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We developed a simple, paper‐based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter‐balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part‐per‐trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On‐paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases. [ABSTRACT FROM AUTHOR]

We developed a simple, paper‐based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter‐balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part‐per‐trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On‐paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases. [ABSTRACT FROM AUTHOR]

Biased and accelerated molecular simulations (BAMS) are widely used tools to observe relevant molecular phenomena occurring on time scales inaccessible to standard molecular dynamics, but evaluation of the physical time scales involved in the processes is not directly possible from them. For this reason, the problem of recovering dynamics from such kinds of simulations is the object of very active research due to the relevant theoretical and practical implications of dynamics on the properties of both natural and synthetic molecular systems. In a recent paper [A. Rapallo et al., J. Comput. Chem. 42, 586–599 (2021)], it has been shown how the coupling of BAMS (which destroys the dynamics but allows to calculate average properties) with Extended Diffusion Theory (EDT) (which requires input appropriate equilibrium averages calculated over the BAMS trajectories) allows to effectively use the Smoluchowski equation to calculate the orientational time correlation function of the head–tail unit vector defined over a peptide in water solution. Orientational relaxation of this vector is the result of the coupling of internal molecular motions with overall molecular rotation, and it was very well described by correlation functions expressed in terms of weighted sums of suitable time-exponentially decaying functions, in agreement with a Brownian diffusive regime. However, situations occur where exponentially decaying functions are no longer appropriate to capture the actual dynamical behavior, which exhibits persistent long time correlations, compatible with the so called subdiffusive regimes. In this paper, a generalization of EDT will be given, exploiting a fractional Smoluchowski equation (FEDT) to capture the non-exponential character observed in the relaxation of intramolecular distances and molecular radius of gyration, whose dynamics depend on internal molecular motions only. The calculation methods, proper to EDT, are adapted to implement the generalization of the theory, and the resulting algorithm confirms FEDT as a tool of practical value in recovering dynamics from BAMS, to be used in general situations, involving both regular and anomalous diffusion regimes. [ABSTRACT FROM AUTHOR]

With the vigorous development of the petroleum industry, improving the efficiency of oil and gas exploitation has become an important issue. Temperature-sensitive materials show great potential for application in the development and production of oil and gas fields due to their unique temperature-responsive properties. This paper reviews the application of temperature-sensitive materials in oil and gas drilling and introduces the characteristics of three types of temperature-sensitive materials: N-substituted acrylamide polymers, amphiphilic block copolymers, and peptides. Because these materials can change their physical state at specific temperatures, this paper discusses in detail the role of various temperature-sensitive materials as plugging agent, thickener, oil displacing agent, flocculant, and tackifier in oil and gas field operations, as well as the mechanism of action and performance of temperature-sensitive materials in practical oil and gas drilling operations. As we have not yet seen relevant similar literature, this paper aims to discuss the innovative application of temperature-sensitive materials in the oil and gas drilling process, and at the same time points out the problems in the current research and applications as well as future development directions. Through analysis and comparison, we provide an efficient and environmentally friendly materials selection option for the petroleum industry in order to promote the progress and sustainable development of oil and gas extraction processes. [ABSTRACT FROM AUTHOR]

A single amino acid in a peptide sequence can play an important role to tune the self‐assembly and hydrogelation behaviour. Here, a C‐terminal cysteine‐containing ultrashort peptide hydrogelator forms hydrogel through non‐covalent and covalent interactions. Interestingly, the hydrogel is insoluble in water and buffer solutions at different pH values (1‐13) and is thixotropic and injectable. In recent years, removing dyes from contaminated water has become a significant concern because of the shortage of freshwater resources. Therefore, the adsorption of dyes through a reliable, straightforward, nontoxic, cheap, and environmentally friendly adsorbent has become a popular topic. Hence, the hydrogelator was exploited to remove organic dyes from wastewater, harnessing its applicability in the gel phase and solid supports (filter paper and cotton). [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel dual-functional probe FAHK was design and synthesized based on copper peptide backbone. • FAHK showed sequential response towards Cu2+/Hg2+ and S2− via fluorescent and colorimetric methods. • The detection limit of 37.1 nM for Cu2+, 20.8 nM for Hg2+ and 0.27 μM/0.12 μM for S2−, respectively. • FAHK has low toxicity and was successfully used to image Cu2+, Hg2+ and S2− in living cells. • Test strips of FAHK were prepared for rapid and visual detection for Cu2+, Hg2+ and S2− with naked eye. In this study, a novel peptide-based fluorescent and colorimetric dual-functional probe (FAHK) was designed and synthesized by simulating the structure of copper peptide. FAHK exhibited high selectivity and rapid response to Cu2+ and Hg2+ with two non-fluorescence ensembles FAHK- Cu2+ and FAHK- Hg2+ formation by the 2:1 coordination mode, and the limits of detection for Cu2+ and Hg2+ were 37.1 nM and 20.8 nM, respectively. FAHK showed a naked eye colorimetric response for Cu2+ and Hg2+ in an aqueous solutions under visible light. As two new promising cascade probes, FAHK- Cu2+ and FAHK- Hg2+ ensemble were used for sequential selective recognition of S2− according to the displacement approach with fluorescence "turn-on" response and colorimetric change, and the limit of detection were 0.27 μM (FAHK -Cu2+ ensemble) and 0.12 μM (FAHK -Hg2+ ensemble) for S2−, which were well below the safety level the H 2 S standard in drinking waters (14.8 µM, WHO guidelines). What' more, in view of low toxicity and biocompatibility, the potential application of FAHK in biological systems was demonstrated via living cells imaging. More importantly, FAHK could also be made into the paper test strips for visual detection of Cu2+, Hg2+ and S2− with the naked eye under 365 nm UV light and visible light, which suggested that better portability and operation simplicity that is favourable for on-site analysis. [ABSTRACT FROM AUTHOR]

The process of oxidation is believed to be mainly responsible for different chronic diseases and the deterioration of food by reducing shelf life. Antioxidants are known to scavenge various free radicals like hydroxyl radicals, and peroxyl radicals, and also inhibit lipid peroxidation. An increasing number of peptides and hydrolysates possessing antioxidant capacity have been characterized by soybean and other soy-based products. Due to their high protein content, soybeans, and other soy products are considered to be a great source for generating antioxidative peptides using enzymatic hydrolysis or microbial fermentation. This paper focuses on the recent advances in soy-derived antioxidative peptides, especially the methods for producing the peptides, evaluating the antioxidant capacity in vitro and in vivo, and purifying and identifying the most active peptide fraction and the factors influencing their antioxidant activity. • Soybean and soy-based products hold significant potential as rich sources of antioxidative peptides. • This paper provides a comprehensive summary of bioactive peptides, with a particular focus on those derived from soybean. • The review explores the structure-activity relationship of soybean peptides, shedding light on their functional properties. • Further research is necessary to explore and optimize the utilization of these bioactive peptides for various applications. [ABSTRACT FROM AUTHOR]

A relaxin‐like gonad‐stimulating peptide (RGP), Aso‐RGP, featuring six cysteine residues, was identified in the Crown‐of‐Thorns Starfish (COTS, Acanthaster cf. solaris) and initially produced through recombinant yeast expression. This method yielded a single‐chain peptide with an uncleaved C‐peptide (His Tag) and suboptimal purity. Our objective was to chemically synthesize Aso‐RGP in its mature form, comprising two chains (A and B) and three disulfide bridges, omitting the C‐peptide. Furthermore, we aimed to synthesize a newly identified relaxin‐like peptide, Aso‐RLP2, from COTS, which had not been previously synthesized. This paper reports the first total chemical synthesis of Aso‐RGP and Aso‐RLP2. Aso‐RGP synthesis proceeded without major issues, whereas the A‐chain of Aso‐RLP2, in its reduced and unfolded state with two free thiols, presented considerable challenges. These were initially marked by "messy" RP‐HPLC profiles, typically indicative of synthesis failure. Surprisingly, oxidizing the A‐chain significantly improved the RP‐HPLC profile, revealing the main issue was not synthesis failure but the peptide's aggregation tendency, which initially obscured analysis. This discovery highlights the critical need to account for aggregation in peptide synthesis and analysis. Ultimately, our efforts led to the successful synthesis of both peptides with purities exceeding 95 %. [ABSTRACT FROM AUTHOR]

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their conformational rigidity improves proteolytic stability and leads to rapid penetration into tissues via any possible route of administration. Moreover, elimination of renal metabolism is of great importance, for example, for people with a history of liver diseases. In addition, each ring can function independently, making bicyclic peptides extremely versatile molecules for further optimization. In this paper, we compared the potentiometric and spectroscopic properties studied by UV–vis, MCD, and EPR of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH) (BCL). In particular, we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL1 (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position, i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position, i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively; and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2). Potentiometric results have shown that the bicyclic structure promotes the involvement of the side chain imidazole donors in Cu(II) binding. On the other hand, the results obtained for the mono-cyclic analogues lead to the conclusion that the coordination of the histidine moiety as an anchoring group is promoted by its location in the peptide sequence further from the nonbinding cycle, strongly influencing the involvement of the amide donors in Cu(II) coordination. [ABSTRACT FROM AUTHOR]

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer Metastasis has been mostly misunderstood and underestimated by the general public regarding cancer deaths. The aims and objectives of the present report was to more fully describe the scientific activities and components that are involved in the malignant cell's fulfillment of the metastatic process and to impress the readership that metastasis is the major cause on all cancer deaths. The paper proceeds to enumerate and describe certain factors that contribute to cancer cell proliferation and subsequent metastasis such as; (a) calcium levels, (b) multiple cell membrane channels, and (c) the chemokine/receptor system. These latter components could serve to provide ideal molecular targets for possible future peptide therapeutic applications in treating cancer patients. Metastasis (Met) largely contributes to the major cause of cancer deaths throughout the world, rather than the growth of the tumor mass itself. The present report brings together several of the pertinent contributors to cancer growth and metastatic processes from an activity standpoint. Such biological activities include the following: (1) cell adherence and detachment; (2) cell-to-cell contact; (3) contact inhibition; (4) the cell interfacing with the extracellular matrix (ECM); (5) tumor cell-to-stroma communication networks; (6) chemotaxis; and (7) cell membrane potential. Moreover, additional biochemical factors that contribute to cancer growth and metastasis have been shown to comprise the following: (a) calcium levels in the extracellular matrix and in intracellular compartments; (b) cation voltage and ATP-regulated potassium channels; (c) selective and non-selective cation channels; and (d) chemokines (cytokines) and their receptors, such as CXCL12 (SDF-1) and its receptor/binding partner, CXCR4. These latter molecular components represent a promising group of an interacting and synchronized set of candidates ideal for peptide therapeutic targeting for cancer growth and metastasis. Such peptides can be obtained from naturally occurring proteins such as alpha-fetoprotein (AFP), an onco-fetal protein and clinical biomarker. [ABSTRACT FROM AUTHOR]

Background: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. Methods: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. Results: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4–16; after 12 months: 1, interquartile range: 0–3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16–30; after 12 months: 5, interquartile range: 4–7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. Conclusion: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache. [ABSTRACT FROM AUTHOR]

INTRODUCTION: One of the main allergens in soybeans is glycinin, which seriously impacts the normal lives of allergic people. Previous studies have confirmed that thermal processing and thermal processing combined with ultrahigh‐pressure processing could significantly reduce the antigenicity of glycinin. The dominant antigen region of acidic peptide chain A2 of G2 subunit was located by phage display experiment. METHODS: In this paper, overlapping peptides and alanine substitution techniques were used to explore the key amino acids that significantly affect the antigenicity of A2 peptide chain. The purity of peptide 1, peptide 2 and peptide 3 was identified by mass spectrometry and high‐performance liquid chromatography, and the results showed that the purity of the synthesized overlapping peptide was more than 90%. SDS‐PAGE showed that the peptide was successfully coupled with bovine serum albumin. The antigenicity of the coupling peptide was tested by ELISA and Dot‐Blot, and the allergenicity was detected by reacting with the serum of patients with soybean globulin allergy. CONCLUSION: The results showed that peptide 3 has stronger antigenicity and sensitization. Alanine substitution technology allowed one to perform site‐directed mutagenesis on peptide 3. Dot‐Blot and ELISA tests showed that D259, E260, E261, Q263 and C266 may be the key amino acids that significantly affect the antigenicity of peptide 3. The research presented is of great significance for correctly guiding the production of safe food and preventing the occurrence of food allergic diseases. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Styrene-maleic acid (SMA) and similar amphiphilic copolymers are known to cut biological membranes into lipid nanoparticles/nanodiscs containing membrane proteins apparently in their relatively native membrane lipid environment. Our previous work demonstrated that membrane raft microdomains resist such disintegration by SMA. The use of SMA in studying membrane proteins is limited by its heterogeneity and the inability to prepare defined derivatives. In the present paper, we demonstrate that some amphiphilic peptides structurally mimicking SMA also similarly disintegrate cell membranes. In contrast to the previously used copolymers, the simple peptides are structurally homogeneous. We found that their membrane-disintegrating activity increases with their length (reaching optimum at 24 amino acids) and requires a basic primary structure, that is, (XXD)n, where X represents a hydrophobic amino acid (optimally phenylalanine), D aspartic acid, and n is the number of repeats of these triplets. These peptides may provide opportunities for various well-defined potentially useful modifications in the study of membrane protein biochemistry. Our present results confirm a specific character of membrane raft microdomains. [ABSTRACT FROM AUTHOR]

Vigna bean and common bean have received much attention from the functional food and nutraceutical aspects. Upon hydrolysis of beans protein, bioactive peptides from various conditions are produced, with health-promoting properties and a broad spectrum of biological activities, offering nutraceutical or therapeutic potential. There have been few comprehensive investigations into improving the bioactivity and functionality of peptides from vigna and common beans. Therefore, this article describes the key parameters impacting bean derived peptide bioactivity, as well as approaches to improve it. This paper includes a review of papers indicating the stability of peptides obtained from beans under simulated gastrointestinal digestion conditions, as well as some insights into the mechanisms of action of those peptides and their relationship with structure. This review outlines important criteria for rationally designing and selecting bean bioactive peptides with intact structure and therapeutic potential in vivo. This study could be beneficial when conducting future investigations on vigna and common bean protein hydrolysates in vitro or in vivo and the knowledge gained could help with the incorporation of these new bean peptides into functional foods. [ABSTRACT FROM AUTHOR]

Next-generation single-molecule protein sequencing technologies have the potential to significantly accelerate biomedical research. These technologies offer sensitivity and scalability for proteomic analysis. One auspicious method is fluorosequencing, which involves: cutting naturalized proteins into peptides, attaching fluorophores to specific amino acids, and observing variations in light intensity as one amino acid is removed at a time. The original peptide is classified from the sequence of light-intensity reads, and proteins can subsequently be recognized with this information. The amino acid step removal is achieved by attaching the peptides to a wall on the C-terminal and using a process called Edman Degradation to remove an amino acid from the N-Terminal. Even though a framework (Whatprot) has been proposed for the peptide classification task, processing times remain restrictive due to the massively parallel data acquisicion system. In this paper, we propose a new beam search decoder with a novel state formulation that obtains considerably lower processing times at the expense of only a slight accuracy drop compared to Whatprot. Furthermore, we explore how our novel state formulation may lead to even faster decoders in the future. Author summary: Proteomic analyses frequently rely on mass spectrometry, a method characterized by its limited dynamic range, potentially overlooking low-abundant proteins. To address this limitation, single-molecule protein sequencing methods offer a solution. Fluorosequencing is a cutting-edge single-molecule protein sequencing method, which can distinguish peptides or protein molecules massively parallelly. This method has attracted interest from investors, as evidenced by the recent funding of Erisyon, a company developing this technology. This technique contains a challenging classification task: determining the original peptide sequence from light-intensity observations obtained after several Edman cycles. A classifier based on a combination of k Nearest Neighbors (kNN) with Hidden Markov Models (HMM) had been shown to have close-to-optimal accuracy with tractable complexity. We propose in this paper a new algorithm that reduces computation time significantly at the expense of a slight reduction in accuracy compared to state-of-the-art method. [ABSTRACT FROM AUTHOR]

Bacillus anthracis is a fatal biological warfare agent, with a mortality rate of almost 100% when the bacteria are inhaled. Therefore, developing a biosensor for rapidly detecting B. anthracis spores in the ambient air is critical. Conventional techniques tend to be time-consuming, labor-intensive, and require highly trained personnel, thereby preventing rapid onsite detection. Moreover, low-cost, stable probes are required for continuous monitoring of multiple airborne targets. This study presents a paper-based electrochemical peptide sensor for rapid, label-free, sensitive, and economical quantification of liquid-borne and airborne Bacillus subtilis spores, widely used nonpathogenic B. anthracis simulant spores. These sensors were fabricated using wax printing on Whatman filter paper along with stencil-printed carbon paste electrodes and Ag/AgCl ink, as well as subsequent peptide (NHFLPKV) immobilization. These low-cost quickly fabricated sensors were characterized by differential pulse voltammetry and could detect spore concentrations as low as 6.9 × 102 colony-forming units (CFU) mL-1 in 30 min with high specificity towards the spores and stability. Furthermore, spore concentrations were determined from air samples obtained using the BioSampler, which demonstrated that these measurements agreed with those using the plate-counting assay; therefore, the surface proteins of the spores were intact through sampling with the BioSampler. These paper-based peptide sensors can be used for onsite rapid and continuous airborne spore-monitoring systems. • The first study to use a peptide-immobilized electrochemical paper-based sensor for detection of whole bacteria. • Rapid, label-free, sensitive, and economical quantification of airborne B. subtilis spores is presented. • The sensors detected spore concentrations as low as 6.9 × 102 CFU/mL in 30 min with low-cost and fast fabrication. • Measurements of air-sampled spores agreed with those using the plate-counting assay. • The surface proteins of the spores were intact through sampling with the BioSampler. [ABSTRACT FROM AUTHOR]

In this paper, we report an open system consisting of three self-replicating peptides, in which peptide 1 inhibits the duplex template of peptide 2, peptide 2 inhibits duplex 3, and peptide 3 inhibits duplex 1 to complete the negative feedback loop. This interacting chemical network yields oscillations in the concentrations of all species over time and establishes a possible mechanism for pre-biotic chemical systems organization. The first focus of our analysis is the effect of altering rates of duplex formation and inhibition on oscillations. We then examine the autocatalytic rate constant in the symmetric and asymmetric cases. [ABSTRACT FROM AUTHOR]

Dipeptidyl Peptidase IV (DPP-IV) inhibitory peptides are attracting increasing attention, owing to their potential role in glycemic regulation by preventing the inactivation of incretins. However, few reviews have summarized the current understanding of DPP-IV inhibitory peptides and their knowledge gaps. This paper reviews the production, identification and structure-activity relationships (SAR) of DPP-IV inhibitory peptides. Importantly, their bioavailability and hypoglycemic effects are critically discussed. Unlike the traditional method to identifying peptides after separation step by step, the bioinformatics approach identifies peptides via virtual screening that is more convenient and efficient. In addition, the bioinformatics approach was also used to investigate the SAR of peptides. Peptides with proline (Pro) or alanine (Ala) residue at the second position of N-terminal are exhibit strong DPP-IV inhibitory activity. Besides, the bioavailability of DPP-IV inhibitory peptides is related to their gastrointestinal stability and cellular permeability, and in vivo studies showed that the glucose homeostasis has been improved by these peptides. Especially, the intestinal transport of DPP-IV inhibitory peptides and cell biological assays used to evaluate their potential role in glycemic regulation are innovatively summarized. For further successful development of DPP-IV inhibitory peptides in glycemic regulation, future study should elucidate their SAR and in vivo hypoglycemic effects. [ABSTRACT FROM AUTHOR]

Background: Viral infections have been the main health issue in the last decade. Antiviral peptides (AVPs) are a subclass of antimicrobial peptides (AMPs) with substantial potential to protect the human body against various viral diseases. However, there has been significant production of antiviral vaccines and medications. Recently, the development of AVPs as an antiviral agent suggests an effective way to treat virus-affected cells. Recently, the involvement of intelligent machine learning techniques for developing peptide-based therapeutic agents is becoming an increasing interest due to its significant outcomes. The existing wet-laboratory-based drugs are expensive, time-consuming, and cannot effectively perform in screening and predicting the targeted motif of antiviral peptides. Methods: In this paper, we proposed a novel computational model called Deepstacked-AVPs to discriminate AVPs accurately. The training sequences are numerically encoded using a novel Tri-segmentation-based position-specific scoring matrix (PSSM-TS) and word2vec-based semantic features. Composition/Transition/Distribution-Transition (CTDT) is also employed to represent the physiochemical properties based on structural features. Apart from these, the fused vector is formed using PSSM-TS features, semantic information, and CTDT descriptors to compensate for the limitations of single encoding methods. Information gain (IG) is applied to choose the optimal feature set. The selected features are trained using a stacked-ensemble classifier. Results: The proposed Deepstacked-AVPs model achieved a predictive accuracy of 96.60%%, an area under the curve (AUC) of 0.98, and a precision-recall (PR) value of 0.97 using training samples. In the case of the independent samples, our model obtained an accuracy of 95.15%, an AUC of 0.97, and a PR value of 0.97. Conclusion: Our Deepstacked-AVPs model outperformed existing models with a ~ 4% and ~ 2% higher accuracy using training and independent samples, respectively. The reliability and efficacy of the proposed Deepstacked-AVPs model make it a valuable tool for scientists and may perform a beneficial role in pharmaceutical design and research academia. [ABSTRACT FROM AUTHOR]

Synthetic therapeutic peptides are a complex and popular class of pharmaceuticals. In recent years, peptides with proven therapeutic activity have gained significant interest in the market. The determination of synthetic peptide enantiomeric purity plays a critical role in the evaluation of the quality of the medicine. Since racemization is one of the most common side reactions occurring in AAs or peptides, enantiomeric impurities such as D‐isomers can form during the peptide synthesis or can be introduced from the starting materials (e.g., AAs). The therapeutic effect of a synthetic or semi‐synthetic bioactive peptide molecule depends on its AA enantiomeric purity and secondary/tertiary structure. Therefore, the enantiomeric purity determination for synthetic peptides is supportive for interpreting unwanted therapeutic effects and determining the quality of synthetic peptide therapeutics. However, enantiomeric purity analysis encounters formidable analytical challenges during chromatographic separation, as D/L isomers have identical physical–chemical properties except stereochemical configuration. To ensure peptides AA stereochemical configuration whether in the free or bound state, sensitive and reproducible quantitative analytical method is mandatory. In this regard, numerous analytical techniques were emerged for the quantification of D‐isomeric impurities in synthetic peptides, but still, very few reports are available in the literature. Thus, the purpose of this paper is to provide an overview of the importance, regulatory requirements, and various analytical methods used for peptide enantiomeric purity determination. In addition, we discussed the available literature in terms of enantiomeric impurity detection, common hydrolysis procedural aspects, and different analytical strategies used for sample preparation. [ABSTRACT FROM AUTHOR]

The aim of the paper was to develop chitosan-coated nanoliposomes for carrying bioactive peptides derived from hydrolyzed shrimp waste (SW) with chitosan coating (concentrations of 0, 0.5 and 1% W/ V). The study involved producing SW hydrolysates using protease enzymes from Bacillus salsus bacteria, followed by investigating the physicochemical, antioxidant, and antimicrobial properties of the peptide-loaded nanoliposomes. The dispersion index ranged from 0.17 to 0.65, and the particle size varied from 500 to 685 nm. Increasing the chitosan concentration to 1% significantly increased the particle size (P < 0.05). The Zeta potential of the nanoliposomes became positive as the chitosan concentration increased, starting from − 47.73 mV and reaching + 36.40 mV. The highest encapsulation efficiency (84.67%) was observed in nanoliposomes with 1% chitosan, while uncoated liposomes had the lowest encapsulation efficiency (44%). Scanning electron microscopy (SEM) revealed that the nanoparticles exhibited homogeneous, spherical, and cluster-shaped structures with smooth surfaces. Chitosan coating enhanced the stability of the peptides in simulated stomach and intestinal environments, with higher stability observed at higher chitosan concentrations (P < 0.05). Chitosan-coated nanoliposomes exhibited higher antioxidant and antimicrobial activities compared to uncoated nanoliposomes. Increasing the chitosan concentration resulted in greater inhibition of free radicals (DPPH and ABTS free radical activities increased significantly in nanoliposomes with 1% chitosan compared to uncoated samples: 32.56–70.28% and 41.58–80.28% respectively) and enhanced antimicrobial properties (P < 0.05). In conclusion, coating hydrolyzed SW with nanoliposomes and chitosan improved the structural, physicochemical, antioxidant, and antimicrobial properties of the peptides, making them suitable for direct application in food products requiring antioxidant and antimicrobial effects. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area. [ABSTRACT FROM AUTHOR]

Simple Summary: This review mainly focuses on epigenetic changes in a few selective genes associated with insulin insensitivity in the periphery and how this peripheral insulin insensitivity is linked with impaired signaling of insulin in the brain, thus causing Alzheimer's disease. DNA methylation and histone modifications are the focus of this review, with primary importance given to DNA methylation. Moreover, there has been a focus shift from the amyloid β hypothesis to epigenetic mechanisms. Furthermore, we discuss the advanced drug delivery systems that can be used for the delivery of drugs targeting the brain during Alzheimer's disease. The advanced drug delivery systems discussed in this paper are nanoparticles, vesicular systems, network systems and dendrimers, hydrogel-based systems, and biologics. Alzheimer's disease (AD) is a neurodegenerative condition that predominantly affects the hippocampus and the entorhinal complex, leading to memory lapse and cognitive impairment. This can have a negative impact on an individual's behavior, speech, and ability to navigate their surroundings. AD is one of the principal causes of dementia. One of the most accepted theories in AD, the amyloid β (Aβ) hypothesis, assumes that the buildup of the peptide Aβ is the root cause of AD. Impaired insulin signaling in the periphery and central nervous system has been considered to have an effect on the pathophysiology of AD. Further, researchers have shifted their focus to epigenetic mechanisms that are responsible for dysregulating major biochemical pathways and intracellular signaling processes responsible for directly or indirectly causing AD. The prime epigenetic mechanisms encompass DNA methylation, histone modifications, and non-coding RNA, and are majorly responsible for impairing insulin signaling both centrally and peripherally, thus leading to AD. In this review, we provide insights into the major epigenetic mechanisms involved in causing AD, such as DNA methylation and histone deacetylation. We decipher how the mechanisms alter peripheral insulin signaling and brain insulin signaling, leading to AD pathophysiology. In addition, this review also discusses the need for newer drug delivery systems for the targeted delivery of epigenetic drugs and explores targeted drug delivery systems such as nanoparticles, vesicular systems, networks, and other nano formulations in AD. Further, this review also sheds light on the future approaches used for epigenetic drug delivery. [ABSTRACT FROM AUTHOR]

Effective drug delivery is essential for cancer treatment. Drug delivery systems, which can be tailored to targeted transport and integrated tumor therapy, are vital in improving the efficiency of cancer treatment. Peptides play a significant role in various biological and physiological functions and offer high design flexibility, excellent biocompatibility, adjustable morphology, and biodegradability, making them promising candidates for drug delivery. This paper reviews peptide-mediated drug delivery systems, focusing on self-assembled peptides and peptide–drug conjugates. It discusses the mechanisms and structural control of self-assembled peptides, the varieties and roles of peptide–drug conjugates, and strategies to augment peptide stability. The review concludes by addressing challenges and future directions. [ABSTRACT FROM AUTHOR]

Chagas disease and leishmaniasis are both neglected tropical diseases that affect millions of people around the world. Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization records approximately 0.7–1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000–30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Pentavalent antimonials, amphotericin B, miltefosine, paromomycin, and pentamidine are currently used to treat leishmaniasis. Also, nifurtimox and benznidazole are two drugs currently used to treat Chagas disease. These drugs are associated with toxicity problems such as nephrotoxicity and cardiotoxicity, in addition to resistance problems. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Overall, there is a need for new and effective treatments for Chagas disease and leishmaniasis, as the current drugs have significant limitations. Peptide-based drugs are attractive due to their high selectiveness, effectiveness, low toxicity, and ease of production. This paper reviews the potential use of peptides in the treatment of Chagas disease and leishmaniasis. Several studies have demonstrated that peptides are effective against Chagas disease and leishmaniasis, suggesting their use in drug therapy for these diseases. Overall, peptides have the potential to be effective therapeutic agents against Chagas disease and leishmaniasis, but more research is needed to fully investigate their potential. [ABSTRACT FROM AUTHOR]

Background: Endometrial receptivity (ER), a pivotal event for successful embryo implantation, refers to the capacity of endometrium to allow the adhesion of the trophectoderm of the blastocyst to endometrial cells. In this paper, we set to elucidate whether the peptides encoded by lncRNAs could influence trophoblast cells' adhesion to endometrial cells. Methods: WGCNA construction and bioinformatics were used to find out the ER-related lncRNAs with coding potential. Protein analysis was done by immunoblotting and immunofluorescence (IF) microscopy. CCK-8 and Calcein-AM/PI double staining assays were employed to evaluate cell viability. The effect of the peptide on trophoblast spheroids' adhesion to endometrial cells was evaluated. The RNA sequencing (RNA-seq) analysis was applied to identify downstream molecular processes. Results: lncRNA LINC00339 was found to be related to ER development and it had been predicted to have protein-coding potential. LINC00339 had high occupancy of ribosomes and was confirmed to encode a 49-aa peptide (named LINC00339-205-49aa). LINC00339-205-49aa could promote the attachment of JAR trophoblast spheroids to Ishikawa endometrial cells in vitro. LINC00339-205-49aa also upregulated the expression of E-cadherin in Ishikawa cells. Mechanistically, MAPK and PI3K-Akt signaling pathways were involved in the modulation of LINC00339-205-49aa, which were activated by LINC00339-205-49aa in Ishikawa cells. Conclusion: These data demonstrate that a previously uncharacterized peptide encoded by lncRNA LINC00339 has the ability to enhance JAR trophoblast spheroids' adhesion to Ishikawa endometrial cells, highlighting a new opportunity for the development of drugs to improve ER. [ABSTRACT FROM AUTHOR]

The detection of botulinum neurotoxin A (BoNT/A) endopeptidase activity by pregnancy test paper based on human chorionic gonadotropin (hCG)-functionalized peptide-modified magnetic nanoparticles (MNs) is described for the first time. HCG-functionalized SNAP-25 peptide substrate with hydrolysis recognition sites was optimally designed. HCG can be recognized by pregnancy test strips. BoNT/A light chain (BoNT-LcA) is the central part of the endopeptidase function in holotoxin, which can specifically hydrolyze SNAP-25 peptide to release the hCG-peptide probe, and the hCG-peptide probe released can be quantitatively detected by pregnancy test strips, achieving indirect determination of BoNT/A. By quantifying the T-line color intensity of test strips, the visual detection limit for BoNT-LcA is 12.5 pg/mL, and the linear range of detection for BoNT-LcA and BoNT/A holotoxin was 100 pg/mL to 1 ng/mL and 25 to 250 ng/mL. The ability of the method to quantify BoNT/A was validated in human serum samples. This method shows the potential for sensitive detecting BoNT/A and has prospects for the diagnosis and prognosis of clinical botulism. [ABSTRACT FROM AUTHOR]

α-Amylase inhibitory peptides are used to treat diabetes, but few studies have statistically characterized their interaction with α-amylase. This study performed the molecular docking of α-amylase with inhibitory peptides from published papers. The key sites, side chain chargeability, and hydrogen bond distribution characteristics were analyzed. Molecular dynamics simulated the role of key sites in complex stability. Moreover, partial least squares regression (PLSR) was used to analyze the contribution of different amino acids in the peptides to inhibition. The results showed that, for the α-amylase molecule, His201 and Gln63, with the highest interaction numbers (INs, 15, 15) and hydrogen bond values (HBVs, 11.50, 10.33), are the key sites on α-amylase, and amino acids with positively charged side chains were important for inhibitory activity. For the inhibitory peptides, Asp and Arg had the highest HBVs, and amino acids with charged side chains were more likely to form hydrogen bonds and exert inhibitory activity. In molecular dynamics simulations, peptides involving key binding sites formed more stable complexes with α-amylase than α-amylase alone, suggesting enhanced inhibitory effects. Further, PLSR results showed that amino acids close to the N-terminus of the inhibitory peptide, located in the third and fifth positions, were significantly correlated with its inhibitory activity. In conclusion, this study provides a new approach to developing and screening α-amylase inhibitors. [ABSTRACT FROM AUTHOR]

Biohybrid catalysts that operate in aqueous media are intriguing for systems chemistry. In this paper, we investigate whether control over the self‐assembly of biohybrid catalysts can tune their properties. As a model, we use the catalytic activity of functional hybrid molecules consisting of a catalytic H‐dPro‐Pro‐Glu tripeptide, derivatized with fatty acid and nucleobase moieties. This combination of simple biological components merged the catalytic properties of the peptide with the self‐assembly of the lipid, and the structural ordering of the nucleobases. The biomolecule hybrids self‐assemble in aqueous media into fibrillar assemblies and catalyze the reaction between butanal and nitrostyrene. The interactions between the nucleobases enhanced the order of the supramolecular structures and affected their catalytic activity and stereoselectivity. The results point to the significant control and ordering that nucleobases can provide in the self‐assembly of biologically inspired supramolecular catalysts. [ABSTRACT FROM AUTHOR]

Mass spectrometry is widely employed in various analytical fields for both compound identification and quantification. While in the case of compound identification, the high‐resolution instrument has increased selectivity and characterization efficiency; in the case of quantitative analysis, some critical tasks actually remain. In particular, different compounds exhibit different ionization efficiency, and this introduces the need to have a calibration standard for each analyte. In this paper, we present a new elaborative data technology, which makes it possible to standardize calibration between different instruments and molecules, making it absolute. The method was applied to data acquired by means of liquid chromatography mass spectrometry by means of an ion trap analyzer. The approach is based on the correlation of the ion trap space charge effect and the analyte concentration. The method was validated in the analysis of compounds having different polarity: hydrossitirosol, arginine, thyodiglicolic acid, and a peptide mixture of bacteria cultures derived the human gut microbiome where was found poliovirus. Moreover, it was used to obtain the absolute quantitation of peptides originating from the tryptic digestion of bacterial proteins in the fecal samples. It was therefore possible to identify and quantify different derived bacterial proteins of the poliomyelitis virus coded in bacteria derived from the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Leptin is a tonic appetite-regulating hormone, which is integral for the long-term regulation of energy balance. The current evidence suggests that the typical orexigenic or anorexigenic response of many of these appetite-regulating hormones, most notably ghrelin and cholecystokinin (CCK), require leptin to function whereas glucagon-like peptide-1 (GLP-1) is required for leptin to function, and these responses are altered when leptin injection or gene therapy is administered in combination with these same hormones or respective agonists. The appetite-regulatory pathway is complex, thus peptide tyrosine tyrosine (PYY), brain-derived neurotrophic factor (BDNF), orexin-A (OXA), and amylin also maintain ties to leptin, however these are less well understood. While reviews to date have focused on the existing relationships between leptin and the various neuropeptide modulators of appetite within the central nervous system (CNS) or it's role in thermogenesis, no review paper has synthesised the information regarding the interactions between appetite-regulating hormones and how leptin as a chronic regulator of energy balance can influence the acute appetite-regulatory response. Current evidence suggests that potential relationships exist between leptin and the circulating peripheral appetite hormones ghrelin, GLP-1, CCK, OXA and amylin to exhibit either synergistic or opposing effects on appetite inhibition. Though more research is warranted, leptin appears to be integral in both energy intake and energy expenditure. More specifically, functional leptin receptors appear to play an essential role in these processes. [ABSTRACT FROM AUTHOR]

Obesity is a global health concern with limited treatment options due to side effects and limited efficacy. Bioactive peptides (BAPs) derived from food proteins have shown promise as safe and effective anti-obesity agents by regulating adipocyte differentiation through various signaling pathways. BAPs derived from milk, eggs, fish, and marine sources have been extensively studied for their anti-obesity effects in vitro and in vivo. These peptides can alter gut hormones and appetite to regulate energy balance while decreasing adipogenesis and increasing adipocyte apoptosis. This paper provides a comprehensive overview of the studies investigating the potency of BAPs in managing obesity. It focuses on their ability to modulate adipogenesis and regulate appetite and lipid metabolism. Key findings and Conclusions: BAPs derived from various food sources such as milk, eggs, fish, and marine byproducts have the potential to act as anti-obesity agents. These peptides have been shown to be able to regulate adipogenesis, lipid metabolism, and appetite control through different mechanisms, making them promising candidates for developing functional foods or nutraceuticals for obesity prevention and management. This paper also highlights the advantages of using BAPs over conventional anti-obesity drugs, such as their safety, natural origin, and lower risk of adverse effects. Further research and development in this field can lead to the identification and utilization of specific BAPs with optimized efficacy and minimal side effects, ultimately contributing to the development of novel anti-obesity therapies. [Display omitted] • Various food proteins as potential source of bioactive peptides is summarized. • Bioactive peptides derived from food is promising anti-obesity agent. • In vitro and in vivo experiment proven an anti-obesity activity through various mechanism. • Food derived bioactive peptides are prospective for development of functional foods or nutraceuticals. [ABSTRACT FROM AUTHOR]

The atomistic description of the folding process of a structureless chain of amino acids to a functioning protein is still considered to be a challenge for computational biophysics. An in-depth understanding of protein-folding can be achieved through atomistic dynamics accounting for the solvent effects, combined with the theoretical description of conformational changes in shorter polypeptide chains. The present paper studies the folding transitions in short polypeptide chains consisting of 11 alanine residues in explicit solvent employing all-atom molecular dynamics. The multiple observed folding ↔ unfolding events of the peptide are interpreted as a dynamic process and rationalised through the analysis of the potential energy surface of the system. It is demonstrated that alanine polypeptide folding dynamics is governed by the backbone dihedral angles and involves the formation of spontaneously folded α -helices which emerge and live for ca. 1–20 picoseconds. The helical content within the polypeptide at different temperatures was quantified through a statistical mechanics approach, which showed a reasonable agreement with the results of molecular dynamics simulations and experiments performed for alanine-rich peptides. [ABSTRACT FROM AUTHOR]

The assembly of the β-amyloid peptide (Aβ) to form oligomers and fibrils is closely associated with the pathogenesis and progression of Alzheimer's disease. Aβ is a shape-shifting peptide capable of adopting many conformations and folds within the multitude of oligomers and fibrils the peptide forms. These properties have precluded detailed structural elucidation and biological characterization of homogeneous, well-defined Aβ oligomers. In this paper, we compare the structural, biophysical, and biological characteristics of two different covalently stabilized isomorphic trimers derived from the central and C-terminal regions Aβ. X-ray crystallography reveals the structures of the trimers and shows that each trimer forms a ball-shaped dodecamer. Solution-phase and cell-based studies demonstrate that the two trimers exhibit markedly different assembly and biological properties. One trimer forms small soluble oligomers that enter cells through endocytosis and activate capase-3/7-mediated apoptosis, while the other trimer forms large insoluble aggregates that accumulate on the outer plasma membrane and elicit cellular toxicity through an apoptosis-independent mechanism. The two trimers also exhibit different effects on the aggregation, toxicity, and cellular interaction of full-length Aβ, with one trimer showing a greater propensity to interact with Aβ than the other. The studies described in this paper indicate that the two trimers share structural, biophysical, and biological characteristics with oligomers of full-length Aβ. The varying structural, assembly, and biological characteristics of the two trimers provide a working model for how different Aβ trimers can assemble and lead to different biological effects, which may help shed light on the differences among Aβ oligomers. [ABSTRACT FROM AUTHOR]

Human infection with the intestinal nematode Strongyloides stercoralis is persistent unless effectively treated, and potentially fatal in immunosuppressed individuals. Epidemiological data are lacking, partially due to inadequate diagnosis. A rapid antigen detection test is a priority for population surveillance, validating cure after treatment, and for screening prior to immunosuppression. We used a targeted analysis of open access 'omics' data sets and used online predictors to identify S. stercoralis proteins that are predicted to be present in infected stool, Strongyloides-specific, and antigenic. Transcriptomic data from gut and non-gut dwelling life cycle stages of S. stercoralis revealed 328 proteins that are differentially expressed. Strongyloides ratti proteomic data for excreted and secreted (E/S) proteins were matched to S. stercoralis, giving 1,057 orthologues. Five parasitism-associated protein families (SCP/TAPS, prolyl oligopeptidase, transthyretin-like, aspartic peptidase, acetylcholinesterase) were compared phylogenetically between S. stercoralis and outgroups, and proteins with least homology to the outgroups were selected. Proteins that overlapped between the transcriptomic and proteomic datasets were analysed by multiple sequence alignment, epitope prediction and 3D structure modelling to reveal S. stercoralis candidate peptide/protein coproantigens. We describe 22 candidates from seven genes, across all five protein families for further investigation as potential S. stercoralis diagnostic coproantigens, identified using open access data and freely-available protein analysis tools. This powerful approach can be applied to many parasitic infections with 'omic' data to accelerate development of specific diagnostic assays for laboratory or point-of-care field application. Author summary: The worm Strongyloides stercoralis causes infectious disease in people throughout tropical and sub-tropical regions, leading to an extensive reduction in quality of life and even death. Millions of people are at risk of infection with this parasite and improved diagnostic and control methods and technologies are urgently required. Currently, most diagnosis is carried out through methods involving visual inspection of patient's faeces, which has a number of drawbacks, particularly its poor sensitivity. This paper presents a new method to develop improved diagnostic tests for S. stercoralis, by computational analysis of publicly available gene and protein sequences to predict proteins that may be detectable in faeces. This would enable the development of rapid diagnostic tests in the form of lateral flows or dipsticks, with better predictive ability and fewer drawbacks than current diagnostic methods. A number of potential proteins, predicted to have all the desired characteristics for use in such tests were found through the new method and have been presented in this paper. With validation, new diagnostic tests for S. stercoralis could be developed from these results and the computational approach could be used to target other parasitic diseases. [ABSTRACT FROM AUTHOR]

A selected ion monitoring (SIM) approach combined with high resolution mass spectrometry is employed to identify and distinguish common SARS-CoV2 omicron and recombinant variants in clinical specimens. Mutations within the receptor binding domain (RBD) within the surface spike protein of the virus result in a combination of peptide segments of unique sequence and mass that were monitored to detect BA.2.75 (including CH.1.1) and XBB (including 1.5) variants prevalent in the state's population in early 2023. SIM detection of pairs of peptides unique to each variant were confidently detected and differentiated in 57.3% of the specimens, with a further 10 or 17.5% (for a total of 74.8%) detected based on a single peptide biomarker. The BA.2.75 sub-variant was detected in 18.7%, while recombinant variants XBB and XBB.1.5 were detected in 13.3% and 25.3% of the specimens respectively, consistent with circulating levels in the population characterised by RT-PCR. Virus was detected in 75 SARS-CoV2 positive specimens by mass spectrometry down to the low or mid 104 copy level, with a single false positive and no false negative identified. This article is the first paper to characterise recombinant strains of the SARS-CoV2 virus by this, or any other, MS method. [ABSTRACT FROM AUTHOR]

The purpose of the paper was to explore the effect of adding different levels of soybean active peptides to the diet on the growth performance, carcass traits, serum biochemical indexes and intestinal microorganisms of finishing pigs. A total of 120 finishing pigs with a weight of (72.40±1.10) kg were randomly divided into four groups, with three replicates in each group and 10 pigs in each replicate. The finishing pigs in the control group were fed a basic diet, and group A, group B and group C added 0.2%, 0.4% and 0.6% soybean active peptides in the basic diet, respectively. The experiment lasted for 42 days. The results showed that the average daily gain of the finishing pigs was significantly increased by adding soybean active peptide (P<0.05). Compared with the control group, the feed-to-weight ratio of the group B was significantly reduced (P<0.05), and the feed-to-weight ratio and average back fat thickness of the group C were significantly reduced ( P<0.05). Adding soybean active peptide could improve the meat color and significantly reduce the dripping loss of the finishing pigs in the group B and group C (P<0.05). Compared with the control group, the content of serum MDA in the experimental groups decreased significantly (P<0.05), the content of serum BUN in the group B and group C decreased significantly (P<0.05), the content of IgM and T-AOC increased significantly (P<0.05). The activity of serum AST and GSH-Px in the group C decreased significantly, and the content of IgG increased significantly (P<0.05). The flora with a relative abundance of more than 1% at the phylum level in each experimental group included Firmicutes, Proteobacterium and Bacteroides, and the relative abundance of Proteobacterium in the group C was significantly lower than that in the control group (P<0.05). The flora with a relative abundance over 1% at the genus level included Actinomycetes, Coprococcus, Clostridium and Enterobacter, and there was no significant difference in the relative abundance of each genus compared with the control group (P>0.05). The study indicates that adding 0.4%~0.6% soybean active peptide to the diet can improve the growth performance, modify carcass traits, adjust serum biochemical indexes, and affect the intestinal microbial composition of finishing pigs. [ABSTRACT FROM AUTHOR]

AbstractNLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family, plays an essential role in the inflammation initiation and inflammatory mediator secretion, and thus is also associated with many disease progressions. Food-derived bioactive peptides (FDBP) exhibit excellent anti-inflammatory activity in both in vivo and in vitro models. They are encrypted in plant, meat, and milk proteins and can be released under enzymatic hydrolysis or fermentation conditions, thereby hindering the progression of hyperuricemia, inflammatory bowel disease, chronic liver disease, neurological disorders, lung injury and periodontitis by inactivating the NLRP3. However, there is a lack of systematic review around FDBP, NLRP3, and NLRP3-related diseases. Therefore, this review summarized FDBP that exert inhibiting effects on NLRP3 inflammasome from different protein sources and detailed their preparation and purification methods. Additionally, this paper also compiled the possible inhibitory mechanisms of FDBP on NLRP3 inflammasomes and its regulatory role in NLRP3 inflammasome-related diseases. Finally, the progress of cutting-edge technologies, including nanoparticle, computer-aided screening strategy and recombinant DNA technology, in the acquisition or encapsulation of NLRP3 inhibitory FDBP was discussed. This review provides a scientific basis for understanding the anti-inflammatory mechanism of FDBP through the regulation of the NLRP3 inflammasome and also provides guidance for the development of therapeutic adjuvants or functional foods enriched with these FDBP. [ABSTRACT FROM AUTHOR]

Angiotensin and kinin metabolic pathways are reported to be altered by many diseases, including COVID-19. Monitoring levels of these peptide metabolites is important for understanding mechanisms of disease processes. In this paper, we report dimethyl labeling of amines in peptides by addition of formal-dehyde to samples and deutero-formaldehyde to internal standards to generate nearly identical isotopic standards with 4 m/z units larger per amine group than the corresponding analyte. We apply this approach to rapid, multiplexed, absolute LC-MS/MS quantitation of renin angiotensin system (RAS) and kallikrein-kinin system (KKS) peptides in human blood serum. Limits of detection (LODs) were obtained in the low pg mL−1 range with 3 orders of magnitude dynamic ranges, appropriate for determinations of normal and elevated levels of the target peptides in blood serum and plasma. Accuracy is within ±15% at concentrations above the limit of quantitation, as validated by spike-recovery in serum samples. Applicability was demonstrated by measuring RAS and KKS peptides in serum from COVID-19 patients, but is extendable to any class of peptides or other small molecules bearing reactive –NH2 groups. [ABSTRACT FROM AUTHOR]

Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustainedrelease behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP doublemodified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-a and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE. [ABSTRACT FROM AUTHOR]

Ongoing research is gradually broadening the idea of cancer treatment, with attention being focused on nanoparticles to improve the stability, therapeutic efficacy, targeting, and other important metrics of conventional drugs and traditional drug delivery methods. Studies have demonstrated that drug delivery carriers based on biomaterials (e.g., protein nanoparticles and lipids) and inorganic materials (e.g., metal nanoparticles) have potential anticancer effects. Among these carriers, self-assembled proteins and peptides, which are highly biocompatible and easy to standardize and produce, are strong candidates for the preparation of anticancer drugs. Breast cancer (BC) and cervical cancer (CC) are two of the most common and deadly cancers in women. These cancers not only threaten lives globally but also put a heavy burden on the healthcare system. Despite advances in medical care, the incidence of these two cancers, particularly CC, which is almost entirely preventable, continues to rise, and the mortality rate remains steady. Therefore, there is still a need for in-depth research on these two cancers to develop more targeted, efficacious, and safe therapies. This paper reviews the types of self-assembling proteins and peptides (e.g., ferritin, albumin, and virus-like particles) and natural products (e.g., soy and paclitaxel) commonly used in the treatment of BC and CC and describes the types of drugs that can be delivered using self-assembling proteins and peptides as carriers (e.g., siRNAs, DNA, plasmids, and mRNAs). The mechanisms (including self-assembly) by which the natural products act on CC and BC are discussed. The mechanism of action of natural products on CC and BC and the mechanism of action of self-assembled proteins and peptides have many similarities (e.g., NF-KB and Wnt). Thus, natural products using self-assembled proteins and peptides as carriers show potential for the treatment of BC and CC. [ABSTRACT FROM AUTHOR]

Medium sized molecules such as peptides and macrocycles have recently drawn much attention as potent sources of medicinal lead compounds, whereas the possibility of obtaining a practical drug from them remains limited. The present paper describes a concept of discovering novel medicinal targets or binding modes as well as lead compounds by the one‐peptide‐on‐one‐bead (OPOB) technology for comprehensive screening. The difficulty and problems in conventional drug discovery methods that generally deal with one predetermined target are considered. The building blocks used for the present libraries were selected based on previous results in development of peptidic drugs. Each constituent has the common structure of cyclic form prepared by disulfide of cysteinyl residues or thioether linkages, additionally a methionine residue was inserted for the site‐specific rapid cleavage by cyanogen bromide to liberate the immobilized peptides allowing reliable characterization by MALDI‐TOF‐MS/MS without LC‐purification. Thus, a high throughput construction method for cyclic peptide libraries as well as characterization of single bead are proposed for drug discovery. [ABSTRACT FROM AUTHOR]

Interferences from isobaric and isomeric compounds represent a common problem in liquid chromatography coupled to mass spectrometry (LC-MS). In this paper, in-source purification and chromatographic separation were combined with the aim of identifying isobaric contamination and quantifying accurately a compound despite the presence of an isobaric co-eluted interference. This is achieved by totally fragmenting in-source the precursor ions of the isobaric interference providing then LC-pseudo-MS2 capability, which allows an accurate quantification without the need for optimizing the chromatographic conditions to separate the co-eluted interference. To illustrate this concept, mixtures of tryptic and non-tryptic peptides were used. The ratio of peak areas of the tryptic peptide and its isotopically labelled internal standard was used not only for quantification with an internal standard calibration curve but also to know (1) if an isobaric interference co-eluted with the tryptic peptide; and (2) what is the minimum cone voltage necessary to ensure the complete removal of isobaric interference. This strategy was applied to quantify the tryptic peptide of two standards with known concentrations and, intentionally contaminated with the isobaric interference. The confidence intervals of the concentrations calculated with the internal standard calibration curve were 8.0 ± 0.5 μM (prepared at 8.0 μM) and 15.7 ± 0.5 μM (prepared at 16.1 μM) that confirm the tryptic peptide can be correctly quantified by in-source purification without the need for improving the chromatographic separation from its isobaric interference. [ABSTRACT FROM AUTHOR]

Sequential peptide coupling plays a central role in chemical protein synthesis. This paper describes a new peptide derivative, peptide-aminothiazoline (At), whereof the C-terminus is functionalized with 2-aminothiazoline. Peptide-At streamlined the sequential peptide ligation in a one-pot manner and demonstrated the convergent synthesis of a circular protein and homogeneous glycoproteins. [ABSTRACT FROM AUTHOR]

Bioactive peptides derived from diverse food proteins have been part of diverse investigations. Whey is a rich source of proteins and components related to biological activity. It is known that proteins have effects that promote health benefits. Peptides derived from whey proteins are currently widely studied. These bioactive peptides are amino acid sequences that are encrypted within the first structure of proteins, which required hydrolysis for their release. The hydrolysis could be through in vitro or in vivo enzymatic digestion and using microorganisms in fermented systems. The biological activities associated with bio-peptides include immunomodulatory properties, antibacterial, antihypertensive, antioxidant and opioid, etc. These functions are related to general conditions of health or reduced risk of certain chronic illnesses. To determine the suitability of these peptides/ingredients for applications in food technology, clinical studies are required to evaluate their bioavailability, health claims, and safety of them. This review aimed to describe the biological importance of whey proteins according to the incidence in human health, their role as bioactive peptides source, describing methods, and obtaining technics. In addition, the paper exposes biochemical mechanisms during the activity exerted by biopeptides of whey, and their application trends. [ABSTRACT FROM AUTHOR]

Blood-brain barrier penetrating peptides (BBBPs) are short peptide sequences that possess the ability to traverse the selective blood-brain interface, making them valuable drug candidates or carriers for various payloads. However, the in vivo or in vitro validation of BBBPs is resource-intensive and time-consuming, driving the need for accurate in silico prediction methods. Unfortunately, the scarcity of experimentally validated BBBPs hinders the efficacy of current machine-learning approaches in generating reliable predictions. In this paper, we present DeepB3P3, a novel framework for BBBPs prediction. Our contribution encompasses four key aspects. Firstly, we propose a novel deep learning model consisting of a transformer encoder layer, a convolutional network backbone, and a capsule network classification head. This integrated architecture effectively learns representative features from peptide sequences. Secondly, we introduce masked peptides as a powerful data augmentation technique to compensate for small training set sizes in BBBP prediction. Thirdly, we develop a novel threshold-tuning method to handle imbalanced data by approximating the optimal decision threshold using the training set. Lastly, DeepB3P3 provides an accurate estimation of the uncertainty level associated with each prediction. Through extensive experiments, we demonstrate that DeepB3P3 achieves state-of-the-art accuracy of up to 98.31% on a benchmarking dataset, solidifying its potential as a promising computational tool for the prediction and discovery of BBBPs. [ABSTRACT FROM AUTHOR]

Charged short peptides and glucose oxidase (GOx) were studied in this paper to reveal how these peptides alter the activity and structure of GOx. Results showed that the synthesized negatively charged peptides T 8 − and positively charged peptides T 9 + could increase and decrease enzyme activity, respectively. The T 8 − treated GOx potential increased by 33.6%. Meanwhile, the α-helix content decreased by 5.5%, and the root mean square deviation (RMSD) value decreased significantly. The fluorescence and UV–visible spectra revealed varying degrees of changes in peak and peak intensity, respectively. Overall, in the absence of contact reactions between T 9 + and T 8 − with GOx, the CPs changed the microenvironment around GOx and the charge arrangement on its surface, causing conformational changes in GOx and altering its enzymatic activity. The effect of CPs on GOx was further investigated using the molecular docking technique. After T 8 - treatment, the number of hydrogen bonds increased from 3 without short peptide treatment to 8 [Display omitted] • Uncovering the mechanism by which tiny charged substances alter enzyme activity.Provide a new strategy to change enzyme activity. • Provide new ideas for revealing the nature of the reaction between enzyme and substrate. • Enhance the potential of glucose oxidase application in industry. [ABSTRACT FROM AUTHOR]