel candidates against SARS-CoV-2 and other potential emerging respiratory virus, the searching and development of safe mucosal adjuvants constitute a current need.

Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement activating peptide were used to induce selective depletion of ACPA producing B cells. Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a short, neutral spacer. This peptide detects antibodies in RA sera with 66 % sensitivity and 98 % specificity in ELISA and is recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targets and depletes ACPA producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed on the basis of ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. Aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. The therapeutical peptide and proteins are remarkable therapeutic agents in today’s world that allows the treatment of severe, chronic and life‐threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis in an easy manner. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. The primary objective of this article is to review current issues concerned with the therapeutics peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. The article will also review literature concerning classification of hydrogels on different basis, polymers used, release mechanisms their physical and chemical characteristics and diverse applications.

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

One of the most important objectives of the studies worldwide is to improve the performance of automotive engines to reduce fuel consumption and environmental pollution. Accordingly, the principal motivation of this research study is improving the tribological behavior of the piston ring/cylinder liner interfaces as a promising and straightforward approach in automotive fuel economy and increasing engine durability using Al₂O₃ and TiO₂ nanomaterials as smart nano-lubricant additives that adapted to different operating conditions by replenishing mechanisms anti-friction and anti-wear in automotive engines.

In this study, the impact of the addition of high-aspect-ratio nano-ettringite to photocurable epoxy acrylate resin was explored, with a specific focus on the changes observed in viscosity, shrinkage, tensile strength, and elongation at the break of composites formed. Herein, the nano-ettringite samples were modified using KH-570. The 3 wt% or 6 wt% KH-570-modified and unmodified nano-ettringite were dispersed into the resin by ultrasonic treatment in conjunction with mechanical stirring. The grafting effects of nano-ettringite onto KH-570 were analyzed through scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric (TG) analysis, and Fourier transform infrared spectroscopy (FTIR). The results demonstrate that increased dosages of unmodified and modified nano-ettringite led to increased viscosity of the composite while reducing shrinkage. At the same dosage, the photocurable resin with modified nano-ettringite demonstrated a lower shrinkage and a higher tensile strength. Notably, when the amount of modified nano-ettringite was 3 wt%, the highest tensile strength of the composite was 64.61 MPa, presenting a 72.57% increase compared to the blank sample. Furthermore, the incorporation of modified nano-ettringite as a filler provides a new perspective for improving the performance of photocurable epoxy acrylate resin composites.

A new method is proposed for performance assessment of lubricating compositions based on industrial lubricants that contain nano-additives of different chemical composition for higher wear resistance of heavy-loaded steel friction pairs. The method is based on the joint analysis of the experimental data on the wear kinetics, change of the relative hardness, and damage in the surface layers of the metal of friction pairs. The level of structural damage to the materials in the contact zone is determined by using the statistical parameters of dispersion of the hardness values. The paper investigates the known experimental results of assessment of the level of damage to structural materials of various grades under the conditions of long-term, cyclic, static loading, and lubricated friction. It is demonstrated that the structural changes occurring in the materials during loading correlate to the changes in the statistical dispersion characteristics of hardness measurement results. Experimental substantiation of the method is carried out for steel friction pairs using lubricating compositions based on industrial oil Greaseline Lithium BIO Rail 000 by AIMOL and nano-additives of copper of M2 grade, magnesium alloy of MA2 grade, aluminum alloy of Al-Mg system, graphite of medium carbon steel grades, i.e. rail and industrial. Under system of indicators presented in the paper, the highest efficiency in terms of increase in the wear resistance of steel friction pairs is demonstrated by the lubricating composition based on industrial lubricant with the additive of nano-powder made of rail steel, as it provided the optimum value of friction coefficient, minimum damage and wear of friction surface.

Both the use of plastic and its decomposition products lead to the distribution of plastic all over the earth and finally to the uptake by all kind of living beings including humans. Still, it is widely unknown what risks harbor the widespread uptake of plastics for human health, espe-cially regarding contributing factors like size, shape and surface composition. We assessed the uptake of polymethylmethacrylate (PMMA)-nano- and microbeads for HEK293-, A549- and MRC5 cells. Via confocal microscopy, we localized multiple PMMA-beads inside the cytosol of cells. Uptake of PMMA-beads did not alter cell growth and cell division, implying no short-term toxicity towards human cells. Further, we used a cAMP response element binding protein (CREB)-mediated reporter assay to assess whether internalized PMMA-nanobeads alter cell-signaling pathways. In contrast to the in vitro transcription, where the addition of PMMA-nanobeads abolished the transcription, no changes regarding CREB-mediated cell sig-naling are given in HEK293-cells. Our data led to the assumption that PMMA-nano-and mi-crobeads are internalized via endocytosis and end up as lysosomes within the cells cytosol. Therefore, we concluded differences regarding the surface composition of the PMMA-nanobeads mainly affect its potential to alter cell signaling. These findings emphasize the key role the sur-face composition plays regarding microplastic and its risks for human health.

Some of Iran's gas resources are known as sour gas because one of the major by-products of this gas is water. In fact, natural gas is combined with water vapor in underground reservoirs. In some areas, the amount of water vapor in natural gas is so high that it can be used as a source of drinking water. However, it should be noted that water vapor in natural gas may exacerbate corrosion in pipes and industrial equipment, and the combustion of more natural gas produces high temperatures that can lead to the production of nitrogen oxides (NOx), which They are the cause of air pollution. This is while the processed gas has a standard percentage composition in which the amount of water has the lowest position. The removal of moisture from natural gas is due to the need to prevent the reduction of the calorific value of the gas and also to purify the gas in order to achieve the necessary standards for delivering gas to petrochemicals, industries and domestic uses. The main goal of this research is to investigate the influencing parameters on zeolite TiO2 nanocomposite membranes in order to absorb moisture from gas. For this reason, with the construction of a TiZ-V membrane as a standard membrane, the result of the initial evaluation of a suitable membrane for gas dehumidification was made, and this membrane was placed as a standard for measuring the effect of the manufacturing parameters in a way that in each stage of membrane construction It was found that it was different from standard TiZ-V membrane only in terms of one parameter. This type of investigation made it possible to determine the effect of various effective parameters in membrane construction on efficiency. The findings showed that increasing the concentration of SiO2 has the greatest effect on increasing the water flux of the membrane. According to the other findings of this study, the effect of increasing the reaction time of the vapor phase carrier has been to reduce the process of paternity selectivity loss at higher pressures. Although due to the safety limitation of the equipment to measure the efficiency of the membrane at pressures higher than 7 bar, this measurement was not carried out, but charts were presented regarding the state of the water in the water, which were a measure of the superiority of the water in the water in comparison to the gas in the water, which is the higher water in the water It is an indicator of the appropriateness of the membrane's efficiency at its corresponding pressure, so that the examination of the difference between these two graphs shows the possibility of using the membrane at higher pressures

Magnesium ions play an important immune-regulatory role during bone repair. For this study, we prepared micro-nano bioactive glass containing magnesium, which can release magnesium, silicon, and calcium ions and has a positive impact on osteogenic differentiation and vascular regeneration. In this study, MgMNBG was compounded and combined with PLGA and PCL for 3D printing. Afterwards, the physicochemical properties and bone repair performance of the scaffolds were evaluated through in vitro and in vivo experiments. We also investigated the effects of MgMNBG on osteogenic differentiation, immune regulation, and vascular regeneration. The results showed that MgMNBG can inhibit inflammation and promote osteogenesis and angiogenesis by regulating macrophages. PLGA/PCL/MgMNBG scaffolds have good osteogenic and angiogenic effects, and the composite scaffolds have excellent bone repair performance and potential application value.

Nanomaterials exhibit novel properties and profound attributes as an additive in asphalt binder modification. However, the application of nano-silica in asphalt binders and mixture modification is still limited and further research is required. Along these lines, in this work, nano-silica with a content from 2% to 8% and an increment of 2% were utilized in modifying the bitumen binder type C320, which is considered the most conventional type of bitumen used in Western Australia road asphalt mixtures. Various tests were performed to assess their properties including dynamic shear rheometer, penetration, softening point, and multiple stress creep recovery (MSCR) test. The extracted results revealed an increase in the strength and stiffness properties by lowering the penetration, improving the softening point, and increasing the complex shear modulus of all nano-silica modified bitumen samples. Interestingly, a relatively big content of nano-silica leads to a higher rutting resistance. Nevertheless, the rutting resistance was affected by the size of the nano-silica coated with the silane coupling agent. The ideal sample of nano-silica modified C320 was determined as NS-15nm (NS-A), which can improve the rutting resistance. Nevertheless, the rutting resistance of the modified asphalt mixtures needs to be further investigated in the future to elaborate on the impact of nano-silica as modified binders on the mechanical properties of Australian asphalt mixtures.

In the current study nanocellulose was isolated from walnut shell using mechanical and chemical methods. This study highlights the particle size, morphology and these methods’ efficiency in nano structure extraction. The difference between morphology and size of the particles (of the both extracted methods) were investigated by field emission scanning electron microscopy (FESEM). Walnut shell is an agro-waste material with source of lignin and cellulose. Ball mill-ing with different times, in the presence and absence of additive and acid hydrolysis were used as mechanical and chemical methods, respectively. The result showed mechanical method is unable to extract nanoparticle and just reshape the walnut shell. Milling time were also found important in morphology of fiber extracted. FE-SEM images represented that structure mean diameter of using ball mill was 1± 5 μm while hydrolysis acid method extract nano particle with mean diameter of 40± 20 nm.

In this study, grit blasting pretreatment was used to improve the adhesion and corrosion resistance and microhardness of Ni-W/SiC nanocomposite coatings fabricated using conventional electrodeposition technique. Prior to deposition, grit blasting and polishing (more commonly used) pretreatment were used to prepare the surface of the substrate and the 3D morphology of the pretreated substrates was characterized using laser scanning confocal microscopy. The coatings surface and the cross section morphology were analyzed using scanning electron microscopy (SEM). The chemical composition, crystalline structure, microhardness, adhesion, and the corrosion behavior of the deposited coatings were characterized using energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), microhardness tester, scratch tester and electrochemical workstation, respectively. The results indicated that the grit blasting and SiC addition, improved the microhardness, adhesion and corrosion resistance. The Ni-W-SiC nanocomposites pretreated by grit blasting exhibited the best adhesion strength, up to 36.5 ± 0.75 N. Its hardness was the highest and increased up to 673 ± 5.47Hv and its corrosion resistance was the highest compared to the one pretreated by polishing.

The present study examines the effect of SiO2 nano-additives on the performance and emission characteristics of a diesel engine fuelled with soybean biodiesel. Soybean biofuel was prepared using the transesterification process. Nano-additives characterisations were done using different tests such as FESEM, XRD, EDS, etc., to study the morphology of nano-additives. For proper blending of nano-additives with biodiesel, the ultrasonication process was used. Surfactant was used for the stabilisation of nano-additives. After making all the combinations of nano fuel blends, physicochemical properties were measured as per ASTM standards. Performance and emissions readings were taken at different load conditions. It was found that with the addition of SiO2 nano-additives, brake thermal efficiency (BTE) and brake specific fuel consumption (BSFC) was increased by 3.48-6.39% and 5.81-9.88%, respectively. Significant reduction of CO, CO2, NOx, and smoke emissions were also observed compared to baseline fule due to better combustion efficiency with the use of SiO2 nano-additive.

The evolution of metals micro/nano-structure upon severe plastic deformation (SPD) is still far to be theoretically explained, while experimental datasets are persistently growing for several decades. Major problem associated with understanding of SPD is related to a fact that the latter is a synergetic product of several competing physical effects which alter the material micro/nano-structure. In attempt to find deformational boundaries, where predominantly one mechanism determines the micro/nano-structure, in this paper we propose a continuous piecewise model for the analysis of experiments on material hardness vs strain of SPD processed materials. The novelty of this approach lies in its ability to find, as free-fitting parameters, the strain breakpoints which separate different micro/nano-structure modes generated upon SPD process. The model is applied to analyse experimental data for polycrystalline samples of pure iron and two distinctive strain breakpoints are revealed with good accuracies. This finding is in a good agreement with our earlier results on TEM microscopy studies on pure iron polycrystals after SPD treatment.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Antimicrobial peptides (AMPs) are essential components of the innate immune system, present across a spectrum of organisms. Their versatility lies in their ability to effectively inhibit a wide range of pathogens including bacteria, fungi, parasites, and viruses. As the challenge of antibiotic resistance escalates and concerns surrounding antibiotic use grow, AMPs have emerged as promising alternatives. Their applications span diverse domains such as medicine, agriculture, food production, animal husbandry, and aquaculture, primarily due to their efficacy against resistant pathogens, signifying their crucial role in combating infections. Beyond their antimicrobial properties, research illuminates their intricate involvement in the immune response network. These peptides impact crucial processes including cytokine release, chemotaxis, wound healing, angiogenesis and the activation of the adaptive immune system. This comprehensive review delves into the multifaceted realm of AMPs, encompassing their classification, varied applications across industries and notably, their significance in diverse disease conditions like infections, skin diseases, cancer, oral diseases, lung diseases and cardiovascular ailments. Special attention is directed towards current advancements in clinical applications of peptide-based therapeutics, offering invaluable insights into their potential future integration within clinical settings.

Membrane processes, such as microfiltration, ultrafiltration, and nanofiltration are increasingly used for various applications in both upstream and downstream processing. Membrane-based processes play a critical role in the field of separation/purification of biotechnological products, including protein production/purification. The possibility of using membranes to separate peptides from a chicken byproduct hydrolysate and the effect of the performed downstream processing on the DPP-IV inhibitory activity of MDCR (mechanical deboning chicken residue) has been investigated. The chicken byproduct hydrolysate was prepared by enzymatic hydrolysis followed by MF, UF, NF, and RO separation. The LC-OCD analysis confirmed that NF and RO would retain the bioactive peptides in the concentrate in comparison to MF and UF. Bioactivity was correlated with molecular weight distribution profiles and average molecular weights. Permeates after ultrafiltration showed an IC50 value of 0.75 mg/mL, comparable to other potent DPP-IV inhibitors derived from various food sources, and significantly more potent compared to the microfiltration sample, which showed an IC50 value of 1.04 mg/mL. The average molecular weight of the permeates calculated from the SEC chromatograms was 883 g/mol for UF and 1437 g/mol for MF. Of the four membranes studied, the UF membrane showed the best separation properties with respect to maximizing the yield and up-concentration of the bioactive peptides. Overall, UF was demonstrated to be a feasible technology for the removal of the undesired high molecular weight substances and up-concentration of small molecular weight bioactive peptides from chicken byproduct hydrolysate.

Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

This study focuses on the enzymatic hydrolysis of hemoglobin, the main component of cruor that gives blood its red color in mammals. The antibacterial and antioxidant potential of human hemoglobin hydrolysates were evaluated in comparison to bovine hemoglobin. The results showed strong antimicrobial activity of the peptide hydrolysates against six bacterial strains, independent of the initial substrate concentration level. The hydrolysates also showed strong antioxidant activity measured by four different tests. In addition, the antimicrobial and antioxidant activity of the human and bovine hemoglobin hydrolysates showed little or no significant difference, with only the concentration level being the determining factor in their activity. The results of the mass spectrometry study showed the presence of a number of bioactive peptides, the majority of which have characteristics similar to those mentioned in the literature. New bioactive peptides were also identified in human hemoglobin, such as antibacterial peptides PTTKTYFPHF (α37-46), FPTTKTYFPH (α36-45), TSKYR (α137-141) and STVLTSKYR (α133-141), as well as an antioxidant TSKYR (α137-141). According to these findings, human hemoglobin represents a promising source of bioactive peptides beneficial to the food or pharmaceutical industries.

New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.

Antimicrobial peptides (AMPs) are a promising alternative to antibiotics to combat drug resistance in pathogenic bacteria. However, the development of AMPs with high potency and specificity remains a challenge, and new tools to evaluate antimicrobial activity are needed to accelerate the discovery process. As a step toward direct prediction of the experimental minimum inhibitory concentration (MIC) of AMPs, we proposed MBC-Attention, a combination of a multi-branch CNN architecture and attention mechanism. Using a curated dataset of 3929 AMP against Escherichia coli, the optimal MBC-Attention model achieved an average Pearson correlation coefficient of 0.775 and an RMSE of 0.533 (log μM) in three independent tests of 393 sequences each. This results in a 5–12% improvement in PCC and 7–13% improvement in RMSE compared with RF and SVM models. Ablation studies confirmed that both attention mechanisms contributed to performance improvement.

Antibiotic resistance (ABR) is concerning issue due to its direct and indirect repercusions on public health, since decreased therapeutic effect of certain antibiotic to treatment complications that can cause death. There are several mechanism as to how ABR can be transferred from one microoorganisms to another, and many of them are dependant many environmental factors. The food supply chain is a environment in which ABR gene transfer can occur is multiple pathways, which generate concerns regarding food safety. Here, we summarize relevant mechanisms which are implied in ABR in food supply chain but also we are addressing routes of transmission and prevalence of ABR, implications on public health, and the application of new alternatives to antibiotics such as antimicrobial peptides, mainly bacteriocins, in order to countermeasure ABR.

Electrostatic interactions have a determining role in conformational and dynamic behavior of polyelectrolyte molecules [1]. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in water solution with the most commonly used K+ or Na+ counterions were investigated using atomistic molecular dynamics (MD) simulations. Seven common force fields, AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and with the non-bonded fix (NBFIX) and electronic continuum corrections (ECC) to were studied. These corrections have bene introduced to correct for the problem of overbinding of ions to the charged groups of polyelectrolytes. Physical properties, such as molecular sizes, local structure and dynamics, were studied using two types of common counterions, potassium and sodium. The results show that in some cases, the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of ions and charged side chain groups. The local structures and dynamics are more sensitive on dihedral angle parameterization resulting in a preference for defined monomer conformations amd the type of correction used.

Staphylococcus aureus can develop resistance by mutation, tranfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells was evaluated by measuring release of dyes and ATP and nucleic acids. S. aureus did not develop resistance to the AMPs but resistance increased to ciprofloxacin by 128 times after 30 passages. Only peptides reduced biofilms of ciprofloxacin resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released  66 nM ATP, more than either peptide alone (p  0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was 3 times more than released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatments of S. aureus biofilms.

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

Heterocytous cyanobacteria are among the most prolific source of bioactive secondary metabolites, including anabaenopeptins (APTs). A terrestrial filamentous Brasilonema sp. CT11 collected in Costa Rica bamboo forest, as black mat was studied using a multidisciplinary approach: genome mining and HPLC-HRMS/MS coupled with bionformatic analyses. Herein, we report the nearly complete genome consisting 8.79 Mbp with a GC content of 42.4%. Moreover, we report on three novel tryptophane-containing APTs; anabaenopeptin 788 (1), anabaenopeptin 802 (2) and anabaenopeptin 816 (3). Further, the structure of two homologues, i.e., anabaenopeptin 802 (2a) and anabaenopeptin 802 (2b) was determined by spectroscopic analysis (NMR and MS). Both compounds were shown to exert weak to moderate antiproliferative activity against HeLa cell lines. This study also provides the unique and diverse potential of biosynthetic gene clusters and an assessment of the predicted chemical space yet to be discovered from this genus.