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Although data-independent acquisition (DIA) has the ability to identify and quantify all peptides in a sample, highly complex mixed mass spectra present difficulties for accurate peptide and protein identification. Additionally, the correspondence between the precursor and its fragments is broken, making it challenging to perform peptide identification directly using conventional DDA search engines. In this paper, we propose a cosine-similarity-based deconvolution method: CorrDIA. This is achieved by reconstructing the correspondence between precursor and fragment ions based on the consistency of extracted ion chromatograms (XICs). A deisotope peak cluster operation is added and centered on the MS/MS spectrum to improve the accuracy of spectrum interpretation and increase the number of identified peptides. The resulting MS/MS spectra can be identified using any data-dependent acquisition (DDA) sequencing software. The experimental results demonstrate that the number of peptide results increased by 12 percent and 21 percent respectively, and the repetition rate decreased by 12 percent. This reduces mass spectra complexity and difficulties in mass spectra analysis without the need for any mass spectra libraries. [ABSTRACT FROM AUTHOR]

Background: In a previous paper, we classified populated HLA class I alleles into supertypes and subtypes based on the similarity of 3D landscape of peptide binding grooves, using newly defined structure distance metric and hierarchical clustering approach. Compared to other approaches, our method achieves higher correlation with peptide binding specificity, intra-cluster similarity (cohesion), and robustness. Here we introduce HLA-Clus, a Python package for clustering HLA Class I alleles using the method we developed recently and describe additional features including a new nearest neighbor clustering method that facilitates clustering based on user-defined criteria. Results: The HLA-Clus pipeline includes three stages: First, HLA Class I structural models are coarse grained and transformed into clouds of labeled points. Second, similarities between alleles are determined using a newly defined structure distance metric that accounts for spatial and physicochemical similarities. Finally, alleles are clustered via hierarchical or nearest-neighbor approaches. We also interfaced HLA-Clus with the peptide:HLA affinity predictor MHCnuggets. By using the nearest neighbor clustering method to select optimal allele-specific deep learning models in MHCnuggets, the average accuracy of peptide binding prediction of rare alleles was improved. Conclusions: The HLA-Clus package offers a solution for characterizing the peptide binding specificities of a large number of HLA alleles. This method can be applied in HLA functional studies, such as the development of peptide affinity predictors, disease association studies, and HLA matching for grafting. HLA-Clus is freely available at our GitHub repository (https://github.com/yshen25/HLA-Clus). [ABSTRACT FROM AUTHOR]

Context: The inhibitory effect of asparagine (Asn) and its derivatives on iron (Fe) corrosion was studied by performing density functional theory (DFT) calculations. In this paper, the global and local reactivity descriptors of Asn in the protonated and neutral forms were evaluated. Also, the changes in reactivity were investigated when dipeptides were combined with Asn. Due to the increase in the reaction centers within their molecular structure, there was an enhancement in the inhibitory effect of these dipeptides. Moreover, the adsorption energies (Eads) and the adsorption configurations of Asn and small peptides (SPs) with most stability were determined on the surface of Fe(111). It was found that dipeptides had a chemical adsorption on these substrates. In the protonated forms, there was an enhancement in the absolute values of Eads between the inhibitors and the Fe(111) surfaces. Peptides were more likely to be adsorbed on the Fe surfaces, showing the great inhibitory effect of these moieties. The results of the current research demonstrate the possibility of utilizing SPs as efficient "green" corrosion inhibitors. Methods: DFT computations were undertaken by employing the BIOVIA Material Studio with B3LYP-D3 functional and 6–31 + G* basis set. The theoretical evaluation of the inhibitory effect of asparagine (Asn) dipeptides, and the potential analysis of small peptides to protect against the corrosion of Fe, was done. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Many fundamental decisions in the process design of a separation task are conducted in an early stage where, unfortunately, process simulation does not have the highest priority. Subsequently, during the setup of the digital twin, dedicated experiments are carried out in the design space that was established earlier. These experiments are most often too complicated to conduct directly. This paper addresses the idea of a combined approach. The early-stage buffer screening and optimization experiments were planned with the Design of Experiments, carried out and then analyzed statistically to extract not only the best buffer composition but also the crucial model parameters, in this case the isotherm dependency on the buffer composition. This allowed the digital twin to predict the best buffer composition, and if the model-predicted control was applied to keep the process at the optimal productivity at a predetermined purity. The methodology was tested with an industrial peptide purification step. [ABSTRACT FROM AUTHOR]

Simple Summary: This article is mainly about that molecular characterization and expression pattern of leptin in yellow cheek carp (Elopichthys bambusa) and its transcriptional changes in response to fasting and refeeding. In this study, the authors used PCR to clone the CDS of leptin in yellow cheek carp, and analyzed the sequence differences of the gene with other species, constructed the phylogenetic tree, used real-time PCR for analyzing the expression of leptin in different tissues, including the expression of leptin in the brain and liver after fasting–refeeding of yellow cheek carp. This paper found that the full-length cDNA sequence of Eblep was 1140 bp and the length of the open reading frame (ORF), which can encode a protein of 174 amino acids, was 525 bp. The Eblep mRNA transcript was detected in all tested tissues, with the highest expression in the liver and lowest expression in the spleen. It was found that the change in the mRNA expression of EbLep may be an adaptive strategy for different energy levels by studying the expression of EbLep mRNA in the brain and liver under fasting and refeeding. Leptin, a secretory protein encoded by obese genes, plays an important role in regulating feeding and energy metabolism in fish. To study the structure and function of the Leptin gene in yellow cheek carp (Elopichthys bambusa), the full-length cDNA sequence of leptin was cloned, named EbLep. The full-length cDNA of Eblep was 1140 bp, and the length of the open reading frame (ORF), which can encode a protein of 174 amino acids, was 525 bp. The signal peptide was predicted to contain 33 amino acids. Sequence alignment showed that the amino acid sequence of Leptin was conserved in cyprinid fish. Despite large differences between primary structures, the tertiary structure of the EbLep protein was similar to that of the human protein and had four α-helices. The EbLep mRNA transcript was detected in all tested tissues, with the highest expression in the liver and lowest expression in the spleen. In this study, short-term fasting significantly increased the mRNA expression of EbLep in the liver, which returned to a normal level after 6 days of refeeding and was significantly lower than the normal level after 28 days of refeeding. In the brain, the mRNA expression of EbLep significantly decreased during short-term fasting and significantly increased to a higher value than the control group after 1 h of refeeding. It then rapidly decreased to a lower value than the control group after 6 h of refeeding, returning to the normal level after 1 day of refeeding, and significantly decreasing to a lower value than the control group after 28 days of refeeding. To sum up, the change in the mRNA expression of EbLep in the brain and liver may be an adaptive strategy for different energy levels. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs), which are parts of the innate immune response found among all classes of life, are promising in broad-spectrum antibiotics and drug-resistant infection treatments. Although AMPs effectively kill bacteria, numerous AMPs widely distributed in the sequence space remain unknown to humans. Therefore, the de novo design of AMPs involves the exploration of vast sequence space to identify peptides with high antimicrobial activity and good diversity among the known AMPs. Computational intelligence approaches have successfully identified some AMPs; however, most of them fail to address the diversity of the obtained AMPs. This paper reports an evolutionary multi-objective approach for AMP design to optimize both the antimicrobial activity and diversity among identified AMPs. Our approach employs a deep learning model to predict a peptide's antimicrobial activity and a niche sharing method to estimate a peptide's density. Then, an evolutionary multi-objective algorithm is presented to simultaneously optimize the objectives of antimicrobial activity and diversity. The algorithm takes the advantage of a decomposition-based framework to search for AMPs with good diversity. These AMPs are collected by an elite archive during the evolution process. Moreover, a local search strategy is applied to enhance the quality of the identified AMPs. The experimental results show that the proposed approach outperforms the state-of-the-art designs in searching for various AMPs. The AMPs generated by the proposed approach have high antimicrobial activities and are distinct from each other and among the AMPs in the datasets. [ABSTRACT FROM AUTHOR]

Thiol catalysts are essential in native chemical ligation (NCL) to increase the reaction efficiency. In this paper, we report the use of thiocholine in chemical protein synthesis, including NCL-based peptide ligation and metal-free desulfurization. Evaluation of thiocholine peptide thioester in terms of NCL and hydrolysis kinetics revealed its practical utility, which was comparable to that of other alkyl thioesters. Importantly, thiocholine showed better reactivity as a thiol additive in desulfurization, which is often used in chemical protein synthesis to convert Cys residues to more abundant Ala residues. Finally, we achieved chemical synthesis of two differently methylated histone H3 proteins via one-pot NCL and desulfurization with thiocholine. [ABSTRACT FROM AUTHOR]

In recent years, numerous reports have described bioactive peptides (biopeptides)/hydrolysates produced from various food sources. Biopeptides are considered interesting for industrial application since they show numerous functional properties (e.g., anti-aging, antioxidant, anti-inflammatory, and antimicrobial properties) and technological properties (e.g., solubility, emulsifying, and foaming). Moreover, they have fewer side effects than synthetic drugs. Nevertheless, some challenges must be overcome before their administration via the oral route. The gastric, pancreatic, and small intestinal enzymes and acidic stomach conditions can affect their bioavailability and the levels that can reach the site of action. Some delivery systems have been studied to avoid these problems (e.g., microemulsions, liposomes, solid lipid particles). This paper summarizes the results of studies conducted on biopeptides isolated from plants, marine organisms, animals, and biowaste by-products, discusses their potential application in the nutricosmetic industry, and considers potential delivery systems that could maintain their bioactivity. Our results show that food peptides are environmentally sustainable products that can be used as antioxidant, antimicrobial, anti-aging, and anti-inflammatory agents in nutricosmetic formulations. Biopeptide production from biowaste requires expertise in analytical procedures and good manufacturing practice. It is hoped that new analytical procedures can be developed to simplify large-scale production and that the authorities adopt and regulate use of appropriate testing standards to guarantee the population's safety. [ABSTRACT FROM AUTHOR]

This paper reviews some of the graph theory-based methods that were recently developed in our group for post-processing molecular dynamics trajectories. We show that the use of algorithmic graph theory not only provides a direct and fast methodology to identify conformers that are sampled over time, but it also allows to follow in time the interconversions between the conformers through graphs of transitions, also provides statistical characterisations, that would otherwise be hard to obtain. Examples for a gas phase peptide and for the more complex inhomogeneous charged air–liquid water interface are presented in order to demonstrate the power of topological 2D-graphs and their versatility and transferability. [ABSTRACT FROM AUTHOR]

For the further study of [19F]‐alfatide, the development of highly sensitive analytical methods for its determination is an urgent issue. In this paper, a method for simultaneously determining [19F]‐alfatide and alfatide using liquid chromatography/tandem mass spectrometry was created and validated. The plasma samples were pretreated using the protein precipitation method. Poroshell 120 EC‐C18 (4.6 × 50 mm, 2.7 μm, Agilent) was used for the separation of the analytes to be measured. The mobile phase, consisting of acetonitrile and water (0.1% acetic acid, 50:50, v/v), was delivered at a flow rate of 0.60 ml/min for sample analysis. Positive electrospray ionization was performed using multiple‐reaction monitoring with transitions of m/z 715.2 → 636.6 for [19F]‐alfatide, the ion pairs 700.3 → 851.5 for alfatide and the ion pairs 237.1 → 194.2 for carbamazepine (internal standard). According to the results, the method had high specificity, precision and accuracy as well as an extended linear range. The matrix effect and extraction recovery were also acceptable. The method was successfully applied to the pharmacokinetic study of [19F]‐alfatide in rats. [ABSTRACT FROM AUTHOR]

Objective: Bioinformatics analyses have been becoming important research tools in the field of life science since 2000. New tools have been developed for the detection of allergens in food sources. This study investigated potential allergen proteins similar to the endochitinase class 1(Pers a 1) protein found in avocado using bioinformatics analysis tools. Materials and Methods: The potential allergens were examined with four different in silico tools: Clustal W for multiple sequence comparison, Swiss-MODEL for homology modeling, ProtParam for comparing protein parameters, and AlgPred for allergen prediction. Results: In silico analyses revealed high rates of similarities in protein sequences among the studied species. The highest percent identity was found in Cinnamomum micranthum f. kanehirae as 97.55 while the lowest percent identity was found in Diospyros kaki as 70.23. It is very important to note that 9 of the 10 potential allergen species investigated are plats consumed in daily life and these species were identified as allergens. According to the algorithm of BLAST search on allergen representative peptides (ARPs), ARPs were found in eight potential allergen proteins except for Prunus avium and Citrus unshiu. The ARP sequence related to Persea americana is LQLTWNYNYGAAGNSIGFNGLSNP. Conclusion: People who are allergic to avocado (Persea americana) may be advised to be careful while consuming foods such as Phoenix dactylifera, Allium sativum, Citrus unshiu, Diospyros kaki, and Spinacia oleracea. The present paper can be considered as a model study for understanding allergens in foods by using in silico tools. [ABSTRACT FROM AUTHOR]

Temporins are short peptides secreted by frogs from all over the world. They exert antimicrobial activity, mainly against Gram-positive bacteria, including resistant pathogens; recent studies highlight other possible applications of these peptides as anticancer or antiviral agents. This review is meant to describe the main features of temporins produced by different ranid genera. Due to the abundance of published papers, we focus on the most widely investigated peptides. We report studies on their mechanism of action and three-dimensional structure in model systems mimicking bacterial membranes or in the presence of cells. The design and the antimicrobial activity of peptide analogues is also described, with the aim of highlighting elements that are crucial to improve the bioactivity of peptides while reducing their toxicity. Finally, a short section is dedicated to the studies aimed at applying these peptides as drugs, to produce new antimicrobial materials or in other technological uses. [ABSTRACT FROM AUTHOR]

The emergence of antibiotic-resistant-bacteria is a serious public health threat, which prompts us to speed up the discovery of novel antibacterial agents. Phage display technology has great potential to screen peptides or antibodies with high binding capacities for a wide range of targets. This property is significant in the rapid search for new antibacterial agents for the control of bacterial resistance. In this paper, we not only summarized the recent progress of phage display for the discovery of novel therapeutic agents, identification of action sites of bacterial target proteins, and rapid detection of different pathogens, but also discussed several problems of this technology that must be solved. Breakthrough in these problems may further promote the development and application of phage display technology in the biomedical field in the future. [ABSTRACT FROM AUTHOR]

Copyright of Science & Technology of Cereals, Oils & Foods is the property of Science & Technology of Cereals, Oils & Foods Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: There are no diagnostic and/or prognostic markers of the treatment outcome in patients receiving allergen immunotherapy (AIT). Although numerous allergen epitopes are known, their value in this context has not been investigated. This paper deals with re‐evaluation of sera from patients who underwent AIT against rBet v 1 for treatment of their soya allergy (BASALIT trial). Objective: To evaluate the diagnostic and/or prognostic potential of allergen epitopes recognition by antibodies from patients with birch‐related soya allergy before and after rBet v 1‐immunotherapy. Methods: PR‐10 epitope‐binding profiles from 34 patients were identified in silico using a statistical peptide phage display at start and at end of AIT. IgE‐ and IgG‐binding to these peptide epitopes was measured in peptide microarrays. Clinical relevance of epitopes was evaluated by comparing these measurements to a number of treatment outcome measures recorded during double‐blind placebo‐controlled food challenge at start and end of AIT. Results: We showed that IgG‐ and IgE‐recognition of peptide epitopes after AIT were surrogate markers of 5 out of 12 analysed treatment outcome measures using this patient cohort. Seven epitopes were identified from multiple PR‐10 allergen sequences. Twenty‐six peptide epitopes were used for IgG and IgE measurements. IgE‐binding to one of the epitopes was associated with stronger intensity of oral tingling/itching after ingesting soya at start of AIT. IgG recognizing two other epitopes at start of AIT could predict decreased Cor a 1‐specific IgE concentration (p =.043) and decreased lip swelling intensity (p =.016) after AIT. Tolerance to increasing amounts of soy at food challenge correlated with IgG‐binding to another epitope at start of AIT (p =.046). Conclusion: IgG‐ and IgE‐binding to peptide epitopes in PR‐10 is a potential indicator of the outcome and clinical course of AIT of soya‐sensitized patients with rBet v 1. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pegcetacoplan is the newest inhibitor of the complement system to be approved by the FDA and EMA for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH). The cyclic peptide inhibitor of C3 was evaluated in several clinical trials in PHN leading to its approval. The focus of this paper will review the efficacy and safety of Pegcetacoplan (PEG), and considerations for use in patients with PNH. [ABSTRACT FROM AUTHOR]

Degradable and non-degradable biomaterials are two categories that can be used to classify the existing biomaterials, being a solution for eliminating a second surgical intervention of the implant when the tissue has properly recovered. In the present paper, the effect of deposition temperature on the structure, morphology, hardness, electrochemical evaluation, degradation properties and functional peptides adhesion of Mg and Si-doped hydroxyapatite was investigated. The coatings were obtained by RF magnetron sputtering technique at room temperature (RT) and 200 °C on AZ31B alloy substrate. Results showed that an increase in deposition temperature led to an improvement in hardness and reduced modulus of about 47%. From an electrochemical point of view, a comparative assessment of corrosion resistance was made as a function of the immersion medium used, highlighting the superior behaviour revealed by the coating deposited at elevated temperature when immersed in DMEM medium (icorr~12 µA/cm2, Rcoat = 705 Ω cm2, Rct = 7624 Ω cm2). By increasing the deposition temperature up to 200 °C, the degradation rate of the coatings was slowed, more visible in the case of DMEM, which had a less aggressive effect after 14 days of immersion. Both deposition temperatures are equally suitable for further bio-inspired coating with a mussel-derived peptide, to facilitate biointegration. [ABSTRACT FROM AUTHOR]

Experimental observations have shown that peptides are chemically modified under plasma treatment, which impacts the function and lifetime of a protein. This paper investigates the interactions of reactive oxygen species (ROS) produced in atmospheric plasmas and peptides. Results show that the reactions typically start with the H abstraction from the side chain of amino acids. As the reactions continue, the introduction of O atoms is the most common reaction, and the formation of double C = C bonds, detachment of carboxyl groups, and cleavage of the ring are also observed. Moreover, the degree of oxidative modification of the peptides increases with increasing doses of ROS. This study reveals the formation and breaking of chemical bonds and the generation of new reactive groups in the structure of peptides under plasma treatment, which enables us to understand the mechanisms of plasma medicine deeply. [ABSTRACT FROM AUTHOR]

Accurate quantification of low-abundance protein Cystatin-C (CysC) in serum by liquid chromatography tandem mass spectrometry (LC–MS/MS) method is very difficult. After sample processing and tryptic digestion, the matrix of CysC surrogate peptides is very complexity, and the concentrations of them are very low, so solid-phase extraction (SPE) must be used to make the surrogate peptides purification and enrichment. In this paper, we used C18 reversed-phase SPE (RP-SPE) and mixed-mode SPE as SPE cartridges. We quantitatively assessed and compared the CysC surrogate peptides recoveries and matrix effects by different SPE cartridges. The sequence of CysC surrogate peptide is ALDFAVGEYNK, and sequence-specific subions y 6 (VGEYNK+, m/z 709.3) and y 9 (DFAVGEYNK+, m/z 1042.4) were selected for quantification of CysC, because the two fragment ions showed the highest sensitivity. In neat solution, the highest recoveries were similarly for y 9 and y 6 when used RP-SPE and mixed-mode SPE. However, in serum matrix, the recoveries were significantly higher when used mixed-mode SPE than RP-SPE, which was caused by matrix effects. Results showed that both RP-SPE and mixed-mode SPE were resulted in ion enhancement for CysC surrogate peptides quantification by LC–MS/MS, but mixed-mode SPE reduced more matrix effects. So mixed-mode SPE was more suitable SPE type for purification and enrichment of CysC surrogate peptides. [ABSTRACT FROM AUTHOR]

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects. [ABSTRACT FROM AUTHOR]

Mental disorders such as anxiety and depression induced by chronic pain are common in clinical practice, and there are significant sex differences in their epidemiology. However, the circuit mechanism of this difference has not been fully studied, as preclinical studies have traditionally excluded female rodents. Recently, this oversight has begun to be resolved and studies including male and female rodents are revealing sex differences in the neurobiological processes behind mental disorder features. This paper reviews the structural functions involved in the injury perception circuit and advanced emotional cortex circuit. In addition, we also summarize the latest breakthroughs and insights into sex differences in neuromodulation through endogenous dopamine, 5-hydroxytryptamine, GABAergic inhibition, norepinephrine, and peptide pathways like oxytocin, as well as their receptors. By comparing sex differences, we hope to identify new therapeutic targets to offer safer and more effective treatments. [ABSTRACT FROM AUTHOR]

Being a natural active substance with a wide variety of sources, easy access, significant curative effect, and high safety, active peptides have gradually become one of the new research directions in food, medicine, agriculture, and other fields in recent years. The technology associated with active peptides is constantly evolving. There are obvious difficulties in the preservation, delivery, and slow release of exposed peptides. Microencapsulation technology can effectively solve these difficulties and improve the utilization rate of active peptides. In this paper, the commonly used materials for embedding active peptides (natural polymer materials, modified polymer materials, and synthetic polymer materials) and embedding technologies are reviewed, with emphasis on four new technologies (microfluidics, microjets, layer-by-layer self-assembly, and yeast cells). Compared with natural materials, modified materials and synthetic polymer materials show higher embedding rates and mechanical strength. The new technology improves the preparation efficiency and embedding rate of microencapsulated peptides and makes the microencapsulated particle size tend to be controllable. In addition, the current application of peptide microcapsules in different fields was also introduced. Selecting active peptides with different functions, using appropriate materials and efficient preparation technology to achieve targeted delivery and slow release of active peptides in the application system, will become the focus of future research. [ABSTRACT FROM AUTHOR]

Copyright of Feed Research is the property of Editorial Board of Feed Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Synaptic dysfunction caused by soluble β‐amyloid peptide (Aβ) is a hallmark of early‐stage Alzheimer's disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP‐responsive element‐binding protein (CREB), a master regulator of cell survival and plasticity‐related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking of Jacob, a protein that connects a NMDA‐receptor‐derived signalosome to CREB, in AD patient brains and mouse hippocampal neurons. Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of CREB leading to impairment and loss of synapses in mouse models of AD. The small chemical compound Nitarsone selectively hinders the assembly of a Jacob/LIM‐only 4 (LMO4)/ Protein phosphatase 1 (PP1) signalosome and thereby restores CREB transcriptional activity. Nitarsone prevents impairment of synaptic plasticity as well as cognitive decline in mouse models of AD. Collectively, the data suggest targeting Jacob protein‐induced CREB shutoff as a therapeutic avenue against early synaptic dysfunction in AD. Synopsis: The synapto‐nuclear shuttling protein Jacob assembles and docks a signalosome to the transcriptional regulator CREB to promote CREB de‐phosphorylation and neuronal cell death. Here, β‐amyloid peptide (Aβ) is found to cause Alzheimer‐associated synapse loss by regulating nuclear translocation of Jacob, providing a potential target for therapeutic intervention. Aβ promotes nuclear translocation of Jacob in Alzheimer's disease (AD) patient brains and mouse hippocampal neurons.Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of cAMP‐responsive element‐binding protein (CREB), leading to synapse impairment and loss in an AD mouse model.The small‐molecular compound Nitarsone selectively prevents the assembly of the Jacob/LMO4/PP1 signalosome to promote CREB transcriptional activity.Nitarsone prevents synaptic plasticity impairment and cognitive decline in mouse models of AD. [ABSTRACT FROM AUTHOR]

Almost 65% of the human protein supply in the world originates from plants, with legumes being one of the highest contributors, comprising between 20 and 40% of the protein supply. Bioactive peptides from various food sources including legumes have been reported to show efficacy in modulating starch digestion and glucose absorption. This paper will provide a comprehensive review on recent in vitro studies that have been performed on leguminous antidiabetic peptides, focusing on the α-amylase inhibitor, α-glucosidase inhibitor, and dipeptidyl peptidase-IV (DPP-IV) inhibitor. Variations in legume cultivars and methods affect the release of peptides. Different methods have been used, such as in sample preparation, including fermentation (t, T), germination (t), and pre-cooking; in protein extraction, alkaline extraction, isoelectric precipitation, phosphate buffer extraction, and water extraction; in protein hydrolysis enzyme types and combination, enzyme substrate ratio, pH, and time; and in enzyme inhibitory assays, positive control type and concentration, inhibitor or peptide concentration, and the unit of inhibitory activity. The categorization of the relative scale of inhibitory activities among legume samples becomes difficult because of these method differences. Peptide sequences in samples were identified by means of HPLC/MS. Software and online tools were used in bioactivity prediction and computational modelling. The identification of the types and locations of chemical interactions between the inhibitor peptides and enzymes and the type of enzyme inhibition were achieved through computational modelling and enzyme kinetic studies. [ABSTRACT FROM AUTHOR]

Hydrophobicity is an important physicochemical property of peptides in solution. As well as being strongly associated with peptide stability and aggregation, hydrophobicity governs the solution based chromatographic separation processes, specifically reversed-phase liquid chromatography (RPLC). In addition, hydrophobicity is a major physicochemical property of peptides in comparison to H-bonding, electrostatic, and aromatic properties in intermolecular interactions. However, a wide range of molecular factors can influence peptide hydrophobicity, with accurate predictions depending on specific peptide amino acid compositions, structure, and conformation. It is noticeable that peptide composition, the position of the amino acid, and its neighbouring groups play a crucial role in the elution process. In light of this, the same amino acid behaved differently depending on its position and neighbouring amino acid in the peptide chain. Extra attention should be paid to the denaturation process during the course of elution, as it has been shown to complicate and alter the elution pattern. This paper reports on the key peptide properties that can alter hydrophobicity and, consequently, the RPLC elution behaviour of the peptides, and it will conclude by proposing improved prediction algorithms for peptide elution in RPLC. [ABSTRACT FROM AUTHOR]

This paper presents an investigation of liposome deformation and shape distortion using four membrane-binding peptides: TAT and C105Y as cell-penetrating peptides (CPPs), and melittin and ovispirin as antimicrobial peptides (AMPs). Liposome deformation was monitored utilizing fluorescent microscopy, while the binding of peptides to the DOPC membrane was estimated through capacitance measurements. The degree of liposome deformation and shape distortion was found to be higher for the CPPs compared to the AMPs. Additionally, it was observed that C105Y did not induce liposome rupture, unlike the other three peptides. We propose that these variations in liposome distortion may be attributed to differences in secondary structure, specifically the presence of an α-helix or random coil. Our studies offer insight into the use of peptides to elicit control of liposome architecture and may offer a promising approach for regulating the bodies of liposomal molecular robots. [ABSTRACT FROM AUTHOR]

In recent years, self-assembled peptide nanotechnology has attracted a great deal of attention for its ability to form various regular and ordered structures with diverse and practical functions. Self-assembled peptides can exist in different environments and are a kind of medical bio-regenerative material with unique structures. These materials have good biocompatibility and controllability and can form nanoparticles, nanofibers and hydrogels to perform specific morphological functions, which are widely used in biomedical and material science fields. In this paper, the properties of self-assembled peptides, their influencing factors and the nanostructures that they form are reviewed, and the applications of self-assembled peptides as drug carriers are highlighted. Finally, the prospects and challenges for developing self-assembled peptide nanomaterials are briefly discussed. [ABSTRACT FROM AUTHOR]

Infectious diseases caused by microbial pathogens (bacteria, virus, fungi, parasites) claim millions of deaths per year worldwide and have become a serious challenge to global human health in our century. Viral infections are particularly notable in this regard, not only because humankind is facing some of the deadliest viral pandemics in recent history, but also because the arsenal of drugs to combat the high levels of mutation, and hence the antigenic variability of (mostly RNA) viruses, is disturbingly scarce. Therefore, the search for new antivirals able to successfully fight infection with minimal or no adverse effects on the host is a pressing task. Traditionally, antiviral therapies have relied on relatively small-sized drugs acting as proteases, polymerases, integrase inhibitors, etc. In recent decades, novel approaches involving targeted delivery such as that achieved by peptide–drug conjugates (PDCs) have gained attention as alternative (pro)drugs for tackling viral diseases. Antiviral PDC therapeutics typically involve one or more small drug molecules conjugated to a cell-penetrating peptide (CPP) carrier either directly or through a linker. Such integration of two bioactive elements into a single molecular entity is primarily aimed at achieving improved bioavailability in conditions where conventional drugs are challenged, but may also turn up novel unexpected functionalities and applications. Advances in peptide medicinal chemistry have eased the way to antiviral PDCs, but challenges remain on the way to therapeutic success. In this paper, we review current antiviral CPP–drug conjugates (antiviral PDCs), with emphasis on the types of CPP and antiviral cargo. We integrate the conjugate and the chemical approaches most often applied to combine both entities. Additionally, we comment on various obstacles faced in the design of antiviral PDCs and on the future outlooks for this class of antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Different attempts have been made in the past two decades to develop radiolabeled peptide conjugates with enhanced pharmacokinetic properties in order to improve the application for tumor imaging and peptide receptor radionuclide therapy (PRRT), which targets the cholecystokinin-2 receptor (CCK2R). In this paper, the influence of different side chain and peptide bond modifications has been explored for the minigastrin analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH2 (DOTA-MGS5). Based on this lead structure, five new derivatives were synthesized for radiolabeling with trivalent radiometals. Different chemical and biological properties of the new derivatives were analyzed. Receptor interaction of the peptide derivatives and cell internalization of the radiolabeled peptides were studied in A431-CCK2R cells. The stability of the radiolabeled peptides in vivo was investigated using BALB/c mice. Tumor targeting of all 111In-labeled peptide conjugates, and of a selected compound radiolabeled with gallium-68 and lutetium-177, was evaluated in BALB/c nude mice xenografted with A431-CCK2R and A431-mock cells. All 111In-labeled conjugates, except [111In]In-DOTA-[Phe8]MGS5, showed a high resistance against enzymatic degradation. A high receptor affinity with IC50 values in the low nanomolar range was confirmed for most of the peptide derivatives. The specific cell internalization over time was 35.3–47.3% for all radiopeptides 4 h after incubation. Only [111In]In-DOTA-MGS5[NHCH3] exhibited a lower cell internalization of 6.6 ± 2.8%. An overall improved resistance against enzymatic degradation was confirmed in vivo. Of the radiopeptides studied, [111In]In-DOTA-[(N-Me)1Nal8]MGS5 showed the most promising targeting properties, with significantly increased accumulation of radioactivity in A431-CCK2R xenografts (48.1 ± 9.2% IA/g) and reduced accumulation of radioactivity in stomach (4.2 ± 0.5% IA/g). However, in comparison with DOTA-MGS5, a higher influence on the targeting properties was observed for the change of radiometal, resulting in a tumor uptake of 15.67 ± 2.21% IA/g for [68Ga]Ga-DOTA-[(N-Me)1Nal8]MGS5 and 35.13 ± 6.32% IA/g for [177Lu]Lu-DOTA-[(N-Me)1Nal8]MGS5. [ABSTRACT FROM AUTHOR]

About ten years ago, Wenhui Li's research group in China identified the sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter predominantly expressed in the liver, as a functional receptor for hepatitis B virus (HBV) and its satellite hepatitis delta virus (HDV) through biochemical and genetic studies. This finding unraveled a longtime mystery in the HBV field and led to the establishment of efficient and easy-to-use HBV infection models, which paved the way for the in-depth study of the HBV entry mechanism and facilitated the development of therapeutics against HBV and HDV. The whole picture of the complex HBV entry process became clear upon the follow-up studies over the years, including the recent resolution found for the NTCP structure. As one of the first authors of the 2012 eLife paper on NTCP identification, here, I (H. Y.) share our experience on the bumpy and exciting journey of receptor hunting, particularly on the photo-cross-linking study and some detailed descriptions of the "fishing" process and summarize the key factors for our successful receptor identification. This review may also provide helpful insights for identifying a protein target by peptide or protein baits through cross-linking and immunoprecipitation. [ABSTRACT FROM AUTHOR]

Proteolytic enzymes are one of the important biomarkers that enable the early diagnosis of several diseases, such as cancers. A specific proteolytic enzyme selectively degrades a certain sequence of a polypeptide. Therefore, a particular proteolytic enzyme can be selectively quantified by changing detectable signals causing degradation of the peptide chain. In addition, by combining polypeptides with various functional nanomaterials, proteolytic enzymes can be measured more sensitively and rapidly. In this paper, proteolytic enzymes that can be measured using a polypeptide degradation method are reviewed and recently studied functional nanomaterials-based proteolytic biosensors are discussed. We anticipate that the proteolytic nanobiosensors addressed in this review will provide valuable information on physiological changes from a cellular level for individual and early diagnosis. [ABSTRACT FROM AUTHOR]

Amyloid aggregates play a major role in diseases as well as in normal physiological function. Receptor-interacting protein kinases 1 and 3 (RIP1/RIP3) aggregates complexes in cellular necroptosis is one example of protein aggregation in normal cellular function. Although recently there have been several studies on full kinase proteins aggregation, the aggregation potential of small peptide sequences of RIP1/RIP3, the physicochemical properties, and the potential in biomedical applications have not been explored. Hence, in this paper, we study the aggregation propensity of peptides consisting of four and twelve amino acid sequences in the RHIM region of RIP1/RIP3 proteins that are known to drive the beta-sheet formation and the subsequent aggregation. The aggregation kinetics, physicochemical characterization, mechanosensitive properties, cellular effects, and potential as a cancer drug depot have been investigated. The results show that the number and concentration of amino acids play a role in amyloid-like aggregates' properties. Further, the aggregates when formulated with cisplatin-induced significant lung cancer cell toxicity compared to an equal amount of cisplatin with and without ultrasound. The study would serve as a platform for further investigation on RIP1/RIP3 peptide and protein aggregates, their role in multiple cellular functions and diseases, and their potential as drug depots. [ABSTRACT FROM AUTHOR]

The α-kinase, eEF2K, phosphorylates the threonine 56 residue of eEF2 to inhibit global peptide elongation (protein translation). As a master regulator of protein synthesis, in combination with its unique atypical kinase active site, investigations into the targeting of eEF2K represents a case of intense structure-based drug design that includes the use of modern computational techniques. The role of eEF2K is incredibly diverse and has been scrutinized in several different diseases including cancer and neurological disorders—with numerous studies inhibiting eEF2K as a potential treatment option, as described in this paper. Using available crystal structures of related α-kinases, particularly MHCKA, we report how homology modeling has been used to improve inhibitor design and efficacy. This review presents an overview of eEF2K related drug discovery efforts predating from the 1990's, to more recent in vivo studies in rat models. We also provide the reader with a basic introduction to several approaches and software programs used to undertake such drug discovery campaigns. With the recent exciting publication of an eEF2K crystal structure, we present our view regarding the future of eEF2K drug discovery. [ABSTRACT FROM AUTHOR]

Currently, it remains unclear which specific peptides could be appropriate for applications in different fields of dentistry. The aim of this scoping review was to scan the contemporary scientific papers related to the types, uses and applications of peptides in dentistry at the moment. Literature database searches were performed in the following databases: PubMed/MEDLINE, Scopus, Web of Science, Embase, and Scielo. A total of 133 articles involving the use of peptides in dentistry-related applications were included. The studies involved experimental designs in animals, microorganisms, or cells; clinical trials were also identified within this review. Most of the applications of peptides included caries management, implant osseointegration, guided tissue regeneration, vital pulp therapy, antimicrobial activity, enamel remineralization, periodontal therapy, the surface modification of tooth implants, and the modification of other restorative materials such as dental adhesives and denture base resins. The in vitro and in vivo studies included in this review suggested that peptides may have beneficial effects for treating early carious lesions, promoting cell adhesion, enhancing the adhesion strength of dental implants, and in tissue engineering as healthy promotors of the periodontium and antimicrobial agents. The lack of clinical trials should be highlighted, leaving a wide space available for the investigation of peptides in dentistry. [ABSTRACT FROM AUTHOR]

Auxin efflux through plasma-membrane-integral PIN-FORMED (PIN) carriers is essential for plant tissue organization and tightly regulated. For instance, a molecular rheostat critically controls PIN-mediated auxin transport in developing protophloem sieve elements of Arabidopsis roots. Plasma-membrane-association of the rheostat proteins, BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX), is reinforced by interaction with PHOSPHATIDYLINOSITOL-4-PHOSPHATE-5-KINASE (PIP5K). Genetic evidence suggests that BRX dampens autocrine signaling of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 45 (CLE45) peptide via its receptor BARELY ANY MERISTEM 3 (BAM3). How excess CLE45-BAM3 signaling interferes with protophloem development and whether it does so directly or indirectly remains unclear. Here we show that rheostat polarity is independent of PIN polarity, but interdependent with PIP5K. Catalytically inactive PIP5K confers rheostat polarity without reinforcing its localization, revealing a possible PIP5K scaffolding function. Moreover, PIP5K and PAX cooperatively control local PIN abundance. We further find that CLE45-BAM3 signaling branches via RLCK-VII/PBS1-LIKE (PBL) cytoplasmic kinases to destabilize rheostat localization. Our data thus reveal antagonism between CLE45-BAM3-PBL signaling and PIP5K that converges on auxin efflux regulation through dynamic control of PAX polarity. Because second-site bam3 mutation suppresses root as well as shoot phenotypes of pip5k mutants, CLE peptide signaling likely modulates phosphoinositide-dependent processes in various developmental contexts. In this paper the authors demonstrate that auxin efflux in the phloem vascular tissue of plants is determined by antagonism between CLE peptide signaling pathways and phosphoinositide kinases. [ABSTRACT FROM AUTHOR]

In this paper we study two lysine-based peptide dendrimers with Lys-His-Arg and Lys-Arg-His repeating units and terminal lysine groups. Combination of His and Arg properties in a dendrimer could be important for biomedical applications, especially for prevention of dendrimer aggregation and for penetration of dendrimers through various cell membranes. We describe the synthesis of these dendrimers and the confirmation of their structure using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. NMR spectroscopy and relaxation are used to study the structural and dynamic properties of these macromolecules and to compare them with properties of previously studied dendrimers with Lys-2Arg and Lys-2His repeating units. Our results demonstrate that both Lys-His-Arg and Lys-Arg-His dendrimers have pH sensitive conformation and dynamics. However, properties of Lys-His-Arg at normal pH are more similar to those of the more hydrophobic Lys-2His dendrimer, which has tendency towards aggregation, while the Lys-Arg-His dendrimer is more hydrophilic. Thus, the conformation with the same amino acid composition of Lys-His-Arg is more pH sensitive than Lys-Arg-His, while the presence of Arg groups undoubtedly increases its hydrophilicity compared to Lys-2His. Hence, the Lys-His-Arg dendrimer could be a more suitable (in comparison with Lys-2His and Lys-Arg-His) candidate as a pH sensitive nanocontainer for drug delivery. [ABSTRACT FROM AUTHOR]

Research on food-derived bioactive peptides is expanding and the need for a convenient online platform that combines a foolproof and intuitive user interface with a reliable database and tools for prediction and analysis is rising. In this regard, this paper presents an open-access web-based platform PepLab (Peptides Laboratory). The database contains 2764 peptide sequence entries, grouped into sixteen classes according to their biological activity and into seven classes according to the source from which they were derived. Moreover, it includes bioinformatic tools for their processing and analysis. The DMpep tool allows extracting information about a number of physicochemical characteristics of a peptide or a set of peptides, including those that are not recorded in the database. The main advantages of PepLab are a user-friendly interface, a responsive design, and optimized search engines for better visibility on the Internet. Prediction of non-reported activity is available based on amino acid sequence analysis. In addition, users can download data and results in a convenient format (text and/or graphic) that was limited in the existing platforms. In this way, the presented PepLab platform will be helpful for researchers from various fields—bioinformatics, pharmaceuticals, food sciences, dietetics, biotechnology, analytical chemistry, etc. [ABSTRACT FROM AUTHOR]

Spoilage bacteria play a remarkable role in the spoilage of chilled chicken. In this paper, a total of 42 isolates belonging to 16 species of four genera were isolated from chilled chicken and displayed different characterizations of psychrotrophic spoilage. Six isolates of J7, J8, Q20, Q23, R1, and R9 with differences in proteolytic capabilities were further characterized for in situ spoilage potential evaluation. Pseudomonas lundensis J8 exhibited the strongest spoilage potential in situ, displaying a fast growth rate, increased pH velocity, high total volatile basic nitrogen, and high peptide content in the chicken samples. The volatile flavor analysis of chicken samples via electronic nose indicated that the content of characteristic odors representing spoilage, including sulfides, organic sulfide, and hydride, increased during storage. Additionally, the principle component and correlation analyses revealed that the spoilage odors produced by different species of bacteria were significantly different and positively correlated with the results of protease activity in vitro. The characteristics of spoilage bacteria in chilled chicken provided a comprehensive insight into microbial assessment during storage. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Biochemistry is the property of Society of Medical Biochemists of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Bioinformatics is the property of Bioinformatics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper aims to examine the value of different biochemical markers in predicting the outcome of COVID-19 infection. A total of 140 patients with confirmed COVID-19 infection by polymerase chain reaction (PCR), different biochemical markers were tested, their relation to the outcome of the disease was monitored, and the most reliable tests were determined. The study found a significant correlation between all evaluated biochemical markers and severity of the disease, including C-reactive protein (CRP), D-dimer, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), prothrombin time (PT), activated partial thromboplastin time (aPTT). In addition, ferritin, lactate dehydrogenase (LDH), procalcitonin (PCT) and Pro-Brain natriuretic peptide (proBNP) demonstrated highly sensitivity and specificity as well as significant prognostic performance. These markers were also independently significant in predicting mortality. Early assessment of biochemical markers in patients with COVID-19 can help clinicians in tailoring treatment and providing more intensive care to those with greater mortality risk. In particular, the assessment of ferritin, LDH, procalcitonin and proBNP can independently predict mortality. [ABSTRACT FROM AUTHOR]

Cancer is one of the main diseases threatening human life, accounting for millions of deaths around the world each year. Traditional physical and chemical methods for cancer treatment are extremely time-consuming, lab-intensive, expensive, inefficient and difficult to be applied in a high-throughput way. Hence, it is an urgent task to develop automated computational methods to enable fast and accurate identification of anticancer peptides (ACPs). In this paper, we develop a novel model named iACP-GE to identify ACPs. Multi-features are extracted by using binary encoding, enhanced grouped amino acid composition and BLOSUM62 encoding based on the N5C5 sequence, as well as detrended forward moving-average auto-cross correlation analysis based on physicochemical properties of 20 natural amino acids. Thus, 835 features are obtained for each sample, in order to avoid information redundancy, gradient boosting decision tree was adopted as the feature selection strategy. Then, the optimal feature subset is input to the extra tree classifier. The accuracies of ACP740 and ACP240 datasets with the 5-fold cross-validation were 90.54% and 91.25%, respectively. Experimental results indicate that iACP-GE significantly outperforms several existing models on ACP740 and ACP240 datasets and can be used as an effective tool for the identification of ACPs. The datasets and source codes for iACP-GE are available at . [ABSTRACT FROM AUTHOR]

The transformation of yellow nutsedges into nutritional flour and snack food could be important for expanding consumption and enriching the variety of products. This paper used peeled yellow nutsedges as raw materials to explore the effect of roasting on antioxidant capacity, active ingredients, and aroma. The results showed that the antioxidant capacity, DPPH (2,2-Diphenyl−1-picrylhydrazyl) free radical scavenging rate and ABTS+ (2,2'-azinobis-(3-ethylbenzothiazoline−6-sulfonate)) scavenging rate were significantly improved after baking compared with the control, but the hydroxyl-free radical scavenging rate was not obvious. A total of 6 kinds antimicrobial peptides with high scores were detected, including 2 kinds in the roasted group and four kinds in the control group. ACE (angiotensin converting enzyme) inhibitors, dipeptidyl peptidase IV inhibitors, antimicrobial peptides, antioxidant peptides and blood–brain barrier peptides were changed by roasted treatment. The processing can enhance the kinds of esters from 4 to 8 compared with non-roasted group. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Tea Science is the property of Journal of Tea Science Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Obtaining compounds with specificity for certain isoforms of ion channels is a significant problem of curent physiology and pharmacology. In a series of papers, we have shown that the α-hairpinin fold can serve as a template for the rational design of peptide ligands of potassium channels. Here, we used molecular modeling to optimize the structure of the previously obtained Tk-hefu-10 peptide, a selective KV1.3 channel blocker, with a half-maximal inhibitory concentration (IC50) of ≈150 nM. Molecular dynamics simulation of the Tk-hefu-10–KV1.3 complex provided information on the interaction of individual amino acid residues of the peptide and channel, and the analysis of these interactions made it possible to propose amino acid substitutions in the structure of Tk-hefu-10 to increase its affinity. Novel Tk-hefu-12 peptide is a truncated analog of Tk-hefu-10 by one residue with five substitutions; it is characterized by an IC50 value of ≈70 nM against KV1.3. In addition, there are no methionine residues in the structure of Tk-hefu-12, which makes it possible to obtain Tk-hefu peptides using cyanogen bromide. [ABSTRACT FROM AUTHOR]

Anticancer peptides (ACPs) are the types of peptides that have been demonstrated to have anticancer activities. Using ACPs to prevent cancer could be a viable alternative to conventional cancer treatments because they are safer and display higher selectivity. Due to ACP identification being highly lab-limited, expensive and lengthy, a computational method is proposed to predict ACPs from sequence information in this study. The process includes the input of the peptide sequences, feature extraction in terms of ordinal encoding with positional information and handcrafted features, and finally feature selection. The whole model comprises of two modules, including deep learning and machine learning algorithms. The deep learning module contained two channels: bidirectional long short-term memory (BiLSTM) and convolutional neural network (CNN). Light Gradient Boosting Machine (LightGBM) was used in the machine learning module. Finally, this study voted the three models' classification results for the three paths resulting in the model ensemble layer. This study provides insights into ACP prediction utilizing a novel method and presented a promising performance. It used a benchmark dataset for further exploration and improvement compared with previous studies. Our final model has an accuracy of 0.7895, sensitivity of 0.8153 and specificity of 0.7676, and it was increased by at least 2% compared with the state-of-the-art studies in all metrics. Hence, this paper presents a novel method that can potentially predict ACPs more effectively and efficiently. The work and source codes are made available to the community of researchers and developers at https://github.com/khanhlee/acp-ope/. [ABSTRACT FROM AUTHOR]

Phosphorylation of beta-amyloid peptide (Aβ) at the Ser8 residue affects its neurotoxicity, metal-dependent oligomerisation, amyloidogenicity, and other pathogenic properties. Phosphorylated Aβ (pS8-Aβ) was detected in vivo in AD model mice and in the brains of patients with AD. However, the pS8-Aβ production and the regulation of its levels have not been previously studied in detail. In this paper, immunochemical methods together with radioactive labelling were used to study the Aβ phosphorylation by intracellular and surface protein kinases of HEK293 cells and brain endothelial cells (bEnd.3). It was found that HEK293 robustly phosphorylated Aβ, likely with contribution from casein kinase 2 (CK2), whereas in bEnd.3, the activity of Aβ phosphorylation was relatively low. Further, the study showed that both HEK293 and bEnd.3 could dephosphorylate pS8-Aβ, mainly due to the activity of protein phosphatases PP1 and PP2A. The Aβ dephosphorylation efficiency in bEnd.3 was three times higher than in HEK293, which correlated with the reduced abundance of pS8-Aβ in vascular amyloid deposits of patients with AD compared to senile plaques. These data suggest an important role of CK2, PP1, and PP2A as regulators of Aβ phosphorylation, and point to the involvement of the blood–brain barrier in the control of Aβ modification levels. [ABSTRACT FROM AUTHOR]